Stopping the Grand Pandemic: A Framework for Action Addressing Antimicrobial Resistance through World Bank Operations May 2024 Copyright © 2024 by International Bank for Reconstruction and Development / The World Bank 1818 H Street NW, Washington, DC 20433 Telephone: 202-473-1000 Internet: www.worldbank.org Some rights reserved. This work is available under the Creative Commons Attribution-3.0 IGO license (CC BY 3.0 IGO) https://creativecommons.org/licenses/by/3.0/igo/. Suggested citation: Rupasinghe, N., C. Machalaba, T. Muthee, and A. Mazimba. Stopping the Grand Pandemic: A Framework for Action. Addressing Antimicrobial Resistance through World Bank Operations. Washington, DC: World Bank; 2024. License: CC BY 3.0 IGO. This work is a product of the staff of The World Bank with external contributions. The findings, interpretations, and conclusions expressed in this work do not necessarily reflect the views of The World Bank, its Board of Executive Directors, or the governments they represent. The World Bank does not guarantee the accuracy, completeness, or currency of the data included in this work and does not assume responsibility for any errors, omissions, or discrepancies in the information, or liability with respect to the use of or failure to use the information, methods, processes, or conclusions set forth. The boundaries, colors, denominations, and other information shown on any map in this work do not imply any judgment on the part of The World Bank concerning the legal status of any territory or the endorsement or acceptance of such boundaries. Any queries on rights and licenses, including subsidiary rights, should be addressed to: World Bank Publications, The World Bank Group, 1818 H Street NW, Washington, DC 20433, USA. Fax: 202-522-2625 Email: pubrights@worldbank.org Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 2 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Contents Introduction Foreword 8 Acknowledgements 9 Abbreviations 11 Executive Summary 14 Chapter Guide 17 A Primer on AMR 20 Chapter 1 Summary 30 Why Addressing AMR Remains Antimicrobial resistance as a threat to global health security Critical to Global Health Security and global development 31 and Global Development Purpose of the framework for action 35 Audience 35 Rationale for World Bank involvement 36 Higher-level objectives 40 Global, regional, and national issues 41 References 42 Chapter 2 Summary 46 Four Thematic Entry Points for Introduction 47 Addressing AMR Reducing infections: A focus on IPC, vaccination, and nutrition 47 Strengthening monitoring and surveillance of AMR and AMU 50 Improving access and the rational use of antimicrobials: A focus on antimicrobial stewardship and regulatory frameworks 51 Strengthening sectoral and multisectoral coordination and governance 54 References 61 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 3 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 3 Summary 66 Twenty Intervention Areas Introduction 67 Methodology 68 Entry points for Global Practices and sectors for AMR interventions 69 Bibliography 81 Health sector 85 Agriculture and food sector 103 Water and environment sector 119 Multisector 134 Chapter 4 Summary 147 Investing in AMR through World Bank Operations Introduction 148 Overview of the 2022 portfolio review 148 Menu of options by sector 150 Health sector approaches 151 Agricultural and food sector approaches 157 Water and environment sector approaches 161 References 166 Chapter 5 Summary 168 Implementation Guidance for Introduction 169 Investing in Interventions to Address AMR through World National institutional arrangements 171 Bank Operations Regional institutional arrangements 174 Takeaways 178 References 179 Three implementation case studies  180 Case study 1: Indonesia 180 Case study 2: Tanzania 192 Case study 3: Nigeria 202 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 4 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 6 Summary 214 Tools to Support the Design and Introduction 215 Implementation of Operations Phase 1: Project identification, preparation, and appraisal 216 Phase 2: Implementation 218 Phase 3: Completion and evaluation 220 Tools 222 Costing and implementing AMR interventions, including NAPs 240 References 241 Appendices Appendix 1: An Overview of the World Bank Project Cycle and Instruments 245 Appendix 2: Further details on the methodology for the Evidence Review of Interventions 249 Appendix 3: Environmental and Social Safeguards Guidance 271 Tables Table 1. Intervention Areas  15 Table 2. AMR and the SDGs 36 Table 3. Summary of Interventions across Four Thematic Entry Points for Addressing AMR in Key Sectors 57 Table 4. Intervention Areas  70 Table 5. Evidence Assessment for the Intervention Areas 71 Table 6. Addressing AMR across Sectors: Challenges and Existing Interventions 182 Table 7. Actions Taken and the Enablers of Progress 185 Table 8. Tricycle Pilot: Partners and Implementation Arrangements 187 Table 9. Actions Taken to Respond to AMR in Tanzania: 2013–2018 195 Table 10. AfyaData Implementation Activities across Tanzania and Neighboring Countries 196 Table 11. Barriers and Solutions to Community-Led AMR Surveillance in Tanzania 199 Table 12. Implementation Activities and Actions Taken to Respond to AMR across Nigeria 206 Table 13. List of Tools 222 Table 14. Tools Organized by Project Phase 235 Table 15. Key Background Literature for Intervention List, by Drivers, Issues, Context, and Possible Interventions 250 Table 16. Search Strategy for Intervention Reviews 254 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 5 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 17. Long List of Interventions 262 Table 18. Intervention Areas for Addressing AMR, by Sector 272 Table 19. Environmental and Social Assessment of AMR Projects 275 Table 20. Examples of Activities to Integrate Gender and Vulnerable Groups in AMR Projects 282 Table 21. Examples of Possible Stakeholders by Sector 286 Table 22. Material Measures and Actions for a Selection of AMR Interventions, by ESS 287 Boxes Box 1. Examples of Resistant Bacteria 20 Box 2. Examples of Viral, Fungal, and Protozoal Drug Resistance 22 Box 3. Definitions: AMR-Sensitive and AMR-Specific Interventions 26 Box 4. Combatting AMR through WASH and IPC in Health Care Settings: Key Data Points 49 Box 5. Common Challenges for Multisectoral Implementation on AMR 169 Box 6. Regional Sahel Pastoralism Support Project 171 Box 7. East Africa Public Health Lab Networking Project: Burundi 172 Box 8. Africa CDC Regional Investment Financing Project  175 Box 9. Regional Disease Surveillance Systems Enhancement Project: Phases 1–4 177 Box 10. REDISSE Project in Nigeria 204 Box 11. Highlighted Tools within the Project Identification, Preparation, and Appraisal Category 216 Box 12. Highlighted Tools within the Implementation Category 218 Box 13. Highlighted Tools in the Completion and Evaluation Category 220 Box 14. Overview of the Environmental and Social Standards 271 Figures Figure 1. Drivers of Antimicrobial Resistance 24 Figure 2. Timeline of Key Steps to Address AMR 184 Figure 3. The World Bank Project Cycle 245 Figure 4. Overview of Methodology 249 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 6 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction Foreword 8 CHEVRON- Acknowledgments 9 CHEVRON- Abbreviations 11 CHEVRON- Executive Summary 14 CHEVRON- Chapter Guide 17 CHEVRON- A Primer on AMR 20 CHEVRON- We rely on antimicrobials to save lives, bolster the resilience of health systems, protect the sustainability of food systems, and safeguard livelihoods…the inappropriate use of antimicrobials threatens their sustainability, and the devastating impact of this development, in which the drugs we know and rely on cease to work, is already emerging Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 7 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Foreword MAMTA MURTHI In 1928, when Sir Alexander Fleming made the serendipitous discovery of penicillin, few could Vice President imagine how antimicrobials would transform societies, save lives, and enable livelihoods across for Human the globe. Able to prevent a simple cut from becoming a death sentence and to support sustainable Development agricultural and food systems across the world, antimicrobials are powerful public goods and World Bank essential infrastructure. Importantly, they are a powerful tool for health security and economic development. They support communities around the world, many of whom are battling complex PROFESSOR and multifaceted crises across the human health, climate, and environment nexus. DAME SALLY DAVIES Yet the fight to preserve these powerful tools is being lost and a “Grand Pandemic” is already here. UK Special Envoy In 2019, antimicrobial resistance (AMR) was associated with close to 5 million deaths globally. on Antimicrobial That’s more than the number attributed to HIV/AIDS or malaria—making AMR the world’s third Resistance leading underlying killer. AMR impacts every community and every country, but the data show that Government of the those in low-income settings are disproportionately impacted. As the drugs stop working, we will United Kingdom lose our ability to treat diseases and perform life-enhancing surgeries, let alone to treat emerging pathogens of pandemic potential. As resistance is not confined to one pathogen but characterizes an increasing number of pathogens for which we have no medical countermeasures, the compounded impact of AMR on health, social, and economic outcomes across countries and regions stands to be staggering. Meanwhile, tackling AMR will save millions of lives, help our world to realize the Sustainable Development Goals, build resilient and sustainable societies, and increase human capital and productivity. Much like COVID-19, AMR knows no borders. Addressing the spread of AMR requires improving health and animal systems at the local, regional, and country levels, and ensuring that those systems are connected. . The experience of the COVID-19 pandemic made clear the importance of sustainable investments in health systems in pursuit of eradicating poverty and boosting shared prosperity on a livable planet. A new and actionable consensus—one that recognizes the importance of preventive action and specific investments to improve human, animal, and environmental health systems—is essential. Each country should help avert the Grand Pandemic. This Framework for Action is intended to support countries in designing and implementing interventions to address AMR. It provides options across the health, water, and agricultural sectors, evidence on how to shape those interventions, and examples of what has worked in multiple settings. This report showcases actions that have been and can be taken to address AMR. Moreover, the World Bank will support countries—with financing and technical assistance—in implementing these actions. The World Bank is currently supporting more than 60 operations that address AMR and remains committed to ensuring that communities all over the world have sustainable access to life-saving antimicrobials. The discovery of antimicrobials was one of the most important public health advances of the 20th century, and we hope to ensure that generations to come can benefit from these powerful tools. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 8 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Acknowledgments This report was led and written by Naomi Rupasinghe (Lead Author, Senior Health Specialist), Catherine Machalaba (Lead Author, Senior One Health Specialist Consultant), Tonny Brian Mungai Muthee (Lead Author, Health Specialist), and Angela Mazimba (Lead Author, Health Specialist Consultant), with contributions from Brianne Ciferri (Scientific Consultant, EcoHealth Alliance), Franck Berthe (Senior Livestock Specialist), Jonathan Wadsworth (Lead Agriculture Specialist), Akiko Kitamura (Health Specialist), Sarah-Ann Bolongaita (Health Specialist Consultant), Marelize Prestidge (Senior Monitoring and Evaluation Specialist), Jean-Martin Brault (Senior Water and Sanitation Specialist), Ruth Kennedy-Walker (Senior Water Supply and Sanitation Specialist), Claire Chase (Senior Water Economist), Shrutha Sivakumar (Water and Sanitation Specialist Consultant), Ana Cristina Canales Gomez (Agriculture Economist), Artavazd Hakobyan (Senior Agriculture Economist), Christian Berger (Senior Agriculture Economist), Dinesh Nair (Senior Health Specialist), Dipti Thapa (Agriculture Economist), Kate Mandeville (Senior Health Specialist), Luz Berania Diaz Rios (Senior Agribusiness Specialist), John Paul Clark (Lead Health Specialist), Marcelo Bortman (Lead Health Specialist), Mark Cackler (Lead Agriculture Specialist), Julian Lampietti (Practice Manager, Global Engagement within Agriculture and Food), Pierre Gerber (Senior Agriculture Economist), Sambe Duale (Senior Health Specialist Consultant), Shiyong Wang (Senior Health Specialist), Tahira Syed (Senior Agriculture Economist), Tania Dmytraczenko (Practice Manager, Health, Nutrition and Population, Latin America and the Caribbean), Gabriel Francis (Operations Analyst), Juliette Guantai (Program Assistant), Jocelyn Hale (Program Assistant), Anna Elisabeth Larsen (Junior Professional Officer) and Feng Zhao (Practice Manager, Health, Nutrition and Population, South Asia). The case studies were authored by Francesca Chaira and Natalie Vestin of the Center for Infectious Disease Research and Policy and Chioma Rita Achi (Health Specialist Consultant), and reviewed by Pandu Harimurti (Senior Health Specialist), Netsanet Walelign Workie (Senior Economist), Mariam Ally (Senior Economist), Joao Pires (Senior Health Specialist), Carolyn Shelton (Senior Health Specialist), Andre Carletto (Senior Economist), and Moussa Dieng (Senior Economist) under the guidance of Aparnaa Somanathan (Practice Manager, Health, Nutrition and Population, East Asia and the Pacific), Magnus Lindelow (Practice Manager, Health, Nutrition and Population, Africa West), Ernest Massiah (Practice Manager, Health, Nutrition and Population, Africa East). The report was written under the guidance of Monique Vledder (Practice Manager for Global Engagement within Health, Nutrition and Population), Juan Pablo Uribe (Global Director, Health, Nutrition and Population) and Martien Van Nieuwkoop (Global Director, Agriculture and Food). The team is grateful for the peer review guidance provided by Mirfin Mpundu (Director, ReAct Africa), Daniel Arias (Health Specialist Consultant), Hajime Inoue (Adviser), Patricio Marquez (Lead Health Specialist), Mariela Huelden Varas (Livestock Specialist) and Leah Germer (Livestock Specialist). The team is also grateful for the guidance and advice of Anand Balachandran, Unit Head, National Action Plans and Monitoring and Evaluation Unit, AMR Division, World Health Organization (WHO); Ben Parks, Chief, International Infection Control Program, Centers for Disease Control (CDC); Benedetta Allegranzi, Technical Lead, IPC Hub and Task Force (WHO); Breeda Hickey, Technical Officer, National Action Plans and Monitoring and Evaluation Unit, AMR Division (WHO); Carmen Bullon, Legal Officer, Food and Agriculture Organization (FAO); Claire Oxlade (Private Secretary to the UK Special Envoy on Antimicrobial Resistance, UK Department of Health and Social Care); Dawn Sievert, Lead Science Advisor for the Antibiotic Resistance Coordination and Strategy Unit (CDC); Dibesh Karmacharya, Founder (Center for Molecular Dynamics, Nepal); Elizabeth Tayler, Team Leader, National Action Plans and Monitoring and Evaluation Unit, AMR Division (WHO); Erica Westwood, Implementation Research Advisor (ICARS); Francesca Latronico, AMR Laboratory Specialist (FAO); Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 9 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Ghada Zoubiane, Head of Partnerships and Stakeholder Engagement (ICARS); Helle Engslund Krarup, Director of Operations (ICARS); Jieun Choi Kim, Animal Health Officer, Animal Production and Health Division, Animal Health Service (FAO); Jing Xu, Animal Production and Health Division, Animal Health Service (FAO); Jorge Pinto Ferreira, Food Safety Officer (FAO); Junxia Song, Senior Animal Health Officer, Animal Production and Health Division, Animal Health Service (FAO); Jyoti Joshi, AMR Advisor (ICARS); Louise Norton-Smith, Head of Global Antimicrobial Resistance (AMR) Strategy (UK Department of Health and Social Care); Koen Mintiens, Animal Health and Welfare Consultant, Animal Production and Health Division, Animal Health Service (FAO); Olafur Valsson, Deputy Head, AMR and Veterinary Products (WHO); Otto Cars, Founder and Senior Advisor (REACT); Parameswaran Iyer, Executive Director (World Bank), Ramanan Laxminarayan, Founder and President (One Health Trust); Robert Leo Skov, Scientific Director (ICARS); Sabiha Essack, Senior Implementation Research Advisor, International Centre for Antimicrobial Resistance Solutions (ICARS); Sally Davies, UK Envoy for Antimicrobial Resistance (UK Department of Health and Social Care); Sanne Frost Helt, Senior Director Policy, Programme and Partnerships (World Diabetes Foundation); Sarah Jones, Public Health Analyst (CDC); Sarah Paulin, Technical Officer, National Action Plans and Monitoring and Evaluation Unit, AMR Division (WHO); Tom Pilcher, Head of Country Coordination (The Fleming Fund); and William B. Karesh, Executive Vice President for Health and Policy (EcoHealth Alliance). The team is grateful for the editorial support provided by Anne Himmelfarb and Richard Crabbe, and typsetting and design support from Sammi Loerns and Tomoko Furukawa at TDL Creative. The report was funded by the Danish Ministry of Foreign Affairs as part of the World Bank’s program on Antimicrobial Resistance. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 10 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Abbreviations Africa CDC Africa Centres for Disease Control and Prevention AGF Agriculture and Food AMC antimicrobial consumption AMR antimicrobial resistance AMS antimicrobial stewardship AMU antimicrobial use aPAD antibiotic paper analytical device ARG antibiotic-resistant gene/antimicrobial-resistant gene ASP antimicrobial stewardship program AST antimicrobial sensitivity testing ATLASS Assessment Tool for Laboratory and Antimicrobial Resistance AWaRe access, watch, reserve BSL biosafety level CERC Contingent Emergency Response Component CILSS Permanent Interstate Committee for Drought Control in the Sahel COP Community of Practice CSC Country Steering Committee DLI disbursement linked indicator DODRES Disease Outbreak Detection and Response in East and Southern Africa DPO Development Policy Operations ECCAS Economic Community of Central African States ECOWAS Economic Organization of West African States ECSA-HC East, Central and Southern African Health Community ENB Environment, Natural Resources and the Blue Economy E&S environmental and social ESBL extended-spectrum beta-lactamase ESCP Environmental and Social Commitment Plan ESF Environmental and Social Framework ESS environmental and social standard FAO Food and Agriculture Organization of the United Nations FAO-PMP-AMR FAO Progressive Management Pathway for AMR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 11 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices FELTP Field Epidemiology and Laboratory Training Program (Nigeria) FMARD Federal Ministry of Agriculture and Rural Development (Nigeria) FMOE Federal Ministry of Environment (Nigeria) FMOH Federal Ministry of Health (Nigeria) GLASS Global Antimicrobial Resistance and Use Surveillance System GMU Grant Management Unit GP Global Practice HCF health care facility HIC high-income country HNP Health, Nutrition and Population IBRD International Bank of Reconstruction and Development IDA International Development Association IEC information, education, and communication IEG Independent Evaluation Group IHR International Health Regulations IMSC High-Level Inter-Ministerial Steering Committee (Indonesia) IPC infection prevention and control IPF Investment Project Financing IR intermediate results JEE Joint External Evaluation LMICs low- and middle-income countries MDR multidrug resistance/resistant M&E monitoring and evaluation MoH Ministry of Health MPTF Multi-Partner Trust Fund NAP National Action Plan NAPHS National Action Plan for Health Security NCDC Nigeria Centre for Disease Control NiCaDe Capacity Development for Preparedness and Response for Infectious Diseases N-PCU National Project Coordination Unit NPHI National Public Health Institute NRL National Reference Library (Nigeria) NSC National Steering Committee NVRI National Veterinary Research Institute OECD Organisation for Economic Co-operation and Development Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 12 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices PforRs Programs for Results PAD paper analytical device PCR polymerase chain reaction PCT procalcitonin PCU Project Coordination Unit PHC primary health care PIU Project Implementation Unit PRAPS Regional Sahel Pastoralism Support Project PVS Performance of Veterinary Services qPCR quantitative polymerase chain reaction RAP Regional Advisory Panel REDISSE Regional Disease Surveillance Systems Enhancement RKI Robert Koch Institute RSC Regional Steering Committee SACIDS Southern African Centre for Infectious Disease Surveillance SDG Sustainable Development Goal SF substandard and falsified TAP Tailoring Antimicrobial Resistance Programmes TB tuberculosis TC Technical Committee TISSA Tripartite Integrated Surveillance System on AMR/AMU TrACSS Tripartite AMR Country Self-Assess¬ment Survey UHC universal health coverage USAID United States Agency for International Development US CDC United States Centers for Disease Control and Prevention UTI urinary tract infection UV ultraviolet VMP veterinary medical product WAHO West African Health Organization WASH water, sanitation, and hygiene WHO World Health Organization WOAH World Organisation for Animal Health WWTP wastewater treatment plant XDR extensive drug resistance All dollar amounts are US dollars unless otherwise indicated. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 13 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Executive Summary Antimicrobial resistance (AMR) is a global health security and development challenge that poses a threat to public health and economic prosperity. It is a challenge that is often overlooked. As antimicrobials have become part of the infrastructure of modern society, it has become all too easy to take them for granted; but their longevity is under threat. Antimicrobials and antibiotics are widely used for health, industrial, and agricultural purposes. In health care, they are inextricably linked to the advances in modern public health that societies have witnessed in recent decades. They have become a go-to medication for a variety of infections, from strep throat to sepsis. They have also become essential to agricultural and food systems and are used in crop and livestock management. Nevertheless, inappropriate use of antimicrobials threatens their sustainability, and the devastating impact of this development, in which the drugs we know and rely on cease to work, is already emerging. In 2019, an estimated 4.95 million deaths were associated with bacterial AMR, more than the number of deaths attributed to AIDS, HIV, and malaria—making AMR one of the world’s biggest killers (Antimicrobial Resistance Collaborators 2022). The impact of AMR is not limited to human health. In 2017, the World Bank estimated that by 2050, unchecked AMR could wipe away 3.8 percent of global gross domestic product each year and push 28 million people into poverty (World Bank 2017). In the face of this challenge, the World Bank stands ready to support governments in designing and implementing approaches to preserve antimicrobials with financing and technical assistance. This Framework for Action (Framework) aims to support World Bank task teams and clients in designing interventions that address AMR, with a focus on low- and middle- income countries (LMICs), which stand to be disproportionately impacted. This Framework outlines 20 intervention areas across the health, agriculture, and water sectors that can serve as starting points for discussions to develop sustainable systems addressing AMR at the national and regional levels. Tackling AMR is crucial to achieving universal health coverage, promoting good health, and attaining the Sustainable Development Goals (SDGs). To the challenge of addressing AMR, the World Bank brings operational expertise, finance, and the ability to mobilize additional resources for multisectoral programs through its operations and technical support. The challenge posed by AMR is not universally intractable; from improving handwashing in health care settings to banning the use of antimicrobials as growth promoters in agriculture, there is much that can be done. The perceived complexity of AMR, lack of awareness about the steps that can be taken to address the issue, and insufficient financing have been identified as barriers to investing in relevant interventions. However, based on a review of existing evidence, the World Bank has identified several key intervention areas to highlight in the design and development of World Bank operations. These are shown in Table 1. This list is not exhaustive or intended to imply that other interventions are not as valuable, but rather aims to provide a starting point for action. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 14 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 1. Intervention Areas Health Water and environment 1 Improving infection prevention and CHEVRON- 12 Improving infrastructure to provide CHEVRON- control in health care settings access to water and sanitation in health care centers 2 Improving prescribing practices CHEVRON- through guidelines for health 13 Implementing effective treatment and CHEVRON- care workers disposal of sewage and wastewater 3 Conducting public CHEVRON- 14 Improving waste management CHEVRON- awareness campaigns practices in agricultural and aquaculture production/processing 4 Increasing human health laboratory CHEVRON- capacity and access to diagnostics 15 Improving safe disposal of CHEVRON- unused antimicrobials 5 Strengthening surveillance of CHEVRON- antimicrobial use (AMU) and AMR in 16 Monitoring presence of antimicrobial CHEVRON- human populations residues and antibiotic-resistant bacteria and genes in water and sanitation systems Agriculture and food Multisectoral 6 Increasing oversight of AMU by CHEVRON- veterinarians 17 Detecting and deterring substandard CHEVRON- 7 Monitoring AMU, surveillance of CHEVRON- and falsified antimicrobials (customs/ AMR, and increasing oversight in law enforcement/health/agriculture) plant/crop production 18 Improving human and animal CHEVRON- 8 Improving animal husbandry practice CHEVRON- nutrition (health/agriculture) and biosecurity 19 Expanding vaccination coverage CHEVRON- 9 Monitoring sales and use of CHEVRON- in humans and animals (health/ antimicrobials and surveillance of agriculture) AMR in animals 20 Using closed water systems in CHEVRON- 10 Promoting behavior change CHEVRON- aquaculture (agriculture/environment) campaigns in animal production 11 Increasing veterinary laboratory CHEVRON- capacity and access to diagnostics Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 15 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices While AMR is a multisectoral issue, sector-specific entry points are important for mobilizing prompt action. The driving forces behind AMR are shaped by actions in multiple sectors, but entry points for addressing AMR can be sector-specific. Several World Bank Global Practices—Health, Nutrition and Population (HNP), Agriculture and Food (AGF), Environment, Natural Resources and Blue Economy (ENB), and Water—and their relevant sectors can all play an important role, and their respective leadership is critical to ensuring that action is taken. Each of the intervention areas can also be viewed as part of broader, comprehensive programming, and this report offers and discusses four thematic areas to enable countries to make informed choices about prioritizing and staging their approach to AMR management. The four thematic areas are reducing infections; strengthening monitoring and surveillance of AMR and antimicrobial use (AMU); improving the rational use of antimicrobials; and strengthening sectoral and multisectoral coordination and governance. Countries are at different states of readiness to address AMR, so a comprehensive approach may not always be feasible; however, a broader vision of the range of options can help maximize the effectiveness and sustainability of any given intervention. In instances where there is greater readiness, and where a strong enabling environment and political consensus to address AMR are present, comprehensive programming will be more feasible. In other settings, programming may need to be more opportunistic and targeted. Nevertheless, across different states of readiness, a vision of the range of options remains important, as it offers a window to ensuring that financial and nonfinancial resources are utilized well and sustainably. In all states of readiness, actions can be taken to address AMR. References Antimicrobial Resistance Collaborators. 2022. “Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis.” Lancet 399 (10325): 629–55. https://www.thelancet.com/ journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext. World Bank. 2017. Drug-Resistant Infections: A Threat to Our Economic Future (Vol. 2): Final Report. Washington, DC: World Bank Group. http://documents.worldbank.org/curated/ en/323311493396993758/final-report. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 16 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter Guide Chapter 1 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 1 emphasizes the importance of addressing antimicrobial Chapter 1 resistance (AMR) for global health security and development. Why Addressing AMR The overuse and misuse of antibiotics is a growing concern that poses a Remains Critical to Global Health Security and Global significant threat to public health; it is a major driver of AMR. The consequences Development of AMR are far-reaching; they threaten the effectiveness of modern medicine and risk undoing decades of progress. The need for sustainable access to Summary Antimicrobial resistance as a threat to global health security 30 CHEVRON- antimicrobials is paramount to the resilience of health systems. Addressing AMR and global development 31 CHEVRON- Purpose of the Framework for Action 35 CHEVRON- Audience 35 CHEVRON- is also critical to achieving the Sustainable Development Goals (SDGs), especially Rationale for World Bank involvement Higher-level objectives 36 40 CHEVRON- CHEVRON- for low- and middle-income countries (LMICs). Without action, AMR could cause Global, regional, and national issues References 41 42 CHEVRON- CHEVRON- significant economic impact, wiping away up to 3.8 percent of global GDP and pushing millions of people into poverty. The responsible use of antimicrobials Addressing AMR is a development challenge that will negatively and disproportionately impact low- and is a global public good that must be closely linked to achieving the SDGs middle-income countries… by 2050, a high-AMR scenario could wipe away 3.8 percent of global gross domestic product each year and push and promoting healthy lives, ending poverty and hunger, and promoting 28 million people into poverty. sustainable and inclusive economic growth. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 29 Jump to ARROW-RI Chapter 2 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 2 describes packages of interventions across four thematic Chapter 2 areas to show practitioners with how a given intervention can Four Thematic Entry Points support comprehensive programming. The four thematic areas are for Addressing AMR reducing infections; strengthening monitoring and surveillance of AMR and Summary 46 CHEVRON- antimicrobial use (AMU); improving access and the rational use of antimicrobials; Introduction Reducinginfections:AfocusonIPC,vaccination,andnutrition 47 47 CHEVRON- CHEVRON- and strengthening sectoral and multisectoral coordination and governance. StrengtheningmonitoringandsurveillanceofAMRandAMU Improvingaccessandtherationaluseofantimicrobials:Afocuson antimicrobialstewardshipandregulatoryframeworks 50 51 CHEVRON- CHEVRON- A range of interventions across health, agriculture and food, and water and Strengtheningsectoralandmultisectoralcoordinationandgovernance References 54 61 CHEVRON- CHEVRON- sanitation sectors are discussed in this chapter for global, regional, and national policy makers and implementers to consider from a thematic perspective. The chapter recognizes that different countries may have varying levels of A wide range of interventions across four thematic areas—reducing infections, strengthening monitoring preparedness to tackle AMR, and that a comprehensive approach may not and surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU), improving access and the always be feasible. Nevertheless, it stresses the importance of having a rational use of antimicrobials, and strengthening sectoral and multisectoral coordination and governance—can help address the emergence broader understanding of the available options to maximize intervention and spread of AMR. effectiveness and sustainability. Additionally, the chapter makes clear that a robust enabling environment and political consensus to address AMR are Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 45 Jump to ARROW-RI essential for comprehensive programming, but that in settings where readiness and funding are limited, more  targeted, sector-specific, and opportunistic programming may be necessary. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 17 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 3 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 3 provides decision-makers and implementers with 20 Chapter 3 intervention areas that can be supported through World Bank Twenty Intervention Areas operations to address AMR. Recognizing that there are barriers to investing in these interventions (e.g., the complexity of the issue, lack of awareness Summary Introduction 66 67 CHEVRON- CHEVRON- about the issue, and insufficient financing), the chapter aims to facilitate Methodology EntryPointsforGlobalPracticesandsectorsforAMRinterventions 68 69 CHEVRON- CHEVRON- 81 better understanding of interventions to address AMR and so promote Bibliography CHEVRON- Healthsector 85 CHEVRON- Agricultureandfoodsector 103 CHEVRON- funding for them. The interventions are based on findings from a review of Waterandenvironmentsector Multisector 119 134 CHEVRON- CHEVRON- evidence and serve as a starting point for discussions between task teams and clients. These interventions are grouped by sector, in recognition of the organization of government ministries. The interventions include measures such as infection prevention and control, vaccination programs, improved While AMR is a multisectoral issue, sector-specific entry points are important for mobilizing prompt action… hygiene and sanitation, enhanced laboratory capacity for AMR testing, the driving forces behind AMR are shaped by actions in multiple sectors but each sector can and establishment of national and regional surveillance systems. Other and should do their part to address AMR. interventions focus on improving access and rational use of antimicrobials, strengthening sectoral and multisectoral coordination and governance, Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 65 Jump to ARROW-RI addressing AMR in animal health, promoting research and development of new antimicrobial drugs and diagnostics, and strengthening health systems and capacity building. By highlighting these interventions, the World Bank aims to support global efforts in combatting AMR and safeguarding global health security and development gains. The list is not intended to be exhaustive or a prioritization but instead aims to highlight what can be done. Chapter 4 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 4 provides options for incorporating interventions to address Chapter 4 AMR into World Bank operations, within and across Health, Nutrition Investing in AMR through World Bank Operations and Population (HNP), Agriculture and Food (AGF), and Water Global Practices. The purpose of this chapter is to assist World Bank task teams Summary 147 CHEVRON- and clients in incorporating interventions to address AMR in World Bank Introduction 148 CHEVRON- Overviewofthe2022PortfolioReview 148 CHEVRON- Menuofoptionsbysector 150 CHEVRON- operations, including Investment Project Financing (IPF), Development Policy Health sector approaches Agricultural and food sector approaches 151 157 CHEVRON- CHEVRON- Operations (DPOs), and Programs for Results (PforRs). The chapter offers a Water and environment sector approaches References 161 166 CHEVRON- CHEVRON- menu of options for the design of operations, based on the interventions areas identified by staff members from the HNP, AGF, and Water Global Practices, as well as external partners such as the United States Centers for Disease Control A menu of options translating the list of intervention areas and Prevention (US CDC), the World Health Organization (WHO), the Food and into World Bank operations can provide teams with scope to flexibly respond to the policy and lending dialogue Agriculture Organization of the United Nations (FAO), and World Organisation in different contexts and in recognition that the intervention areas are a starting point, rather than a comprehensive list. for Animal Health (WOAH). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 146 Jump to ARROW-RI Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 18 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 5 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 5 provides implementation guidance based on the World Bank’s Chapter 5 operational experience and case studies of external experiences. Implementation Guidance for Investing in Interventions to The chapter is divided into two parts. The first part draws on experiences Address AMR through World from World Bank operations and country cases to provide examples of Bank Operations implementation arrangements. The second part explores successes and challenges in addressing the AMR agenda in Nigeria, Indonesia, and Tanzania Summary 168 CHEVRON- Introduction 169 CHEVRON- Nationalinstitutionalarrangements 171 through country case studies. The chapter emphasizes the importance of CHEVRON- Regionalinstitutionalarrangements 174 CHEVRON- Takeaways 178 CHEVRON- early and detailed attention to implementation arrangements. Implementing References Threeimplementationcasestudies 179 180 CHEVRON- CHEVRON- interventions to address AMR can be challenging, not least because they can Case Study 1: Indonesia 180 CHEVRON- Case Study 2: Tanzania 192 CHEVRON- Case Study 3: Nigeria 202 involve collaboration across multiple organizations and sectors. Many projects CHEVRON- have strengthened national coordination bodies, which allow for multiple agencies within a sector and across sectors to be informed and have a stake Early and detailed attention to implementation arrangements is beneficial for the success of interventions to address AMR. in a project’s success. Identifying senior advocates and high-level supporters from presidential and prime ministerial offices can benefit implementation Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 167 by ensuring that the AMR agenda is elevated and prioritized and by providing Jump to ARROW-RI neutrality between ministries. In addition, given that AMR is not confined by geographical boundaries, operations have drawn on regional mechanisms, both to support technical delivery and to receive and coordinate financing and project management. The case studies in the second part of the chapter discuss multisectoral and single-sector implementation initiatives using a One Health approach to build AMR surveillance and laboratory capacity. Chapter 6 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 6 provides task teams and clients with guidance on the range of Chapter 6 tools that can be used to support project design and implementation. Tools to Support the Design and Implementation of Operations The chapter draws on the World Bank’s Landscape Analysis of Tools to Address AMR, which identified over 90 tools for supporting investments in AMR. Summary 214 CHEVRON- The tools are organized in terms of the project cycle across three categories: Introduction 215 CHEVRON- Phase1:ProjectIdentification,PreparationandAppraisal 216 CHEVRON- Phase2:Implementation 218 CHEVRON- project identification, preparation, and appraisal; implementation; and Phase3:CompletionandEvaluation Tools 220 222 CHEVRON- CHEVRON- completion and evaluation. Costing and financing have been identified as a CostingandImplementingAMRInterventions,includingNAPs References 240 241 CHEVRON- CHEVRON- challenge to addressing AMR in LMICs, and the chapter highlights tools that can be used for costing interventions. The chapter also highlights a range of tools that can be used to support the prioritization and leadership of sectors in mobilizing investments; given that only 20 percent of National Action Plans Costing and financing have been identified as a challenge to addressing AMR in low- and middle-income were fully funded in 2020, and 40 percent had a budgeted operational plan, countries…a range of tools exist that can be used to support the prioritization and leadership of sectors in mobilizing investments. such support is very much needed. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 213 Jump to ARROW-RI Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 19 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices A Primer on AMR What are antimicrobials and what is antimicrobial resistance? Antimicrobials, a broad range of products that prevent the growth of or destroy bacteria, fungi, parasites, and even certain viruses, are essential tools that underpin modern society. Antimicrobials are critical to human and animal health systems as well as to the sustainability of food systems. They are widely used to prevent and treat diseases in humans and animals and to manage crop production. Antimicrobials are a global public good. All countries can benefit from the successful management of antimicrobial resistance (AMR) because if left unchecked, the world will confront a reality where many infectious diseases have “no cure and no vaccine” (World Bank 2017). No one has an interest in antimicrobials being exhausted. However, the world’s collective response as each actor pursues short-term goals is leading to the loss of this vital global public good. AMR refers to the ability of microbes and other infective organisms (e.g., fungi) and parasites (e.g., malaria) to grow in the presence of substances specifically designed to kill, inactivate, or slow their growth. AMR occurs when microbes change in ways that reduce or eliminate the effectiveness of drugs, chemicals, or other agents used to prevent or cure the infections they cause. When antimicrobial treatments stop working, as many have already, we lose the ability to treat infections effectively and quickly and, in some cases, even entirely. Pathogens, which are microbes that can cause disease, can also become resistant to multiple antimicrobials, leading to multidrug resistance (MDR), extensive drug resistance (XDR), and pan-drug resistance (PDR). MDR occurs when a pathogen is resistant to two or more antimicrobial agents in three or more antimicrobial classes. XDR occurs when a pathogen is resistant to at least one agent in all but two or fewer antimicrobial categories (i.e., bacterial isolates remain susceptible to only one or two categories). PDR is defined as resistance to all agents in all antimicrobial categories. Microbes that are resistant to multiple drugs can be referred to as “superbugs.” An infection caused by a superbug is harder to treat because fewer drugs are effective against it. In some extreme cases, treatment for superbugs may not even exist. Box 1 describes three examples of resistant bacteria. Box 1. Examples of Resistant Bacteria Multidrug-resistant tuberculosis (MDR-TB): Tuberculosis is caused by the bacterium Mycobacterium tuberculosis. MDR-TB is a form of the disease that is resistant to at least two of the most potent first-line drugs, isoniazid and rifampicin. MDR-TB presents a significant challenge to tuberculosis control due to various factors, including poor public health infrastructure, inadequate treatment, inefficient infection control, and the HIV epidemic, and it requires prolonged and complex treatment regimens. Surveillance gaps, especially in resource-constrained settings, contribute to under-detection of resistant TB, especially in children who often have culture-negative disease. In 2018, approximately 3.9 percent of new TB cases and 21 percent of previously treated cases were estimated to be MDR-TB (Prasad et al. 2018). In 2019, almost 85,000 deaths were attributable to Mycobacterium tuberculosis globally (Antimicrobial Resistance Collaborators 2022). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 20 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multidrug-resistant Gram-negative bacteria: Multidrug-resistant Gram-negative bacteria, like Klebsiella pneumoniae and Acinetobacter baumannii, are a growing concern in low- and middle-income countries (LMICs). Health care– associated infections caused by these resistant bacteria have reached prevalence rates of up to 24 percent in some settings, leading to prolonged hospital stays, increased health care costs, and a 2.3 times higher risk of mortality. These infections also complicate treatment, with failure rates exceeding 50 percent, and hinder medical interventions, such as surgical procedures, with a three-fold increase in postoperative complications (Elwakil 2023). Methicillin-resistant Staphylococcus aureus (MRSA): MRSA is a strain of the bacterium Staphylococcus aureus that has developed resistance to multiple antibiotics, including methicillin and other beta-lactams. MRSA infections are of particular concern in health care settings, where they can cause severe and sometimes life- threatening infections, especially among patients with compromised immune systems or surgical wounds. Infections with MRSA can lead to longer hospital stays and increased health care costs. MRSA infections are a pertinent concern in LMICs, especially in crowded health care settings with limited resources. The prevalence of MRSA varies widely across regions, with studies reporting rates as high as 80 percent among health care–associated infections in some LMICs. The mortality rate for MRSA infections can be as high as 50 percent, especially in critically ill patients with inadequate access to effective antibiotics (Siddiqui and Koirala 2023). In 2019, MRSA caused more than 100,000 deaths (Antimicrobial Resistance Collaborators 2022). Why does AMR matter for people, animals, plants, and human and animal health systems? We rely on antimicrobials to save lives, bolster the resilience of health systems, protect the sustainability of food systems, and safeguard livelihoods—both people’s ability to work and agricultural economies more broadly. AMR matters because the more it grows, the greater the risk to life worldwide. In 2019, drug-resistant infections were a significant contributor to mortality, with an estimated 4.95 million people losing their lives due to such infections. Out of these deaths, 1.27 million were directly attributable to AMR. AMR was one of the world’s biggest killer, responsible for more deaths than AIDS, HIV, and Malaria (Antimicrobial Resistance Collaborators 2022). At an individual level, the more intensive and prolonged treatment regimens required for AMR infections can lead to prolonged hospital stays for patients. As a result, there is a higher risk of catastrophic health expenditure, meaning that more people are vulnerable to poverty due to infections that were previously simpler and cheaper to treat. People who live in poverty are also more susceptible to infectious diseases, enabling a harmful cycle that is complicated by AMR. At a health system level, AMR substantially increases the financial and nonfinancial resources needed to treat and manage diseases. The efficacy of antimicrobials is essential to the sustainability of livelihoods in the livestock and poultry sectors, as well as the agriculture and food sectors, especially in low- and middle-income countries (LMICs) where biosecurity and animal husbandry systems are still being developed. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 21 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices What are the global trends in antimicrobial use and resistance? Use of antimicrobials is expected to increase substantially in the coming decade, and this increase brings an increased risk of AMR. The 2021 report on the State of the World’s Antibiotics (Sriram et al. 2021) found that global antibiotic consumption in humans increased 65 percent between 2000 and 2015, and consumption in animals was projected to increase by 200 percent between 2017 and 2030. Without action, overall antibiotic consumption could increase by 200 percent between 2015 and 2030. AMR is on the rise, and resistance levels are generally higher in LMICs (Sriram et al. 2021). Antimicrobial resistance continues to rise; countries increasingly report high rates of resistance to antimicrobials used to treat common infections. Weighted average resistance levels are generally higher in LMICs. The recent Drug Resistance Index, which includes 41 countries, shows that while resistance and use rates vary across countries, high-income countries have lower resistance levels. Countries with the highest levels of drug resistance are all LMICs (Klein et al. 2019). Box 2 describes examples of viral, fungal, and protozoal drug resistance. Box 2. Examples of Viral, Fungal, and Protozoal Drug Resistance Viral drug resistance: Influenza antiviral resistance Influenza viruses, including seasonal and pandemic strains, have developed resistance to certain antiviral drugs, such as oseltamivir (Tamiflu) and zanamivir (Relenza). Oseltamivir and zanamivir are neuraminidase inhibitors, which work by blocking a viral enzyme essential for the release of newly formed virus particles from infected cells. By inhibiting this enzyme, these drugs effectively reduce the spread and severity of influenza infections. However, influenza viruses can mutate and acquire genetic changes that make them less susceptible to the inhibitory effects of these drugs, leading to resistance. Antiviral resistance can reduce the effectiveness of treatment and limit options for managing flu outbreaks. Influenza viruses resistant to oseltamivir (Tamiflu) have been detected worldwide, with resistance rates varying each season. In some years, resistance to oseltamivir has been reported in up to 30 percent of tested samples (Smyk et al. 2022). HIV drug resistance: HIV antiretroviral resistance HIV can develop resistance to antiretroviral drugs used to manage the infection. Drug resistance can arise due to improper medication adherence or suboptimal treatment regimens, leading to treatment failure and disease progression. The global HIV drug resistance landscape shows significant variations between resource-rich and resource-limited settings. Globally, around 12 percent of people living with HIV who are receiving antiretroviral therapy have developed resistance to at least one of the drugs used in their treatment. In resource-limited settings, high rates of pretreatment and acquired drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) have been reported, particularly in Sub-Saharan Africa. Surveillance data from 2014 to 2018 indicated prevalence of NNRTI pretreatment drug resistance above 10 percent in 12 out of 18 low- and middle-income countries (Nachega et al. 2011). Fungal drug resistance: Multidrug-resistant Candida auris Candida auris is a multidrug-resistant fungus that can cause severe infections. This emerging pathogen is resistant to many antifungal drugs, making outbreaks in health care facilities challenging to treat and control. Since its identification in 2009, Candida auris has spread to over 30 countries, with several outbreaks reported in health care facilities. One of the most Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 22 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices concerning aspects of Candida auris is its resistance to many commonly used antifungal drugs, including azoles, echinocandins, and polyenes. This extensive resistance profile makes it exceptionally challenging for health care providers to effectively treat infections. Moreover, the limited arsenal of antifungal drugs available further exacerbates the difficulty in managing Candida auris infections, leaving health care facilities grappling with the urgent need to develop alternative treatment strategies. The propensity of Candida auris to thrive in health care environments adds to the complexity of controlling its spread. The fungus can persist on environmental surfaces, medical equipment, and even health care workers’ hands, facilitating transmission between patients. Nosocomial outbreaks have been widely reported, leading to heightened infection control measures and a strain on health care resources. Patients with invasive Candida auris infections face grave outcomes, with mortality rates reaching as high as 60 percent (Sanyaolu et al. 2022). Protozoal Drug Resistance Artemisinin-resistant Plasmodium falciparum: Plasmodium falciparum is the parasite responsible for the most severe form of malaria. Some strains have developed resistance to artemisinin-based combination therapies, which are the most effective treatments for malaria. Artemisinin resistance has been reported in several countries in Southeast Asia, including Cambodia, Thailand, Myanmar, and Vietnam, where certain strains of the parasite have shown reduced susceptibility to artemisinin drugs. As the parasite’s resistance to this critical class of antimalarials spreads, it compromises the efficacy of ACTs, rendering them less effective in clearing the infection and reducing the risk of treatment failure. This resistance threatens malaria control efforts and can lead to increased malaria-related morbidity and mortality. Artemisinin resistance is a major concern as it threatens the success of malaria control and elimination efforts (Ouji et al. 2018). What causes AMR? AMR is driven by actions in multiple sectors, and the misuse and overuse of antimicrobials drives the emergence and spread of resistance. AMR is a naturally occurring phenomenon that results from the mutations in and transfers of genetic material between different microbes. Any use of antimicrobials can result in AMR. Misuse and overuse of antimicrobials—for example, when people take substandard antibiotics for viral infections and when antibiotics are used as growth promoters in animals—increases the likelihood of resistance because it offers more opportunities for pathogens, bacteria, and parasites to overcome antimicrobials. Equally, when people cannot access the antimicrobials they need because they are not available, unaffordable or no longer effective, this makes infections difficult to treat and adds to the burden on healthcare systems. Misuse and overuse of antimicrobials, a major driver of AMR, is shaped by actions in multiple areas, as shown in Figure 1. The spread of microbes resistant to antimicrobials can occur between people, animals, and plants and across the environment (in water, soil, and air). As highlighted by the World Health Organization (WHO), poor hygiene and infection control, inadequate sanitary conditions, and inappropriate food handling all contribute to the spread of AMR. AMR drivers operate through a range of causal pathways that lead to high-risk conditions for AMR emergence and spread. Table 17 (see Appendix 2) provides a summary of drivers and pathways. For example, inadequate regulation of antimicrobials in health and agriculture, or inadequate enforcement of legislation, can be a driver of AMR. The pathways related to regulation include overuse and inappropriate use of antimicrobials in health care settings, the widespread presence of substandard and falsified antimicrobials, the availability of over-the-counter antimicrobials (i.e., those dispensed without a prescription), and the lack of new antimicrobial treatments being approved and become available. In the agricultural and Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 23 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices food sectors, antimicrobials are widely used to enhance animal growth, raise animal productivity, and prevent diseases in crops. The lack of good animal husbandry practices, lack of space for isolating sick animals, and lack of veterinary expertise contribute to the inappropriate reliance on antimicrobials to bolster animal health systems. The pathways that result in AMR are often complex and multifaceted; however, actions can be taken across all sectors to reduce the misuse and overuse of antimicrobials. The Framework for Action describes and provides guidance on 20 intervention areas that can be supported through World Bank operations. The perceived complexity of AMR, lack of awareness about the steps that can be taken to address the issue, and insufficient financing have been identified as barriers to investing in relevant interventions. Chapter 3 describes intervention areas of varying scope and scale that contribute to broader programming areas, as well as findings from a review of evidence to support task teams and clients. This list is not exhaustive or intended to imply that other interventions are not as valuable, but rather aims to provide a starting point for action. Figure 1. Drivers of Antimicrobial Resistance microbial r f anti esi cto st a a p nc Im e Source: IACG 2019. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 24 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices What sectors are relevant to AMR? AMR is a problem that affects and is driven by interconnected factors related to people, animals, plants, and ecosystems across a range of sectors, including health, agriculture, food, water and sanitation, and the environment. These sectors are all relevant to mitigating the rising tide of AMR.1 Actors within each of these sectors can each take on leadership in addressing AMR. In the health sector, for example, improved prescription practices and vaccination programming can mitigate AMR. Collaborations between sectors can also be powerful and effective. For example, improving sanitation and hygiene through improved infrastructure for clean water in hospital settings can reduce the emergence and spread of disease and reduce the need for antibiotics. Given the connections between sectors, AMR has been described as a “One Health” issue, and this concept is important for understanding how approaches to addressing AMR can be optimized. One Health is defined as “an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, and ecosystems” (WHO 2021). 2 In terms of practice, a One Health approach involves collaboration and integrated programming and recognizes the interconnected nature of human, animal, and ecosystem health in managing global health security threats. Coordinated One Health action can optimize scarce resources to minimize the emergence and spread of AMR. For example, a disease surveillance system that can monitor the use and rise of resistance in both the animal and human health sectors stands to be more effective than a single-sector surveillance system, given that similar antimicrobials are used in both sectors. However, it is recognized that relying on coordination across sectors can stifle action, so single- sector actions that are cognizant of multisectoral links can be a critical first step. The challenge of coordinating across different sectors, each of which can have competing demands, budgets, and interests, can lead to inaction. Therefore, while multisectoral programming is often an excellent way to optimize scarce resources and is advised, each sector should also understand how its leadership can advance action to address AMR and how such action can enable current or future action in other sectors. For example, a disease surveillance system in the human health sector can be designed and implemented with an understanding of how it will connect with—and engage with stakeholders in— the veterinary and animal health sector. 1  In the context of the World Bank, these sectors are housed under two vice presidencies: Human Development and Sustainable Development. Human Development includes the Health, Nutrition and Population (HNP) Global Practice (GP). Sustainable Development includes the Agriculture and Food (AGF) GP and the Water GP. These GPs work together in areas of crossover; for example, HNP and Water often collaborate on sanitation and hygiene projects. 2  The definition was developed by the One Health High Level Expert Panel (OHHLEP), which is the advisory panel of the Food and Agriculture Organization of the United Nations, World Organisation for Animal Health, United Nations Environment Programme, and World Health Organization. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 25 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices What types of interventions are there to address AMR? Box 3. Definitions: AMR-Sensitive and AMR-Specific Interventions AMR-specific interventions have as their main purpose the reduction of AMR emergence and spread. An example is the promulgation and enforcement of regulations to ensure people can obtain antimicrobial medicines only with a valid prescription. AMR-sensitive interventions have other primary purposes (such as improved animal husbandry or a reduction in disease incidence through vaccination) but contribute indirectly to addressing emergence and spread of AMR. They can be designed and delivered to maximize their impact on AMR. Actions to address AMR can be divided into two categories: AMR-specific and AMR-sensitive (see Box 3). AMR-specific interventions led by the relevant sectors can play a powerful role in addressing AMR. For example, in health, AMR can be addressed by improving prescription practices to increase the rational use of antibiotics and limit unnecessary prescription (e.g., of antibiotics for viral infections). In agriculture, reducing and eliminating the use of antimicrobials as growth promoters and facilitating the uptake of improved husbandry practices have been shown to reduce AMR. 3 Actions to address AMR can also be built into the approach across sectors. These AMR-sensitive approaches are based on the recognition that AMR is driven by anthropological and socioeconomic factors (Collignon et al. 2018), that the spread of resistant strains and genes is a dominant factor in the rise of AMR, and that reducing antimicrobial use alone will not be sufficient to address AMR. Improving sanitation, increasing access to clean water, and improving governance and private health sector regulation are examples of AMR-sensitive measures that are necessary to reduce the emergence and spread of AMR. References Antimicrobial Resistance Collaborators. 2022. “Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis.” Lancet 399 (10325): 629–55. https://www.thelancet.com/ journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext. Bush, K., and P. A. Bradford. 2020. “Epidemiology of β-Lactamase-Producing Pathogens.” Clinical Microbiology Review 33 (2): e00047-19. doi: 10.1128/CMR.00047-19. PMID: 32102899; PMCID: PMC7048014. Collignon, P., J. J. Beggs, T. R. Walsh, S. Gandra, and R. Laxminarayan. 2018. “Anthropological and Socioeconomic Factors Contributing to Global Antimicrobial Resistance: A Univariate and Multivariable Analysis.” Lancet Planet Health 2 (9): e398–e405. doi:10.1016/S2542- 5196(18)30186-4. Elwakil, W. H., S. S. Rizk, A. M. El-Halawany, M. E. Rateb, and A. S. Attia. 2023. “Multidrug-Resistant Acinetobacter baumannii Infections in the United Kingdom versus Egypt: Trends and Potential Natural Products Solutions.” Antibiotics 12 (1): 77. https://doi.org/10.3390/ antibiotics12010077. 3  A new study reveals how the European Union’s Common Agricultural Policy (CAP) 2014–20 has contributed to animal welfare and antimicrobial use reduction. See EU (2022). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 26 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices European Commission. 2022. “New Study Unveils How the Common Agricultural Policy (CAP) 2014–20 Is Contributing to Animal Welfare and Antimicrobial Use Reduction.” https://agriculture. ec.europa.eu/news/new-study-unveils-how-cap-contributing-animal-welfare-and- antimicrobial-use-reduction-2022-05-11_en. Klein, E. Y., K. K. Tseng, S. Pant, and R. Laxminarayan. 2019. “Tracking Global Trends in the Effectiveness of Antibiotic Therapy Using the Drug Resistance Index.” BMJ Global Health 4: e001315. Levitus, M., A. Rewane, and T. B. Perera. 2023. “Vancomycin-Resistant Enterococci.” StatPearls, StatPearls Publishing, July 17, 2023. Nachega, J. B., V. C. Marconi, G. U. van Zyl, E. M. Gardner, W. Preiser, S. Y. Hong, E. J. Mills, and R. Gross. 2011. “HIV Treatment Adherence, Drug Resistance, Virologic Failure: Evolving Concepts.” Infectious Disorders: Drug Targets 2: 167–74. doi: 10.2174/187152611795589663. Ouji, M., J. M. Augereau, L. Paloque and F. Benoit-Vical. 2018. “Plasmodium Falciparum Resistance to Artemisinin-Based Combination Therapies: A Sword of Damocles in the Path toward Malaria Elimination.” Parasite 25: 24. doi: 10.1051/parasite/2018021. Prasad, R., N. Gupta, and A. Banka. 2018. “Multidrug-Resistant Tuberculosis/Rifampicin-Resistant Tuberculosis: Principles of Management.” Lung India 35 (1): 78–81. doi: 10.4103/lungindia. lungindia_98_17. ReAct. 2019. “When the Drugs Don’t Work: Antimicrobial Resistance as a Development Problem.” https://www.reactgroup.org/wp-content/uploads/2019/02/When-the-Drugs- Don%E2%80%99t-Work-Antibiotic-Resistance-as-a-Global-Development-Problem- Feb-2019.pdf. Sriram, Aditi, Erta Kalanxhi, Geetanjali Kapoor, Jessica Craig, Ruchita Balasubramanian, Sehr Brar, Nicola Criscuolo, et al. 2021. State of the World’s Antibiotics 2021: A Global Analysis of Antimicrobial Resistance and Its Drivers. Washington, DC: Center for Disease Dynamics, Economics & Policy. https://cddep.org/wp-content/uploads/2021/02/The-State-of-the- Worlds-Antibiotics-in-2021.pdf. Sanyaolu, A., C. Okorie, A. Marinkovic, A. F. Abbasi, S. Prakash, J. Mangat, Z. Hosein, N. Haider, and J. Chan. 2022. “Candida auris: An Overview of the Emerging Drug-Resistant Fungal Infection.” Infection and Chemotherapy 54 (2): 236–46. doi: 10.3947/ic.2022.0008. Siddiqui, A. H., and J. Koirala. 2023. “Methicillin-Resistant Staphylococcus aureus.” StatPearls, StatPearls Publishing. Smith, H. Z., and B. Kendall. 2023. “Carbapenem Resistant Enterobacteriaceae.” StatPearls, StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK551704/. Smyk, J. M., N. Szydłowska, W. Szulc, and A. Majewska. 2022. “Evolution of Influenza Viruses—Drug Resistance, Treatment Options, and Prospects.” International Journal of Molecular Sciences 23 (20): 12244. doi: 10.3390/ijms232012244. IACG (Interagency Coordination Group on Antimicrobial Resistance). 2019. “No Time To Wait: Securing the Future from Drug-Resistant Infections: Report to the Secretary-General of the United Nations.” https://www.who.int/publications/i/item/no-time-to-wait-securing-the-future- from-drug-resistant-infections. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 27 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization). 2021. “Tripartite and UNEP Support OHHLEP’s Definition of ‘One Health’: Joint Tripartite (FAO, WOAH, WHO) and UNEP Statement.” December 1, 2021. https://www.who.int/news/item/01-12-2021-tripartite-and-unep-support-ohhlep-s- definition-of-one-health. World Bank. 2017. Drug-Resistant Infections: A Threat to Our Economic Future (Vol. 2): Final Report. Washington, DC: World Bank. https://documents1.worldbank.org/curated/ en/323311493396993758/pdf/final-report.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 28 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 1 Why Addressing AMR Remains Critical to Global Health Security and Global Development Summary 30 CHEVRON- Antimicrobial resistance as a threat to global health security and global development 31 CHEVRON- Purpose of the Framework for Action 35 CHEVRON- Audience 35 CHEVRON- Rationale for World Bank involvement 36 CHEVRON- Higher-level objectives 40 CHEVRON- Global, regional, and national issues 41 CHEVRON- References 42 CHEVRON- Addressing AMR is a development challenge that will negatively and disproportionately impact low- and middle-income countries… by 2050, a high-AMR scenario could wipe away 3.8 percent of global gross domestic product each year and push 28 million people into poverty. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 29 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 1 Why Addressing AMR Remains Critical to Global Health Security and Global Development Chapter 1 summary . In 2019, antimicrobial resistance (AMR) was one of the biggest killers worldwide—yet it remains a neglected threat to global health security. Despite AMR’s substantial global impact to date, and the recognition that, if unchecked, AMR stands to kill more than 10 million people each year by 2050 (Antimicrobial Resistance Collaborators 2022), AMR is often overlooked, and antimicrobials taken for granted. Addressing AMR is critical to global health security because antibiotics are an essential tool for quickly and effectively managing and preventing disease. The lack of sustainable access to antimicrobials threatens basic and modern medicine and risks undoing public health gains of the last century. Antimicrobials are vital to the resilience of health systems: they are a first line of defense for a host of health conditions, from minor wounds to complex surgeries, and they enable health systems to manage routine care and respond to shocks such as pandemics. Addressing AMR is a development challenge that will negatively and disproportionately impact low- and middle-income countries (LMICs). By 2050, a high-AMR scenario could wipe away 3.8 percent of global gross domestic product each year and push 28 million people into poverty (World Bank 2017). Antimicrobials are a global public good that are entwined with our ability to meet the Sustainable Development Goals (SDGs). They are vital to our ability to sustain and improve global reductions in child and maternal mortality, to end extreme poverty and promote shared prosperity, to end hunger, to promote healthy lives and well-being, and to achieve sustainable and inclusive economic growth. The purpose of this Framework for Action is to support task teams and clients in designing components of World Bank operations and in addressing AMR through investments across sectors. The Framework presents 20 intervention areas across the health, agriculture, and water sectors that can help to address AMR. The selected interventions are not intended to provide an exhaustive or definitive list. Rather, they are intended as a starting point for discussions between task teams and clients that can facilitate the development of sustainable systems to address AMR in the short, medium, and long term, at both the country and regional level. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 30 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Antimicrobial resistance as a threat to global health security and global development In 2019, antimicrobial resistance was one of the biggest killers worldwide (Antimicrobial Resistance Collaborators 2022); despite this substantial impact on global health security, AMR is often overlooked. Despite its substantial global impact to date, and the recognition that, left unchecked, AMR stands to kill more than 10 million people each year by 2050, AMR is often overlooked, and the power of antimicrobials is taken for granted. Nevertheless, no one is immune from the threat of AMR, and citizens of LMICs stand to be disproportionately and negatively impacted. By 2050, a high-AMR scenario could wipe away 3.8 percent of global gross domestic product each year and push 28 million people into poverty (World Bank 2017). Addressing AMR remains critical to the future of global health security and global development, as antimicrobials are essential for managing human and animal health systems, ensuring the sustainability of our food systems, and protecting life as we know it today. Antimicrobials have become critical infrastructure within modern society; therefore, AMR has the potential to upend ordinary life (World Bank 2019. Antimicrobials are used every day for a wide range of animal and human health needs. They have become commonplace across modern medicine and are used to treat people with infected bites and wounds, patients undergoing complex surgeries, cancer and heart failure patients, and women delivering babies, as well as children, the elderly, and people with HIV or with weakened immune systems. Antimicrobials are also used to treat sick animals and to control the spread of disease. The misuse and overuse of antimicrobials has accelerated AMR, which is aggressively threatening the ability of health systems to manage disease quickly and effectively—in terms of both the quality and cost of care. The treatment of tuberculosis (TB) highlights the negative impact of AMR. In 2019, nearly half a million people developed rifampicin-resistant TB, 78 percent of whom were infected with multidrug- or extensive drug-resistant (MDR-TB or XDR-TB) isolates (WHO 2020a). Drug-resistant TB poses a significant economic threat to households, as treatment can cost up to 25 times more than for drug-susceptible strains and take three times longer to cure (Manjelievskaia et al. 2016). Among people with MDR-TB or XDR-TB and their households, 80 percent face catastrophic costs associated with treatment (defined as costs greater than 20 percent of annual household income) (WHO 2020a). Building sustainable systems across human, animal, and environmental health, as well as water and sanitation, can help keep AMR at bay and preserve vital resources for decades to come. The experience of the COVID-19 pandemic has crystallized the importance of sustainable investments to build and develop the systems that keep citizens and economies around the world healthy. The ability of these systems to support their own sectors, as well as work across sectoral boundaries, will be an important enabler of long-term recovery from COVID-19 and of our collective ability to eradicate poverty and boost shared prosperity. The widespread importance of antimicrobials to modern life requires improving the capacity of health and animal systems at the local, regional, and country levels, and improving the ability of systems to connect, work, and collaborate with other systems. For example, a local surveillance network that connects to a national and regional system will be better placed to understand trends and transmission patterns of resistance, support the development of mitigation measures, and preserve the efficacy of essential medicines. This type of investment can optimize the use of antimicrobials as public goods. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 31 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The world remains at a critical juncture in translating the experience of COVID-19, which painfully demonstrated the importance of strong systems, into tangible investments that safeguard our collective future with global public goods such as efficacious antimicrobials. COVID-19 drove an additional 97 million people into extreme poverty in 2020 (World Bank 2021). A new and actionable consensus—one that recognizes the importance of preventive action and specific investments to improve human, animal, and environmental health systems—is essential. Without it, critical tools such as antimicrobials will not be safeguarded, and our ability to manage disease will be severely limited. The Framework aims to move the global community toward a consensus by highlighting what can and ought to be financed to build systems that preserve the efficacy of antimicrobials. Interventions to address AMR are among the most cost-effective investments that can be made in the health and agricultural sectors, and the economic case for action has been clearly established. The emergence of drug-resistant pathogens is inevitable, but widespread AMR can be controlled through interventions in health, agriculture, water and sanitation, and environmental sectors, as well as many others, as it is accelerated by human behavior. Health systems perform the core functions of early detection and of prompt and effective control of AMR. In 2012, spending on these systems was identified as having a high expected economic return (57–86 percent a year) (World Bank 2012). In 2019, the Organisation for Economic Co-operation and Development (OECD) conducted an analysis of progress toward tackling the burden of AMR in high-income countries and found that investing €1.5 per capita per year in a comprehensive package of mixed public health interventions would avoid 27,000 deaths per year in the European Union. Moreover, the package of interventions would pay for itself in one year alone and return approximately €1.4 billion in savings (OECD 2019). Across the OECD, interventions to promote the prudent use of antibiotics in hospitals were costed at US$0.3 to US$2.7 per capita per year in many OECD countries (OECD 2018). Despite this compelling economic case at the global level, many factors have hindered progress on AMR, including the nature of antimicrobials as global public goods, the need for multisectoral solutions with an integrated systems perspective, the perception of complexity, general lack of awareness, and financing gaps. In 2020, the Wellcome Trust noted that action on AMR has entered a “state of paralysis” (Wellcome 2020a, 11); several barriers have inhibited movement from consensus on the importance of AMR to coordinated action and financing for addressing AMR. One challenge relates to communicating the importance of AMR to policy makers, budget holders, and the general public, given the perceived complexity of the topic. As the shared experience with COVID-19 has shown, simple measures—improved hand hygiene and improved infection prevention and control measures in hospital and everyday settings—can have a powerful impact on the spread of disease. Responding to AMR is no different. The Framework seeks to facilitate increased financing to address AMR by specifying relevant actions and tools that the World Bank and other international financial institutions can use to support countries across the income spectrum. The under-recognition of AMR as a global threat may be attributed to various factors, including funding challenges, the long-term nature of the AMR challenge, and the complex nature of AMR and its multifaceted impact on health systems, economies, and societies. Results for the 2019–2020 Tripartite AMR country self-assessment survey (TrACSS 4.0) conducted by the World Health Organization (WHO) among implementers of National Action Plans (NAPs) highlighted the critical issue of funding as the primary challenge to effective AMR action. The survey revealed that a significant gap exists between the recognition of the problem and the availability of financial resources to address it. As of 2020, only 14 percent of NAPs had been costed and funded, indicating a considerable shortfall in financial support for AMR initiatives (WHO 2022). The consequences of inadequate funding extend beyond the immediate challenges of combating AMR. Insufficient financial support limits the capacity to raise awareness, educate health care professionals and the public, and develop innovative solutions to tackle AMR. It perpetuates a Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 32 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices cycle of limited resources, hindering the development of new antimicrobial drugs, diagnostic tools, and infection prevention measures that are crucial for effectively managing resistant infections. Securing funding for such comprehensive initiatives can be challenging, especially when resources are limited, and competing priorities exist. Additionally, unlike immediate health crises or emergencies, the consequences of AMR may not be readily apparent or easily quantifiable. This can lead to a perception that investing in AMR prevention and control measures is less urgent than for other pressing health care issues. Moreover, the lack of awareness about the potential catastrophic consequences of AMR among policy makers and the general public can contribute to a reduced sense of urgency and, consequently, limited funding. Efforts to raise awareness about AMR, its impacts, and the importance of investing in prevention and control strategies are crucial to mobilize financial support. Another example of under-recognition of AMR is the lack of market incentives for the antimicrobial research and development pipeline. R&D for new antimicrobial drugs has experienced a significant decline since the 1980s (Wellcome Trust 2020b), and the current state of the pipeline can be described as inadequate. This decline can be attributed to various factors. One key factor is the high cost associated with conducting R&D for antimicrobials. Antimicrobials may not be as commercially attractive when compared with drugs that require prolonged usage and can command high prices. This lack of commercial viability diminishes the incentives for pharmaceutical companies to invest in the development of new antimicrobial drugs. Without strong economic incentives, there is limited motivation for pharmaceutical companies to allocate resources to antimicrobial research. As a result, the pipeline for new antimicrobial drugs remains stagnant, with fewer potential treatment options being developed. Given this scenario, it becomes increasingly crucial to preserve the effectiveness of existing antimicrobial drugs by minimizing their misuse and overuse, and ensuring sustainable access plans for the few new drugs that become available. By preventing the emergence and spread of antimicrobial resistance through appropriate and responsible use, the available drugs can be preserved for as long as possible. Individuals, governments, regional entities, multilateral organizations, and development banks all play a role in a proactive response to AMR. Many steps have already been taken, but an unfinished agenda remains. Step one is designing and developing investments to build the strength and resilience of existing systems across the One Health spectrum. The investment case is familiar and clear. Following the COVID-19 pandemic, there is an important opportunity to rebuild systems so they are resilient to future global health security threats. The current moment is a watershed that offers significant opportunities to build human health systems, animal health systems, and food systems that are more proactive, effective, and resilient. An extensive body of work has already set out the importance of addressing AMR and strengthening systems for human, animal, and environmental health to achieve the broader goal of safeguarding antimicrobial effectiveness. The international community recognized the importance of AMR as a global health security threat at the May 2015 World Health Assembly, through the adoption of the World Health Organization (WHO) Global Action Plan on AMR. In 2017, the World Bank analyzed the economic impact of AMR at the global level (World Bank 2017), and in 2019 it identified implementation gaps affecting AMR (World Bank 2019). An OECD (2018) report, Stemming the Superbug Tide, presented the critical financing gap by showing that too few countries have financing in place for their AMR NAPs. As of November 2022, 170 countries had established such plans, which commit countries to aligning with the Global Action Plan. National Action Plans for Health Security (NAPHSs) also include interventions on AMR, making their implementation more broadly relevant. Most recently, at the global level, a report by the United Nations Interagency Coordinating Group on Antimicrobial Resistance (IACG 2019) highlighted the importance of investing for a sustainable response. It stressed the need for increased investments to finance NAP implementation, among other interventions. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 33 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Countries around the world have begun to operationalize a focus on AMR through NAPs; however, financing and implementation have been substantial barriers. Countries with multisectoral NAPs have found it challenging to prioritize, resource, and monitor them, and implementation of activities has often been ad hoc. At the same time, these plans provide a valuable foundation for a response to AMR, and increasing financing to support part or all of a plan is a tangible action that countries can take to preserve the sustainability of systems across different sectors. In addition, as indicted just above, activities to address AMR are also included in NAPHSs, and for many countries, where AMR activities fall under the purview of health emergency teams, these plans can be another important vehicle for identifying and prioritizing investments and interventions. Given its multisectoral drivers, AMR is also closely aligned with the One Health agenda (CDC 2022). A One Health approach can be defined as: an integrated, unifying approach that aims to sustainably balance and optimize the health of people, animals, plants and ecosystems. It recognizes the health of humans, domestic and wild animals, plants, and the wider environment (including ecosystems) are closely linked and interdependent. The approach mobilizes multiple sectors, disciplines and communities at varying levels of society to work together to foster well-being and tackle threats to health and ecosystems, while addressing the collective need for clean water, energy and air, safe and nutritious food, taking action on climate changes and contributing to sustainable development (OHHLEP 2022). Addressing AMR can benefit from a One Health approach because the antimicrobials used to treat infectious diseases in humans may be the same as or similar to those used in animals, and resistant bacteria arising in humans, animals, or the environment can spread from one domain to the others (WHO 2021a). The One Health Joint Plan of Action (2022–2026) launched by the Quadripartite organizations includes curbing AMR as one of its six action tracks (FAO et al. 2022).4 A One Health approach can help to maximize the effectiveness and sustainability of interventions and can also be cost-effective. Where collaboration across sectors is possible, a One Health approach in the design and implementation of programs, policies, legislation, and research can allow all sectors to benefit from collaboration, coordination, communication, and capacity strengthening. It is important to acknowledge that multisectoral action is not always possible; but where sectors can tackle AMR together there is scope to achieve critical human, animal, and environmental health outcomes (WHO 2021b). A multisectoral, One Health approach can help to mitigate AMR’s emergence and spread in all domains, and it also offers benefits in related areas such as food safety and food security, biosecurity and animal welfare, WASH (water, sanitation, and hygiene), pollution reduction, emerging infectious disease prevention, and pandemic preparedness and response. 4  The Quadripartite members are the Food and Agriculture Organization of the United Nations (FAO), the United Nations Environment Programme (UNEP), the World Organisation for Animal Health (WOAH, founded as OIE), and the World Health Organization (WHO). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 34 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Purpose of the Framework for Action This Framework is intended to support task teams and clients in designing components of World Bank operations and addressing AMR through World Bank operations across multiple sectors. This Framework describes 20 intervention areas across the health, agriculture, and water sectors that can help to address AMR. The selected interventions are not intended to provide an exhaustive or definitive list. Rather, they are intended as a starting point for discussions between task teams and clients that can facilitate the development of sustainable systems to address AMR in the short, medium, and long term, at both the country and regional level. More specifically: » The Framework for Action summarizes the current state of evidence, the feasibility of implementing projects across different settings, and considerations for optimizing implementation for 20 intervention areas. » It provides practical guidance on developing approaches to prevent, detect, respond to, and mitigate the emergence and spread of AMR in low- and middle-income settings. » It provides a starting point for sectoral leadership and alignment both within and beyond the World Bank. » It highlights approaches to institutional arrangements that support multisectoral implementation. » It presents existing tools and innovations that can be drawn upon to support successful implementation. Audience The World Bank has both an internal and external audience in its work on AMR. The Framework is intended primarily as a resource for World Bank staff and clients who have an interest in accelerating financing to address AMR. Task team leaders will be able to draw on the Framework for guidance when structuring components, lessons learned from implementation arrangements and descriptions of existing tools and guidance. Management may benefit from the Framework’s articulation of options for sectoral entry points, leadership, and collaboration across Global Practices (GP), including Health, Nutrition and Population (HNP), Agriculture and Food (AGF), Environment, Natural Resources and the Blue Economy (ENB), and Water, as well as global themes like climate change and gender. Beyond the World Bank, organizations and other stakeholders with a shared interest in addressing AMR may find the Framework useful for articulating the role that international financial institutions can play and identifying useful entry points for them. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 35 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Rationale for World Bank involvement AMR’s disproportionate impact on LMICs makes it a development problem that warrants support from development financing organizations; its relationship to the Sustainable Development Goals and its impact on inequity provide an additional rationale for involvement. As highlighted by the World Bank’s (2019) report, AMR is a development issue—and one that could prevent the attainment of the SDGs. 5 A rise in drug-resistant infections and a diminishing ability to rely on antimicrobials compromise advances made in public health over the last century. AMR not only jeopardizes the prospect of ending extreme poverty and promoting shared prosperity, but also compromises the ability to end hunger, promote healthy lives and well-being, and achieve sustained economic growth. Table 2 highlights the relationship between AMR and the SDGs. Table 2. AMR and the SDGs How progress on the SDG helps to Core SDGs How AMR impedes progress on the SDG address AMR • People living in poverty are more prone to • Financial and social protection strategies infectious diseases, and resistant infections will allow poor people to access good- are more likely to spread in poor living quality services and decrease the conditions. The poor are less able to access impact of AMR. effective treatment. Substandard care and partial treatment can drive infection. • High costs of treatment and chronic infections will impoverish millions. An additional 28.3 million people could be pushed into extreme poverty by 2050 because of AMR, most of them living in LMICs (World Bank 2017). • AMR in animals increases costs of animal • Developing sustainable food production health, infections become untreatable, systems with less reliance on production decreases and working animals antimicrobials and with the phasing out cannot carry out their tasks, affecting the of antibiotic use in livestock for growth livelihood of farmers and food security. promotion will be essential for long-term AMR control. • Livestock production in low-income countries would decline the most, with • Increased professional advice and a possible 11 percent loss by 2050 in vaccination of food animals can the high-AMR impact scenario (World reduce the emergence and spread of Bank 2017). drug-resistant infections. 5  World Bank (2019, 65–68) provides a detailed introduction to AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 36 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices How progress on the SDG helps to Core SDGs How AMR impedes progress on the SDG address AMR • Globally, drug-resistant diseases currently • Strategies to reduce the risks of AMR must cause at least 700,000 deaths a year be linked to improving care and ensuring (IACG 2019). access to effective care when needed. • AMR will increase treatment costs, making • Central to addressing AMR is ensuring that effective care unaffordable for many, and health systems are accessible and have universal health care unattainable. a trained workforce providing evidence- based high-quality care in a hygienic • Emerging and increasing resistance to setting (Tayler et al. 2019). drugs to treat HIV, TB, and malaria is one of the key barriers to eliminating these • Increased vaccine coverage reduces diseases. Multi-drug-resistant TB alone the incidence of disease from resistant is estimated to cause 230,000 deaths pathogens and limits the need for annually (IACG 2019). antibiotics; in turn, this prevents the development of AMR (WHO 2020c). • Reducing child and infant mortality relies on effective antibiotics. Currently, 200,000 • Falsified and poor-quality antibiotics neonates die each year from drug-resistant contribute to AMR. Hence, improving infections, such as pneumonia or resistant access to high-quality antimicrobials bloodstream infections (Costello and and preventing falsified and substandard Petersen 2016). medicines from reaching the market will help to reduce AMR. • Reliance on out-of-pocket payment for health care correlates with AMR in LMICs (Alsan et al. 2015). • Globally, 1 in 4 health care facilities have • Each year, hundreds of millions of cases no access to basic water services, 1 in 10 of diarrhea in humans are treated with have no sanitation services available, 1 in antimicrobials. Universal access to WASH 3 do not have adequate facilities to clean could reduce such cases by 60 percent hands at the point of care, and 1 in 3 do not (WHO, FAO, and WOAH 2020). segregate waste safely. Lack of basic WASH • Improved WASH services are critical to services is greatest in least-developed reducing the spread of infection. countries, where 50 percent of health care facilities lack access to water services and 60 percent have no sanitation services at all (WHO 2020c). • Lack of access to adequate WASH services is giving rise to the spread of infectious diseases; in turn, this increases antibiotic use and thus drives the emergence and spread of AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 37 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices How progress on the SDG helps to Core SDGs How AMR impedes progress on the SDG address AMR • By 2030, increased mortality and morbidity due to AMR, and thus reduced labor supply, could cause a decrease in global economic output of 1–3 percent, with estimated losses as high as US$3.1 trillion (World Bank 2017). • Antimicrobial compounds and their • Effective pollution controls on metabolites can be found in the pharmaceutical production, health wastewaters from manufacturing sites facilities, and agricultural production will for medicines and active pharmaceutical substantially decrease the risk of AMR ingredients. In extreme cases, emergence and spread in the environment. antimicrobial compounds have been found in water downstream from manufacturing sites in concentrations higher than those found in the blood of patients taking medicines (WHO, FAO, and WOAH 2020). • To effectively tackle AMR, collaboration • Working in partnership means taking and partnerships are needed across all up the One Health approach to relevant sectors (human, animal, plants, addressing AMR. and the environment) and at all levels (national, regional, and global). Related SDGs Women are more affected by AMR, Addressing overcrowding, poor WASH resulting in gender inequality. For provision, and inadequate regulation of example, women’s exposure to AMR basic services will decrease the risks of and antimicrobial use is higher during infections and hence the emergence and pregnancy, childbirth, menstruation, and spread of AMR in cities. abortion. Women are also more likely than men to be unpaid caregivers, and their greater presence on the front lines of caregiving roles in health and education increases their vulnerability to AMR. Quality-assured local production of Global warming is resulting in antimicrobials, vaccines, and diagnostics changing patterns of disease and can improve access to medical increased reliance on antimicrobials in technologies, and this is an important non-immune populations. part of the strategy for some countries. Taking action on climate change will Investment in R&D is vital for the decrease the likelihood of extreme development of vaccines, new weather events and the associated antibiotics, and diagnostics. spread of resistance. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 38 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Related SDGs AMR can lead to increasing inequalities If countries develop aquaculture, within societies; also, certain groups appropriate regulation is essential may be particularly vulnerable to drug- to ensure access to high-quality resistant infections. These groups include antimicrobial agents and to minimize the women, children, migrants, refugees, overuse and misuse of antimicrobials. people employed in certain sectors (e.g., agriculture or health care), and people living in poverty. Source: Adapted from WHO, FAO, and WOAH 2021. Note: LMICs = low- and middle-income countries; SDG = Sustainable Development Goal; TB = tuberculosis; WASH = water, sanitation, and hygiene. AMR has the potential to increase inequalities among society’s vulnerable and marginalized groups, particularly women, who have a greater risk of experiencing both the direct and indirect consequences of AMR. Pregnancy and childbirth may put women at an increased risk of AMR infections, especially in settings with unsafe or unhygienic health care, inadequate water and sanitation, insufficient or unaffordable antimicrobials, or inadequate knowledge about appropriate medicine use. Gender norms and attitudes can also influence the prescribing practices of health care providers, and they can inform how individuals use antimicrobials (their patterns of compliance, consumption, and self-medication) and how they experience disease more generally (their access to health care and their health-seeking behavior) (ReAct 2020; WHO 2018). Furthermore, women and girls engage in caretaking activities more than their male counterparts; an increase in disease due to AMR stands to exacerbate this inequality, further reducing women’s workforce participation and girls’ schooling. In sum, women are at risk from AMR because of the processes associated with both sex (a biological factor) and gender (social factors) (WHO 2018). Ensuring effective and equitable impact on AMR requires acknowledging and understanding how women and men (as well as other groups in society) may face different risks and different levels of risk, and how they may be impacted by AMR and the efforts to address it (WHO 2018). Other vulnerable groups, such as the elderly, men who have sex with men, and indigenous people, may face significant challenges owing to the rise of AMR. These populations often face unique circumstances that make them susceptible to the adverse effects of AMR. The elderly, who tend to have weakened immune systems and a higher likelihood of chronic illnesses, are more prone to infections that may require antimicrobial treatments (Giarratano et al. 2018). However, AMR limits the effectiveness of these treatments, rendering them less potent. Men who have sex with men and may be at a higher risk of sexually transmitted infections also face a significant burden: as AMR spreads, the ability to treat these infections may become compromised, leading to complications, increased transmission rates, and potential long-term health consequences (European Centre for Disease Prevention and Control 2023). Indigenous communities, often residing in remote and underprivileged areas, face multiple challenges in health care access. The emergence of AMR further exacerbates these difficulties, as limited resources and inadequate health care infrastructure can impede the ability of indigenous communities to address and manage resistant infections effectively. This situation heightens the vulnerability of these populations, as they face higher rates of infectious diseases and limited access to appropriate treatments (Doherty Institute 2019). Addressing AMR in vulnerable groups requires tailored strategies that consider their unique circumstances, including strengthening of health care systems, promotion of education and awareness, and efforts to ensure equitable access to appropriate antimicrobial therapies. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 39 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices In meeting the challenge of AMR, the World Bank brings the comparative advantage of a multisectoral offering, built over many years, as well as the financial and technical resources to support clients in building systems that can safeguard the future of their citizens. The World Bank brings both a global reach and the ability to engage in all sectors that are relevant to addressing AMR (public health, animal health, food systems, environment, disaster risk management, global risk communications). As noted in the World Bank One Health Operational Framework, few development institutions can claim such a country-level track record of engagement through lending and economic work in all these sectors—and, moreover, a capacity for global scope in delivery (World Bank Group 2018). The World Bank has valuable operational expertise supporting multisectoral programs, from design to appraisal to implementation of substantial investments and related policies, and it has worked to improve coherence and coordination across sectors. The World Bank can finance and mobilize additional resources for these programs through its technical support and operations. In the past, the World Bank provided financial support to a bridging framework for national capacity assessment tools developed by the WHO and World Organisation for Animal Health (WOAH); it also supported the response to multiple recent Ebola outbreaks and mobilized the Global Program for Avian Influenza (GPAI). Furthermore, the World Bank has flagship operations currently addressing AMR. One example is the Regional Disease Surveillance Systems Enhancement (REDISSE) program in West Africa, which supports community-level surveillance systems and processes across the human and animal sectors, the development of interoperable surveillance and reporting systems, and the establishment and upgrading of laboratories, among other activities. Higher-level objectives Addressing AMR goes hand in hand with the attainment of universal health coverage (UHC) and with factors that contribute to good health, such as sustainable agriculture and food safety. UHC aims to ensure that people have access to the health services they need, when and where they need them, without financial hardship. UHC includes the full range of essential health services, from health promotion to disease prevention, treatment, rehabilitation, and palliative care.6 In the absence of efficacious antimicrobials, it will become harder to treat many routine diseases without compromising people’s financial health. Addressing AMR and achieving UHC necessitate a systems-focused approach to improving health care (Tayler et al. 2019). Measures that support UHC, such as infection control and prevention interventions, training of health care workers, and provision of routine immunizations, can limit the scope for AMR by reducing the need for antibiotics. Addressing AMR is therefore intertwined with the attainment of UHC, as both aim to ensure that populations can appropriately use antibiotics when needed and that antimicrobials remain efficacious, timely, and cost-effective means of treating infection. AMR is also intrinsically linked to strengthening of primary health care (PHC) and improving the readiness of health systems to prevent and respond to pandemics. Antibiotics can play a critical role in the cost-effective and swift treatment of diseases in PHC settings. Without the ability to draw on antibiotics, PHC costs—and unnecessary referrals to secondary and tertiary care—stand to increase. In the event of a pandemic, or indeed in managing the backlog of a pandemic, the loss of this vital everyday tool puts additional pressure on the health system; this could in turn compromise the resilience of the critical systems that sustain economies, society, and our everyday lives. Within the human health sector, AMR investments can be made more sustainable when they are tied to national health sector plans, strategies, and budgets. These could include national UHC, PHC, and health security plans. 6  World Health Organization, “Universal Health Coverage,” https://www.who.int/health-topics/universal-health-coverage#tab=tab_1. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 40 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR also stands to have a significant impact on human capital because it will reduce the ability of health systems to expediently manage health conditions. Advancing human capital depends on ensuring that populations are able to live healthy lives and that children and adolescents can complete a full cycle of education in preparation for their productive lives. Twenty-two African countries have committed to advancing the human capital agenda. This commitment is focused on key targets for 2023, including increasing learning-adjusted years of school by 20 percent, from 4.94 to 5.88 years, and increasing the overall adult survival rate from 0.73 to 0.81.7 Antimicrobials are critical to effective health systems that can treat diseases; when populations are able to mitigate everyday disease threats with ease, they can learn and support the growth of economies worldwide. Beyond the health sector, addressing AMR goes hand in hand with improving the sustainability of food and agricultural systems and safeguarding the environment, which are also part of the human capital and SDG agendas. The efficacy of antimicrobials is important for the viability of animal production systems—both terrestrial and aquatic—as antimicrobials are an important part of ensuring animal welfare, efficient production, safe trade, and food and nutrition security. 8 Improving the prudent use of antimicrobials in livestock, aquaculture, and crop production is needed to safeguard these critical tools, which contribute to food security. Addressing antimicrobial use on farms helps limit environmental pollution and risks to food consumers. Global, regional, and national issues Sustaining the efficacy of antimicrobials, a global public good, requires tailored approaches at the local, national, and regional levels. World Bank operations provide financing at all three of these levels, and the World Bank recognizes the importance of the local, national, regional, and global perspectives for AMR. First, at the global level, several international references, standards, and regulations have been developed to promote the prudent use of antimicrobials. For example, guidelines from the Codex Task Force on AMR provide a science-based approach to assessing and managing the risks to human health associated with the presence of antimicrobial-resistant microorganisms in food and animal feed. Second, the fact that AMR is not bound by national borders means that national, regional, and global efforts should be connected so that they are additive to one another and maximize the use of scarce resources for AMR. Third, there are specific national and regional dynamics to AMR patterns, which must be understood to inform programming at all levels. In this context, regional mechanisms can play an important role in coordinating efforts to assess and manage risks and in implementing programs to stop the spread and emergence of AMR. 7  World Bank, “Africa Human Capital Plan: Powering Africa’s Potential through Its People,” https://thedocs.worldbank.org/en/ doc/910151554987573474-0010022019/original/HCPAfricaScreeninEnglish.pdf. 8  Food and Agriculture Organization of the United Nations, “Antimicrobial Resistance and Our Food Systems: Challenges and Solutions,” https://www.fao.org/3/i6106e/i6106e.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 41 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices References Antimicrobial Resistance Collaborators. 2022. “Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis.” Lancet (London, England) 399 (10325): 629–55. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02724-0/fulltext. CDC (Centers for Disease Control and Protection). 2022. “One Health.” June 6, 2022. https://www.cdc.gov/onehealth/basics/history/index.html. Costello, A. and S. Petersen. 2016. “Birth in a Time of Antibiotic-Resistant Bacteria.” Project Syndicate. August 25, 2016. https://www.project-syndicate.org/commentary/antibiotic-resistance- maternal-infant-mortality-by-anthony-costello-and-stefan-s--peterson-2016-08. Doherty Institute. 2019. “Antibiotic resistance is an even greater challenge in indigenous communities.” Antibiotic resistance is an even greater challenge in remote Indigenous communities | Doherty Website. ECDC (European Centre for Disease Prevention and Control). 2023. “Spread of Multidrug-Resistant Shigella in EU/EEA among Gay, Bisexual and Other Men Who Have Sex with Men.” Spread of multidrug-resistant Shigella in EU/EEA among gay, bisexual and other men who have sex with men (europa.eu). FAO, UNEP, WHO, and WOAH (Food and Agriculture Organization of the United Nations, United Nations Environment Programme, World Health Organization, and World Organisation for Animal Health). 2022. “One Health Joint Plan of Action (2022–2026): Working Together for the Health of Humans, Animals, Plants and the Environment.” Rome. https://doi.org/10.4060/cc2289en. Giarratano, Angela, Samantha E. L. Green, and David P. Nicolau. 2018. “Review of Antimicrobial Use and Considerations in the Elderly Population.” Clinical Interventions in Aging 13: 657–67. https://doi.org/10.2147%2FCIA.S133640. IACG (Interagency Coordination Group on Antimicrobial Resistance). 2019. “No Time to Wait: Securing the Future from Drug-Resistant Infections. Report to the Secretary-General of the United Nations.” https://www.who.int/docs/default-source/documents/no-time-to-wait-securing- the-future-from-drug-resistant-infections-en.pdf?sfvrsn=5b424d7_6. Manjelievskaia, Janna, Dara Erck, Samina Piracha, and Lewis Schrager. 2016. “Drug-Resistant TB: Deadly, Costly, and in Need of a Vaccine.” Transactions of the Royal Society of Tropical Medicine and Hygiene 110 (3): 186–91. https://doi.org/10.1093/trstmh/trw006. OECD (Organisation for Economic Co-operation and Development). 2018. Stemming the Superbug Tide: Just a Few Dollars More. https://www.oecd.org/health/health-systems/Stemming-the- Superbug-Tide-Policy-Brief-2018.pdf. OECD (Organisation for Economic Co-operation and Development). 2019. “Antimicrobial Resistance: Tackling the Burden in the European Union.” https://www.oecd.org/health/health-systems/ AMR-Tackling-the-Burden-in-the-EU-OECD-ECDC-Briefing-Note-2019.pdf. OHHLEP (One Health High-Level Expert Panel), W. B. Adisasmito, S. Almuhairi, C. B. Behravesh, P. Bilivogui, S. A. Bukachi, N. Casas, et al. 2022. “One Health: A New Definition for a Sustainable and Healthy Future.” PLoS Pathogens 18 (6): e1010537. https://doi.org/10.1371/journal. ppat.1010537. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 42 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices ReAct. 2020. “Scoping the Significance of Gender for Antibiotic Resistance.” https://www.reactgroup. org/wp-content/uploads/2020/09/Scoping-the-Significance-of-Gender-for-Antibiotic- Resistance-IDS-ReAct-Report-October-2020.pdf. Tayler, Elizabeth, Richard Gregory, Gerry Bloom, Peter Salama, and Hanan Balkhy. 2019. “Universal Health Coverage: An Opportunity to Address Antimicrobial Resistance?” The Lancet Global Health 7 (11): E1480–E1481. Wellcome. 2020a. “The Global Response to AMR: Momentum, Success, and Critical Gaps.” https://wellcome.org/reports/global-response-amr-momentum-success-and-critical-gaps. Wellcome. 2020b. “Why Is It So Hard to Develop New Antibiotics.” Why is it so hard to develop new antibiotics? (wellcome.org) WHO (World Health Organization). 2018. “Tackling Antimicrobial Resistance (AMR) Together. Working Paper 5.0: Enhancing the Focus on Gender and Equity.” World Health Organization, Geneva. https://apps.who.int/iris/bitstream/handle/10665/336977/WHO-WSI-AMR-2018.3-eng.pdf. WHO (World Health Organization). 2020a. Global Tuberculosis Report 2020. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789240013131. World Health Organization. 2020b. Global Progress Report on Water, Sanitation and Hygiene in Health Care Facilities: Fundamentals First. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789240017542. WHO (World Health Organization). 2020c. “Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance: An Action Framework.” World Health Organization, Geneva. https://www.who.int/publications/m/item/leveraging-vaccines-to-reduce-antibiotic-use- and-prevent-antimicrobial-resistance. WHO (World Health Organization). 2021a. “Antimicrobial Resistance.” https://www.who.int/news- room/fact-sheets/detail/antimicrobial-resistance. WHO (World Health Organization). 2021b. “Tripartite and UNEP Support OHHLEP’s Definition of ‘One Health’: Joint Tripartite (FAO, WOAH, WHO) and UNEP Statement.” December 1, 2021. https://www.who.int/news/item/01-12-2021-tripartite-and-unep-support-ohhlep-s- definition-of-one-health. WHO (World Health Organization). 2022. “WHO Implementation Handbook for National Action Plans on Antimicrobial Resistance: Guidance for the Human Health Sector.” NAP AMR Implementation Handbook (who.int). WHO (World Health Organization) Food and Agriculture Organization of the United Nations (FAO), and World Organisation for Animal Health (WOAH). 2020. “Technical Brief on Water, Sanitation, Hygiene and Wastewater Management to Prevent Infections and Reduce the Spread of Antimicrobial Resistance.” https://www.who.int/publications/i/item/9789240006416. WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations), and WOAH (World Organisation for Animal Health). 2021. “Antimicrobial Resistance and the United Nations Sustainable Development Cooperation Framework: Guidance for United Nations Country Teams.” https://www.woah.org/app/uploads/2021/10/unsdcf-amr- guidance-en-final-approved.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 43 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices World Bank. 2012. “People, Pathogens and Our Planet: The Economics of One Health.” World Bank, Washington, DC. https://openknowledge.worldbank.org/handle/10986/11892. World Bank. 2017. Drug-Resistant Infections: A Threat to Our Economic Future (Vol. 2): Final Report. Washington, DC: World Bank Group. http://documents.worldbank.org/curated/ en/323311493396993758/final-report. World Bank. 2019. “Pulling Together to Beat Superbugs: Knowledge and Implementation Gaps in Addressing Antimicrobial Resistance.” Washington, DC: World Bank. https://documents1. worldbank.org/curated/en/430051570735014540/pdf/Pulling-Together-to-Beat-Superbugs- Knowledge-and-Implementation-Gaps-in-Addressing-Antimicrobial-Resistance.pdf. World Bank Group. 2018. One Health: Operational Framework for Strengthening Human, Animal, and Environmental Public Health Systems at Their Interface. Washington, DC: World Bank. https://documents1.worldbank.org/curated/en/703711517234402168/pdf/123023-REVISED- PUBLIC-World-Bank-One-Health-Framework-2018.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 44 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 2 Four Thematic Entry Points for Addressing AMR Summary 46 CHEVRON- Introduction 47 CHEVRON- Reducing infections: A focus on IPC, vaccination, and nutrition 47 CHEVRON- Strengthening monitoring and surveillance of AMR and AMU 50 CHEVRON- Improving access and the rational use of antimicrobials: A focus on  antimicrobial stewardship and regulatory frameworks 51 CHEVRON- Strengthening sectoral and multisectoral coordination and governance 54 CHEVRON- References 61 CHEVRON- A wide range of interventions across four thematic areas—reducing infections, strengthening monitoring and surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU), improving access and the rational use of antimicrobials, and strengthening sectoral and multisectoral coordination and governance—can help address the emergence and spread of AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 45 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 2 Four Thematic Entry Points for Addressing AMR Chapter 2 summary A wide range of interventions across four thematic areas—reducing infections, strengthening monitoring and surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU), improving access and the rational use of antimicrobials, and strengthening sectoral and multisectoral coordination and governance—can help address the emergence and spread of AMR. This chapter describes a range of entry points that local, regional, and national policy makers and implementers can consider, across health, agriculture and food, and water and sanitation for implementing the AMR agenda across government. Countries are at different states of readiness to address AMR, so that a comprehensive approach may not always be feasible; however, a broader vision of the range of options can help to maximize the effectiveness and sustainability of any given intervention. Some 170 countries have developed National Action Plans (NAPs); this large number suggests that in many settings there may be an appetite to make inroads across all four thematic areas. In instances where readiness is higher, and where a strong enabling environment and political consensus to address AMR are present, it will be relevant for governments to consider comprehensive programming across multiple areas and to choose from a range of options. In other settings, the appetite and funding to address AMR may be more limited, and programming may need to be more opportunistic and targeted. Nevertheless, across different states of readiness, a vision of the range of options remains important, as it offers a window to ensuring that financial and nonfinancial resources are utilized well and sustainably. This chapter provides an overview of the four themes and discusses options to consider across sectors. AMR programs can typically be thought of in broad categories, i.e., stewardship, monitoring and surveillance, regulatory frameworks, and infection prevention and control (IPC). Understanding the general scope and rationale for each of these categories is important for designing effective programs. In general, all four will have to be in place in some fashion to adequately understand and address sources of AMR, though their scope and application will differ based on the country or regional context. Each of the categories involves more specific interventions and applications (selection of site, scale) that will have to be determined in each context. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 46 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction Efforts to address AMR can be optimized by adopting a systematic, well-planned, and coordinated approach across four thematic areas. These areas are reducing infections; strengthening monitoring and surveillance of AMR and AMU; improving the rational use of antimicrobials; and strengthening sectoral and multisectoral coordination and governance. Where possible, interventions and programming to address AMR are best pursued in concert with an overall focus on strengthening systems (e.g., for human health, animal health, environmental health, water and sanitation, agri-food) and their effective governance. This approach can reinforce entry points for prevention, detection, response, and recovery. The programmatic areas and specific interventions examined promote general good practices; countries are at different baselines for implementing interventions that will shape the immediate feasibility, sequencing, and design of interventions. For example, in some settings regulatory and enforcement capacity will be feasible for central prescribing for human and/or animal use of antimicrobials; in other contexts, however, over-the-counter sales of antimicrobials are standard for a variety of reasons (e.g., infrastructure, workforce capacity, financial, access, etc.). Innovations can support countries’ efforts to shift the baseline in novel ways—for example, using mobile pharmacy technology to support regulation, enforcement, and monitoring of antimicrobial prescribing and access. The broad packages presented in this chapter draw on technical guidance from experts on how clients and teams can go about selecting interventions that build toward a coherent program to address AMR. Context-specific realities and funding constraints often require choosing some interventions over others; hence the importance of understanding how one intervention fits within a suite of options to ensure effective programming. Chapter 3 narrows this focus to specific interventions that can be supported through World Bank operations based on feasibility, key qualifiers, and other considerations to maximize potential for positive impact. Table 3, at the end of this chapter, provides a summary of interventions across four thematic entry points for addressing AMR in various key sectors. Reducing infections: A focus on IPC, vaccination, and nutrition Reducing the incidence of infections in humans and animals is key to addressing the rising burden of AMR (Berthe, Bali, and Batmanian 2022). Prevention is better than cure: by sustainably improving health, animal, and food production systems, it is possible to markedly reduce the demand for antibiotics, thereby reducing the selection pressure of known microorganisms, i.e., minimizing the occurrence of new resistant strains. The past two decades have been seminal in extending knowledge of the origin and emergence of novel diseases. Studies have recognized the importance of the interface between humans, domestic animals, and wild animals in the cross-species transmission of zoonotic diseases. Efforts to prevent and reduce the incidence of infections are the first line of defense against AMR, and each sector has a leadership role to play. This role is best advanced through the One Health approach (World Bank 2018). Globally, several pathogens have been identified as of high concern for transmission in health care settings, based on the burden they cause and their resistance to first- and second-line antimicrobials (leaving only last-resort antimicrobials as options). Examples include Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile (C. diff) infections. Monitoring is essential to detect changing patterns and newly resistant infections and to enhance IPC measures as needed. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 47 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices IPC seeks to reduce the risk of infections and limit spread of AMR. IPC programs in human health are typically focused on communities and health care facilities (in general and for highly infectious or highly susceptible patients), and they operate at national level (Storr et al. 2017). In hospital settings, IPC programs are critical for preventing and containing the spread of health care–acquired (or “nosocomial”) infections in both patients and health care workers. Approximately 10 percent of patients globally develop one or more health care–acquired infections. Both high-income countries (HICs) and low- and middle-income countries (LMICs) face the challenge of health care–acquired infections, though rates of infection are highest in LMICs. These infections cause additional disease burden in already-sick patients (typically with disproportionate impact in intensive care or neonatal units), often requiring additional treatment and use of antimicrobials, and they have the potential to be drug-resistant and challenging to treat. Front-line health care providers play an essential role in IPC, as do sanitation workers, laundry services, hospital administration, and patients themselves. The staffing of trained professionals, often known as infection preventionists, helps maintain a focus on IPC in health care facilities. National programs are focused on ensuring the enabling environment is in place to support implementation—for example, by developing guidance, improving awareness, assessing infrastructure needs to support IPC, and shaping education and training initiatives. Specific interventions under IPC programs often include hand hygiene and other water, sanitation, and hygiene (WASH) interventions, use of personal protective equipment, surface cleaning, waste management, injection safety, limits on invasive procedures and nonessential inpatient stays, and facility capacity limits to ensure sufficient patient spacing (Storr et al. 2017). Surveillance and monitoring play a key role in identifying clusters of health care–acquired infections and assessing efficacy of IPC interventions. Monitoring also helps to identify AMR patterns associated with the highest burden of disease, helping to target interventions. Several IPC good practice guidance documents have been established by the World Health Organization (WHO) and other agencies, based on existing evidence and expert input. Conflict situations can make IPC in hospitals more challenging, for example, through damage to critical infrastructure, workforce shortages, overcrowding, and the interruption of supply chains and access to care (Lowe et al. 2021). These situations may exacerbate common barriers to effective IPC in low-resource setting. A study of 15 LMICs found that bundling IPC interventions, including with in-service training, ongoing performance feedback, and outcome and process surveillance, supported adherence to IPC protocols and yielded significant reductions in incidence of and deaths associated with central line infections (Rosenthal et al. 2010). Just as IPC interventions are essential in human health, improved biosecurity measures are essential for a sustainable farming system. These biosecurity measures are procedures and structures aimed at reducing the probability of the introduction, establishment, survival, or spread of any potential pathogen to, within, or from a farm, operation, or geographical area (Huber et al. 2022; Caveney, Jones, and Ellis 2011). Internal biosecurity involves diminishing the spread of an infectious agent within a herd, while external biosecurity refers to preventing introduction of such agents into the herd or flock. These measures have several key components: good hygiene practices, i.e., hand washing and implementation of cleaning and disinfection routines; isolation of new animals or sick animals; limits on nonessential traffic on the farm; cleaning of materials entering the farm/premises to remove visible dirt; rodent control; and the use of an “all-in, all-out” approach to cleaning and disinfection between batches of animals. Surveillance and monitoring are important in identifying and reporting signs of infections and clusters on the farms. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 48 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The water sector can support the efforts referenced above—i.e., IPC and biosecurity—by improving safe drinking water infrastructure and access in communities, farms, and hospital settings, and by improving sanitation infrastructure to treat community and hospital sewage and other wastewater (see Box 4).9 More broadly, concerted efforts are needed to enhance and expand waste management practices in agriculture and aquaculture production and processing. These efforts may include applying advanced water and waste treatment to destroy resistant genes, supporting infrastructure for closed water systems in aquaculture, and mitigating the effects of climate change that increase the incidence of infections by incorporating flood-proofing interventions and infrastructure. Box 4. Combatting AMR through WASH and IPC in Health Care Settings: Key Data Points Up to 90 percent One in three One in 10 More than 700 million people Source: Joint Monitoring Programme (WHO, UNICEF, and WaterAid), www.washdata.org. In health and agriculture, interventions and investments to scale up vaccinations in the general population and among animals remain central and are highly effective in preventing and curbing the spread of infectious diseases. The potential for vaccines to tackle infections and AMR is threefold: First, existing vaccines can prevent infections that would otherwise require antimicrobial medicines. Second, by reducing the prevalence of primary viral infections, which are often wrongly treated with antibiotics, vaccines can reduce antibiotic misuse and prevent secondary, potentially drug-resistant, bacterial co-infections. Third, the development and use of new or improved vaccines can prevent diseases that are becoming increasingly difficult to treat or untreatable due to AMR (Ginsburg and Klugman 2017; Mishra et al. 2012; Holm et al. 2022). For example, in human health, vaccines against S. pneumoniae, Haemophilus influenza type B (Hib), Salmonella Typhi, Bordetella pertussis, tuberculosis (TB), and Neisseria meningitidis, some of which are part of existing immunization programs, can prevent morbidity and mortality due these pathogens, including drug- resistant forms. There is increasing evidence on the positive impact of some these vaccines, i.e., for S. pneumoniae and Hib on resistant infections (WHO 2020b). Similarly, in animal health, antibacterial vaccines prevent infections that would otherwise require antibiotic treatment. For antiviral vaccines in animals, the positive effect on antimicrobial use is seen through prevention of viral diseases and the associated risk of bacterial co-infections (PACCARB 2019; WOAH 2015). The effects of vaccination in animals can deter the use of antimicrobials as growth promotors, which accounts for the largest proportion of global consumption and is a major driver of AMR. 9  Joint Monitoring Programme (WHO, UNICEF, and WaterAid), www.washdata.org. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 49 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Improved nutrition in humans and animals is additive to these preventative efforts because of its direct link to immune systems that are more robust against infections. Through various mechanisms, nutrition can be a vital determinant of infectious disease susceptibility and disease progression in both animals and humans. Undernutrition often reduces the development and effectiveness of immune responses essential in limiting and clearing infections. For example, in human health, death rates from acute respiratory infections, malaria, diarrhea, and measles are much higher in children who suffer undernutrition than in those who do not. Additionally, micronutrient deficiencies such as vitamin A deficiency have been linked to malaria morbidity and diarrhea severity in some populations; poor maternal nutrition and consequent impaired fetal growth are strongly linked to neonatal deaths from sepsis, pneumonia, and diarrhea (Black et al. 2008). In animal health, young animals such as piglets, broiler chickens, and calves are susceptible to diseases and disorders, leading farmers to increase use of antimicrobials. Animal nutrition strategies can support host defense systems and reduce the presence of pathogens and harmful substances such as mycotoxins in feed and water. Functional nutrition to promote animal health and reduce infections remains an important tool in decreasing the need for antimicrobials in animal production (Coen et al. 2021; Civitello et al. 2018). Strengthening monitoring and surveillance of AMR and AMU Monitoring and surveillance are a strategic priority under the WHO (2015) Global Action Plan on AMR. The two terms are often used interchangeably, though monitoring typically contributes to an overall surveillance system. Policy makers and actors in health, agriculture, water, and the environment need better insight into current and past AMR-related data to elucidate the mechanisms for acquiring new resistance, monitor existing cases, and anticipate future threats. Accelerated investments in better structures for collecting and consolidating data are needed, specifically in these critical areas: antibiotic consumption by humans and animals, resistance rates for available drugs, and research knowledge on the molecular foundations of AMR. Global standards have been established for reporting on two areas of monitoring, which are collected via the Global Antimicrobial Resistance and Use Surveillance System (GLASS): (i) antibiotic consumption, and (ii) the presence or prevalence of antimicrobial-resistant pathogens, resistant genes, or antimicrobial residues. WHO GLASS proposes a master protocol (WHO 2020a) to be used for the generation of reliable estimates of mortality attributable to AMR bloodstream infections (BSIs), focused on the two AMR Sustainable Development Goal indicators.10 Tracking consumption can monitor which antimicrobials are being used, in what quantities, and for what reasons, helping to target inappropriate or excess use (as well as underuse compared to indicated treatment) and guide stewardship campaigns. Tracking residues can be a proxy for consumption, helping to detect the uses and environmental dissemination of antimicrobials and the potential for exposures. Monitoring of resistant pathogens and genes provides information on evolutionary and epidemiological trends, such as detection of new strains or the spread in a population. In general, the design of monitoring interventions comes down to matters of scope and scale, including the location of monitoring (e.g., hospitals, communities, farms), sample type (e.g., clinical, food products, water, soil), and the specific residues or pathogens to be screened. Other information may also be relevant for monitoring, such as the availability of counterfeit products at points along the supply chain, or the results of behavior assessments, using methods such as direct observation or knowledge, attitudes, and practice studies. Several specific applications of monitoring 10  United Nations Statistics Division, “SDG Indicators: Metadata Repository,” https://unstats.un.org/sdgs/metadata?Text=&Goal=3&Target=3.d. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 50 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices are examined in more detail in Chapter 3. In addition, it should be recognized that surveillance is key to inform development and measure effectiveness of all interventions listed in Chapter 3. It can serve a wide range of objectives, such as informing development, implementation, and monitoring and evaluation of national goals and policies to control AMR; informing IPC policies and interventions; informing antimicrobial treatment guidelines and antimicrobial stewardship; informing national Essential Medicines Lists and regulatory and procurement policies; and informing estimates of the burden of AMR (Pezzani et al. 2020). While surveillance activities may be implemented by individual sectors, it is important that there be a mechanism in place for multisectoral integrated surveillance of AMR in line with a One Health approach (FAO 2020; Aenishaenslin et al. 2021). All sector actors need to be aligned and coordinated through a One Health platform on various activities contributing to the readiness and effective functioning of AMR surveillance systems. In health, agriculture, and water, these activities include accelerating investments in laboratory capacities, which involves expanding physical facilities and enhancing laboratory technician training for human, veterinary, and environmental science. These investments are poised to improve antibiotic susceptibility–driven clinical practice and pathogen or residue testing of food on import and other points in the market chain. For agriculture and health, more needs to be done to set up robust prescribing data systems and ensure integration and coordination. In agriculture, this effort is vital for monitoring risks and pharmaceutical use in the food system and for monitoring consumption adherence at regional, local, and farm levels. A similar joint effort is required to enhance waste and wastewater data systems in the water sector. Accelerating the maturity of these data systems will provide improved capacities to monitor AMR and residues in the effluent, e.g., at manufacturing sites, hospitals, and farms. In turn, actors will be able to set and monitor targets for resistance and residue levels in environmental sources. Improving access and the rational use of antimicrobials: A focus on antimicrobial stewardship and regulatory frameworks All antibiotic use, whether appropriate or not, can lead to the emergence of AMR. Unfortunately, inappropriate and excessive use of antibiotics is common in HICs and LMICs and in both human and animal sectors. Limiting inappropriate use of antibiotics is crucial to preserve the effectiveness of antibiotics for both human and veterinary medicine. This effort is well articulated in strategic objective 4 of the Global Action Plan on AMR, which aims to reduce the inappropriate use of antibiotics as an essential element of National Action Plans (WHO 2015). Notably, however, a large proportion of the world’s population lacks access to effective antibiotics. LMICs are disproportionally affected; challenges in consistent and reliable access to antibiotics persist mainly due to affordability of antibiotics and inadequate domestic funding for health, leading to high out-of-pocket spending by patients, among other results. Efforts to increase access to antibiotics are crucial, but they need to be guided by the framework of rational use. Antibiotics should be viewed as a rapidly depleting resource that is a cornerstone of saving human lives. Additionally, in animals with certain diseases, antibiotics are crucial to ensuring survival, welfare, and productivity and reducing the spread of disease. Thus, rational use initiatives aim not always to reduce antibiotic use but to ensure that use is always appropriate. Improving access to antimicrobials, including in LMICs, will also require exploring and implementing push and pull incentives that promote investment in research and development of antimicrobials. For example, according to WHO’s annual review of antibacterial agents in clinical and preclinical development, the R&D pipeline for new antibacterial medicines is insufficient to tackle the challenge of increasing emergence and spread of antibiotic resistance (WHO 2022). Furthermore, while R&D capacities are skewed toward HICs, the general availability of and access to new and existing antibiotics, including generics, is a challenge for countries of all income levels. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 51 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices This antimicrobial pipeline and access crisis requires innovative financing measures to improve the economic conditions for antimicrobial drug development.11 These measures include global pooled efforts and stronger public-private partnerships to stimulate preclinical and clinical development of new antimicrobials and vaccines by closing existing gaps in funding. There is a need for accelerated efforts to ensure equitable access to antibiotics in LIMCs, which are currently facing the double challenge of having the highest AMR burden and lowest access to existing and new antimicrobials. Coordinated action is needed to develop and sustain a favorable market dynamic and create the financial incentives that are needed to drive antimicrobial R&D and innovation. Antimicrobial stewardship (AMS) refers to initiatives that measure and improve how antibiotics are prescribed by clinicians and used by patients (US CDC 2018). AMS is considered one of the pillars of health system strengthening, along with infection prevention and control and patient medicine safety. Programs typically involve a set of coordinated interventions that may entail many components, including prescribing guidelines, training, audits (monitoring), and leadership commitments to ensure the necessary resources and political will are in place for implementation. While stewardship could be relevant for all settings where antimicrobials are used, many programs focus on hospitals, reflecting the relatively high levels of antimicrobial use and susceptibility of patients to clinically important infections. Monitoring of antimicrobial consumption as well as infections can help to guide stewardship actions. Notably, and in line with a comprehensive strategy for monitoring, stewardship interventions should also reflect the reality in LMICs, where the first point of care for most of the population is in communities through private clinics and community pharmacies. AMS in concert with other interventions (e.g., hospital hygiene, policies addressing overuse of antimicrobials) has been projected to save lives and costs—on the order of 1.6 million lives by 2050 and US$4.8 billion annually in Organisation for Economic Co-operation and Development countries (OECD 2018a, 2018b). The WHO’s Essential Medicines List AWaRe classifications provide global guidance on optimal use of a list of antimicrobials (WHO 2021a). The classifications place antimicrobials in three stewardship groups: those to access (antimicrobials with broad uses and relatively lower resistance potential that are recommended for first- or second-line treatment), those to watch (to be prioritized as key targets of stewardship programs), and those to reserve (save for last-resort use). At a national and local level, diagnostic and treatment protocols may be highly specific to the context—that is, may depend on the disease or procedure, availability of laboratory services, and adequacy of infection prevention measures. For example, stewardship initiatives may require that a bacterial culture test be performed to confirm infection to guide the prescription of antibiotics. In addition to antimicrobial resistance, stewardship often considers wider patient safety issues, such as medication allergies. Prescribers, pharmacists, and nurses involved in the prescribing and administration of antimicrobials are typically important target audiences for hospital-based stewardship programs. Improved prescribing practices may also be dependent on access to laboratory services (for timely detection and diagnosis) and information technology to build prescribing protocols into staff workflows. Both inside and outside of health care settings, health care providers have an important role to play in educating patients on appropriate use of antimicrobials, such as adherence to treatment regimens. Suboptimal prescribing may reflect several factors, including overprescription (i.e., prescribing when not needed), selection of overly broad-spectrum antimicrobials, unnecessary combination of multiple antibiotics, wrong antimicrobial based on clinical indication, wrong dose, wrong interval of dosing, wrong route of administration, wrong duration of use, or delays in administration of the antimicrobial dose(s) (WHO 2019). These factors call for a more proactive role from professional organizations in health, agriculture, and environment sectors in steering AMS initiatives to promote best practice through evidence-based guidelines. 11  Meeting note from the Sixth Meeting of the Global Leaders Group on Antimicrobial Resistance. Bridgetown, Barbados. February 2023. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 52 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Several implementation challenges for stewardship programs have been described in LMIC settings (Cox et al. 2017), including barriers related to drug availability, cost of antimicrobials, resistance to change, and limited diagnostic capabilities (Rolfe et al. 2021). Core elements have been identified for health care facility stewardship programs in LMICs, including leadership commitment, accountability and responsibility, AMS actions, education and training, monitoring and surveillance, and reporting and feedback (WHO 2019). WHO has defined 12 core elements for supporting rational use of antimicrobials:12 establishment of a multidisciplinary national body to coordinate policies on medicine use; use of clinical guidelines; development and use of national Essential Medicines Lists; establishment of drug and therapeutics committees in districts and hospitals; inclusion of problem-based pharmacotherapy training in undergraduate curricula; continuing in-service medical education as a licensure requirement; supervision, audit, and feedback; use of independent information on medicines; public education about medicines; avoidance of perverse financial incentives; use of appropriate and enforced regulation; and sufficient government expenditure to ensure availability of medicines and staff. Policy guidance has also been developed for an integrated and programmatic approach to national AMS activities (WHO 2021b). In addition to human health care uses, animal and agricultural uses of antimicrobials have implications for stewardship, including for veterinarians and farmers. Responsible and prudent use is often stressed in these contexts (Ferreira et al. 2022; Góchez et al. 2019). Interventions in the agricultural settings that have implications for AMS include requiring a veterinary prescription when selling antimicrobials for use in animals, preventing the use of antimicrobials for growth promotion in the absence of risk analysis, phasing out antimicrobial use for growth promotion starting with the critically important antimicrobials, enforcing regulations (e.g., checking markets where antibiotics are being sold and checking use in feeds), banning the use of medically important human antimicrobials in animals, establishing a maximum residue limit (MRL) and withdrawal periods in food-producing animals per the World Organisation for Animal Health (WOAH) standards, and harmonizing and complying with international standards, such as Codex Alimentarius (FAO and WHO 2015). In the water and environment sector, this includes setting limits and effectively enforcing these limits on the pathogen and residual levels in drinking water, environmental sources, effluent from manufacturing, and waste materials (e.g., for use as fertilizer). It is also essential to focus on the demand side for comprehensiveness. Interventions to meet the increasing demand for antimicrobials should aim at improving public awareness through addressing disinformation, improving risk communication through community- and national-level public awareness campaigns, and conducting research on behavioral norms, practices, and expectations. Regulations play an important enabling role in policy implementation by incentivizing or disincentivizing certain actions, including those related to antimicrobial production, distribution, use, and disposal (Ming, Puddle, and Wilson 2019). A range of agencies may set regulations relevant to antimicrobial production, sale, or use, such as those with oversight of clinical practice, food and drug safety, commerce, imports and manufacturing, or environmental management. Regulations may span a range of issues, such as licensing of new antimicrobials (or alternatives), prescriber qualification requirements versus over-the-counter sale of antimicrobials, limits on the types and amounts of antimicrobials that may be used for certain purposes (including agriculture and aquaculture), quality and labeling requirements, definition of withdrawal periods (periods between administration of medicines and the processing of the animal for food), and good manufacturing practices for the management of waste and wastewater from antimicrobial production facilities to avoid dissemination of antimicrobial residues into the environment. Enforcement of regulations is a key element that requires ongoing resourcing and can be informed by monitoring to assess compliance. 12  World Health Organization, “Promoting the Rational Use of Medicines,” https://www.who.int/activities/promoting-rational-use-of- medicines. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 53 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Several technical organizations have developed guidelines that can be translated into national regulations, such as the WHO’s guidelines on use of antimicrobials in food-producing animals, which aim to preserve the effectiveness of antimicrobials that are clinically important for human populations (WHO 2017). While regulations provide broad parameters around use, more specific use parameters will usually be determined by professional associations or hospitals as part of stewardship programs. Strengthening sectoral and multisectoral coordination and governance As the determinants of AMR are multisectoral, no single sector has the capacity to address AMR by itself; collective action through the One Health approach is needed to make progress. Such an approach means strengthening coordination through deliberate collaboration within and across sectors to promote the best possible outcomes for all. This can be achieved by setting up regular meetings with defined agendas with a feasible frequency. WHO’s working paper on multisectoral coordination outlines ways in which countries can organize their systems and processes to achieve effective AMR action (WHO 2018). Countries can engage in horizontal collaboration, which involves working across different government departments and nongovernmental stakeholders, and vertical collaboration, which involves working from local to global levels across sectors and from practitioners to central-level policy makers in the sector. Horizontal collaboration can be supported through knowledge-sharing platforms such as multistakeholder forums. Experiences from a set of focal countries, such as Ethiopia, Kenya, the Philippines, and Thailand, point to four categories of tools and tactics that can facilitate the establishment and sustainability of multisectoral collaboration for AMR: political commitment, resources, governance mechanisms, and practical management. Multisectoral communication, coordination, and collaboration, including through a One Health approach, can be beneficial to adequately identify sources of risk and set priorities. One Health approaches can be built into the design of programs—to promote information flow from separate initiatives, to design and undertake joint initiatives (such as joint surveillance or joint training to support stewardship), or to carry out monitoring and evaluation that considers the needs, resources, and entry points and relevant outcomes for different sectors (thereby broadening the co- benefits and minimizing the trade-offs). The creation of national AMR coordination mechanisms with clear cascades to the local level is an important macro-level intervention to improve collaboration. Recognizing the need for multisectoral coordination, the Food and Agriculture Organization of the United Nations (FAO), WOAH, United Nations Environment Programme (UNEP), and WHO have established a Strategic Framework for Collaboration on Antimicrobial Resistance, which will support joint action for a One Health approach (WHO et al. 2022). Political commitment and leadership are essential elements in mobilizing and allocating resources appropriately toward AMR action. Inadequate resource allocation to address AMR continues to be a persistent issue as suggested by the 2021 TrACSS data, which showed that only 20 percent of the countries that had developed AMR NAPs had budgetary resources to support and monitor implementation. Experiential evidence shows that countries with AMR leadership at a senior enough level and with decision-making authority can make and sustain progress over time. The drivers for political commitment often include new and compelling data points related to AMR, AMR champions (persons with respect and authority to work across sectors and galvanize action), global and national advocacy movements, and international agreements such as the Global Action Plan on AMR, which was endorsed at the 68th World Health Assembly in May 2015. The appropriate allocation of resources is fundamental to build trust, strengthen skills and capacity, and secure joint commitment for sustained action on AMR. It is also important to articulate how AMR is relevant to specific sectors, and how addressing AMR contributes to individual sectors’ strategic aims and priorities. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 54 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices This creates an enabling environment that allows for clear and budgeted sector-specific AMR work plans that can be resourced through existing government channels or can leverage funds from development partners. A well-resourced administrative governance structure for AMR at the level above implementing agencies is often required to provide strategic direction and oversight. However, it is important to note that these structures need to be tailored to country setting or context, as there is no one-size-fits-all approach to AMR governance mechanisms. The governance mechanisms should deliver both horizontal and vertical collaboration as discussed above, and the approach should allow for good communication and consultation to successfully cascade action to implementing agencies. Experience from a set of countries shows that governance mechanisms should consider mainstreaming AMR within existing programs to optimize resources—that is, the overall AMR plan should be adequately anchored in various strategic plans across sectors in human, animal, plant, and environmental health. A tiered governance structure can be helpful in differentiating functions across levels. At the top, a high-level multisectoral governing body sets the strategic direction and priorities, ensures coherence, and allocates resources appropriately. The bottom level includes operational units within ministries, civil society, and private sector partners whose main function is to implement interventions, such as those identified and listed in National Action Plans. There is broad consensus on a need to keep governance mechanisms simple and lean, as complex arrangements can quickly become unwieldy and a barrier to effective action (WHO 2018). Lastly, sustaining multisectoral collaboration within the governing structure can be challenging, given that most of the activities will happen in parallel and within vertical programs of individual sectors. Monitoring and evaluation frameworks with timely feedback mechanisms can help track progress, keep collaborators engaged, promote good practice, and foster cross-learning. The next chapter narrows the broad focus on packages or themes, presented in this chapter, to specific intervention areas that can be supported through World Bank operations based on feasibility, key qualifiers such as the evidence base, and other considerations to maximize potential for positive impact across diverse settings. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 55 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Theme 1 Theme 2 Reducing infections: A focus on Strengthening monitoring and IPC, vaccination, and nutrition surveillance of AMR and AMU Four Thematic Entry Points for Addressing AMR Improving access and the rational Strengthening sectoral and use of antimicrobials: A focus on multisectoral coordination and antimicrobial stewardship and governance regulatory frameworks Theme 3 Theme 4 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 56 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 3. Summary of Interventions across Four Thematic Entry Points for Addressing AMR in Key Sectors Four Thematic Entry Points for Addressing AMR Theme 1 Reducing infections: A focus on IPC, vaccination, and nutrition • Sustained training and education on general IPC and IPC for highly infectious patients for all health care workers • Physical resources for health care facilities that optimize the reduction of infections, such as isolation rooms • Public awareness campaigns on IPC • Biosecurity and husbandry enhancements (e.g., quarantine, animal housing and spacing, improved nutrition, decontamination on farms) • Farmer awareness campaigns on biosecurity and IPC • Improved safe drinking water infrastructure/access in community and hospital settings • Improved sanitation infrastructure to treat community and hospital sewage, other waste, and wastewater • Waste management practices in clinical settings and in agricultural and aquaculture production/processing • Application of advanced water and waste treatment to destroy resistance genes • Closed water systems in aquaculture • Flood-proofing infrastructure • Scaling up of vaccination in the general population and in animals • Improved nutrition in humans and animals given the direct link to robust immune systems Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 57 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Theme 2 Strengthening monitoring and surveillance of AMR and AMU • Acceleration of investments in laboratory capacities, such as expanding physical facilities and enhancing laboratory technician training for human, veterinary, and environmental science • Robust prescribing data systems that are integrated and well coordinated • Waste and wastewater monitoring data system • Monitoring of risk and pharmaceutical use in the food system • Pathogen and/or residue testing of foods on import and other points in the market chain • Consumption and adherence monitoring at the regional, local, or farm level, and at the level of the individual veterinarian or other aquatic animal health professional • Setting and monitoring against targets for reduction of use (e.g., by certain percentage or amount by weight of animals) • AMR and residue monitoring in effluent (e.g., at manufacturing sites, at hospitals, at farms, etc.) • Setting and monitoring of against targets for resistance and residue levels in environmental sources Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 58 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Theme 3 Improving access and the rational use of antimicrobials: A focus on antimicrobial stewardship and regulatory frameworks • Health care and animal health workforce training, such as pre-service training for professionals on AMR and rational use, continuous professional development on AMR and rational use • Water management and sanitarian worker training on the interpretation of monitoring levels to guide water and waste treatment; appropriate disposal practices for antimicrobials • Review of national clinical guidelines, protocols, and pathways to ensure rational use of antibiotics and introduction of algorithms and decision support tools to support adherence • Improved public awareness through a focus on addressing disinformation, better risk communication, community- and national-level public awareness campaigns, and research, including on behavioral norms, practices, and expectations • Quality improvement of antibiotic use within primary care: ensuring affordable, reliable, and sustainable access to first-line antibiotics where appropriate; improving access to diagnostics, especially microbiology and susceptibility testing • Quality improvement of antibiotic use within secondary care: restrictions on use of certain antibiotics without infectious disease specialist/ microbiologist approval; improved access to diagnostics, especially microbiology (e.g., urine sample) and susceptibility testing; antimicrobial use review by pharmacists; microbiologist consultations for complex cases; review of hospital clinical pathways and protocols for rational use • Exploration and implementation of push and pull incentives and other innovative financing measures that promote investment in R&D of antimicrobials • Regulatory measures (such as banning the sale or dispensation of antibiotics without a prescription); enforcement mechanisms (such as checking markets where antibiotics are being sold); quality assurance and control of antimicrobial production (including generic production facilities); requiring a veterinary prescription when selling antimicrobials for use in animals; preventing the use of antimicrobials for growth promotion in the absence of a risk analysis; phasing out antimicrobial use for growth promotion starting with the critically important antimicrobials; enforcement of regulation (e.g., by checking for market sale of antibiotics, use in feeds); banning the use of medically important human antimicrobials in animals; establishing maximum residue limit (MRL) and withdrawal periods in food-producing animals per the WOAH standards; harmonizing and complying with international standards, such as Codex Alimentarius, specifically TFAMR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 59 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Theme 4 Strengthening sectoral and multisectoral coordination and governance • Deliberate collaboration within and across sectors to achieve the best possible outcomes for all • A One Health approach to multisectoral collaboration to enhance identification of risk and priority setting • Political commitment and leadership at a senior enough level and with decision-making authority • Mobilization and allocation of resources appropriately toward AMR action, i.e., by articulating clear and budgeted sector-specific AMR work plans that can be resourced through existing government channels or can leverage funds from development partners • Well-resourced administrative governance structure for AMR tailored to country setting or context • Monitoring and evaluation frameworks with timely feedback mechanisms Source: World Bank. Note: AMU = antimicrobial use; IPC = infection prevention and control; TFAMR = Ad Hoc Codex Intergovernmental Task Force on Antimicrobial Resistance; WOAH = World Organisation for Animal Health. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 60 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices References Aenishaenslin, C., B. Häsler, A. Ravel, E. J. Parmley, S. Mediouni, H. Bennani, H., K. D. C. Stärk, and D. L. Buckeridge. 2021. “Evaluating the Integration of One Health in Surveillance Systems for Antimicrobial Use and Resistance: A Conceptual Framework.” Frontiers in Veterinary Science 8. https://doi.org/10.3389/fvets.2021.611931. Alsan, M., L. Schoemaker, K. Eggleston, N. Kammili, P. Kolli, and J. Bhattacharya. 2015. “Out-of-Pocket Health Expenditures and Antimicrobial Resistance in Low-Income and Middle-Income Countries: An Economic Analysis.” Lancet Infectious Diseases 15 (10): 1203–10. https://doi.org/10.1016/s1473-3099(15)00149-8. Berthe, F., S. Bali, and G. Batmanian. 2022. “Putting Pandemics Behind Us: Investing in One Health to Reduce Risks of Emerging Infectious Diseases.” World Bank, Washington, DC. http://documents.worldbank.org/curated/en/099530010212241754/ P17840200ca7ff098091b7014001a08952e. Black, R. E., L. H. Allen, Z. A. Bhutta, L. E. Caulfield, M. de Onis, M. Ezzati, and Maternal and Child Undernutrition Study Group. 2008. “Maternal and Child Undernutrition: Global and Regional Exposures and Health Consequences.” Lancet (London, England) 371 (9608): 243–60. doi:10.1016/S0140-6736(07)61690-0. Caveney, L., B. Jones, and K. Ellis, eds. 2011. Veterinary Infection Prevention and Control. Wiley- Blackwell. https://www.wiley.com/en-us/Veterinary+Infection+Prevention+ and+Control-p-9780813815343. Charani, E., M. Mendelson, S. J. C. Pallett, R. Ahmad, M. Mpundu, O. Mbamalu, C. Bonaconsa, et al. 2023. “An Analysis of Existing National Action Plans for Antimicrobial Resistance-Gaps and Opportunities in Strategies Optimising Antibiotic Use in Human Populations.” Lancet Global Health 11 (3): e466–e474. doi:10.1016/S2214-109X(23)00019-0. Civitello, D. J., B. E. Allman, C. Morozumi, and J. R. Rohr. 2018. “Assessing the Direct and Indirect Effects of Food Provisioning and Nutrient Enrichment on Wildlife Infectious Disease Dynamics.” Philosophical Transactions of the Royal Society B: Biological Sciences 373 (1745). https://royalsocietypublishing.org/doi/10.1098/rstb.2017.0101. Cox, J. A., E. Vlieghe, M. Mendelson, H. Wertheim, L. Ndegwa, M. V. Villegas, P. Nataf, and J.-C. Lucet. 2017. “Antibiotic Stewardship in Low- and Middle-Income Countries: The Same but Different?” Clinical Microbiology and Infection 23 (11): 812–18. https://doi.org/10.1016/j. cmi.2017.07.004. Erlacher-Vindel, Elisabeth. 2019. “Prioritization of Vaccines to Reduce Antibiotic Use in Animals.” Paper presented at PACCARB meeting, Washington, DC, January 30, 2019. https://www.hhs. gov/sites/default/files/erlacher-vindel-paccarb.pdf. FAO (Food and Agriculture Organization) and WHO (World Health Organization). 2015. “Maximum Residue Limits (MRLs) and Risk Management Recommendations (RMRs) for Residues of Veterinary Drugs in Foods.” CAC/MRL 2-2015. Codex Alimentarius Commission. https://www.fao.org/fao-who-codexalimentarius/ sh-proxy/en/?lnk=1&url=https%253A%252F%252Fworkspace.fao. org%252Fsites%252Fcodex%252FStandards%252FCXM%2B2%252FMRL2e.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 61 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Ferreira, J. P., D. Gochez, M. Jeannin, M. W. Magongo, C. Loi, K. Bucher, G. Moulin, and E. Erlacher- Vindel. 2022. “From WOAH Standards to Responsible and Prudent Use of Antimicrobials: Supporting Stewardship for the Use of Antimicrobial Agents in Animals.” JAC-Antimicrobial Resistance 4 (2). https://doi.org/10.1093/jacamr/dlac017. Ginsburg, A. S., and K. P. Klugman. 2017. “Vaccination to Reduce Antimicrobial Resistance.” The Lancet Global Health 5 (12): e1176–e1177. https://doi.org/10.1016/S2214-109X(17)30364-9. Góchez, D., M. Raicek, J. P. Ferreira, M. Jeannin, G. Moulin, and E. Erlacher-Vindel. 2019. “WOAH Annual Report on Antimicrobial Agents Intended for Use in Animals: Methods Used.” Frontiers in Veterinary Science 6: 317. https://doi.org/10.3389/fvets.2019.00317. Holm, M., R. M. Zellweger, N. Poudyal, K. H. Smith, H. S. Joh, and F. Marks. 2022. “Measuring the Link Between Vaccines and Antimicrobial Resistance in Low Resource Settings: Limitations and Opportunities in Direct and Indirect Assessments and Implications for Impact Studies.” Frontiers in Tropical Diseases 3 (2). Huber, N., M. Andraud, E. L. Sassu, C. Prigge, V. Zoche-Golob, A. Käsbohrer, D. D’Angelantonio, et al. 2022. “What Is a Biosecurity Measure? A Definition Proposal for Animal Production and Linked Processing Operations.” One Health 15: 100433. https://doi.org/10.1016/j. onehlt.2022.100433. Lowe, H., S. Woodd, I. L. Lange, S. Janjanin, J. Barnett, and W. Graham. 2021. “Challenges and Opportunities for Infection Prevention and Control in Hospitals in Conflict-Affected Settings: A Qualitative Study.” Conflict and Health 15 (1): 1–10. https://doi.org/10.1186/ s13031-021-00428-8. Ming, A., J. Puddle, and H. Wilson. 2019. “Antimicrobial Resistance: The Role of Regulation.” Workshop Report. Global Governance Institute. https://www.ucl.ac.uk/global-governance/ sites/global-governance/files/antimicriobial_resistance_the_role_of_regulation_final_ draft_report_mb.pdf. Mishra, R. P. N., E. Oviedo-Orta, P. Prachi, R. Rappuoli, and F. Bagnoli. 2012. “Vaccines and Antibiotic Resistance.” Current Opinion in Microbiology 15 (5): 596–602. OECD (Organisation for Economic Co-operation and Development). 2018a. Stemming the Superbug Tide: Just a Few Dollars More. OECD Health Policy Studies. Paris: OECD Publishing. https://doi.org/10.1787/9789264307599-en. OECD (Organisation for Economic Co-operation and Development). 2018b. “Stopping Antimicrobial Resistance Would Cost Just USD 2 per Person a Year.” https://web-archive.oecd.org/2018- 11-07/498198-stopping-antimicrobial-resistance-would-cost-just-usd-2-per-person-a-year. htm. Pezzani, M. D., E. Carrara, M. Sibani, E. Presterl, P. Gastmeier, H. Renk, S. S. Kanj, et al. 2020. “White Paper: Bridging the Gap between Human and Animal Surveillance Data, Antibiotic Policy and Stewardship in the Hospital Sector—Practical Guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net Networks.” Journal of Antimicrobial Chemotherapy 75 (Supplement 2): ii20–ii32. doi:10.1093/jac/dkaa426. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 62 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Rolfe, R., C. Kwobah, F. Muro, A. Ruwanpathirana, F. Lyamuya, C. Bodinayake, A. Nagahawatte, et al. 2021. “Barriers to Implementing Antimicrobial Stewardship Programs in Three Low- and Middle-Income Country Tertiary Care Settings: Findings from a Multi-site Qualitative Study.” Antimicrobial Resistance & Infection Control 10 (1). https://doi.org/10.1186/s13756-021- 00929-4. Rosenthal, V. D., D. G. Maki, C. Rodrigues, C. Álvarez-Moreno, H. Leblebicioglu, M. Sobreyra-Oropeza, R. Berba, et al. 2010. “Impact of International Nosocomial Infection Control Consortium (INICC) Strategy on Central Line–Associated Bloodstream Infection Rates in the Intensive Care Units of 15 Developing Countries.” Infection Control & Hospital Epidemiology 31 (12): 1264–72. https://pubmed.ncbi.nlm.nih.gov/21029008/. Smits, C. H. M, D. Li, J. F. Patience, L. A. den Hartog, E. Annamaria Bruno, and D. Battaglia. 2021. “Animal Nutrition Strategies and Options to Reduce the Use of Antimicrobials in Animal Production.” FAO Animal Production and Health, Paper 184, Food and Agriculture Organization of the United Nations. https://doi.org/10.4060/cb5524en. Storr, J., A. Twyman, W. Zingg, N. Damani, C. Kilpatrick, J. Reilly, L. Price, et al. 2017. “Core Components for Effective Infection Prevention and Control Programs: New WHO Evidence-Based Recommendations.” Antimicrobial Resistance & Infection Control 6 (1). DOI 10.1186/s13756- 016-0149-9. US CDC (United States Centers for Disease Control and Prevention). 2018. “Core Elements of Human Antibiotic Stewardship Programs in Resource-Limited Settings.” US Department of Health and Human Services. https://www.cdc.gov/antibiotic-use/core-elements/resource-limited. html. WHO (World Health Organization). 2015. “Global Action Plan on Antimicrobial Resistance.” World Health Organization, Geneva. https://www.who.int/publications/i/item/9789241509763. WHO (World Health Organization). 2017. WHO Guidelines on Use of Medically Important Antimicrobials in Food-Producing Animals. Geneva: World Health Organization. https://apps.who.int/iris/ bitstream/handle/10665/258970/9789241550130-eng.pdf. WHO (World Health Organization). 2018. “Tackling Antimicrobial Resistance (AMR) Together.” Working paper 1.0: Multisectoral Coordination. World Health Organization, Geneva. https://apps.who.int/iris/handle/10665/336975. WHO (World Health Organization). 2019. Antimicrobial Stewardship Programmes in Health-Care Facilities in Low- and Middle-Income Countries: A WHO Practical Toolkit. Geneva: World Health Organization. https://apps.who.int/iris/handle/10665/329404. WHO (World Health Organization). 2020a. GLASS Method for Estimating Attributable Mortality of Antimicrobial Resistant Bloodstream Infections. Geneva: World Health Organization. WHO (World Health Organization). 2020b. “Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance: An Action Framework.” World Health Organization, Geneva. https://www.who.int/publications/m/item/leveraging-vaccines-to-reduce-antibiotic-use- and-prevent-antimicrobial-resistance. WHO (World Health Organization). 2021a. “2021 AWaRe Classification.” World Health Organization, Geneva. https://www.who.int/publications/i/item/2021-aware-classification. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 63 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization). 2021b. “WHO Policy Guidance on Integrated Antimicrobial Stewardship Activities.” World Health Organization, Geneva. https://www.who.int/ publications/i/item/9789240025530. WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations), WOAH (World Organisation for Animal Health), and UNEP (UN Environment Programme). 2022. “Strategic Framework for Collaboration on Antimicrobial Resistance–Together for One Health.” WHO, FAO, WOAH, and UNEP, Geneva. https://www.who.int/publications/i/ item/9789240045408. WHO (World Health Organization). 2022. “2021 Antibacterial agents in clinical and preclinical development: an overview and analysis.” World Health Organization, Geneva. Licence: CC BY-NC-SA 3.0 IGO. WOAH (World Organisation for Animal Health). 2015. Report of the Meeting of the WOAH Ad Hoc Group on Prioritisation of Diseases for Which Vaccines Could Reduce Antimicrobial Use in Animals. Paris: World Organisation for Animal Health. World Bank. 2018. One Health: Operational Framework for Strengthening Human, Animal, and Environmental Public Health Systems at Their Interface. Washington, DC: World Bank. http://documents.worldbank.org/curated/en/961101524657708673/One-health- operational-framework-for-strengthening-human-animal-and-environmental-public- health-systems-at-their-interface. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 64 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 3 Twenty Intervention Areas Summary 66 CHEVRON- Introduction 67 CHEVRON- Methodology 68 CHEVRON- Entry Points for Global Practices and sectors for AMR interventions 69 CHEVRON- Bibliography 81 CHEVRON- Health sector  85 CHEVRON- Agriculture and food sector 103 CHEVRON- Water and environment sector 119 CHEVRON- Multisector 134 CHEVRON- While AMR is a multisectoral issue, sector-specific entry points are important for mobilizing prompt action… the driving forces behind AMR are shaped by actions in multiple sectors but each sector can and should do their part to address AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 65 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 3 Twenty Intervention Areas Chapter 3 summary To facilitate better understanding (and funding) of interventions to address antimicrobial resistance (AMR), this chapter provides decision-makers and implementers with 20 intervention areas that can be supported through World Bank operations. The perceived complexity of AMR, lack of awareness about the steps that can be taken to address the issue, and insufficient financing have been identified as barriers to investing in relevant interventions. This chapter describes intervention areas of varying scope and scale that contribute to broader programming areas, as well as findings from a review of evidence to support task teams and clients. This list is not exhaustive or intended to imply that other interventions are not as valuable, but rather aims to provide a starting point for action. While AMR is a multisectoral issue, sector-specific entry points are important for mobilizing prompt action. The driving forces behind AMR are shaped by actions in multiple sectors, but entry points for addressing AMR can be sector-specific. Several World Bank Global Practices— Health, Nutrition and Population (HNP), Agriculture and Food (AGF), Environment, Natural Resources and Blue Economy (ENB), and Water—and their relevant sectors can all play an important role, and their respective leadership is critical to ensuring that action is taken. This chapter provides a review of the evidence for intervention areas and guidance on how to optimize investments within these areas across diverse settings. This current state of knowledge for each intervention are provided to orient practitioners to challenges and opportunities. Systematic reviews of the evidence on AMR interventions and conclusions on the widespread applicability of those interventions is limited, and this chapter is intended to provide guidance on the feasibility of interventions and key qualifiers and considerations to maximize the potential for  positive impact. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 66 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction Addressing the significant threat of AMR requires improved awareness of AMR and the interventions that can be taken to address AMR’s emergence and spread. The need for investments in interventions that protect global public goods and ensure no one is left behind in the fight against AMR was highlighted in the World Health Organization (WHO) Global Action Plan on AMR (WHO 2015), and successive Joint External Evaluations (JEEs) have highlighted financing as a constraint to addressing AMR in low- and middle-income countries (LMICs) (WHO 2018; Gupta et al. 2018). The goal of the Global Action Plan was that by 2017, all member states would have a National Action Plan (NAP) on AMR. Countries are in various stages of developing, budgeting, implementing, and evaluating NAPs; however, overall, operationalizing their NAPs remains a challenging process worldwide. The challenge of developing and implementing NAPs is symptomatic of a broader political economy challenge facing AMR, but greater clarity about the steps that World Bank financing can support should allow more progress on AMR to be achieved. As noted by the Wellcome Trust (2020), the global activity and discussion surrounding AMR have been beneficial in raising awareness of critical issues that can all too easily be overlooked. But interest in AMR has not translated into broader implementation of initiatives, especially in LMICs, because AMR competes for attention and resources with other development priorities. This chapter addresses this limitation by highlighting interventions that are beneficial for AMR but that also contribute to the strengthening of the systems that are critical to addressing AMR, across human and animal health, water and sanitation, and the environment. The purpose of this chapter is to provide World Bank teams and clients with a list of interventions that can guide the design of operations at the country and regional level. The intervention areas are aimed at preventing the emergence and spread of diseases and AMR. The evidence reviews examine the state of existing evidence to glean insights and guidance for the design of operations, while recognizing that a current lack of evidence does not indicate ineffectiveness. In some cases, the intervention has not been studied for AMR specifically, and thus the expected outcomes, challenges, and enabling factors cannot yet be fully determined. The intervention areas in this chapter are not definitive or exhaustive. Rather, they are intended to provide a starting point to support clients and World Bank teams in discussing, selecting, and shaping interventions. This chapter also provides guidance on how to draw on existing evidence to maximize the effectiveness of interventions. This chapter discusses the drivers of AMR, discusses the evidence base for 20 intervention areas, and examines the feasibility of and considerations for implementing interventions in diverse settings. The chapter first provides the methodology for selecting the interventions for which an evidence review was conducted; Appendix 2 provides more details. The chapter then lists the intervention areas and discusses their relevance to various sectors and World Bank Global Practices. The last part of the chapter consists of 20 summary assessments, one for each intervention, including state of evidence, feasibility and enabling factors, knowledge gaps, multisectoral considerations, and considerations for optimizing implementation. The intervention areas described in this chapter are broad and do not focus on specific disease management protocols (such as specialty and procedure-based clinical practices). Highly specific practices are not examined in this chapter as separate interventions since they fall under wider themes—e.g., prescribing, infection prevention and control (IPC)—and are dependent on the existing infrastructure, health care services offered, and provider training and practices aligned to a standard of care. However, project implementation efforts should seek out relevant evidence- based interventions and promote their adoption. The adoption of potential interventions should, Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 67 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices where possible, be informed by evidence of effectiveness and feasibility, considering the range of implementation strategies and their associated enablers and barriers. This allows for translation and interpretation of findings and recommendations to relevant contexts (the settings and situations for potential implementation). The role and importance of implementation science and research cannot be overstated for facilitating the adaptation, adoption, integration, and scale-up of these interventions in different country contexts. Methodology To identify potential interventions and assess the weight of the evidence for possible AMR investment priorities, a global literature review was conducted. The literature review was structured into two stages. First, a long list of multisectoral interventions was developed and discussed among World Bank practitioners and external technical experts. Second, to learn more about the current state of evidence and implementation feasibility, the evidence base was reviewed for the 20 intervention areas that were prioritized for examination. The basis for developing the long list of multisectoral interventions was AMR “drivers,” which provide a practical starting point for identifying major causal pathways or conditions creating AMR risk and impact. Interventions can be grouped in several ways, according to the type of intervention (structural, education, protocol), scale (individual, facility, national), primary sector(s), or other attributes. In consultation with World Bank staff and external experts, 20 intervention areas were identified as important areas of focus for addressing major problems related to AMR emergence and spread. The evidence review takes a practical approach to assessing the current state of knowledge for each intervention area to orient practitioners to the challenges and opportunities for potential investments. A caveat is that the AMR landscape is evolving, and studies are in progress that can be expected to provide additional insights from more rigorous evaluation of interventions. A brief literature review was conducted for each intervention, bringing together findings from scientific and grey literature. Further details on the methods, such as key search terms, are provided in Appendix 2. The reviews of each intervention area document the evidence for the interventions by their intent, rationale, and scope as well as their evidence base, current feasibility, gaps in knowledge, and key takeaways for investments. The approach explains to what extent the interventions have been proven effective, how the interventions have been implemented, and what factors have enabled or prevented successful implementation. This provides World Bank staff and clients with a tool to understand how the interventions are best optimized in a wide variety of project contexts and circumstances.13 13  Several factors shape relevance in a given setting. In the agriculture sector, for example, differences in climatic/ecological conditions and the type of agricultural production system can shape how antimicrobials are used and the ways that resistance arises, as well as how interventions are best implemented (for additional guidance about the specific livestock systems and agro-ecological contexts as defined by the World Bank, please see World Bank Group, “Theory Behind the ISL Guide,” https://www.sustainablelivestockguide.org/theory. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 68 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Entry points for Global Practices and sectors for AMR interventions14 In countries of varying income levels, a set of interventions have been used in effective AMR programs across the HNP, AGF, Water, and ENB Global Practices (Table 4). These interventions are not equally effective or feasible in all settings, and prioritization of interventions as part of broader programs is especially important in resource-constrained environments. At the national, subnational, or regional level, intervention prioritization should be risk-based, reflecting estimated levels of risk and scale of impact to target resources. In general, AMR interventions related to surveillance, IPC, and animal husbandry have been found to be highly effective and broadly feasible in a variety of settings. Sector-owned interventions play a critical role in addressing gaps and weaknesses that leave populations vulnerable to the threat and impact of AMR. Multisectoral action, drawing on the principles of One Health, can offer value addition in many cases, and coordination is required to identify how each sector can best contribute; however, multisectoral implementation can be challenging and can often face political challenges. Sector-specific interventions, ideally as part of well-coordinated multisectoral NAPs, can be more feasible in constrained environments and provide an important foundation for advancing toward multisectoral approaches that maximize scarce resources in the longer term. Thus, it remains important for each sector to understand the connections with other sectors so that single-sector interventions are positioned to enable multisectoral approaches and results. For a given intervention area, the relevant sectors may vary widely based on the distribution of mandates in a country, as well as the specific activities; the evidence review thus demonstrates how sectoral involvement could vary. For example, surveillance is examined under the health sector, but could also involve or be led by agriculture and environment; similarly, countering substandard and falsified (SF) antimicrobials could also be an intervention deployed through law enforcement agencies. Multisectoral coordination and governance remains important; for example, quality monitoring of antimicrobial products, surveillance, and stewardship campaigns could serve, be leveraged by, or be taken up by multiple sectors. In fact, the effective implementation of high-priority interventions within the context of multisectoral NAPs requires a multisectoral governance framework or committee with the necessary leadership, mandate, resources, and accountability. Models like the Regional Disease Surveillance Systems Enhancement (REDISSE) project’s human and animal health system strengthening provide proof of concept for addressing sector-specific operational and capacity needs while strengthening multisectoral coordination;15 this coordination makes sense, for example, when considering common issues (such as procurement, supply chain, and access) that need to be addressed in both human and animal health systems. At the country level, One Health or multisectoral coordination platforms are an increasingly important resource for undertaking problem scoping and information sharing, and for optimizing project design, implementation, and evaluation to promote adequate and appropriate action. Therefore, strengthening collaboration within One Health or similar multisectoral coordination platforms is encouraged to support effective understanding of AMR risks and targeting and implementation of solutions, including the effectiveness of national action planning on AMR and related initiatives such as health security. 14  Information is presented for relevance to World Bank Global Practices; for this reason, information may be presented by sector, topic, or typical line ministry, depending on context. 15  World Bank, “Regional Disease Surveillance Systems Enhancement (REDISSE),” https://projects.worldbank.org/en/projects-operations/ project-detail/P154807. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 69 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 4. Intervention Areas 16 Health Water and environment 1 Improving infection prevention and CHEVRON- 12 Improving infrastructure to provide CHEVRON- control in health care settings access to water and sanitation in health care centers 2 Improving prescribing practices CHEVRON- through guidelines for health 13 Implementing effective treatment and CHEVRON- care workers disposal of sewage and wastewater 3 Conducting public CHEVRON- 14 Improving waste management CHEVRON- awareness campaigns practices in agricultural and aquaculture production/processing 4 Increasing human health laboratory CHEVRON- capacity and access to diagnostics 15 Improving safe disposal of CHEVRON- unused antimicrobials 5 Strengthening surveillance of CHEVRON- antimicrobial use (AMU) and AMR in 16 Monitoring presence of antimicrobial CHEVRON- human populations residues and antibiotic-resistant bacteria and genes in water and sanitation systems Agriculture and food Multisectoral 6 Increasing oversight of AMU by CHEVRON- veterinarians 17 Detecting and deterring substandard CHEVRON- 7 Monitoring AMU, surveillance of CHEVRON- and falsified antimicrobials (customs/ AMR, and increasing oversight in law enforcement/health/agriculture) plant/crop production 18 Improving human and animal CHEVRON- 8 Improving animal husbandry practice CHEVRON- nutrition (health/agriculture) and biosecurity 19 Expanding vaccination coverage CHEVRON- 9 Monitoring sales and use of CHEVRON- in humans and animals (health/ antimicrobials and surveillance of agriculture) AMR in animals 20 Using closed water systems in CHEVRON- 10 Promoting behavior change CHEVRON- aquaculture (agriculture/environment) campaigns in animal production 11 Increasing veterinary laboratory CHEVRON- capacity and access to diagnostics 16  This table is identical to Table 1 in the executive summary. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 70 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 5 summarizes the evidence assessment for each of the intervention areas. Summary points are structured in terms of the state of evidence, feasibility, and key qualifiers or multisectoral considerations. Table 5. Evidence Assessment for the Intervention Areas Health sector INTERVENTION SYNTHESIS 1 Improving infection Certain multidrug-resistant bacteria result in a high incidence prevention and and burden of disease from health care–acquired infections and control in health are priorities for IPC in health care settings. IPC measures may care settings encompass a wide set of interventions to help avoid preventable infections. This review examined the effects of IPC measures in Jump to ARROW-RI human health care settings, including uptake of practices and the occurrence of resistant infections.  State of evidence: There is strong evidence of effectiveness in both high-income countries (HICs) and LMICs, and of cost saving in particular in HICs. More research should be supported in LMICs. Implementation is still defective in many countries, in particular LMICs, and in primary health care settings.  Feasibility: IPC interventions are mostly low in cost and feasible. However, implementation of IPC varies widely and requires sustained resource allocation and compliance for success.  Considerations: Synergistic with water, sanitation, and hygiene (WASH), patient safety, quality improvement, health emergencies interventions. Improving prescribing Inappropriate prescribing of antimicrobials contributes to 2 unnecessary AMU and potentially the development of AMR. Rational practices through guidelines for health prescribing guidelines are key to counteract overprescribing and care workers provide clinical guidance on prescribing the correct antimicrobial at the correct dose by the correct route for the correct duration. Studies Jump to ARROW-RI were examined for the effect of prescribing guidelines on provider awareness, adherence to clinical guidelines, and infections.  State of evidence: Evidence is limited in LMICs, but increasing buy- in for this approach indicates that the intervention is promising and has scope to decrease incorrect prescriptions.  Feasibility: Feasibility is challenged by multiple prescribers (not just at point of care), limited access to diagnostics, chronic stockouts of both access and watch antimicrobials especially antibiotics, and poor enforcement of regulations related to over-the-counter antimicrobials. Logistics influence supply, which can affect access and ultimately prescribing practices. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 71 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS  Considerations: Likely to be complementary to demand-side reduction; requires addressing supply-side gaps to create enabling conditions, and may require implementation flexibility in some settings or work best initially for specific diseases. It is also important that national governments, regional bodies and community prescribers align with and utilise the WHO’s AWaRe guidelines, ensuring that the key essential Access antibiotics are accessible and prescribed accordingly. Conducting public The misuse and overuse of antimicrobials is driven in part by public 3 perception. Targeting patient attitudes and perception of appropriate awareness campaigns context for antimicrobial use will help combat further increases Jump to ARROW-RI in resistance. This review looked at the effects of education and awareness campaigns for the general public on knowledge and prescribing practices.  State of evidence: The evidence base shows wide variation in programs and mixed findings. Effectiveness has been demonstrated in a number of studies and across the income spectrum, particularly in terms of prescribing for respiratory infections.  Feasibility: Generally feasible, though requires a baseline understanding of AMU practices and drivers of antimicrobial use, including perceptions, to target campaigns.  Considerations: Appropriateness of campaigns will vary by baseline data on access to antimicrobials and AMUs. Increasing human Limited access to laboratory services, including diagnostics, hinders 4 timely diagnosis and targeted treatment. Increasing laboratory health laboratory capacity and access capacity and rapid diagnostics to rapidly test patient samples to diagnostics could increase the likelihood of correct diagnosis, identify resistant pathogens, and lower the incidence of antimicrobial misuse. Studies Jump to ARROW-RI on laboratory enhancement and access to diagnostics were reviewed for effects on prescribing and resistance.  State of evidence: There is some evidence of effectiveness to inform appropriate prescribing of antimicrobials for select diseases, including in LMICs (for laboratory capacity, apparent benefits are more at the public health system level, whereas point-of-care diagnostics are more patient directed). Except in relation to select pathogens, diagnosis and antimicrobial prescribing generally remain imprecise in HICs and LMICs. For rapid diagnostics, there is an inadequate evidence base to assess effects on resistance-specific outcomes, though research protocols are in progress that will likely make the evidence base more robust. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 72 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS  Feasibility: Feasibility to inform prescribing relies on access (financial, physical) to routine laboratory consumables and rapid diagnostics, as well as integration into care provider workflows. While needs vary by context, broad screening approaches are not widely accessible at present.  Considerations: Training and quality assurance are important enablers for success. Incentives are often not in place to support thorough diagnostic screening. Integration of point-of-care diagnostics should consider links to the broader surveillance system. Inadequate surveillance of AMU/antimicrobial consumption 5 Strengthening surveillance of and AMR means that clinically important trends can be missed. antimicrobial use Enhancing surveillance can enable an understanding of consumption (AMU) and AMR in trends, the early detection of resistant strains of public health human populations importance, and the prompt notification and investigation of outbreaks. This review examined the effects of AMU and AMR Jump to ARROW-RI surveillance programs on public health understanding and action.  State of evidence: The link between antimicrobial resistance and use of antimicrobials is well documented. There is evidence of the effectiveness of AMU surveillance for prescribing patterns in both HICs and LMICs. There is strong evidence of the effectiveness of surveillance for AMR detection in all settings, though programs vary in scope and use.  Feasibility: Broad feasibility, with data on antimicrobial sales already available, and data on antimicrobial use requiring a targeted approach. Quality and scale of information collection and utility for follow-up actions can depend on medicines legislation, data management infrastructure, and technical capacity (training on methodologies for monitoring antimicrobial consumption and use of data for action). The implementation of the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in hospital settings has been successfully demonstrated in a variety of countries. The intervention area is adaptable to relevant context, but functionality requires information management systems and surveillance inputs (sampling, laboratory testing, etc.).  Considerations: This intervention may be considered an anchor to inform selection of other interventions. Optimizing this intervention area requires multisource and multisectoral data coordination. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 73 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector INTERVENTION SYNTHESIS Weak animal health systems often suffer from poor oversight of 6 Increasing oversight of antimicrobial use antimicrobial use. Regulators help ensure that veterinarians prescribe by veterinarians antimicrobials appropriately and only when necessary. Policies and programs on veterinary prescribing were reviewed for effects on AMU Jump to ARROW-RI and appropriate prescribing.  State of evidence: Strong evidence in high- and middle-income countries demonstrating effectiveness for reduction in AMU and resistant isolates in food-producing animals; poorly tested in low-income countries.  Feasibility: Feasibility requires practitioner buy-in and awareness, and is likely to be constrained where veterinary services are weak (e.g., relatively limited access in rural compared to urban settings) and where antimicrobials are differentially regulated in feeds and as stock remedies.  Considerations: Synergistic with monitoring and enforcement (otherwise, unlikely to be broadly effective), and may require reform of over-the-counter purchase of veterinary antimicrobials. 7 Monitoring of AMU, Inappropriate use of antimicrobials in plant/crop production can surveillance of drive the development of AMR. Monitoring programs can improve AMR, and increasing understanding of usage trends and track the development of resistant oversight in strains to guide change in use and regulatory oversight. This review plant/crop production examined the evidence base on monitoring of AMU, surveillance of AMR, and regulatory oversight of AMU in crop production. Jump to ARROW-RI  State of evidence: Good evidence that AMU and AMR monitoring in crop production can detect meaningful scope and sources of AMR threats, whereas the effect of increased oversight is not clear— primarily because of few reported examples of regulatory changes, particularly in LMICs.  Feasibility: Feasibility varies based on the scope and scale of monitoring, and may be challenged by weak agricultural sector governance (and resulting enforcement) and capacities and by lack of suitable alternatives.  Considerations: May inform oversight needs, and may need to address farm-level awareness and use practices. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 74 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS Poor animal welfare and biosecurity conditions contribute to the 8 Improving animal husbandry practice incidence and prevalence of infections and subsequent antimicrobial and biosecurity use on farms. Improving husbandry practices and biosecurity conditions, including in animal production systems that are rapidly Jump to ARROW-RI intensifying, could promote overall animal health and reduce the need for antimicrobials. Husbandry and biosecurity enhancements were reviewed for effects on AMU and animal health.  State of evidence: Strong evidence in LMICs and HICs. Clear outcomes are reducing infections and AMU.  Feasibility: Feasibility demonstrated by tailoring to different productive contexts and settings; may require more intensive or sustained intervention based on status of baseline supporting infrastructure.  Considerations: May need to address farmer perceptions and comparatively low cost of antimicrobials as well as up-front costs to implement on farms. The scale and scope of AMU and AMR in animals are generally poorly 9 Monitoring of sales and use of understood at national and subnational levels. AMU monitoring and antimicrobials and AMR surveillance can improve understanding of current practices to surveillance of AMR guide targeted interventions that limit inappropriate use and detect in animals changes over time. Studies on AMU monitoring and AMR surveillance were reviewed for effects on detection of usage patterns and changes Jump to ARROW-RI in use practices.  State of evidence: Strong evidence from HICs and to some extent LMICs that monitoring and surveillance can provide information about usage as well as possible stakeholders, intervention needs, and entry points, but data capture is uneven.  Feasibility: Broad feasibility, though quality and scale of information collection and utility for follow-up actions will likely depend on veterinary legislation/enforcement, laboratory capacity (including availability of bacteriology services), and data management infrastructure and reporting systems.  Considerations: This intervention may be considered an anchor to inform selection of other interventions and evaluate their effectiveness. For public health relevance, this intervention requires a One Health approach to integrate animal data with other information. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 75 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS Animal production is a major driver of inappropriate antimicrobial 10 Promoting behavior change campaigns in use. Behavior change campaigns aimed at farmers and other animal production animal production stakeholders target an important source of antimicrobial purchasing and administration. Studies on behavior Jump to ARROW-RI change campaigns in farmers were reviewed for effects on knowledge and use.  State of evidence: Promising reductions in AMU were seen in HICs, but evidence base is lacking in LMICs.  Feasibility: Broad feasibility, though interventions will likely require general awareness around appropriate AMU practices first; may be challenging in settings with weak veterinary services.  Considerations: Advisable in settings with sufficient alternatives to support reduced AMU. Limited access to laboratory services, including diagnostics, hinders 11 Increasing veterinary laboratory capacity timely diagnosis and targeted treatment of animals. Increasing and access laboratory capacity and rapid diagnostics to test animal samples to diagnostics could increase the likelihood of correct diagnosis, identify resistant pathogens, and lower the incidence of antimicrobial misuse. Studies Jump to ARROW-RI on laboratory enhancement and access to diagnostics were reviewed for effects on prescribing.  State of evidence: Some promising early evidence from HICs on reduction of AMU for select diseases, but not yet for field-level treatment of disease in LMICs; utility for LMICs is likely for early detection as part of broader animal health surveillance.  Feasibility: Feasibility is challenged by access to routine laboratory consumables, limited access/logistical challenges for diagnostics in rural areas where agriculture is often concentrated, and limited availability of field-ready and rapid diagnostics.  Considerations: Complexities around farmer-veterinarian incentive structures may affect uptake of diagnostics. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 76 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector INTERVENTION SYNTHESIS Improving Health care settings are a significant source of infections, particularly 12 infrastructure to among patients with weakened immune systems. Increasing water provide access to and sanitation infrastructure in health care facilities as part of overall water and sanitation WASH enhancements is a priority for preventing initial infections and in health care centers their spread—and the development of resistance—within facilities and to the broader community. This review examined the evidence Jump to ARROW-RI on the effect of upgraded water and sanitation infrastructure in health care facilities on AMU, water quality, hand hygiene, and infection rates.  State of evidence: Although WASH infrastructure in health care settings is a foundation for IPC, the evidence in relation to AMR- specific outcomes is mixed from both HIC and LMIC settings. Most studies to date report on cross-sectional findings or examine multiple interventions.  Feasibility: In addition to up-front infrastructure, interventions require adequate water supply and continuous sanitation systems. Design must take into account points of contamination and monitoring and disinfection measures.  Considerations: Synergistic with monitoring and system maintenance, as well as hand hygiene and other IPC measures. 13 Implementing Untreated effluent can result in dissemination of residues or effective resistance into the environment, including drinking water sources. treatment and Advanced treatment technologies may help reduce the spread disposal of sewage of antimicrobial residues, drug-resistant microorganisms, and and wastewater antimicrobial-resistant genes (ARGs). This review examined the effects of advanced waste and wastewater treatment technologies on Jump to ARROW-RI antimicrobial residues, resistant bacteria, and genes.  State of evidence: Evidence for both conventional and advanced techniques demonstrates variable results for removal or reduction of resistant pathogens and genes.  Feasibility: Many advanced (tertiary) methods appear experimental, with limited field deployment. There are several advanced treatments, which should be assessed separately.  Considerations: Wastewater composition affects removal ability. 14 Improving waste Waste products from agriculture and aquaculture production and management practices processing are potential sources of antimicrobial residues, resistant in agricultural bacteria, and ARGs. Limiting the flows of wastewater, manure, and and aquaculture agricultural runoff containing antimicrobial residues, drug-resistant production/ processing microorganisms, and ARGs helps limit the spread of resistance. Studies involving anaerobic digestion, composting of manure, and Jump to ARROW-RI manure lagoons were reviewed for effects on residues and genes. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 77 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS  State of evidence: Appears to be effective for reduction of antimicrobial residues in a variety of settings, but inconsistent for antimicrobial-resistant genes. There is lower certainty in this assessment for aquaculture than for livestock production.  Feasibility: Feasibility relies on waste containment and specialized requirements of technologies.  Considerations: Technologies and their application to production systems vary, which provides some flexibility based on infrastructure. Improper disposal can result in dissemination of antimicrobials 15 Improving safe disposal of into the environment via trash, sewage, or other waste, potentially unused antimicrobials contaminating water systems. Improved antimicrobial disposal practices may help to avoid water contamination. This review focused Jump to ARROW-RI on the effects of safe medication disposal initiatives on awareness and utilization.  State of evidence: Some evidence from HICs and LMICs for medicines in general (not just antimicrobials), but most point to limited uptake.  Feasibility: Feasibility challenges relate to centralized collection, awareness, incentives, and responsibility for destruction, particularly where systems for proper disposal are lacking.  Considerations: Programs vary in scope, frequency, geographic coverage, and longevity; a few long-standing take-back programs in HICs do report high rates of return of unused medicine. Contamination of water can result in dissemination of resistant 16 Monitoring presence of antimicrobial bacteria and genes. Monitoring can generate data on the type of residues and antimicrobials being detected in water and waste sources and on antibiotic-resistant resistance patterns to guide epidemiological understanding and bacteria and action. This review focused on effects of monitoring antimicrobials genes in water and (via residues) and antimicrobial resistance in water and sanitation sanitation systems systems on detection and disease investigation. Jump to ARROW-RI  State of evidence: Effectiveness demonstrated from a range of settings to detect residues, drug-resistant microorganisms, and antibiotic-resistant genes (ARGs).  Feasibility: Generally feasible, with standard technologies available in most settings.  Considerations: Requires a One Health approach to put information from monitoring into context for risk determination and to inform risk management strategies. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 78 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multisectoral INTERVENTION SYNTHESIS SF antimicrobials include those that are counterfeit, degraded, 17 Detecting and deterring mislabeled, or expired, and thus may be ineffective (or suboptimally substandard effective) in treatment, prevention, or control of infections. Detection and falsified and deterrence mechanisms can play a role in ensuring the quality of (SF) antimicrobials antimicrobials to promote effective treatment for both humans and animals. Studies involving detection interventions were reviewed Jump to ARROW-RI for effects on tracking, product quality, and legal outcomes (e.g., confiscation, prosecution).  State of evidence: Evidence base comes from a range of settings, but evidence of effectiveness is mixed in low-income countries, with some promising findings for reduction of substandard and falsified products, including antimicrobials.  Feasibility: Feasibility varies based on screening methods and quality and on scale of problem.  Considerations: Likely requires accompanying enforcement and deterrence mechanisms, incentives for reporting, education/ awareness, and alternatives to SF antimicrobials for success. Nutrition status can affect susceptibility to infection and the severity 18 Improving human and animal nutrition and duration of disease in humans and animals, while some infections affect the body’s ability to take up nutrients from food. Good nutrition Jump to ARROW-RI can play a role in preventing infections and potentially reducing the need for antimicrobials and the subsequent selection pressure for resistance. Studies involving nutrition or food security improvements in humans and animals were reviewed for their effect on AMU or AMR.  State of evidence: The evidence base is limited overall and focuses primarily on nutrient or probiotic supplementation. Reported findings are promising overall for effects on AMU.  Feasibility: Likely to vary based on access. Nutrition interventions can vary widely among humans and in animal species, with specific goals that may or may not align with AMR-related objectives.  Considerations: In animals, improved nutrition is often used in tandem with other interventions or to replace nonveterinary medical use of antimicrobials (i.e., for any other purpose than to treat, control, or prevent infectious diseases, such as weight gain). Interventions should also consider food safety implications. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 79 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION SYNTHESIS Infections can lead to AMU and the development of resistant 19 Expanding vaccination coverage in humans pathogens. Vaccination provides individual protection and and animals sometimes indirect effects to curb transmission of disease in humans and animals, reducing incidence of vaccine-preventable Jump to ARROW-RI diseases, including several associated with high disease burden and antimicrobial use and the potential for development of resistant pathogens. Studies were reviewed for effects of vaccination on AMU and AMR in humans and animal populations.  State of evidence: There is evidence in all settings, with promising (but in some cases mixed) results regarding AMU and some resistant pathogens.  Feasibility: Requires infrastructure and resources for campaigns. Dependent on effectiveness against circulating strain(s), which can vary geographically. Some veterinary vaccines have safety challenges leading to narrow indications for use.  Considerations: Existing vaccines are underutilized. Significance may vary based on AMR priorities and ability to target illnesses and syndromes with high AMU. Future vaccines may increase relevance for AMR outcomes specifically. Effluent from aquaculture farms can be a source of environmental 20 Using closed water systems contamination, including the dispersion of antibiotic residues and in aquaculture resistant pathogens and genes through surface water. Recirculating water systems limit the flow of influent and effluent to and from the Jump to ARROW-RI broader environment, playing a role in preventing the introduction and dissemination of contaminants that may be linked to resistance. Studies involving effects of closed aquaculture systems on AMR- related water treatment and water quality outcomes were reviewed.  State of evidence: Studies of this intervention are limited to date in all settings.  Feasibility: Dependent on aquaculture practices as well as infrastructure. Systems may vary widely.  Considerations: May be relevant for biosecurity enhancements, particularly in certain aquaculture production systems or markets. Source: World Bank Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 80 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices For the interventions listed in Table 5, the evidence base was generally limited in terms of effects related to AMR specifically. Because of the challenges of monitoring AMR or burden of disease from AMR as an endpoint, most studies focus on intermediate indicators or proxies (such as antimicrobial use). The interventions target many primary effects, which may or may not be directly indicative of effects related to AMR (for example, rapid diagnostics and ensuring sustainable access, leading to change in mortality or length of stay in a patient population would be inherently relevant for AMR, unless tracking something like health care–acquired resistant infections). Similarly, interventions were often implemented in concert; therefore, measurement cannot usually isolate the effects specifically from one component. More routine or increased monitoring will help to observe patterns that inform how the direction of AMR is changing. Selecting appropriate indicators for monitoring and evaluating interventions related to AMR can pose challenges, primarily due to variations in the readiness of different countries to assess AMR and antimicrobial use systems. These variations extend to measuring additional outcomes, such as access to and the quality of medicines, and biosecurity in food production. In this context, the “Monitoring and Evaluation of the Global Action Plan on AMR” toolkit (WHO, FAO, and WOAH 2019) emerges as a reference standard for guiding the selection of core indicators. The toolkit strikes a crucial balance that allows global comparability while also accounting for unique contextual factors and data availability within countries. It provides a structured framework for countries seeking to align their monitoring and evaluation efforts with global standards, thereby fostering a more comprehensive and standardized approach to monitoring the emergence of resistance. Overall, the evidence review provides a starting point to guide operations addressing AMR. The evidence reviews in this chapter provide a template that can be replicated for future intervention areas under consideration. They can help support the design of World Bank operations, increase awareness of potential challenges and realistic results to be expected, and guide selection and design of project components addressing AMR that can be applied across different settings and scales. Bibliography Booton, R. D., A. Meeyai, N. Alhusein, H. Buller, E. Feil, H. Lambert, S. Mongkolusk, et al. 2021. “One Health Drivers of Antibacterial Resistance: Quantifying the Relative Impacts of Human, Animal and Environmental Use and Transmission.” One Health 12: 100220. https://doi.org/10.1016/j.onehlt.2021.100220. Cox, J. A., E. Vlieghe, M. Mendelson, H. Wertheim, L. Ndegwa, M. V. Villegas, I. Gould, and G. Levy Hara. 2017. “Antibiotic Stewardship in Low- and Middle-Income Countries: The Same but Different?” Clinical Microbiology and Infection 23 (11): 812–18. https://doi.org/10.1016/j. cmi.2017.07.010. FAO (Food and Agriculture Organization) and WHO (World Health Organization). 2021a. “Code of Practice to Minimize and Contain Foodborne Antimicrobial Resistance.” CXC 61-2005. Adopted 2005; revised 2021. Codex Alimentarius Commission. CXC_061e.pdf (directoriolegislativo.org). FAO (Food and Agriculture Organization) and WHO (World Health Organization). 2021b. “Guidelines on Integrated Monitoring and Surveillance of Foodborne Antimicrobial Resistance.” CXG 94-2021. Adopted 2021. Codex Alimentarius Commission. https://www.fao.org/fao-who- codexalimentarius/sh-proxy/ar/?lnk=1&url=https%253A%252F%252Fworkspace.fao.org%2 52Fsites%252Fcodex%252FStandards%252FCXG%2B94-2021%252FCXG_94e.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 81 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Gupta, V., J. D. Kraemer, R. Katz, A. K. Jha, V. B. Kerry, J. Sane, J. Ollgren, and M. O. Salminen. 2018. “Analysis of Results from the Joint External Evaluation: Examining Its Strength and Assessing for Trends among Participating Countries.” Journal of Global Health 8 (2): 020416. https://doi.org/10.7189/jogh.08.020416. IACG (Interagency Coordination Group on Antimicrobial Resistance). 2018. “Surveillance and Monitoring for Antimicrobial Use and Resistance.” IACG discussion paper. https://cdn.who. int/media/docs/default-source/antimicrobial-resistance/iacg-surveillance-and-monitoring- for-amu-and-amr-110618.pdf?sfvrsn=8a07c166_4. Lowe, H., S. Woodd, I. L. Lange, S. Janjanin, J. Barnett, and W. Graham. 2021. “Challenges and Opportunities for Infection Prevention and Control in Hospitals in Conflict-Affected Settings: A Qualitative Study.” Conflict and Health 15 (1): 94. https://doi.org/10.1186/s13031- 021-00428-8. Mackenzie, J. S., and M. Jeggo. 2019. “The One Health Approach—Why Is It So Important?” Tropical Medicine and Infectious Disease 4 (2): 88. https://doi.org/10.3390/tropicalmed4020088. Ming, A., J. Puddle, and H. Wilson. 2019. “Antimicrobial Resistance: The Role of Regulation.” Workshop Report. UCL Global Governance Institute. https://www.ucl.ac.uk/global-governance/sites/ global-governance/files/antimicriobial_resistance_the_role_of_regulation_final_draft_ report_mb.pdf. OECD (Organisation for Economic Co-operation and Development). 2018. Stemming the Superbug Tide: Just a Few Dollars More. OECD Health Policy Studies. Paris: OECD Publishing. https://doi.org/10.1787/9789264307599-en. Pezzani, M. D., E. Carrara, M. Sibani, E. Presterl, P. Gastmeier, H. Renk, S. S. Kanj, et al. 2020. “White Paper: Bridging the Gap between Human and Animal Surveillance Data, Antibiotic Policy and Stewardship in the Hospital Sector—Practical Guidance from the JPIAMR ARCH and COMBACTE-MAGNET EPI-Net Networks.” Journal of Antimicrobial Chemotherapy 75 (Supplement 2): ii20–32. https://doi.org/10.1093/jac/dkaa426. Rolfe Jr., R., C. Kwobah, F. Muro, A. Ruwanpathirana, F. Lyamuya, C. Bodinayake, A. Nagahawatte, et. al. 2021. “Barriers to Implementing Antimicrobial Stewardship Programs in Three Low- and Middle-Income Country Tertiary Care Settings: Findings from a Multi-site Qualitative Study.” Antimicrobial Resistance & Infection Control 10 (1): 60. https://doi.org/10.1186/s13756-021- 00929-4. Rosenthal, V. D., D. G. Maki, C. Rodrigues, C. Alvarez-Moreno, H. Leblebicioglu, M. Sobreyra-Oropeza, R. Berba, et al. 2010. “Impact of International Nosocomial Infection Control Consortium (INICC) Strategy on Central Line-Associated Bloodstream Infection Rates in the Intensive Care Units of 15 Developing Countries.” Infection Control & Hospital Epidemiology 31 (12): 1264–72. https://doi.org/10.1086/657140. Schar, D., E. Y. Klein, R. Laxminarayan, M. Gilbert, and T. P. Van Boeckel. 2020. “Global Trends in Antimicrobial Use in Aquaculture.” Scientific Reports 10 (1): 21878. https://doi.org/10.1038/ s41598-020-78849-3. US CDC (United States Centers for Disease Prevention and Control). 2021. “Core Elements of Antibiotic Stewardship.” https://www.cdc.gov/antibiotic-use/core-elements/index.html. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 82 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Van Boeckel, T. P., C. Brower, M. Gilbert, B. T. Grenfell, S. A. Levin, T. P. Robinson, A. Teillant, and R. Laxminarayan. 2015. “Global Trends in Antimicrobial Use in Food Animals.” Proceedings of the National Academy of Sciences 112 (18): 5649–54. https://doi.org/10.1073/ pnas.1503141112. Wellcome Trust. 2016. “Tackling Drug-Resistant Infections Globally: Final Report and Recommendations.” https://wellcomecollection.org/works/thvwsuba. Wellcome Trust. 2020. “The Global Response to AMR: Momentum, Success, and Critical Gaps.” https:// cms.wellcome.org/sites/default/files/2020-11/wellcome-global-response-amr-report.pdf. WHO (World Health Organization). 2015. “Global Action Plan on Antimicrobial Resistance.” World Health Organization, Geneva. https://apps.who.int/iris/handle/10665/193736. WHO (World Health Organization). 2016. Guidelines on Core Components of Infection Prevention and Control Programmes at the National and Acute Health Care Facility Level. Geneva: World Health Organization. Core components for IPC (who.int). WHO (World Health Organization). 2017. WHO Guidelines on Use of Medically Important Antimicrobials in Food-Producing Animals. Geneva: World Health Organization. WHO guidelines on use of medically important antimicrobials in food-producing animals. WHO (World Health Organization). 2018a. “Joint External Evaluation Tool.” 2nd ed. International Health Regulations (2005). World Health Organization, Geneva. https://apps.who.int/iris/bitstream/handle/10665/259961/9789241550222-eng. pdf;jsessionid=A71AD97883319FBA12E74297798158C6?sequence=1. WHO (World Health Organization). 2018b. “Tackling Antimicrobial Resistance (AMR) Together.” https://cdn.who.int/media/docs/default-source/antimicrobial-resistance/amr-spc-npm/ nap-working-papers/tackling-amr-together-working-paper-5-genderandequity-sept2018- en.pdf?sfvrsn=8b53f887_1. WHO (World Health Organization). 2019a. Antimicrobial Stewardship Programmes in Health-Care Facilities in Low- and Middle-Income Countries. A Practical Toolkit. Geneva: World Health Organization. https://apps.who.int/iris/handle/10665/329404 | https://www.who.int/ publications/i/item/9789241515481. WHO (World Health Organization). 2021a. “2021 AWaRe Classification.” World Health Organization, Geneva. https://www.who.int/publications/i/item/2021-aware-classification. WHO (World Health Organization). 2021b. “Antimicrobial Resistance and the United Nations Sustainable Development Cooperation Framework: Guidance for United Nations Country Teams.” World Health Organization, Geneva. https://www.who.int/publications/i/ item/9789240036024. WHO (World Health Organization). 2021c. “WHO Policy Guidance on Integrated Antimicrobial Stewardship Activities.” World Health Organization, Geneva. https://apps.who.int/iris/ handle/10665/341432. WHO (World Health Organization). 2022. WHO Implementation Handbook for National Action Plans on AMR. NAP AMR Implementation Handbook (who.int). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 83 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations), and WOAH (World Organisation for Animal Health). 2019. “Monitoring and Evaluation of the Global Action Plan on Antimicrobial Resistance: Framework and Recommended Indicators.” World Health Organization, Geneva. https://www.who.int/publications/i/item/monitoring- and-evaluation-of-the-global-action-plan-on-antimicrobial-resistance. WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations), WOAH (World Organisation for Animal Health), and UNEP (United Nations Environment Programme). 2022. “Strategic Framework for Collaboration on Antimicrobial Resistance— Together for One Health.” WHO, FAO, WOAH, and UNEP, Geneva. https://www.who.int/ publications/i/item/9789240045408. WOAH (World Organisation for Animal Health). 2020. WOAH Standards, Guidelines and Resolutions on Antimicrobial Resistance and the Use of Antimicrobial Agents. 2nd ed. Paris: WOAH. https://www.WOAH.org/app/uploads/2021/03/book-amr-ang-fnl-lr.pdf. World Bank. 2017. Drug-Resistant Infections: A Threat to Our Economic Future (Vol. 2): Final Report. Washington, DC: World Bank. https://documents1.worldbank.org/curated/ en/323311493396993758/pdf/final-report.pdf. World Bank. 2018a. Operational Framework for Strengthening Human, Animal and Environmental Public Health Systems at Their Interface. Washington, DC: World Bank Group. http:// documents.worldbank.org/curated/en/703711517234402168/Operational-framework-for- strengthening-human-animal-and-environmental-public-health-systems-at-their-interface. World Bank. 2018b. “World Bank One Health Framework: Operationalizing One Health.” https:// documents1.worldbank.org/curated/en/703711517234402168/pdf/123023-REVISED- PUBLIC-World-Bank-One-Health-Framework-2018.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 84 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector 1 Improving infection prevention and control in health care settings Improving IPC is an evidence-based approach to avoid preventable infections. It has 1 relevance for humans, animals, environment, water, and sanitation; the human health care– relevant aspects are explored here. Globally, 1 in 10 patients gets an infection in the process 2 of accessing care (WHO 2011). Certain multidrug-resistant pathogens (for example, Klebsiella pneumoniae) result in a high incidence and burden of disease from health care–acquired infections and are priorities for IPC in health care settings. IPC is recognized as a core component 3 of patient and occupational safety in health care, contributing to quality of care. National and local applications can also support reduced exposure to animal and other disease hazards, as well as community-based spread. Often implemented with water, sanitation, and hygiene (WASH) 4 measures, programs may include infection prevention experts, microbiology laboratory support, training, monitoring, built environment (e.g., ventilation), equipment, standard precautions, 5 vaccination, decontamination, and personal protective equipment (WHO 2016). The review looked at effects of IPC measures in human health care settings on AMR, including uptake of practices and the occurrence of resistant infections. IPC is a proven strategy in HIC and LMIC settings, with effectiveness demonstrated in avoiding or reducing pandemic spread, including for antimicrobial-resistant strains, and saving lives and money. In systematic reviews performed by WHO to support the global recommendations on IPC at the national and facility level, evidence of effectiveness was found for all eight core components of IPC; the highest number of studies demonstrated impact on health care–associated infection reduction, training and education, multi-modal IPC interventions, surveillance, appropriate staffing levels and bed occupancy, and built environment, materials, and equipment for IPC (Storr et al. 2017). A report by the Organisation for Economic Co-operation and Development (OECD 2018) showed that the most cost-saving interventions to limit the spread of antimicrobial resistance in health care were those aimed at improving hospital hygiene and antimicrobial stewardship (AMS), as these had the potential to prevent three out of four attributable deaths. It also showed that the increasing availability of IPC equipment and infrastructure (such as alcohol-based handrubs) at the point of care and isolation beds were associated with a proportionate reduction of the most common patterns of antimicrobial resistance that are associated with health care. However, effectiveness of IPC is hindered by the level of resources available and compliance challenges that affect uptake or sustainment. Notably, in several assessments, progress of IPC programs was shown to be significantly lower, and the frequency of infection and antimicrobial resistance significantly higher, in low- and middle-income countries compared to high-income countries (WHO 2022). Case studies from Israel, Sierra Leone, Tanzania, and Uganda are reviewed. In Israel, an aggressive IPC intervention in an intensive care unit saw a significant decrease in acquired Carbapenem-resistant Acinetobacter baumannii infections, and reduced colistin use after one year (Ben-Chetrit et al. 2018). These benefits extended into the wider hospital, likely linked to patients moving to other wards. A retrospective cost analysis at another Israeli hospital indicated a saving of US$200,000 when comparing the cost of isolation procedures, infection control specialists, and screening against averted cases of methicillin-resistant S. aureus (Chowers et al. 2015). In Sierra Leone, a post-Ebola study of IPC in a district hospital and peripheral health units found some rising compliance scores over a three-year period (screening and isolation, personal protective equipment, decontamination) and some decreasing scores (e.g., waste management, sharps safety) (Squire et al. 2021). IPC is also often paired with rational prescribing as part of overall stewardship. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 85 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices In Tanzania, a joint IPC–antimicrobial stewardship program was shown to reduce surgical site infections following cesarean sections from 48 percent to 17 percent. While the intervention was associated with a reduction in gram-positive strains, an increase in gram-negative organisms—in some cases multidrug resistant—was also detected (Gentilotti et al. 2020v). These mixed findings reinforce the need for continuous monitoring with IPC. In Uganda, a One Health program on AMR involved training with human and animal health workers and schoolchildren, as well as a 1 hospital-based Medicine and Therapeutics Committee that reviewed IPC guidelines. Participants reported use of enhanced practices after the program, including reductions in unnecessary 2 antimicrobial prescribing (Musoke et al. 2020). Feasibility varies based on the scope of IPC and existing infrastructure. A review on 3 adherence barriers identified issues with supply volumes, insufficient space to isolate patients, and lack of training on guidelines (Houghton et al. 2020). Interventions should be sensitive to vulnerabilities (power disruption, flooding). As infections may be introduced by patients 4 admitted to multiple facilities, data sharing on hospital–acquired infections among hospital networks is necessary (Tosas Auget et al. 2018). In addition to IPC within health care settings, pretreatment of waste emitted from these settings can also play a role in reducing environmental 5 health impacts. Knowledge gaps relate to marginal benefit of different options, as well as adequate incentives for organizational, social, and behavioral determinants of uptake and sustainment (Lacotte et al. 2020). Research gaps in the field of IPC were identified within the WHO guidelines of core components (WHO 2016), and research has been encouraged in these areas; a review of progress is underway. Overall, IPC improvements have high potential to reduce preventable infections when compliance is sustained. IPC minimum requirements should be in place at national and health care facility levels to ensure minimal safety for patients, health workers, and visitors. This intervention is synergistic with prescribing guidelines and wider WASH interventions, and also informed by monitoring and surveillance that may indicate need for tailored interventions at the local level. Community-based IPC, as well as improved animal and environmental biosecurity, are other important entry points for IPC interventions. IPC should also be included in planning for climate-smart health systems. References Ben-Chetrit, E., Y. Wiener-Well, E. Lesho, P. Kopuit, C. Broyer, L. Bier, M. V. Assous, et al. 2018. “An Intervention to Control an ICU Outbreak of Carbapenem-resistant Acinetobacter baumannii: Long-Term Impact for the ICU and Hospital.” Critical Care 22 (1): 319. doi: 10.1186/s13054-018-2247-y. Chowers, M., Y. Carmeli, P. Shitrit, A. Elhayany, and K. Geffen. 2015. “Cost Analysis of an Intervention to Prevent Methicillin-Resistant Staphylococcus Aureus (MRSA) Transmission.” PLOS ONE 10 (9): e0138999. doi: 10.1371/journal.pone.0138999. Gentilotti, E., P. De Nardo, B. Nguhuni, A. Piscini, C. Damian, F. Vairo, Z. Chaula, et al. 2020. “Implementing a Combined Infection Prevention and Control with Antimicrobial Stewardship Joint Program to Prevent Caesarean Section Surgical Site Infections and Antimicrobial Resistance: A Tanzanian Tertiary Hospital Experience.” Antimicrobial Resistance & Infection Control 9 (1): 69. doi: 10.1186/s13756-020-00744-4. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 86 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Houghton, C., P. Meskell, H. Delaney, M. Smalle, C., Glenton, A. Booth, X. H. S. Chan, D. Devane, and L. M. Biesty. 2020. “Barriers and Facilitators to Healthcare Workers’ Adherence with Infection Prevention and Control (IPC) Guidelines for Respiratory Infectious Diseases: A Rapid Qualitative Evidence Synthesis.” Cochrane Database of Systematic Reviews (4): CD013582. 1 Lacotte, Y., C. Årdal, M. C. Ploy, and European Union Joint Action on Antimicrobial Resistance and Healthcare-Associated Infections (EU-JAMRAI). 2020. “Infection Prevention and Control Research Priorities: What Do We Need to Combat Healthcare-Associated Infections and 2 Antimicrobial Resistance? Results of a Narrative Literature Review and Survey Analysis.” Antimicrobial Resistance & Infection Control 9 (1): 142. doi: 10.1186/s13756-020-00831-6. 3 Musoke, D., F. E. Kitutu, L. Mugisha, S. Amir, C. Brandish, D. Ikhile, H. Kajumbula, et al. 2020. “A One Health Approach to Strengthening Antimicrobial Stewardship in Wakiso 4 District, Uganda.” Antibiotics 9 (11): 764. doi: 10.3390/antibiotics9110764. OECD (Organisation for Economic Co-operation and Development). 2018. Stemming the Superbug 5 Tide: Just a Few Dollars More. OECD Health Policy Studies. Paris: OECD Publishing. https://doi.org/10.1787/9789264307599-en. Squire, J. S., I. Conteh, A. Abrahamya, A. Maruta, R. Grigoryan, H. Tweya, C. Timire, K. Hann, R. Zachariah, and M. A. Vandi. 2021. “Gaps in Infection Prevention and Control in Public Health Facilities of Sierra Leone after the 2014–2015 Ebola Outbreak.” Tropical Medicine and Infectious Disease 6 (2): 89. doi: 10.3390/tropicalmed6020089. Storr, J., A. Twyman, W. Zingg, N. Damani, C. Kilpatrick, J. Reilly, L. Price, et al. 2017. “Core Components for Effective Infection Prevention and Control Programs: New WHO Evidence-Based Recommendations.” Antimicrobial Resistance & Infection Control 6 (6). doi: 10.1186/s13756-016-0149-9. Tosas Auguet, O., R. A. Stabler, J. Betley, M. D. Preston, M. Dhaliwal, M. Gaunt, A. Ioannou, et al. 2018. “Frequent Undetected Ward-Based Methicillin-Resistant Staphylococcus aureus Transmission Linked to Patient Sharing between Hospitals.” Clinical Infectious Diseases 66 (6): 840–48. https://doi.org/10.1093/cid/cix901. WHO (World Health Organization). 2011. Report on the Burden of Endemic Health Care– Associated Infection Worldwide. Geneva: World Health Organization. https://apps.who. int/iris/bitstream/handle/10665/80135/9789241501507_eng.pdf?sequence=1. WHO (World Health Organization). 2016. Guidelines on Core Components of Infection Prevention and Control Programmes at the National and Acute Health Care Facility Level. Geneva: World Health Organization. Guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (who.int). WHO (World Health Organization). 2022. “Infection Prevention and Control Report by the Director-General.” EB150/12. January 10, 2022. Infection prevention and control (who.int). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 87 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector 2 Improving prescribing practices through guidelines for health care workers as part of antimicrobial stewardship programs 1 Prescribing guidelines help ensure that health care workers prescribe antimicrobials only when necessary and primarily provide the correct medication. Antimicrobials are a critical 2 medical tool. The WHO has estimated that more than 50 percent of medicines prescribed, dispensed, and/or sold are done so inappropriately, and that half of all patients do not take their medication as prescribed (WHO 2004). Additionally, research has identified an association 3 between antimicrobial prescription and perception of better medical care, creating a social platform for antimicrobial use to treat a range of diseases without rational clinical purpose and 4 reinforcing the need for a shift in prescribing practices.17 In concert with provider education and behavioral interventions, monitoring of antimicrobial use and use of diagnostics including algorithms, and in support of stewardship programs, rational prescribing guidelines can provide 5 a tool to help counteract overprescribing and provide clinical guidance to ensure prescription of the correct antimicrobial at the correct dose by the correct route for the correct duration. Studies were examined for the effect of prescribing guidelines on provider awareness, adherence to clinical guidelines, and infections. Such interventions are already underway in HICs but evidence is limited in LMICs; however, initial findings look promising. A systematic review of studies (n = 33) on antibiotic prescribing guideline adherence from 16 LMICs found that interventions and outcomes examined were highly varied, but most (85 percent) were multifaceted with several combined activities, and the majority indicated a beneficial effect, most commonly for clinical guideline adherence (Foxlee et al. 2021). As antimicrobial stewardship programs (ASPs) are most often carried out in the hospital setting, few programs have been addressing rational use in the community, where the bulk of antibiotics18 are used, driving resistance. However, the use of multifaceted approaches was reinforced in a review of AMS interventions targeted to prescribers outside of hospitals (i.e., in community settings); the review found that education on updated clinical guidelines appeared to be an important component (Lam et al. 2021). Case studies are presented from Kenya, India, and West Africa. The Antibiotic Stewardship Program was created in six hospitals in Kenya and led by a group of physicians and scientists. The program follows an 18-month stepwise implementation strategy, which includes identification of the unique patterns of disease and resistance at each hospital, regular ward rounds, prescription audits and monitoring, staff education, and prescribing consultations (Gitaka et al. 2020). The program was ongoing at the time of review; however, the researchers published a nested qualitative analysis from three facilities, indicating that health managers in the institutions recognize AMR as a serious threat to health and support AMS interventions (Mbugua et al. 2020). A similar intervention in India (albeit on a smaller scale) focused on reducing surgical site infections by implementing an ASP focusing on both rational prophylaxis and treatment. 17  Changing practices may also require improving public awareness and cultural shifts to change patients’ and providers’ expectations (see for example “Improving public awareness campaigns” intervention review below). Prescribing guidelines are thus one tool that can be considered part of broader efforts to change prescribing practices. Practices related to over-the-counter sale of antimicrobials also need to be changed. 18  Antibiotics are a subset of critical tools for human medicine and thus are the focus of some studies (and antibiotic resistance is particularly important in terms of AMU and disease burden in health care settings specifically); however, other types of antimicrobials are also relevant for stewardship programs. In general, the focus of ASP is increasingly shifting to antimicrobials more broadly. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 88 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The study determined that an ASP using a collaborative approach is feasible to reduce surgical site infection incidence in the hospital and may be reproducible elsewhere (Sarang et al. 2020). In West Africa, researchers evaluated the efficacy of introducing a clinical decision support system—an electronic system to provide prescribers with rapid updated information and guidance on the correct antibiotic to prescribe based on input of symptoms and basic patient medical information. This intervention is currently in the early stages of implementation but has 1 shown itself to be effective in decreasing incorrect prescriptions and eventually reducing AMR in those communities (Peiffer-Smadja et al. 2020). Programs such as Choosing Wisely, now rolled 2 out in 20 countries including Brazil, involve a bottom-up approach to national guidelines based on input from prescribers (the program is currently not specific to antimicrobials) (Born and Levinson 2018). 3 Key issues are the use of antimicrobials when none are indicated and the use of inappropriate antimicrobials (e.g., using antimicrobials classified as watch by the 4 AWaRe framework when one classified as access would suffice). Many HIC stewardship campaigns are rooted in rules on which members of the medical field are allowed to prescribe, whereas in some LMICs the scope of primary care and prescribing is wider (i.e., village doctor, 5 pharmacists, midwives, etc.) and enforcement may be more limited. Due to the lack of AMU data, community-based AMS studies are difficult to perform in LMICs. Education and awareness are important enablers in all settings (Kunstler, Lennox, and Bragge 2019); computerized clinical decision support systems are a promising tool and can increasingly be accessed via smartphones to support behavioral interventions (Meeker et al. 2016). The limited availability of precise diagnostic information is a major bottleneck, and frequent stock-outs/shortages of antimicrobials may constrain implementation in some cases (Le Doare et al. 2015). The WHO (2021) Essential Medicines antibiotic book and the WHO AWaRe classifications provide global guidance but greater awareness by clinicians and translation into practice is needed, especially at subnational levels. Regular guideline updates and local adaptation of international guidance are needed, e.g., based on differences in the epidemiology of AMR. Surveillance and monitoring are needed to evaluate effectiveness of guidelines on an ongoing basis, with auditing and proactive feedback to providers in conjunction with training and other support. The broader workflow interaction with (or alternately, the distinction from) clinical decision- making algorithms, Standard Treatment Guidelines, and Essential Medicines Lists should also be examined. Preliminary research and knowledge are lacking concerning where and how to design and implement guidelines given the range of resource availability, individual prescribing allocation, infrastructure, and sociocultural barriers. Baseline research and surveillance are needed to answer key questions: what type of infrastructure and resources are available, what are current trends in prescribing, what AMR disease is seen the most, what is the most frequent disease/symptom receiving antimicrobials, who is able to prescribe, and who is prescribing the most. Prescribing guidelines are a foundation for prudent use in human medicine, but should allow for flexibility in implementation and be paired with demand-side reduction. To support implementation of the AWaRe framework, a draft handbook has been developed that aims to provide clinical guidance for the management of common infections appropriate for all settings, including guidance on the choice of treatment, dose, and duration (WHO 2021). When paired with training and other stewardship interventions, this type of intervention could be ideal for results-based financing projects. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 89 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices References Born, K. B., and W. Levinson. 2018. “Choosing Wisely Campaigns Globally: A Shared Approach to Tackling the Problem of Overuse in Health Care.” Journal of General and Family Medicine 20 (1): 9–12. doi:10.1002/jgf2.225. 1 Foxlee, N. D., N. Townell, C. Heney, L. McIver, and C. L. Lau. 2021. “Strategies Used for Implementing and Promoting Adherence to Antibiotic Guidelines in Low- and Lower- 2 Middle-Income Countries: A Systematic Review.” Tropical Medicine and Infectious Disease 6 (3): 166. doi:10.3390/tropicalmed6030166. 3 Gitaka, J., M. Kamita, D. Mureithi, D. Ndegwa, M. Masika, G. Omuse, M. Ngari, et al. 2020. “Combating Antibiotic Resistance Using Guidelines and Enhanced Stewardship in Kenya: A Protocol for an Implementation Science Approach.” BMJ Open. 4 https://doi.org/10.1136/bmjopen-2019-030823. Kunstler, B. E., A. Lennox, and P. Bragge. 2019. “Changing Prescribing Behaviours with Educational 5 Outreach: An Overview of Evidence and Practice.” BMC Medical Education 19 (311). https://doi.org/10.1186/s12909-019-1735-3. Lam, T. T., D. A. Dang, H. H. Tran, D. V. Do, H. Le, J. Negin, S. Jan, et al. 2021. “What Are the Most Effective Community-Based Antimicrobial Stewardship Interventions in Low- and Middle-Income Countries? A Narrative Review.” Journal of Antimicrobial Chemotherapy 76 (5): 1117–29. doi:10.1093/jac/dkaa556. Le Doare, K., C. I. S. Barker, A. Irwin, and M. Sharland. 2015. “Improving Antibiotic Prescribing for Children in the Resource-Poor Setting.” British Journal of Clinical Pharmacology 79 (3): 446–55. Mbugua, S. M., G. Njoroge, C. Kijogi, M. Kamita, R. Kimani, P. Mwaura, B. W. Waiganjo-Aidi, and J. Gitaka. 2020. “Exploring Perspectives on Antimicrobial Stewardship: A Qualitative Study of Health Managers in Kenya.” Global Health Research and Policy 5. https://doi.org/10.1186/s41256-020-00177-w. Meeker, D., J. A. Linder, C. R. Fox, M. W. Friedberg, S. D. Persell, N. J. Goldstein, T. K. Knight, J. W. Hay, J. N. Doctor. 2016. “Effect of Behavioral Interventions on Inappropriate Antibiotic Prescribing Among Primary Care Practices: A Randomized Clinical Trial”. JAMA. 315 (6):562-70. doi: 10.1001/jama.2016.0275. Peiffer-Smadja, N., A. Poda, A. S. Ouedraogo, J. B. Guiard-Schmid, T. Delory, J. Le Bel, E. Bouvet, et al. 2020. “Paving the Way for the Implementation of a Decision Support System for Antibiotic Prescribing in Primary Care in West Africa: Preimplementation and Co-design Workshop with Physicians.” Journal of Medical Internet Research 22 (7). https://doi.org/10.2196/17940. Sarang, B., A. Tiwary, A. Gadgil, and N. Roy. 2020. “Implementing Antimicrobial Stewardship to Reduce Surgical Site Infections: Experience and Challenges from Two Tertiary-Care Hospitals in Mumbai, India.” Journal of Global Antimicrobial Resistance 20 (March): 105–09. https://doi.org/10.1016/j.jgar.2019.08.008. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 90 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization). 2004. “The world medicines situation, 2nd ed.” World Health Organization. WHO (World Health Organization). 2021. “The WHO Essential Medicines List Antibiotic Book: Improving Antibiotic AWaReness.” Draft for consultation, November 18, 2021. The WHO Essential Medicines List Antibiotic Book: improving antibiotic AWaReness. 1 2 3 4 5 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 91 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector 3 Conducting public awareness campaigns Increasing awareness and knowledge of the significant and negative impacts of AMR 1 can help limit demand for antimicrobials where they are not relevant or appropriate. One of the main drivers of AMR is the misuse and overuse of antimicrobial medications. 2 Current attitudes toward antimicrobials center around the belief that they are the gold standard in treatment, and that any illness, even if not treatable with antimicrobials, is best managed with antibiotics. The narrative on AMR has been too technical, limiting public understanding 3 (Cars et al. 2021). Public awareness of the proper use and necessity of antimicrobials is a critical component in reducing the incidence of AMR and in slowing it. In LMICs, unique challenges in increasing public awareness and perception exist given the availability of medications through 4 a range of formal and informal sources and self-medication. Targeting patient attitudes and perceptions of appropriate context for antimicrobial use will help combat further increases in 5 resistance. Studies have reported an association between patient satisfaction and antibiotics prescription even when the medication should not have been prescribed. This review looked at the effects of education and awareness campaigns for the general public on knowledge and prescribing practices. The evidence base reflects a heterogenous scope of approaches, and the evidence demonstrating effectiveness in changing awareness or prescribing outcomes is mixed, though some results are promising. A systematic review conducted by the RAND Corporation reported on a variety of educational interventions on change in awareness and practices related to antimicrobial use and awareness of antimicrobial resistance,19 finding weak or inconsistent results from most (King et al. 2015). However, a subsequent systematic review on antibiotic prescribing for respiratory tract infections specifically (n = 14 studies) found communication campaigns to be highly effective (Cross, Tolfree, and Kipping 2017). Case studies from Thailand, the Czech Republic, and Arab Republic of Egypt are presented. Researchers conducted a study in Thailand to identify the population’s current knowledge and awareness of antibiotic resistance by incorporating a module on antibiotic awareness into the 2017 Health and Welfare Survey (conducted by the National Statistical Office). This survey also included data on socioeconomic status, which created a comprehensive picture of the current awareness. Data collected from the module have been used to construct targeted strategies for public communication on antibiotic use and misuse (Tangcharoensathien et al. 2018). In the Czech Republic, the e-Bug teaching pack was rolled out in 2006 in elementary schools, with endorsement from the Ministry of Education (Heretova, Kostkova, and Benes 2011). An evaluation of e-Bug in the Czech Republic, England, and France found knowledge was significantly improved, though effect varied by region, and was still retained six weeks post-intervention (Lecky et al. 2010). However, it should be noted that knowledge does not necessarily equate to a change in behavior. While there is more limited study of prescribing or use outcomes among the public and prescribers, the population in Minya, Egypt, received messaging to raise awareness about rational prescribing. The study reported a 23.1 percent reduction in antimicrobial prescribing for acute respiratory infections (Kandeel et al. 2019). 19  Search terms used in the RAND Corporation’s systematic review encompassed antibiotics and other antimicrobials; the majority of studies included in the analysis pertained to antibiotics (likely because of the relative focus in studies on antibiotics). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 92 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Feasibility is generally demonstrated but could be pursued in a range of different formats. The consensus across current literature reports high shares of low health literacy in LMICs, including lack of knowledge of antimicrobial misuse. To address public awareness, baseline data must be collected to determine the current state of knowledge so a targeted intervention can be implemented (Thornber et al. 2019; Chatterjee et al. 2020; Kosiyaporn et al. 2021). A campaign to increase awareness and knowledge may include a range of educational materials, such as 1 distributed pamphlets, billboards, commercials, and school-based curriculums. A key knowledge gap may relate to the utility of awareness campaigns in settings 2 where antimicrobial access is limited, and campaigns may be a less prudent investment in settings with a weak enabling environment for prudent use (e.g., with insufficient 3 antimicrobial alternatives, a lack of precise diagnostics, and poor prescribing practices). Additionally, there is poor understanding of whether awareness and behavior change are maintained over the long term. 4 This could be a more challenging intervention to mobilize in settings where the enabling environment is weaker, unless it is part of an upstream approach to address 5 norms. To maximize the effectiveness of the intervention it would be advisable to consider the inclusion of education and training, awareness, and targeted messaging, as well as access factors (information, treatment, and diagnostics), ensuring inclusivity so vulnerable communities are reached in a beneficial way. When targeting prescribing practices, public awareness oriented at demand reduction appears to be more effective when combined with supply-focused interventions. Overall, any public outreach campaign requires sociocultural understanding and should be developed carefully with behavior change and communications experts. References Cars, O., S. J. Chandy, M. Mpundu, A.Q. Peralta, A. Zorzet, and A. D. So. 2021. “Resetting the Agenda for Antibiotic Resistance through a Health Systems Perspective.” Lancet Global Health. 9 (7): e1022–e1027. doi: 10.1016/S2214-109X(21)00163-7. Chatterjee, S., A. Hazra, R. Chakraverty, N. Shafiq, A. Pathak, N. Trivedi, B. Sadasivam, et al. 2020. “A Multicentric Knowledge-Attitude-Practice Survey in the Community about Antimicrobial Use and Resistance in India.” Transactions of the Royal Society of Tropical Medicine and Hygiene 155 (7): 785 – 91. https://doi.org/10.1093/trstmh/traa124. Cross, E. L., R. Tolfree, and R. Kipping. 2017. “Systematic Review of Public-Targeted Communication Interventions to Improve Antibiotic Use.” Journal of Antimicrobial Chemotherapy 72 (4): 975–87. https://doi.org/10.1093/jac/dkw520. Herotova, T., P. Kostkova, and J. Benes. 2011. “E-Bug Implementation in the Czech Republic.” Journal of Antimicrobial Chemotherapy 66 (Suppl 5): v55-7. doi:10.1093/jac/dkr125. Kandeel, A., W. El-Shoubary, L. A. Hicks, M. A. Fattah, K. L. Dooling, A. L. Lohiniva, O. Ragab, R. Galal, and M. Talaat. 2014. “Patient Attitudes and Beliefs and Provider Practices Regarding Antibiotic Use for Acute Respiratory Tract Infections in Minya, Egypt.” Antibiotics 3 (4): 632–44. https://doi.org/10.3390/antibiotics3040632. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 93 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices King, S., J. Exley, J. Taylor, K. Kruithof, J. Larkin, and M. Pardal. 2015. Antimicrobial Stewardship: The Effectiveness of Educational Interventions to Change Risk-related Behaviours in the General Population: A Systematic Review. Santa Monica, CA: RAND Corporation. https://www.rand.org/pubs/research_reports/RR1066.html. Kosiyaporn, H., S. Chanvatik, T. Issaramalai, W. Kaewkhankhaeng, A. Kulthanmanusorn, N. 1 Saengruang, W. Witthayapipopsakul, et al. 2020. “Surveys of Knowledge and Awareness of Antibiotic Use and Antimicrobial Resistance in General Population: A Systematic Review.” PLOS ONE 15 (1): e0227973. 2 Lecky, D. M., C. A. McNulty, P. Touboul, T. K. Herotova, J. Benes, P. Dellamonica, N. Q. Verlander, P. 3 Kostkova, and J. Weinberg, on behalf of the e-Bug Working Group. 2010. “Evaluation of e-Bug, an Educational Pack, Teaching about Prudent Antibiotic Use and Hygiene, in the Czech Republic, France and England.” Journal of Antimicrobial Chemotherapy 65 (12): 4 2674–84. doi: 10.1093/jac/dkq356. Tangcharoensathien, V., A. Sommanustweechai, S. Chanvatik, H. Kosiyaporn, and K. Tisocki. 2018. 5 “Addressing the Threat of Antibiotic Resistance in Thailand: Monitoring Population Knowledge and Awareness.” WHO South-East Asia Journal of Public Health 7 (2): 73–78. DOI: 10.4103/2224-3151.239417. Thornber, K., D. Huso, M. M. Rahman, H. Biswas, M. H. Rahman, E. Brum, and C. R. Tyler. 2019. “Raising Awareness of Antimicrobial Resistance in Rural Aquaculture Practice in Bangladesh through Digital Communications: A Pilot Study.” Global Health Action 12 (Suppl 1): 1734735. doi: 10.1080/16549716.2019.1734735. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 94 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector 4 Increasing human health laboratory capacity and access to diagnostics 1 Rapid detection and diagnosis can help health care workers determine the most effective treatment for patients and limit the use of antimicrobials where they are not needed; 2 access to antimicrobial susceptibility testing can increase surveillance data. In resource- limited settings, clinicians often diagnose based on self-reported patient symptoms and a physical exam, which can cause misdiagnosis and lead to incorrect prescription. While access 3 to timely, high-quality, and affordable diagnostics is a major gap in most low-income countries, this practice reflects norms also seen also in high- and middle-income countries and collectively 4 drives overuse. Patients experiencing illness, such as a common cold, may be prescribed a broad-spectrum antibiotic even when not clinically necessary. Increasing laboratory capacity and rapid diagnostics to rapidly test patient samples could increase the likelihood of correct 5 diagnosis and lower the incidence of antimicrobial misuse; and antimicrobial sensitivity testing (AST) will provide updated information to surveillance networks to monitor and report the levels of resistance. Studies on laboratory enhancement and access to point-of-care diagnostics were reviewed for effects on prescribing and resistance. While increasing laboratory capacity generates many benefits, the current evidence points generally to broader public health system benefits versus individual patient diagnosis and change in AMU; for diagnostics, the breadth of accessible rapid/bedside tests is limited, and antimicrobial prescribing remains imprecise in HICs and LMICs. Outside of prescribing, the evidence base for this intervention was insufficient to assess effects on AMR endpoints. 20 There are some exceptions, including guidance of tuberculosis treatment. Examples are highlighted from Uganda, Pakistan, Vietnam, Malawi, Australia, and southern Africa. In Uganda researchers improved surveillance and laboratory capacity by leveraging an existing surveillance system to collect data on expanded causes of illness, facilitate real-time surveillance, and provide AMR data (Lamorde et al. 2018). In Pakistan researchers sought to identify gaps within limited-capacity laboratories to determine if AST is a feasible target. The study examined a cohort of five laboratories in which additional training and resources for AST were provided. It found that with close mentoring and support, AST is a feasible intervention to increase surveillance, and creating a laboratory network is a meaningful tool in decreasing AMR (Saeede et al. 2018). In Vietnam, work with microbiology laboratories found some patients were tested for antimicrobials not indicated, thereby wasting resources. The study found high vancomycin- resistant S. aureus rates from erroneous testing methods (Wertheim et al. 2013). Susceptibility testing guidelines were translated into Vietnamese and a collaboration was formed with an international reference laboratory for external quality assurance and confirmatory testing. At the point of care, most testing enhancements correspond to pathogen-based versus broad screening. For the latter, one such laboratory-based intervention is using patient-specific procalcitonin (PCT) biomarker levels to guide prescribing (Rhee 2016). Several studies have evaluated the potential for PCT-based guidelines on antibiotic prescription rates generally, and find that antibiotic prescribing in patients was enhanced (e.g., more accurate diagnosis, shorter course) for patients with severe pancreatic infection and sepsis (Sager et al. 2017). 20  It should be noted that several research protocols were published in recent years announcing studies that will shed more light on the effects of point-of-care diagnostics in relation to AMR (though most appear to be focused on prescribing practices rather than clinical outcomes). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 95 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices While malaria rapid diagnostic tests are now widely used in malaria-endemic settings, a study of febrile patients (n = 25,486) in Malawi found that nearly 70 percent had non-malaria febrile illness; although there was high antibiotic prescribing, the lack of available tests to confirm diagnoses hindered determination of whether prescribing was appropriate (Kapito-Tembo et al. 2020). In Australia, a survey of general practitioners (n = 386) found that only 18.4 percent used point-of-care diagnostics for influenza or pharyngitis as part of antimicrobial stewardship 1 programs, despite reportedly good access to rapid diagnostic tests in the country (Saha et al. 2020). In terms of cost, a multisite tuberculosis study in South Africa, Tanzania, Zambia, and 2 Zimbabwe (n = 1,502 patients) found use of the Xpert platform (an automated, cartridge-based test platform) for TB detection was cheaper in a central laboratory setting than in primary care facilities; however, compared to point-of-care microscopy, facility-based use of the Xpert 3 platform was likely cost-effective when willingness to pay is US$3,820 per treatment completion. (While resistant strain detection was not examined in the study, the Xpert platform does support resistance screening; the authors discussed how point-of-care access could support faster 4 determination of drug-resistant TB and thus potentially increase cost-effectiveness, noting the potential trade-off of more false positives compared to microscopy) (Pooran et al. 2019). 5 The key for success of this intervention is reliable access to routine laboratory consumables and rapid screening tools fit to their specific contexts. It should be packaged with training, equipment, resource needs, supply chain management, and ongoing external quality assurance. Implementation of PCT and other broad screening technologies (e.g., multiplex PCR [polymerase chain reaction]) for diagnosis may not be feasible in many areas without access to testing infrastructure (primarily equipment and maintenance, electricity, reagents, trained personnel, and informatics support for interpretation) (Bunduki et al. 2019; Turner et al. 2021). At present, most available technologies are cost-prohibitive for high- volume, point-of-care testing, though some express screening tools (e.g., cartridge-based molecular diagnostic machines for specific pathogens) reduce time and workforce barriers in health care facilities. Depending on the country, the availability of over-the-counter antibiotics would make this intervention alone unusable and ineffective. Training and feedback may enhance effectiveness, given that test sensitivity and specificity vary. Other targets to increase laboratory capacity must prioritize core functions such as automated blood cultures and urine testing protocols for accuracy of diagnosis. For diagnostics (including rapid and point-of- care diagnostics), there are two separate needs: increasing access to existing diagnostics and investing in new ones. Even when rapid screening equipment is available in health care settings, use may be focused on specific pathogens (e.g., tuberculosis, COVID-19), with limited ability to screen for other pathogens (Okeke et al. 2020). Meaningful point-of-care tests may depend on the context and include detection of specific pathogens 21 (as well as co-infections), determination of viral versus bacterial infections, and antimicrobial susceptibility testing to support prescribing, among other indicators. Pipelines for validation, field testing, and regulatory approval processes for availability of point-of-care diagnostics—as well as price subsidies for affordability, distribution channels, workflow integration, and provider engagement to ensure their access and uptake—should be considered as crucial enabling factors (Sharma et al. 2021). Integration of point-of-care diagnostics should consider links to the broader surveillance system to ensure reporting is maintained. 21  Point-of-care testing needs are also likely to vary widely by setting (for example, to support diagnosis or rule out endemic infections that patients commonly present with in primary health care centers or pharmacies, versus detection of health care–acquired infections from ESKAPE pathogens). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 96 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Low willingness (and ability) to pay for diagnostics in comparison to antimicrobials presents a gap in knowledge about how to incentivize use of diagnostic screening. Poor  baseline understanding of bacterial, viral, or protozoal infections raises some uncertainty for diagnostics and treatment. One starting point can be exploring ways to make access to diagnostics and their maintenance cheaper and easier to procure in LMICs. Innovations for low-cost point-of-care diagnostics and aggregating volumes to decrease costs stand to become 1 increasingly important in this regard. Provider perceptions have been found to be mixed about the accuracy of rapid tests (Saliba-Gustafsson et al. 2021), but it is not known to what extent this 2 may affect their uptake or utility. Laboratory capacity has high utility for AMR, but relies on a trained workforce, reliable 3 supply chain, and appropriate external quality assurance; point-of-care diagnostics are currently a partial but incomplete solution to support precise prescribing. Investments may vary, from enhancing current systems to establishing new national or regional laboratory 4 systems. Making access to point-of-care diagnostics and their maintenance cheaper in LMICs— with the necessary breadth of testing scope for each context—will be key to support clinical decision-making. In addition to informing clinical practice, laboratory strengthening and 5 diagnostics are important components of AMR surveillance and prescribing guidelines. References Bunduki, G. K., J. M. Kambale, I. S. Katembo, and I. S. Kamwira. 2019. “Antimicrobial Resistance in a War-Torn Country: Lessons Learned in the Eastern Democratic Republic of the Congo.” One Health (Amsterdam, Netherlands) 9 (June): 100120. Kapito-Tembo, A., D. Mathanga, A. Bauleni, O. Nyirenda , P. Pensulo, D. Ali, C. Valim, T. E. Taylor, and M. K. Laufer. 2020. “Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.” American Journal of Tropical Medicine and Hygiene 103 (2): 887–93. Lamorde, M., A. Mpimbaza, R. Walwema, M. Kamya, J. Kapisi, H. Kajumbula, A. Serwanga, et al. 2018. “A Cross-Cutting Approach to Surveillance and Laboratory Capacity as a Platform to Improve Health Security in Uganda.” Health Security 16 (S1): S76–S86. Okeke, I. N., N. Feasey, J. Parkhill, P. Turner, D. Limmathurotsakul, P. Georgiou, A. Holmes, and S. J. Peacock. 2020. “Leapfrogging Laboratories: The Promise and Pitfalls of High- tech Solutions for Antimicrobial Resistance Surveillance in Low-income Settings.” BMJ Global Health 5 (12): e003622. Pooran, A., G. Theron, L. Zijenah, D. Chanda, P. Clowes, L. Mwenge, F. Mutenherwa, et al. 2019. “Point of Care Xpert MTB/RIF Versus Smear Microscopy for Tuberculosis Diagnosis in Southern African Primary Care Clinics: A Multicentre Economic Evaluation.” Lancet Global Health 7 (6): e798-e807 [published correction appears in Lancet Global Health 7 (9) (2019): e1179]. Rhee, C. 2016. “Using Procalcitonin to Guide Antibiotic Therapy.” Open Forum Infectious Diseases 4 (1): ofw249. doi:10.1093/ofid/ofw249. Saeed, D. K., R. Hasan, M. Naim, A. Zafar, E. Khan, K. Jabeen, S. Irfan, et al. 2017. “Readiness for Antimicrobial Resistance (AMR) Surveillance in Pakistan; A Model for Laboratory Strengthening.” Antimicrobial Resistance and Infection Control 6 (September): 101. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 97 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Sager, R., A. Kutz, B. Mueller, and P. Schuetz. 2017. “Procalcitonin-guided Diagnosis and Antibiotic Stewardship Revisited.” BMC Medicine 15 (1): 15. https://doi.org/10.1186/s12916-017- 0795-7. Saha, S. K., D. C. M. Kong, K. Thursky, and D. Mazza. 2020. “A Nationwide Survey of Australian General Practitioners on Antimicrobial Stewardship: Awareness, Uptake, Collaboration 1 with Pharmacists and Improvement Strategies.” Antibiotics 9 (6): 310. https://doi.org/10.3390/antibiotics9060310. 2 Saliba-Gustafsson, E. A., A. Nyberg, M. A. Borg, S. Rosales-Klintz, and C. Stålsby Lundborg. 2021. “Barriers and Facilitators to Prudent Antibiotic Prescribing for Acute Respiratory Tract 3 Infections: A Qualitative Study with General Practitioners in Malta.” PLOS ONE 16 (2): e0246782. https://doi.org/10.1371/journal.pone.0246782. 4 Sharma, M., R. R. Gangakhedkar, S. Bhattacharya, and K. Walia. 2021. “Understanding Complexities in the Uptake of Indigenously Developed Rapid Point-of-care Diagnostics for Containment of Antimicrobial Resistance in India.” BMJ Global Health 6 (9): e006628. 5 https://doi.org/10.1136/bmjgh-2021-006628. Turner, P., P. Rupali, J. A. Opintan, W. Jaoko, N. A. Feasey, S. J. Peacock, and E. A. Ashley. 2021. “Laboratory Informatics Capacity for Effective Antimicrobial Resistance Surveillance in Resource-limited Settings.” The Lancet Infectious Diseases 21 (6): E170–E174. https://doi.org/10.1016/S1473-3099(20)30835-5. Wertheim, H. F. L., A. Chandna, P. D. Vu, C. V. Pham, P .D. T. Nguyen, Y. M. Lam et al. 2013. “Providing Impetus, Tools, and Guidance to Strengthen National Capacity for Antimicrobial Stewardship in Viet Nam.” PLoS Medicine 10 (5): e1001429. https://doi.org/10.1371/journal.pmed.1001429. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 98 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector 5 Strengthening surveillance of AMU and AMR in human populations Surveillance of AMU and AMR enables an understanding of consumption trends, the early 1 detection of resistant strains of public health importance, and the prompt notification and investigation of outbreaks. There are many possible purposes of surveillance systems 2 and uses for the information they generate. Associations between the level of AMU (particularly related to misuse and overuse) and the development of AMR are well established (WHO 2018). Surveillance of antimicrobial use enables the early detection of inappropriate use and/ 3 or poor access to antimicrobials and supports the interventions for optimal prescribing and access to antimicrobials. AMR surveillance is a multitiered approach that includes tracking the emergence and increase or decline of resistant strains, and categorizing which strains 4 remain susceptible. Such data will allow authorities to quickly respond to urgent threats, create targeted interventions based on triage of communities at highest risk, evaluate the efficacy of 5 interventions, and provide clinicians with up-to-date prescribing guidelines to ensure real-time rational prescribing. Evidence was reviewed on the effect of AMU (captured by consumption— sales—and reported uses) and AMR surveillance on public health understanding and action. There is strong evidence of the effectiveness of surveillance for AMR in hospital settings at all income levels; while surveillance interventions vary in scope and breadth, they point to the utility of data for treatment guidelines, outbreak investigations, and early warning of escalating trends. A review of AMU surveillance in 65 countries from 2016 to 2018, reflecting early implementation of a standard methodology on consumption monitoring, analyzed antimicrobial use by the AWaRe classifications for essential medicines and reported total and population-adjusted consumption (WHO 2018). The analysis indicated variation in the reporting of data disaggregated by hospital or community-level consumption, and demonstrated that consumption data can be sourced from a variety of stakeholders, such as wholesalers and importers. Case studies for AMR surveillance are presented from Vietnam, Israel, Republic of Korea, Brazil, Uganda, and India. The Viet Nam Antimicrobial Resistance (VINARES) initiative involves hospital self-reporting on use, infection control, and antimicrobial susceptibility, with feedback provided to benchmark against other facilities (Vu et al. 2019). In Israel, surveillance reports detected an outbreak of carbapenem-resistant Enterobacterales in hospitals, with genomic analysis identifying the source strain. This information led to hospital-based actions and monitoring, and ultimately a 10-fold decrease in transmission in acute care settings (and subsequent detection of other antimicrobial strains in post-acute care settings introduced from other countries) (Schwaber and Carmelli 2014). In 2015 the WHO implemented the Global Antimicrobial Resistance Surveillance and Use System (GLASS). Each country is responsible for the communication and sharing of data to build a global resistance network, which in 2021 was expanded to include reporting on consumption. In Korea, a modified version (with added bacterial species and antimicrobials) was created called Kor-GLASS. Kor-GLASS is based on the principles of representativeness, specialization, harmonization, and localization, via a network of eight sentinel hospitals (Liu et al. 2019). Brazil’s national AMR surveillance system, BR-GLASS, was established in 2018; an analysis of the first year of the program examined data from three hospital microbiology labs representing patients from 301 cities. A total of 200,874 antimicrobial susceptibility tests were conducted from 11,347 isolates, yielding estimates of the number of hospital-acquired infections compared to community-acquired infections and identifying important trends, including the most prevalent pathogens, associations with specimen types, and antimicrobial susceptibility and resistance profiles of pathogens (Pillonetto et al. 2021). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 99 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices In Africa, Uganda was the first country to implement a GLASS system, first reporting in 2016 and subsequently benchmarking resistance prevalence findings against other countries in the region to support interpretation (Nabadda et al. 2021). In India, the Council of Medical Research developed a tool called i-AMRSS, which creates a network of institutions of varying capacity and medical specialties to collect AMR data and establish real-time reports (Kaur et al. 2014; Walia et al. 2019). 1 In addition to the traditional surveillance approach used by most existing national AMR surveillance systems, which is based on data collection through routine clinical sampling 2 of patients, application of complementary strategies—such as national surveys to improve quality, completeness, and representativeness of data—should be promoted. 3 Comprehensive data collection is required to obtain a complete picture of AMU and AMR, whether in a hospital or country (Gandra et al. 2020). Actual use is more precise than sales data, but requires more resource-intensive downscaling of surveillance to the point of use. Important 4 features of surveillance are the tools used for data collection, management, and analysis, including standard operation procedures for sample collection and quality assurance in testing strategies. As many countries already struggle with health management information systems 5 for reporting on routine diseases, particularly at facility level, data management training, infrastructure, and incentives may influence reporting effort. A multisectoral surveillance approach is critical to monitor consumption, emerging resistance, and susceptibility trends. To implement an effective surveillance network, country data must be collected from various institutions (including public health, veterinary services, and environment and water) and from laboratories; this will help create a standardized central hub where resistance and relevant prescribing data are reported and can efficiently support international reporting. In health care settings, supporting the clinician-laboratory interface is important to ensure that samples are sent for microbiology testing, and that results can be translated into practice in ways that account for key constraints (e.g., antimicrobial stock-outs). The time needed to strengthen AMR surveillance, and the degree to which it can be improved, depend on the functionality, infrastructure, and capacity of the human, animal, and environmental health and laboratory systems as well as the available resources. Knowledge gaps related to AMR ecology and epidemiology mean that there may be challenges in putting surveillance findings into context. Further investigation may be needed to determine sources of risk, and to differentiate between baseline incidence (including background levels of resistance in nature) and changing trends. In these cases, use of more sophisticated (and costly) technologies such as genomic sequencing can be valuable. In addition, in the case of some reporting systems, the impact of falsified or mislabeled antimicrobials on the reliability and interpretation of consumption data is unclear. Surveillance is a foundation of public health systems and of AMU and AMR detection and quantification, and is a relevant intervention for all settings. However, the scale and scope may require modification and planning to align with or leverage (and not disrupt) other priority surveillance programs, such as HIV and TB AMR surveillance, and to inform follow-up action as needed, such as stewardship policies (Pezzani et al. 2020). Needed modification can be supported by linking data from surveillance of AMR and AMU within regular health facility audits to monitor “quality of health care services” whether in primary, secondary, or tertiary care. This step will enable different medical specialties to work together and use surveillance data for action. Overall, ways to strengthen AMR surveillance include strengthening laboratory capacities; strengthening epidemiological data management and IT capacities; investing in development of hospital/health information systems; and implementing complementary surveillance strategies Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 100 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices such as national prevalence surveys (which can also help to address the knowledge gap on impact of AMR on human health, including attributable mortality due to AMR, and assess the extra health care costs due to AMR). References 1 Gandra, S., G. Alvarez-Uria, P. Turner, J. Joshi, D. Limmathurotsakul, and H. R. van Doorn. 2020. “Antimicrobial Resistance Surveillance in Low- and Middle-income Countries: 2 Progress and Challenges in Eight South Asian and Southeast Asian Countries.” Clinical Microbiology Reviews 33 (3). https://doi.org/10.1128/CMR.00048-19. 3 Kaur, J., A. Sharma, A. S. Dhama, H. Buttolia, V. C. Ohri, K. Walia, A. K. Sharma, K. Yahara, R. Ahmad, and H. Singh. 2019. “Developing a Hybrid Antimicrobial Resistance Surveillance System in India: Needs & Challenges.” Indian Journal of Medical Research 149 (2): 4 299–302. doi: 10.4103/ijmr.IJMR_2074_17. Liu, C., E.-J. Yoon, D. Kim, J. H. Shin, J. S. Shin, K. S. Shin, Y. A. Kim, et al. 2019. “Antimicrobial 5 Resistance in South Korea: A Report from the Korean Global Antimicrobial Resistance Surveillance System (Kor-GLASS) for 2017.” Journal of Infection and Chemotherapy 25 (11): 845–59. doi: 10.1016/j.jiac.2019.06.010. Nabadda, S., F. Kakooza, R. Kiggundu, R. Walwema, J. Bazira, J. Mayito, I. Mugerwa, et al. 2021. “Implementation of the World Health Organization Global Antimicrobial Resistance Surveillance System in Uganda, 2015–2020: Mixed-methods Study Using National Surveillance Data.” JMIR Public Health and Surveillance 7 (10): e29954. doi: 10.2196/29954. Pezzani, M. D., F. Mazzaferri, M. Compri, L. Galia, N. T. Mutters, G. Kahlmeter, T. E. Zaoutis, et al. 2020. “Linking Antimicrobial Resistance Surveillance to Antibiotic Policy in Healthcare Settings: The COMBACTE-Magnet EPI-Net COACH Project.” Journal of Antimicrobial Chemotherapy 75 (Supplement 2), ii2–ii19. doi: 10.1093/jac/dkaa425. Pillonetto, M., R. T. de S. Jordão, G. S. Andraus, R. Bergamo, F. B. Rocha, M. C. Onishi, B. Almeida, et al. 2021. “The Experience of Implementing a National Antimicrobial Resistance Surveillance System in Brazil.” Frontiers in Public Health 8. https://doi.org/10.3389/ fpubh.2020.575536. Schwaber, M. J., and Y. Carmeli. (2014). “An Ongoing National Intervention to Contain the Spread of Carbapenem-Resistant Enterobacteriaceae.” Clinical infectious Diseases 58 (5): 697–703. doi:10.1093/cid/cit795. Vu, T. V. D., T. T .N. Do, U. Rydell, et al. 2019. “Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-2013.” Journal of Global Antimicrobial Resistance 18: 269-278. doi:10.1016/j.jgar.2019.06.002. Walia, K., J. Madhumathi, B. Veeraraghavan, A. Chakrabarti, A. Kapil, P. Ray, H. Singh, S. Sistla, and V. C. Ohri. 2019. “Establishing Antimicrobial Resistance Surveillance & Research Network in India: Journey so Far.” Indian Journal of Medical Research 149 (2): 164–79. doi: 10.4103/ijmr.IJMR_226_18. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 101 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization). 2018. WHO Report on Surveillance of Antibiotic Consumption: 2016–2018 Early Implementation. Geneva: World Health Organization. https://apps.who. int/iris/handle/10665/277359. 1 2 3 4 5 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 102 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 6 Increasing oversight of antimicrobial use by veterinarians Prescribing algorithms and guidelines help ensure that veterinarians prescribe antimicrobials appropriately and only when necessary.22 In situations where animal health systems are weak, this oversight also entails developing viable alternatives so that farmers can transition away from a reliance on antimicrobials. Prudent use guidelines may vary widely in scope, intended audience, and issuer (government, professional association, facility). Th absence of national animal prescribing guidelines has been reported; filling this gap can potentially contribute to the overall capacity strengthening and good governance of veterinary 6 services and the veterinary workforce. Policies and programs on veterinary prescribing were reviewed for effects on AMU, appropriate prescribing, and AMR. 7 Pre-and-post studies of veterinary prescribing vary in scope, but some indicate promising trends. Case studies are presented from the Netherlands, China, the US, Tanzania, 8 and Singapore. A systematic review with a total of 181 studies examined restricted use of antimicrobials in food-producing animals, with a mix of interventions (external restrictions, organic classification, self-labeled antibiotic-free, and voluntary restriction). A meta-analysis of a 9 subset of the data (n = 81 studies) found strong evidence that restricted use of antimicrobials in food-producing animals was associated with a lower prevalence of resistant isolates in animals (reductions of 10–15 percent); a reduction was also observed for humans among farm workers 10 and their contacts (Tang et al. 2017). After a rise in antimicrobial use, the Netherlands instituted compulsory and voluntary regulations in 2007, with a 56 percent decrease in use in farm animals by 2012 (Speksnijder et al. 2015). In China, regulations introduced in 2014 requiring prescription 11 for veterinary use helped to reverse rising use trends in food-producing animals, which falling antibiotic prices had incentivized (Wu 2019). A study of swine veterinarians (n = 42) in the US on the effect of the Veterinary Feed Directive, which prohibited use of medically important antibiotics for growth pro¬motion, found most participated in training on the directive and shared information with client farms (Rademacher, Pudenz, and Schulz 2019). Over half of the veterinarians’ clients phased out AMU for growth promotion altogether, and use of vaccinations, non-antibiotic feed additives, improved biosecurity, and improved nutrition all increased. However, restrictions alone are insufficient; a 2014 study of antimicrobial use in poultry production in Tanzania found prohibited antimicrobials available at veterinary stores and on farms, indicating the need for both expanded residue monitoring in poultry products beyond approved drugs and heightened enforcement at retail outlets (Mubito et al. 2014). A study of aquaculture producers in Singapore, where farmers can purchase antimicrobials freely, found that oversight by the Agri-Food and Veterinary Authority, including regular farm visits and sampling, was one deterrent factor for AMU, along with standards imposed by exporters (Lim et al. 2020). 22  Appropriate use prescribing reflects two key components: determining if antimicrobial therapy is warranted (when to prescribe) and, if prescribing is warranted, ensuring appropriate/prudent prescribing in terms of antimicrobial choice (narrowest spectrum informed by microbiological investigation/diagnostic stewardship), dose, route, and dosing frequency and duration. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 103 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Feasibility depends on a strong veterinary authority, enforcement of regulations, or buy- in from veterinary practitioners. A review of national-level regulations on AMU in animals in Asia indicated key implementation gaps, among them continued use of antibiotics for growth promotion, and poor consideration of research on alternatives (Goutard et al. 2017). Some studies report mixed results, demonstrating occurrence of intended changes, such as a shift from third- to first-line antibiotics, but also an increase in other AMU, reinforcing the need for pretesting, training, monitoring, and refinement. Illegal online sale of veterinary antibiotics from several continents is a challenge (Garcia et al. 2020). The jurisdiction under which animal feed belongs (e.g., in regard to antibiotics in feed for growth promotion) is often not clear, with fragmented authority across agencies. There are gaps in knowledge about efficacy and reach of veterinary prescribing regulations 6 where sale of antimicrobials directly to farmers is common practice and access to veterinary services is limited. Socioeconomic factors must be considered when tackling the self-administration of antimicrobials by farmers (Chauhan et al. 2018). Studies in HICs continue 7 to report pressure to prescribe antimicrobials and owner unwillingness to pursue diagnostics to help target AMU. In LMICs, dual registration of antimicrobials (with some available only by prescription from veterinarians and others freely available as stock remedies) can mean that 8 availability bypasses prescribing practices in some cases. Investments in veterinary prescribing should also involve reform of over-the-counter 9 purchase of antimicrobials where relevant. Tailoring may be needed for certain classes of antimicrobials. For the success of this intervention, there is a wider need for overall animal health 10 system strengthening, including a strong veterinary regulatory authority, monitoring, ability to reach the multiple channels typically in place for prescribing or purchasing of antimicrobials for animal use, and improved animal owner practices. 11 References Chauhan, A. S., M. S. George, P. Chatterjee, J. Lindahl, D. Grace, and M. Kakkar. 2018. “The Social Biography of Antibiotic Use in Smallholder Dairy Farms in India.” Antimicrobial Resistance & Infection Control 7: 60. https://doi.org/10.1186/s13756-018-0354-9. Garcia, J. F., M. J. Diez, A. M. Sahagun, R. Diez, M. Sierra, J. J. Garcia, C. López, and M. N. Fernandez. 2022. “Availability of Antibiotics for Veterinary Use on the Internet: A Cross- Sectional Study.” Frontiers in Veterinary Science 8: 798850. https://doi.org/10.3389/ fvets.2021.798850. Goutard, F. L., M. Bordier, C. Calba, E. Erlacher-Vindel, D. Góchez, K. de Balogh, C. Benigno, W. Kalpravidh, F. Roger, and S. Vong. 2017. “Antimicrobial Policy Interventions in Food Animal Production in South East Asia.” BMJ 358: j3544. https://doi.org/10.1136/bmj. j3544. Lim, J. M., M. C. Duong, L. Y. Hsu, and C. C. Tam. 2020. “Determinants Influencing Antibiotic Use in Singapore’s Small-Scale Aquaculture Sectors: A Qualitative Study.” PLOS ONE 15 (2): e0228701. https://doi.org/10.1371/journal.pone.0228701. Mubito, E. P., F. Shahada, M. E. Kimanya, and J. J. Buza. 2014. “Antimicrobial Use in the Poultry Industry in Dar-es-salaam, Tanzania and Public Health Implications.” American Journal of Research Communication 2 (4): 51–63. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 104 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Rademacher, C. J., C. C. Pudenz, and L. L. Schulz. 2019. “Impact Assessment of New US Food and Drug Administration Regulations on Antibiotic Use: A Post-enactment Survey of Swine Practitioners.” Journal of Swine Health and Production 27 (4): 210–20. Speksnijder, D. C., D. J. Mevius, C. J. Bruschke, and J. A. Wagenaar. 2015. “Reduction of Veterinary Antimicrobial Use in the Netherlands: The Dutch Success Model.” Zoonoses and Public Health 62 (Suppl 1): 79–87. https://doi.org/10.1111/zph.12167. Tang, K. L., N. P. Caffrey, D. B. Nóbrega, S. C. Cork, P. E. Ronksley, H. W. Barkema, A. J. Polachek, et al. 2017. “Restricting the Use of Antibiotics in Food-Producing Animals and Its Associations with Antibiotic Resistance in Food-Producing Animals and Human Beings: A Systematic Review and Meta-analysis.” The Lancet: Planetary health 1 (8): e316–e327. 6 https://doi.org/10.1016/S2542-5196(17)30141-9. Wu, Z. 2019. “Antibiotic Use and Antibiotic Resistance in Food-producing Animals in China.” OECD 7 Food, Agriculture and Fisheries Papers, No. 134. OECD Publishing. http://dx.doi.org/10.1787/4adba8c1-en. 8 9 10 11 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 105 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 7 Monitoring of antimicrobial use, surveillance of antimicrobial resistance, and increasing oversight in plant/crop production Antimicrobials are in some cases used for the prevention and treatment of plant/crop diseases, particularly fungal and bacterial diseases that can cause major production losses and associated economic damage. The use of streptomycin, oxytetracycline, copper-based products, and some fungicides has been associated with resistance in plant pathogens, and while most plant pathogens are not considered a disease threat to humans, some (such as 6 Aspergillus species) are increasingly recognized as causing human infections through food production and consumption (Miller, Ferreira, and LeJeune 2022). Mixed crop-livestock systems and their intensification add a layer of complexity in terms of antimicrobial use and 7 links to the development and spread of resistance. Two linked aspects of interventions should be considered: addressing inappropriate AMU in cropping systems, and the monitoring and surveillance of the type of issues that arise from inappropriate AMU. This review examined the 8 evidence base on monitoring of AMU and AMR and use patterns and regulatory oversight of AMU in plant/crop production. 9 Overall, the evidence base suggests that AMU and AMR monitoring in plant/crop production can detect meaningful scope and sources of AMR threats, whereas the effect of increased oversight is not clear—primarily because there are few reported examples 10 of regulatory changes, particularly in LMICs. Monitoring interventions varied widely in their scope. Three case studies are reviewed, from Tanzania, the Netherlands, and Denmark. In 11 Tanzania, a study documented imported and registered antimicrobials used in crop production and classified the uses and sources of antimicrobial introduction via literature review and stakeholder consultation (Mdegela et al. 2021). In the Netherlands, azole-resistant Aspergillus fumigatus was found in plant waste containing azole residues (Zhang et al. 2021). In Denmark, integrated pest management has been reported to help limit fungicide use in crops, resulting in lower usage than in the UK, Germany, and France; decision support during the crop season is facilitated through factors such as a disease monitoring network and use control thresholds (Jørgensen et al. 2008). Feasibility varies based on the scope and scale of monitoring. Depending on the goals and baseline knowledge, qualitative studies can be useful for examining the types of antimicrobials used, including by specific production systems and farms. Linking use data to AMR outcomes, including via screening for residues and pathogens, requires access to laboratory infrastructure. Plant/crop monitoring cannot typically distinguish potential sources of antimicrobial contamination, such as direct spraying versus application of manure-based fertilizer (genomic methods may help pinpoint sources of resistance, but are resource-intensive). For oversight, feasibility may be challenged by a weak agricultural sector, especially where enforcement of agricultural practices is limited, awareness of antimicrobial or pesticide resistance is limited overall (e.g., Rahaman, Islam, and Jahan 2018), and the right incentives (e.g., compensation to farmers for losses) are not in place. A major challenge to feasibility is the lack of suitable alternatives, given potential trade-offs for plant/crop production in phasing out use and given challenges in registering new products (Lucas, Hawkins, and Fraaije 2015). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 106 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices For oversight of use, knowledge gaps include the relative effectiveness of voluntary versus mandatory regulations, especially in connection with limited availability of suitable alternatives and varying enforcement levels. Optimal training, including on general cropping and other plant production good practices, and behavior change incentives at the level of the production system and individual farm also need to be articulated for AMR relevance. For monitoring, the direct epidemiological relevance of detection of residues and AMR in plants/ crops for human health is poorly understood even for the currently limited set of plant pathogens of concern. While there is extensive focus on plant/crop resistance to disease and pests, much of this research is still experimental and targeted to genetic determinants, with only limited evaluation of responses related to disease and pest management activities (e.g. Tabashnik and Carrière 2019). 6 Monitoring in plant/crop production can help clarify the scope of use and possible relevance for AMR, and may inform areas of focus for potential oversight changes. Another relevant scope for consideration will be farm-level awareness and use practices, 7 including availability and demand for alternatives to antimicrobials of concern. In addition to direct AMR threats to human health, plant pathogen resistance can lead to other important outcomes that require separate review, such as effects on food production volumes and 8 ultimately food security. 9 References Jørgensen, L. N., G. C. Nielsen, J. E. Ørum, J. E. Jensen, and H. O. Pinnschmidt. 2008. “Integrating 10 Disease Control In Winter Wheat—Optimizing Fungicide Input.” Outlooks on Pest Management 19 (5): 206–13. https://doi.org/10.1564/19oct04. 11 Lucas, J. A., N. J. Hawkins, and B. A. Fraaije. 2015. “The Evolution of Fungicide Resistance.” Advances in Applied Microbiology 90: 29–92. doi:10.1016/bs.aambs.2014.09.001. Mdegela, R. H., Mwakapeje, E. R., Rubegwa, B., D. T. Gebeyehu, S. Niyigena, V. Msambichaka, H. E. Nonga, N. Antoine-Moussiaux, and F. O. Fasina. 2021. “Antimicrobial Use, Residues, Resistance and Governance in the Food and Agriculture Sectors, Tanzania.” Antibiotics (Basel) 10 (4): 454. doi:10.3390/antibiotics10040454. Miller, S. A., J. P. Ferreira, and J. T. LeJeune. 2022. “Antimicrobial Use and Resistance in Plant Agriculture: A One Health Perspective.” Agriculture 12 (2) : 289. https://doi.org/10.3390/ agriculture12020289. Rahaman, M. M., K. S. Islam, and M. Jahan. 2018. “Rice Farmers’ Knowledge of the Risks of Pesticide Use in Bangladesh.” Journal of Health Pollution 8 (20): 181203. doi:10.5696/2156-9614-8.20.181203. Tabashnik, B. E., and Y. Carrière. 2019. “Global Patterns of Resistance to Bt Crops Highlighting Pink Bollworm in the United States, China, and India.” Journal of Economic Entomology 112 (6): 2513–23. doi:10.1093/jee/toz173. Zhang, J., L. Lopez Jimenez, E. Snelders, A. J. M. Debets , A. G. Rietveld, B. J. Zwaan , P. E. Verweij, and S. E. Schoustra. 2021. “Dynamics of Aspergillus fumigatus in Azole Fungicide- containing Plant Waste in the Netherlands (2016–2017).” Applied and Environmental Microbiology 87 (2): e02295-20. doi:10.1128/AEM.02295-20. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 107 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 8 Improving animal husbandry and biosecurity practices Good biosecurity and animal husbandry at farm level will reduce the risk of infections and ensure healthier animals, thereby limiting the need for treatment. Underinvestment in biosecurity is recognized as a major contributor to the incidence and prevalence of infections and subsequent antimicrobial use on farms. Improving husbandry practices and biosecurity conditions, including in animal production systems that are rapidly intensifying, may promote overall animal health, reduce the need for antimicrobials, and help reduce occupational exposures by farm workers. Husbandry and biosecurity enhancements were reviewed for 6 effects on AMU and animal health. Animal husbandry and biosecurity interventions overall appear highly effective in 7 improving animal health and reducing antimicrobial use; the evidence base is strong on the benefits across income settings. Case studies are reviewed from Vietnam, Switzerland, 8 and the UK. In Vietnam, a three-year intervention provided small-scale chicken farms with regular veterinary advice on flock health and husbandry and antimicrobial replacement products. It found that antimicrobial use decreased by 66 percent, bodyweight increased, and 9 weekly mortality fell from the intervention (Phu et al. 2021). In Italy, a study on improving welfare standards and biosecurity on beef cattle farms found a reduction in antimicrobial use associated with improved welfare (Diana et al. 2020). The “outdoor veal calf” model tested in Switzerland 10 involving vaccination, a three-week quarantine, open-air housing, and health screening checks resulted in five times lower use of antimicrobials compared to control farms (Moser et al. 2020). A study in the UK points to the ability to improve early warning for potential disease events, 11 such as via change in feeding behavior indicative of animal health status (Duthie et al. 2021). Overall, husbandry enhancements appear feasible with some limitations, particularly when adapted to specific context and productive settings. Farm management practices pursued as a foundation for animal health, or in some cases as direct alternative(s) to antimicrobials, vary widely across different settings and production systems, with some innovative but overall low-technology approaches available. Baseline biosecurity, farm education, environmental determinants of contamination, and other factors will likely vary widely, though needs and opportunities for biosecurity and welfare improvements are reported from a range of HICs and LMICs. However, there are some key limitations; the low cost of antimicrobials (e.g., ~2 percent of farm production costs from a study of pig farmers in Vietnam) provides low incentive to invest in alternate risk management strategies (Coyne et al. 2020). Additionally, perceptions about the need for widespread use of antimicrobials for farm production could limit willingness, and some alternatives (e.g., zinc oxide) have other detrimental effects. Multiyear guided support and external resourcing appear to be beneficial for implementation. While this review focuses on biosecurity at the farm level, the movement of animals between locations (e.g., for rearing, veterinary, or trade purposes) demonstrates the need to share information on health care–acquired and other infections in animals. Gaps in knowledge include willingness to pay or willingness to accept husbandry interventions, as well as an appropriate source of guidance for design and implementation support in settings where the capacity of veterinary services is weak. There are also questions around necessary supporting infrastructure (e.g., farmer education) and sustainment of biosecurity over time, particularly with changes in livestock industries. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 108 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices This intervention can be financed in LMIC and HIC settings when tailored to local conditions, production systems, scales, and needs for accompanying education, infrastructure, and incentives. Building in husbandry and biosecurity from the onset as requisite for livestock investments may help to reduce AMU upstream in animal production systems. As part of biosecurity enhancements, worker education could include a focus on awareness around the costs of occupational exposures to antimicrobials to reinforce the importance of uptake. References Coyne, L., C. Benigno, V. N. Giang, L. Q. Huong, W. Kalprividh, P. Padungtod, I. Patrick, T. N. Pham, and J. Rushton. 2020. “Exploring the Socioeconomic Importance of Antimicrobial Use 6 in the Small-scale Pig Sector in Vietnam.” Antibiotics (Basel) 9 (6): 299. https://doi.org/10.3390/antibiotics9060299. 7 Diana, A., V. Lorenzi, M. Penasa, E. Magni, G. L. Alborali, L. Bertocchi, and M. De Marchi. 2020. “Effect of Welfare Standards and Biosecurity Practices on Antimicrobial Use in Beef 8 Cattle.” Scientific Reports 10 (1): 20939. https://doi.org/10.1038/s41598-020-77838-w. Duthie, C. A., J. M. Bowen, D. J. Bell, G. A. Miller, C. Mason, and M. J. Haskell. 2021. “Feeding 9 Behaviour and Activity as Early Indicators of Disease in Pre-weaned Dairy Calves.” Animal 15 (3): 100150. https://doi.org/10.1016/j.animal.2020.100150. 10 Moser, L., J. Becker, G. Schüpbach-Regula, S. Kiener, S. Grieder, N. Keil, E. Hillman, A. Steiner, and M. Meylan. 2020. “Welfare Assessment in Calves Fattened According to the ‘Outdoor Veal Calf’ Concept and in Conventional Veal Fattening Operations in Switzerland.” 11 Animals 10 (10): 1810. https://doi.org/10.3390/ani10101810. Phu, D. H., N. V. Cuong, B. D. Truong, B. T. Kiet, V. B. Hien, H. T. Viet Thu, L. K. Yen, et al. 2021. “Reducing Antimicrobial Usage in Small-scale Chicken Farms in Vietnam: A Three-year Intervention Study.” Frontiers in Veterinary Science 7, 612993. https://doi.org/10.3389/ fvets.2020.612993. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 109 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 9 Monitoring of sales and use of antimicrobials and surveillance of AMR in animals Monitoring sales and use patterns and conducting AMR surveillance in animals supports more targeted interventions to limit or restrict improper antimicrobial use, including around critically important molecules or growth promoters. Antimicrobials in animals are used to treat, control, or prevent disease or increase weight. The scale and scope of AMU in animals is poorly understood at national and subnational levels, though AMU is known to 6 be widespread and increasing with intensification of production systems. This situation can make it difficult to differentiate excess or inappropriate use from judicious (legitimate) use and adherence to guidance or regulations. It also limits understanding of the role of animal 7 AMU in dissemination and human outcomes, and it results in a lack of baseline information for intervention comparisons. Antimicrobial sales and use data (e.g., class, volume, purpose, setting, and dosing) can improve understanding of current practices to guide targeted interventions and 8 detect changes over time. Studies on AMU monitoring and surveillance of AMR in animals were reviewed for effects on detection of usage patterns and changes in use practices. 9 Overall, there is strong evidence that animal antimicrobial use monitoring and AMR surveillance provide useful information to identify AMR concerns and target interventions, though data capture is uneven and major gaps remain. Monitoring systems are in place in 10 most European and North American countries, and AMU studies have been conducted in a variety of settings. Outside of Europe, most studies appear to be research-based versus reporting 11 through a routine national or subnational monitoring system. Surveillance programs for AMR in animals occur across country income levels but vary in their scope and scale, such as long-term studies versus studies conducted at one point in time. Case studies are presented from Denmark, Cameroon, Thailand, the United States, China, and Brazil and the UK. Denmark launched its Integrated Antimicrobial Resistance Monitoring and Research Programme in 1995 (Dibner and Richards 2005). Patterns observed vary, from specific uses (e.g., respiratory disorders), to seasonal trends in use, to animal daily doses. In Denmark, the VetStat database tracked veterinary prescribing practices under its “yellow card” system and observed a 25 percent decline in per-pig use between 2009 and 2011 (Jensen et al. 2014). In Cameroon, import and livestock biomass data were used to analyze veterinary AMU in food-producing animals between 2014 and 2019. The study estimated total consumption, an increase in use of 104 percent over the time period, and identified substantial overlap with the WHO AWaRe categories for critically important, reserve, and watch antimicrobials (Mouiche et al. 2020). In Thailand, a study was conducted to analyze distribution of antibiotics; it found that in addition to farm households, approximately 30,000 individuals involved in animal feed imports, feed mills and stores, and animal health facilities were relevant to distribution of antibiotics and other medicines for animal use (Sommanustweechai et al. 2018). In the United States, samples collected from diseased pigs were screened for resistance at a state veterinary diagnostic laboratory between 2006 and 2016 as part of a continuous surveillance study; changes were found in AMR patterns over the time frame (Hayer et al. 2020). In China, data reported to the China Surveillance on Antimicrobial Resistance of Animal Origin database indicated that the prevalence of colistin-resistant E. coli in pig feces declined from 34.0 percent in 2015–2016 to 5.1 percent in 2017–2018; similar trends were found in human populations, indicating that the ban on colistin as a growth promoter (and reduction in its sale as tracked by the database) was having the intended effect (Wang et al. 2020). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 110 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices In Brazil, a surveillance study in poultry was linked to surveillance of chicken products imported from Brazil into the UK; the findings indicated that while the prevalence of multidrug-resistant Salmonella was increasing over time, the strains were likely linked to animal vaccination practices and did not constitute a threat to human health (Alikhan et al. 2022). Monitoring requires infrastructure for tracking and aggregating information, and relies on reporting effort (e.g., from seller, animal health professional, or farmer).23 Considering use relative to animal biomass (via weight and the relevant animal population) is crucial to put monitoring information into context, allow for comparison, and identify where problems are. There are some challenges with biomass adjustments particularly for fish production, which may affect precision of per-animal or animal population use estimates (Narbonne et al. 2021). Similarly, illegal importation channels may affect quantity estimates. Poor standardization 6 and harmonization, with variation in sample types, testing methods, and criteria, may affect interpretation of results (Schaekel et al. 2017). Stakeholder or value chain mapping to determine relevant distribution channels may be a useful input to shape monitoring scope. International 7 initiatives, such as reporting to the World Organisation for Animal Health (WOAH), can encourage monitoring (WOAH 2022), as can industry standards and consumer demand. Surveillance of AMR in animals requires enhanced laboratory capacity, particularly national and subnational 8 bacteriology services as well as PCR or sequencing platforms. Depending on the specific objectives, surveillance may involve a range of potential inputs, including sample types and 9 settings (e.g., live animals on farms, clinical specimens from sick animals, or animal products in the food chain); selection should consider logistics and cost in addition to information needed to assess risk and target action as warranted. Links with the private sector can supplement data 10 collection but require mandates or other mechanisms to incentivize participation in surveillance. Standard monitoring and surveillance methodologies allow for findings to be aggregated across different data providers, such as provincial offices; however, initial studies can provide the basis 11 for developing a national or subnational system (Tate et al. 2022). Improving data completeness will also require digitization as well as data integration (clinical, laboratory, pharmacy) to pair resistance and consumption data for epidemiological analysis (MAAP 2022). Linking surveillance findings to action requires supportive mechanisms to be in place to interpret and make use of information in prescribing and other policies and practices. It is crucial to ensure both formal and informal (e.g., unregistered) farming systems are reached in monitoring and surveillance programs and served by associated interventions. Knowledge gaps include understanding of the ideal supportive infrastructure (e.g., training, buy-in), mode, and frequency of reporting at subnational (retail store or farm) level. It is not known how reporting validity is affected by substandard or falsified medicines, or by consumers’ limited ability to differentiate antimicrobials. Incentives for reporting of antimicrobial use and AMR are unclear at present, other than where required for prescribers and importers (and potentially sellers and farmers). For AMR surveillance, since baseline resistance levels in animal populations are not always well established, the epidemiological significance of detection and link to antimicrobial use practices cannot always be inferred with additional information. 23  The World Organisation for Animal Health (WOAH) collects information on use of antimicrobials in animals, acknowledging that additional work is needed to improve precision, including for on-farm data reporting of administration to animals. To date, most reporting is based on products sold, imported, or manufactured that are intended for use in animals. See WOAH (2022). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 111 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Overall, the ongoing monitoring of sales and use for animal antimicrobials and AMR surveillance in animals should be considered as a basis to inform other interventions. Government authorities should also be empowered to act on findings as appropriate, e.g., via change in regulations or via enforcement. Monitoring and surveillance programs may vary widely in their scale and scope (and current completeness, requiring capacity enhancement); for example, programs’ focus may range from individual farms to aggregated points in the value chain. But programs should allow for comparability of findings to track trends over time. References Alikhan, N.-F., L. Z. Moreno, L. R. Castellanos, M. A. Chattaway, J. McLauchlin, M. Lodge, J. O’Grady, et al. 2022. “Dynamics of Salmonella enterica and Antimicrobial Resistance in the 6 Brazilian Poultry Industry and Global Impacts on Public Health.” PLoS Genetics 18 (6): e1010174. https://doi.org/10.1371/journal.pgen.1010174. 7 Dibner, J. J., and J. D. Richards. 2005. “Antibiotic Growth Promoters in Agriculture: History and Mode of Action.” Poultry Science 84 (4) : 634–43. https://doi.org/10.1093/ps/84.4.634. 8 Hayer, S. S., A. Rovira, K. Olsen, T. J. Johnson, F. Vannucci, A. Rendahl, A. Perez, and J. Alvarez. 2020. “Prevalence and Trend Analysis of Antimicrobial Resistance in Clinical Escherichia 9 coli Isolates Collected from Diseased Pigs in the USA between 2006 and 2016.” Transboundary and Emerging Diseases 67 (5): 1930–41. https://doi.org/10.1111/ tbed.13528. 10 Jensen, V. F., L. V. de Knegt, V. D. Andersen, and A. Wingstrand. 2014. “Temporal Relationship between Decrease in Antimicrobial Prescription for Danish Pigs and the ‘Yellow Card’ 11 Legal Intervention Directed at Reduction of Antimicrobial Use.” Preventive Veterinary Medicine 117 (3-4): 554–64. https://doi.org/10.1016/j.prevetmed.2014.08.006. MAAP (Mapping AMR and AMU Partnership). 2022. “Incomplete Antimicrobial Resistance (AMR) Data in Africa: The Crisis within the Crisis.” https://aslm.org/resource/policy-brief-and- infographics-on-antimicrobial-resistance-amr-in-africa/. Mouiche, M. M. M., F. Moffo, J. D. B. Betsama, N. P. Mapiefou, C. K. Mbah, S. E. Mpouam, R. E. Penda, et al. 2020. “Challenges of Antimicrobial Consumption Surveillance in Food- producing Animals in Sub-Saharan African Countries: Patterns of Antimicrobials Imported in Cameroon from 2014 to 2019.” Journal of Global Antimicrobial Resistance 22: 771–78. https://doi.org/10.1016/j.jgar.2020.06.021. Narbonne, J. A., B. R. Radke, D. Price, P. C. Hanington, A. Babujee, and S. J. G. Otto. 2021. “Antimicrobial Use Surveillance Indicators for Finfish Aquaculture Production: A Review.” Frontiers in Veterinary Science 8: 595152. https://doi.org/10.3389/ fvets.2021.595152. Schaekel, F., T. May, J. Seiler, M. Hartmann, and L. Kreienbrock. 2017. “Antibiotic Drug Usage in Pigs in Germany—Are the Class Profiles Changing?” PLOS ONE, 12 (8) : e0182661. https://doi.org/10.1371/journal.pone.0182661. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 112 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Sommanustweechai, A., S. Chanvatik, V. Sermsinsiri, S. Sivilaikul, W. Patcharanarumol, S. Yeunga, and V. Tangcharoensathien. 2018. “Antibiotic Distribution Channels in Thailand: Results of Key-informant interviews, Reviews of Drug Regulations and Database Searches.” Bulletin of the World Health Organization 96 (2): 101–09. https://doi.org/10.2471/ BLT.17.199679. Tate, H., S. Ayers, E. Nyirabahizi, C. Li, S. Borenstein, S. Young, C. Rice-Trujillo, et al. 2022. “Prevalence of Antimicrobial Resistance in Select Bacteria from Retail Seafood—United States, 2019.” Frontiers in Microbiology 13: 928509. doi: 10.3389/fmicb.2022.928509. Wang, Y., C. Xu, R. Zhang, Y. Chen, Y, Shen, F. Hu, D. Liu, et al. 2020. “Changes in Colistin Resistance and mcr-1 Abundance in Escherichia coli of Animal and Human Origins Following 6 the Ban of Colistin-positive Additives in China: An Epidemiological Comparative Study.” The Lancet. Infectious Diseases 20 (10): 1161–71. https://doi.org/10.1016/S1473- 3099(20)30149-3. 7 WOAH (World Organisation for Animal Health). 2022. “Sixth Annual Report on Antimicrobial Agents Intended for Use in Animals.” https://www.woah.org/en/document/annual- 8 report-on-antimicrobial-agents-intended-for-use-in-animals/. 9 10 11 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 113 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 10 Promoting behavior change campaigns in animal production Working with farmers, veterinarians, paraveterinarians, and other stakeholders to support behavior change away from the use of antimicrobials in animal production can help to increase the responsible and prudent use of antimicrobials. AMU for animal production is substantial and is projected to increase with rising demand for animal protein. Inappropriate use ranges from growth promotion, to incorrectly targeted or administered antimicrobials, to use of critically important antibiotics for human medicine (van Boeckel et al. 2017). As antimicrobial purchase and administration occurs directly by farmers in many settings, 6 engaging farmers and others working in animal production and animal health and creating the necessary incentives (including possible enforcement strategies) will be important for changing 7 demand and use practices. Studies on baseline behaviors and behavior change campaigns in farmers were reviewed for effects on knowledge and use. 8 While most baseline studies document poor understanding of AMR, there are some promising results that suggest effectiveness for behavior change. Case studies are reported from Cambodia, Kenya, the Netherlands, and Europe (a multicountry study). In Cambodia, 9 a study of commercial farmers, feed retailers, and veterinarians found that overuse was linked to belief that antibiotics were necessary for animal raising, limited knowledge, unrestricted antibiotic access, and weak monitoring and control systems (Om and McLaws 2016). A study 10 of poultry producers in Kenya found that antibiotics were used for a range of reasons, from egg production improvement to growth promotion to managing disease symptoms (Kiambi et al. 2021). Specific behavior change interventions in the animal production industry are 11 limited. A review conducted in 2017 on farm and veterinarian AMU and prescribing found only seven intervention studies and 45 studies on facilitators and barriers (Gozdzielewska et al. 2020). In the Netherlands the RESET (Rules, Education, Social Pressure, Economics and Tools) Mindset Model was used as a basis for designing a behavior change intervention with required and voluntary components; it resulted in a 47 percent reduction in antibiotic use and a decline in use of critically important antibiotics to very low levels by the dairy sector between 2009 and 2015 (Lam et al. 2017). In a study of 70 pig farms in Belgium, France, Germany, and Sweden, herd farmers and herd veterinarians set targets for AMU and saw substantial reductions in use (Collineau et al. 2017). Withdrawal times have been set in a number of countries to require a period of nonuse prior to sale, with varying adherence outcomes reported. In theory, behavior change campaigns can be feasibly implemented in a range of settings, and there appears to be a need to strengthen general awareness around appropriate AMU as a first step. Possible reasons for success or failure vary, and include religious beliefs and policies, participation in farm collective organizations, and lack of awareness about the importance of adherence or enforcement. AMU tracking is necessary to guide precise interventions. The intervention examples above involved intensive national, industry, or veterinarian-supported initiatives versus relying solely on individual farm-level decisions. This supporting architecture is likely to be a constraint in countries with weak veterinary services. Viable solutions vary widely between smallholder and large-scale commercial livestock producers, and affordability of antimicrobials is a factor influencing low investment in basic hygiene and biosecurity measures (Caudell et al. 2020). “Nudges” in product labeling and marketing have been suggested as possible interventions, e.g., availability of vaccines in smaller vial sizes for small-scale producers, and awareness campaigned accompanied by basic animal health training programs for farmers (Mupfunya, Qekwana, and Naidoo 2021). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 114 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Knowledge gaps include the optimal format and length of interventions. Current practices and motivations, as well as production systems and stakeholders, require context-specific approaches to understand AMU, set realistic targets, and develop behavior change strategies. It is unclear how AMU for symptomatic illness will be reduced/targeted in the absence of widespread diagnostic services. Behavior change interventions are advisable in settings with sufficient alternatives to support reduced AMU. Appropriate practices should be tailored to the specific agricultural production context, given differing ecological and climatic conditions, access to services, and disease risks. 24 Enabling factors, including support from national, industry, or veterinarian initiatives and incentives for farmers (including cost considerations and regulations), are likely to promote success of this intervention as opposed to relying on individual farmers’ 6 decisions alone. 7 References Caudell, M. A., A. Dorado-Garcia, S. Eckford, C. Creese, D. K. Byarugaba, K. Afakye, T. Chansa- 8 Kabali, et al. 2020. “Towards a Bottom-up Understanding of Antimicrobial Use and Resistance on the Farm: A Knowledge, Attitudes, and Practices Survey across Livestock Systems in Five African Countries.” PLOS ONE 15 (1): e0220274. https://doi.org/10.1371/ 9 journal.pone.0220274. Collineau, L., C. Rojo-Gimeno, A. Léger, A. Backhans, S. Loesken, E. O. Nielsen, M. Postma, et al. 10 2017. “Herd-specific Interventions to Reduce Antimicrobial Usage in Pig Production without Jeopardising Technical and Economic Performance.” Preventive Veterinary Medicine 144: 167–78. https://doi.org/10.1016/j.prevetmed.2017.05.023. 11 Gozdzielewska, L., C. King, P. Flowers, D. Mellor, P. Dunlop, and L. Price. 2020. “Scoping Review of Approaches for Improving Antimicrobial Stewardship in Livestock Farmers and Veterinarians.” Preventive Veterinary Medicine 180: 105025. https://doi.org/10.1016/j. prevetmed.2020.105025. Kiambi, S., R. Mwanza, A. Sirma, C. Czerniak, T. Kimani, E. Kabali, A. Dorado-Garcia, et al. 2021. “Understanding Antimicrobial Use Contexts in the Poultry Sector: Challenges for Small- scale Layer Farms in Kenya.” Antibiotics (Basel): 10 (2): 106. https://doi.org/10.3390/ antibiotics10020106. Lam, T. J. G. M., J. Jansen, and R. J. Wessels. 2017. “The RESET Mindset Model Applied on Decreasing Antibiotic Usage in Dairy Cattle in the Netherlands.” Irish Veterinary Journal 70: 5. https://doi.org/10.1186/s13620-017-0085-x. Mupfunya, C. R., D. N. Qekwana, and V. Naidoo. 2021. “Antimicrobial Use Practices and Resistance in Indicator Bacteria in Communal Cattle in the Mnisi Community, Mpumalanga, South Africa.” Veterinary Medicine and Science 7 (1): 112–21. doi: 10.1002/vms3.334. Om, C., and M. L. McLaws. 2016. “Antibiotics: Practice and Opinions of Cambodian Commercial Farmers, Animal Feed Retailers and Veterinarians.” Antimicrobial Resistance & Infection Control 5: 42. doi: 10.1186/s13756-016-0147-y. 24  See World Bank Group, “Theory Behind the ISL Guide,” https://www.sustainablelivestockguide.org/theory Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 115 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Van Boeckel, T. P., E. E. Glennon, D. Chen, M. Gilbert, T. P. Robinson, B. T. Grenfell, S. A. Levin, S. Bonhoeffer, and R. Laxminarayan. 2017. “Reducing Antimicrobial Use in Food Animals.” Science 357 (6358): 1350–52. doi: 10.1126/science.aao1495. 6 7 8 9 10 11 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 116 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agriculture and food sector 11 Increasing veterinary laboratory capacity and access to diagnostics Rapid diagnosis and determination of sensitivity to antimicrobials can help veterinarians determine the most effective and appropriate treatment for sick animals and limit the use of antimicrobials where they are not needed or are unlikely to treat infection. As a part of this effort, strong laboratory capacity plays a key role in the animal health system, contributing to a number of functions and purposes. 25 As with human medicine, access to rapid diagnostics can be extremely limited, and prescribing often defaults to symptom-based clinical diagnosis. This understanding was reinforced by a study of animal health professionals 6 in 20 African countries, which found that lack of diagnostic facilities and susceptibility tests is a major challenge (Tebug et al. 2021). Several major bacterial and viral livestock diseases have 7 similar clinical signs that often require laboratory diagnosis for determination. Susceptibility and quality testing can also inform change in treatment protocols and/or enforcement and veterinary medicine supply chain strengthening. Studies on laboratory enhancement and access to 8 diagnostics were reviewed for effects on prescribing. The development of rapid tests is being pursued and shows promise for the future, 9 and findings indicate the utility of laboratory services; but few field-ready technologies are available to inform immediate AMU and susceptibility testing. Evidence is largely focused around diagnosis of a specific disease, typically one commonly associated with a given 10 production system. Case studies are reported from New Zealand, Chile, and the UK. Several studies do discuss the increasing availability of point-of-care options for diagnosis of clinical mastitis, a bacterial disease affecting dairy cows (e.g., Malcata et al. 2020). In New Zealand, 11 where mastitis is the primary reason for antibiotic use in dairy cows, an intervention was tested that compared waiting for diagnosis and antibiotic susceptibility test results (which take at least 24 hours) versus immediate treatment. No difference was detected in cure rates nor in the days of milk withheld from supply, but the group undergoing testing saw a 24 percent reduction in antimicrobial use (Bates et al. 2020). Technologies such as multiplex real-time quantitative polymerase chain reaction (qPCR) assay can allow for broader screening and an alternative to bacterial culture tests, but require formal laboratory facilities. In addition to immediate diagnosis and treatment needs, laboratory capacity for surveillance has utility for long-term data monitoring to determine susceptibility profiles and to link use and resistance patterns, as conducted via secondary data analysis in the US (Yin et al. 2021). In Chile, a risk- based surveillance effort for diagnosis of Piscirickettsia salmonis, the main reason for antibiotic use in salmon farms, was identified as a cost-effective early detection strategy (Delphino et al. 2021). A study of perceptions of veterinarians working at UK livestock farms found that rapid diagnosis introduces complexities into antimicrobial stewardship, including changing the flow of information and responsibilities in food production chains, with possible implications for disease reporting and management (Buller et al. 2020). 25  In addition to contributing to surveillance and diagnostics as examined in this review, laboratory capacity plays an important role in monitoring the quality of medicines, including antimicrobials, though the types of laboratories and skills required vary by function. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 117 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices At present, rapid tests are not widely available for animal disease, but standard microbiology laboratory infrastructure can be leveraged and strengthened for ongoing population-level surveillance as well as outbreak investigation support. The intervention relies on access to laboratory services and animal owners’ willingness to pay for diagnostics (or provision of testing via veterinary services). Because of the possible implications for the relationship between the veterinarian (or other animal health extension service worker) and the farmer in disease reporting, any design and rollout of this intervention should be informed by ongoing farmer and veterinarian consultation. As with laboratory capacity for humans, there is poor baseline knowledge of co-infections and in some cases poor test sensitivity and specificity. There are also knowledge gaps on incentives to promote farmer uptake of rapid diagnostics and possible changes in disease 6 reporting structures. Improvements of veterinary laboratory capacity for AMR outcomes may require phasing 7 in with more vertical (disease-based) strategies that can be deployed for rapid diagnosis. These should be pursued in tandem with broader animal health surveillance and monitoring for infections, antimicrobial use, and resistance. 8 References 9 Bates, A., R. Laven, O. Bork, M. Hay, J. McDowell, and B. Saldias. 2020. “Selective and Deferred Treatment of Clinical Mastitis in Seven New Zealand Dairy Herds.” Preventive Veterinary 10 Medicine 176: 104915. https://doi.org/10.1016/j.prevetmed.2020.104915. Buller, H., K. Adam, A. Bard, A. Bruce, K. W. Chan, S. Hinchliffe, L. Morgans, G. Rees, and K. 11 K. Reyher. 2020. “Veterinary Diagnostic Practice and the Use of Rapid Tests in Antimicrobial Stewardship on UK Livestock Farms.” Frontiers in Veterinary Science 7: 569545. https://doi.org/10.3389/fvets.2020.569545. Delphino, M. K. V. C., F. O. Mardones, J. Neumann Heise, A. Gallardo, D. Jimenez, A. Peña, M. Rozas-Serri, and I. A. Gardner. 2021. “Cost-effectiveness of Longitudinal Surveillance for Piscirickettsia salmonis Using qPCR in Atlantic Salmon Farms (Salmo salar) in Chile.” Journal of Fish Diseases 44 (3): 315–26. https://doi.org/10.1111/jfd.13285. Malcata, F. B., P.T. Pepler, E. L. O’Reilly, N. Brady, P. D. Eckersall, R. N. Zadoks, and L. Viora. 2020. “Point-of-care Tests for Bovine Clinical Mastitis: What Do We Have and What Do We Need?” Journal of Dairy Research 87(S1): 60–66. https://doi.org/10.1017/ S002202992000062X. Tebug, S. F., M. M. M. Mouiche, W. A. Abia, G. Teno, C. K. Tiambo, F. Moffo, and J. Awah-Ndukum. 2021. “Antimicrobial Use and Practices by Animal Health Professionals in 20 Sub- Saharan African Countries.” Preventive Veterinary Medicine 186: 105212. https://doi.org/10.1016/j.prevetmed.2020.105212. WHO. “WHO report on surveillance of antibiotic consumption: 2016-2018 early implementation.” 2018. Geneva: World Health Organization. Yin, X., N. M. M’ikanatha, E. Nyirabahizi, P. F. McDermott, and H. Tate. 2021. “Antimicrobial Resistance in Non-Typhoidal Salmonella from Retail Poultry Meat by Antibiotic Usage- related Production Claims—United States, 2008–2017.” International Journal of Food Microbiology 342: 109044. https://doi.org/10.1016/j.ijfoodmicro.2021.109044. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 118 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector 12 Improving infrastructure to provide access to water and sanitation in health care centers Improved water and sanitation contribute to the improvement of population health outcomes through reduced burden of disease. Health care settings are a significant source of infections, particularly among patients with weakened immune systems; this problem is exacerbated by inadequate infrastructure in some LMIC settings. Increasing water and sanitation infrastructure in health care facilities as part of overall WASH enhancements is a priority for preventing initial infections, their spread, and the development of resistance—both within facilities and in the broader community. Piped water systems (e.g., for safe drinking water) and waste treatment technologies (e.g., for sewage and health care waste management) are among the key infrastructure improvements that are a foundation for IPC. The evidence was reviewed on the impact of upgraded water and sanitation infrastructure in health care facilities on AMU, water quality, hand hygiene, and infection rates. 12 WASH infrastructure in health care settings is a foundation for IPC, though the evidence in relation to AMR-specific outcomes is mixed from both HIC and LMIC settings, and most studies to date report on cross-sectional findings or examine multiple interventions. 13 A systematic review of waterborne contamination sources and transmission routes in neonates and their mothers in health care settings included papers (n = 25) from mostly high and middle- 14 income settings; of these, the select studies that examined control measures indicated that faucet cleaning helped to control infections (Moffa et al. 2017). Case studies are presented from Bangladesh, Liberia, South Africa, Rwanda, and Ireland. In a study of health care facilities in 15 Bangladesh, environmental contamination and poor hand hygiene practices were observed even in facilities with improved water sources, indicating that infrastructure may not automatically translate to improved hygiene behavior and may require a broader scope of interventions for 16 success (Horng et al. 2016). In Liberia, renovations were conducted to provide basic WASH services in two hospitals originally without WASH services, resulting in an increase in hand hygiene compliance among health care workers from 36 percent to 89 percent in one hospital and from 86 percent to 88 percent in another (Kanagasabai et al. 2021). In South Africa, a study found that of 50 clinics examined in the country’s rural Vhembe district, 80 percent used an improved water source, but microbial quality in 17–64 percent of water taps was below the safe drinking water standard set by the country and WHO (Potgieter et al. 2021). In Rwanda, women undergoing caesarean section at a rural hospital were less likely to develop surgical site infections in hospitals with consistent piped water in a postpartum ward, whereas interruptions in water supply for a day or more were linked to a 2.6 times higher likelihood of such infections (Robb et al. 2020). A separate study of 17 health care facilities with piped water in Rwanda found that not all had functional water access points; of 142 handwashing locations in the facilities, only 32 percent had water and soap, and none had on-site capacity for performing repairs (Huttinger et al. 2017). A study in a dental hospital in Dublin, Ireland, indicated the presence of Pseudomonas aeruginosa bacteria in washbasins, likely through the wastewater piping network, though any clinical burden from this exposure route was not determined (Moloney et al. 2020). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 119 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Feasibility and enabling factors include access to infrastructure, such as adequate water source(s), facilities, and sanitation systems, and ongoing disinfection as needed. Some types of water taps have been found in studies to be more susceptible to microbial contamination, and piping conditions may facilitate the formation of biofilms (e.g., with stagnant water and low water pressure), reinforcing the importance of IPC expertise in design and ongoing monitoring and maintenance of WASH infrastructure (Halabi et al. 2001; Moloney et al. 2020). Access to functional water points also presents a challenge for hospitals in drought or conflict-affected settings, where other IPC measures may be more readily implementable in the short term (Lowe et al. 2021). A study of rural health care facilities with maternity wards in 14 LMICs found that availability of an improved water source was one of the four system-level factors associated with having the “six cleans” recommended by WHO (the other three factors were an IPC protocol, a budget for WASH, and IPC outreach with the community) (Cronk et al. 2021). WASH infrastructure is important, but likely insufficient, in IPC; proper handwashing and cleaning services must also follow, and management-related approaches may also be beneficial to enable a water safety plan (Dyck, Exner, and Kramer 2007; WHO Regional Office for Europe 2022). The placement of handwashing stations can also play a role in uptake, with inaccessibility reported as an impediment to good hand hygiene (Engdaw, Gebrehiwot, and Andualem 2019). 12 Knowledge gaps include the relative importance of WASH infrastructure compared to other infrastructure among different settings, depending on transmission routes and pathogens of concern. For example, ventilation and patient distancing can play a crucial role 13 in reducing some airborne infections (Stiller et al. 2016). The relative benefits to improved hand hygiene and other IPC enabled by WASH infrastructure may require examination, particularly where water and sanitation quality varies. The epidemiological significance of improved hospital 14 WASH infrastructure compared to improved community WASH infrastructure in reducing environmental dissemination and community transmission of resistant pathogens and genes 15 is likely to be context dependent. Sufficient WASH infrastructure underpins IPC and the prevention and control of 16 health care–acquired infections, and further study will help elucidate how it affects AMR- relevant outcomes in practice alone and with community-based WASH interventions. This intervention is likely to be synergistic with hand hygiene and other IPC measures, as well as quality monitoring and system maintenance. References Cronk, R., A. Guo, C. Folz, P. Hynes, A. Labat, K. Liang, and J. Bartram. 2021. “Environmental Conditions in Maternity Wards: Evidence from Rural Healthcare Facilities in 14 Low- and Middle-income Countries.” International Journal of Hygiene and Environmental Health 232: 113681. https://doi.org/10.1016/j.ijheh.2020.113681. Dyck, A., M. Exner, and A. Kramer. 2007. “Experimental Based Experiences with the Introduction of a Water Safety Plan for a Multi-located University Clinic and Its Efficacy According to WHO Recommendations.” BMC Public Health 7: 34. doi: 10.1186/1471-2458-7-34. Engdaw, G. T., M. Gebrehiwot, and Z. Andualem. 2019. “Hand Hygiene Compliance and Associated Factors among Health Care Providers in Central Gondar Zone Public Primary Hospitals, Northwest Ethiopia.” Antimicrobial Resistance and Infection Control 8: 190. https://doi.org/10.1186/s13756-019-0634-z. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 120 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Halabi, M., M. Wiesholzer-Pittl, J. Schöberl, and H. Mittermayer. 2001. “Non-touch Fittings in Hospitals: A Possible Source of Pseudomonas aeruginosa and Legionella spp.” Journal of Hospital Infection 49 (2): 117–21. doi: 10.1053/jhin.2001.1060. Horng, L. M., L. Unicomb, M. U. Alam, A. K. Halder, A. K. Shoab, P. K. Ghosh, M. Opel, M. P. Islam, and S. P. Luby. 2016. “Healthcare Worker and Family Caregiver Hand Hygiene in Bangladeshi Healthcare Facilities: Results from the Bangladesh National Hygiene Baseline Survey.” Journal of Hospital Infection 94 (3): 286–94. doi: 10.1016/j. jhin.2016.08.016. Huttinger, A., R. Dreibelbis, F. Kayigamba, F. Ngabo, L. Mfura, B. Merryweather, A. Cardon, and C. Moe. 2017. “Water, Sanitation and Hygiene Infrastructure and Quality in Rural Healthcare Facilities in Rwanda.” BMC Health Services Research 17 (1): 517. https://doi.org/10.1186/s12913-017-2460-4. Kanagasabai, U., K. Enriquez, R. Gelting, P. Malpiedi, C. Zayzay, J. Kendor, S. Fahnbulleh, et al. 2021. “The Impact of Water Sanitation and Hygiene (WASH) Improvements on Hand Hygiene at Two Liberian Hospitals during the Recovery Phase of an Ebola Epidemic.” 12 International Journal of Environmental Research and Public Health 18 (7): 3409. doi: 10.3390/ijerph18073409. 13 Lowe, H., S. Woodd, I. L. Lange, S. Janjanin, J. Barnet, and W. Graham. 2021. “Challenges and Opportunities for Infection Prevention and Control in Hospitals in Conflict-affected Settings: A Qualitative Study.” Conflict and Health 15 (1): 94. doi: 10.1186/s13031-021- 14 00428-8. Moffa, M., W. Guo, T. Li, R. Cronk, L. S. Abebe, and J. Bartram. 2017. “A Systematic Review of 15 Nosocomial Waterborne Infections in Neonates and Mothers.” International Journal of Hygiene and Environmental Health 220 (8): 1199–1206. doi: 10.1016/j.ijheh.2017.07.011. 16 Moloney, E. M., E. C. Deasy, J. S. Swan, G. I. Brennan, M. J. O’Donnell, and D. C. Coleman. 2020. “Whole-Genome Sequencing Identifies Highly Related Pseudomonas aeruginosa Strains in Multiple Washbasin U-bends at Several Locations in One Hospital: Evidence for Trafficking of Potential Pathogens via Wastewater Pipes.” Journal of Hospital Infection 104 (4): 484–91. doi: 10.1016/j.jhin.2019.11.005. Potgieter, N., N. T. Banda, P. J. Becker, and A. N. Traore-Hoffman. 2021. “WASH Infrastructure and Practices in Primary Health Care Clinics in the Rural Vhembe District Municipality in South Africa.” BMC Family Practice 22 (1): 8. doi: 10.1186/s12875-020-01346-z. Robb, K. A., C. Habiyakare, F. Kateera, T. Nkurunziza, L. Dusabe, M. Kubwimana, B. Powell, et al. 2020. “Variability of Water, Sanitation, and Hygiene Conditions and the Potential Infection Risk Following Cesarean Delivery in Rural Rwanda.” Journal of Water and Health 18 (5): 741–52. https://doi.org/10.2166/wh.2020.220. Stiller, A., F. Salm, P. Bischoff, and P. Gastmeier. 2016. “Relationship between Hospital Ward Design and Healthcare-associated Infection Rates: A Systematic Review and Meta-analysis.” Antimicrobial Resistance and Infection Control 5: 51. https://doi.org/10.1186/s13756-016- 0152-1. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 121 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization) Regional Office for Europe. 2022. “Drinking-water, Sanitation and Hygiene in the WHO European Region: Highlights and Progress towards Achieving Sustainable Development Goal 6.” World Health Organization Regional Office for Europe, Copenhagen. https://www.who.int/europe/publications/i/ item/9789289058063. 12 13 14 15 16 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 122 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector 13 Implementing effective treatment and disposal of sewage and wastewater Advanced treatment technologies can help reduce the spread of antimicrobial residues and antibiotic-resistant bacteria and genes into the environment. Untreated effluent and dissemination of residues and resistant pathogens and genes are documented from a number of sources, including hospital effluent. The limited capture of resistant bacteria presents potential risks of dissemination via drinking water, irrigation, and aquatic environments, including through surface water contamination. Waste treatment is particularly important in potential AMR hot spots such as hospitals and intensive food-animal production systems, as demonstrated by detection of resistant strains in effluent (e.g., King et al. 2021). Where waste is effectively captured, wastewater treatment plants (WWTPs) may use multiple technologies for treatment of raw waste before release into the environment or reuse. Multiple stages are usually involved, from initial stages of removing solid materials to tertiary stages of removing nutrients and disinfecting liquid effluent. Conventional tertiary methods focus on chlorination, 12 which is recognized as having limited impact on removal of resistant pathogens and genes. More advanced treatments such as ozonation, ultraviolet (UV) irradiation, and advanced 13 oxidation processes (chemical reactions to treat wastewater) were reviewed for effects on antimicrobial residues, resistant bacteria, and genes. 14 Both conventional and advanced methods produce variable effects on microbial organisms. Case studies are presented from India, China, and Brazil. A study in Tamil Nadu, India, reported a decrease in the number of bacterial colonies along seven stages of hospital 15 effluent treatment, ultimately finding removal of some but not all types of resistant pathogens, meaning these pathogens are present in wastewater entering the lagoon to be recycled (Kalaiselvi et al. 2016). Several studies have been conducted on constructed wetlands in China. 16 One study compared the concentration and removal of seven antimicrobial resistant genes in wastewater and biosolids from three municipal WWTPs using different advanced treatment methods (Chen and Zhang 2013). Compared to the standard WWTP treatment, the constructed wetland was found to have similar efficacy in removing resistant genes (reductions of one to three orders of magnitude) while being more effective in reducing relevant abundance. Biological aerated filter had a more limited effect, and no effect was found from UV disinfection. In Brazil, constructed wetlands demonstrated successful elimination of ciprofloxacin by the time of outflow (Sakurai et al. 2021). Another promising technology involves the solar photo-Fenton and electro-Fenton methods; experimental studies indicate high rates (~80 percent) of inactivation of resistance-conferring plasmids (which carry resistant genes), including in real wastewater samples sourced from a treatment plant in Brazil with resistance-conferring plasmids added (Vilela et al. 2021; Chen et al. 2020). Feasibility varies by setting and method. Wastewater chlorination has been found to increase some resistant bacteria and genes, and for sewage (biosolids), anaerobic digestion can result in a shift in microbial diversity, such as favoring survival of heat-tolerant microbes (Zhao and Liu 2019). Advanced treatments have been tested in laboratory-based studies, which indicate the effectiveness of advanced oxidation (e.g., thermal plasma, UV/H2O2) in partial or complete degradation—but results vary by complexity of the wastewater “matrix” (composition) as well as duration of treatment, temperature, pH, and number of methods used. These technologies entail high energy consumption, reagent use, and cost. PCR testing is often used to assess effectiveness Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 123 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices of removal of antimicrobial-resistant bacteria and genes. Additionally, use of WWTPs assumes well-maintained sewage infrastructure and the absence of open defecation, both of which are substantial challenges in some LMIC settings. Gaps in knowledge relate to field deployment of methods (which are largely experimental at present). The current gold standard can be considered sequential treatment using multiple technologies to promote comprehensive removal of contaminants; however, even in studies in developed countries, some results from on-site (versus laboratory-based) treatment show improved but not full removal of bacteria and genes (Paulus et al. 2019). Waste and wastewater treatment is important for several outcomes, and financing of this intervention for AMR outcomes should consider water composition and viability of removal. Wastewater composition analysis will be important in the design of advanced wastewater treatment interventions, along with ongoing maintenance of infrastructure and monitoring. Since antimicrobial residues, resistant bacteria, and genes can have different implications for disease burden, the epidemiological significance of incomplete removal can be assessed on a localized basis to determine if additional waste or wastewater treatment steps are needed. When incomplete removal does present a threat, other interventions may also be needed (e.g., vaccination or reduction of water source contamination). 12 References 13 Chen, H., and M. Zhang. 2013. “Effects of advanced treatment systems on the removal of antibiotic resistance genes in wastewater treatment plants from Hangzhou, China.” Environmental 14 Science & Technology 47 (15): 8157–63. https://doi.org/10.1021/es401091y. Chen, H., Wang, C., Zhang, J. et al. 2020. “NOx attenuation in flue gas by •OH/SO4•--based 15 advanced oxidation processes.” Environ Sci Pollut Res (27). https://link.springer.com/ article/10.1007/s11356-020-09782-1#citeas 16 Kalaiselvi, K., V. Mangayarkarasi, D. Balakrishnan, and V. Chitraleka, V. 2016. “Survival of Antibacterial Resistance Microbes in Hospital-generated Recycled Wastewater.” Journal of Water and Health 14 (6): 942-949. https://doi.org/10.2166/wh.2016.154. King, T. L., S. Schmidt, S. Thakur, P. Fedorka-Cray, S. Keelara, L. Harden, and S. Y. Essack. 2021. “Resistome of a Carbapenemase-producing Novel ST232 Klebsiella michiganensis Isolate from Urban Hospital Effluent in South Africa.” Journal of Global Antimicrobial Resistance 24: 321–24. https://doi.org/10.1016/j.jgar.2021.01.004. Paulus, G. K., L. M. Hornstra, N. Alygizakis, J. Slobodnik, N. Thomaidis, and G. Medema. 2019. “The Impact of On-site Hospital Wastewater Treatment on the Downstream Communal Wastewater System in Terms of Antibiotics and Antibiotic Resistance Genes.” International Journal of Hygiene and Environmental Health 222 (4): 635–44. https://doi.org/10.1016/j.ijheh.2019.01.004. Sakurai, K. S. I., C. M. E. Pompei, I. N. Tomita, Á. J. Santos-Neto, and G. H. R. Silva. 2021. “Hybrid Constructed Wetlands as Post-treatment of Blackwater: An Assessment of the Removal of Antibiotics.” Journal of Environmental Management 278 (Part 2) : 111552. https://doi.org/10.1016/j.jenvman.2020.111552. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 124 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Vilela, P. B., A. S. Martins, M. C. V. M. Starling, F. A. R. de Souza, G. F. F. Pires, A. P. Aguilar, M. E. A. Pinto, T. E.O. Mendes, and C. C. de Amorim. 2021. “Solar Photon-Fenton Process Eliminates Free Plasmid DNA Harboring Antimicrobial Resistance Genes from Wastewater.” Journal of Environmental Management 285: 112204. https://doi.org/10.1016/j.jenvman.2021.112204. Zhao, Q., and Y. Liu. 2019. “Is Anaerobic Digestion a Reliable Barrier for Deactivation of Pathogens in Biosludge?” Science of the Total Environment 668: 893–902. https://doi.org/10.1016/j. scitotenv.2019.03.063. 12 13 14 15 16 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 125 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector 14 Improving waste management practices in agricultural and aquaculture production/processing Limiting the flows of wastewater, manure, and agricultural runoff containing antimicrobials, antimicrobial residues, and antimicrobial-resistant bacteria helps limit the spread of resistance. Waste products from agriculture and aquaculture production and processing are potential sources of antimicrobial residues, resistant bacteria, and antimicrobial resistant genes. A major concern relates to product formulations for livestock, which result in low absorption of antimicrobials in some species (with as much as 90 percent excreted unmetabolized), as well as poor targeting of antimicrobials in aquaculture. The recycling of manure and other agricultural waste products may facilitate environmental dissemination. Relevant practices and risks should be considered in the context of different production systems; in general, intensive monogastric production (commercial pig, cattle, poultry) is a major source of agricultural waste. Proper waste management and pretreatment of waste from agriculture and aquaculture are thus recognized as potentially important to avoid dissemination of active 12 pharmaceuticals and resistant microbes and genes into the environment. Studies involving impact of anaerobic digestion, composting of manure, and manure lagoons on antimicrobial 13 residues and genes were reviewed. The few available studies point to reduction of residues and in some cases genes, though 14 results are not uniform. While studies report effects of waste treatment for a number of contaminants, the evidence base specifically on antimicrobial residues and resistance is limited. Case studies from the US, China, Vietnam, and Japan are presented. In the US, manure from a 15 dairy farm (n = 650 cows) was processed in a rotary drum composter, with significant decrease in oxytetracycline residues and the four antibiotic-resistant genes (ARGs) screened for (Oliver et al. 2020). In China, the mcr-1 colistin gene was detected in livestock waste in 2016 prior to the 16 ban on use the following year; while genes were found to increase in dried versus fresh manure, anaerobic digestion was found to reduce gene abundance (Xia et al. 2019). In Vietnam, a study of pig farming operations found most farms (70 percent) used biogas systems to treat animal waste, while a portion (19 percent) used composting and the remainder discharged waste into water sources. Fluoroquinolones and sulfonamides were found respectively in 6.3 percent and 22.9 percent of wastewater samples (Pham-Duc et al. 2020). A study in Japan of recycled organic material from several sources found that swine manure was the only one to contain certain antimicrobials, reflecting different antibiotic absorption rates in different species. In the US, upstream sources at three swine farms were found to have similar concentrations and abundances of tetracycline-resistant genes, but varying levels (some decreasing and some increasing) in the manure lagoons. As with the mcr-1 study above, increases in resistant genes were likely due to their positive selection by specific environmental conditions (Barkovskii, Manoylov, and Bridges 2012). Waste treatment relies on containment of waste as it is generated, which may not be practical in certain settings or production systems. Containment is especially a challenge for aquaculture production. Each technology has specialized requirements (e.g., moisture, temperature, and number of days for fermentation) (Motoyama et al. 2011), and high ARG abundance may reduce effectiveness of anaerobic digestion for gene degradation (Xia et al. 2019). Farmer education on optimal use of waste treatment technologies is important to support implementation success. In noncommercial farm settings, access to equipment and/or infrastructure for waste treatment is likely to require external assistance. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 126 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Regulatory requirements may incentivize farmers to participate in waste treatment, as will cost considerations (promoting low-cost but effective methods). The species of animal and AMU practices will drive relevance of this intervention for addressing emergence and spread of AMR. There is poor understanding of how different technologies and practices across production systems may potentially increase or decrease presence and dissemination of residues and genes. There are knowledge gaps on the epidemiological significance of residues, and particularly genes, released via waste from agriculture and aquaculture for human and animal health, in relation to antimicrobials not considered important for use in human medicine. To better understand the environmental determinants of the reduction or proliferation of genes, it will likely be necessary to test and potentially refine protocols for each treatment method and its use in different production systems and environmental settings. Treatment of waste/wastewater and runoff from animal production is prudent in all settings, but the overall picture of effects on AMR is uncertain, especially for aquaculture. Investments should be paired with farmer access to innovation, treatment technology, and education/incentives on use, as well as monitoring to inform refinements in waste management as necessary. 12 References 13 Barkovskii, A. L., K. M. Manoylov, and C. Bridges. 2012. “Positive and Negative Selection towards Tetracycline Resistance Genes in Manure Treatment Lagoons.” Journal of Applied Microbiology 112 (5): 907-919. https://doi.org/10.1111/j.1365-2672.2012.05252.x. 14 Motoyama, M., S. Nakagawa, R. Tanoue, Y. Sato, K. Nomiyama, and R. Shinohara. 2011. “Residues of Pharmaceutical Products in Recycled Organic Manure Produced 15 from Sewage Sludge and Solid Waste from Livestock and Relationship to Their Fermentation Level.” Chemosphere 84 (4): 432–38. https://doi.org/10.1016/j. 16 chemosphere.2011.03.048. Oliver, J., P. J. Lammers, J. Yeager, M. J. Rothrock Jr., J. A. Chase, S. A. Carey, and N. A. Sindt. 2020. “On-Farm Screw Press and Rotary Drum Treatment of Dairy Manure-associated Antibiotic Residues and Resistance.” Journal of Environmental Quality 49 (6): 1478–87. https://doi.org/10.1002/jeq2.20176. Pham-Duc, P., H. Nguyen-Viet, T. Luu-Quoc, M. A. Cook, P. Trinh-Thi-Minh, D. Payne, T. Dao-Thu, D. Grace, and S. Dang-Xuan. 2020. “Understanding Antibiotic Residues and Pathogens Flow in Wastewater from Smallholder Pig Farms to Agriculture Field in Ha Nam Province, Vietnam.” Environmental Health Insights 14: 1178630220943206. https://doi.org/10.1177/1178630220943206. Xia, X., Z. Wang, Y. Fu, X. D. Du, B. Gao, Y. Zhou, J. He, et al. 2019. “Association of Colistin Residues and Manure Treatment with the Abundance of mcr-1 Gene in Swine Feedlots.” Environment International 127: 361–70. https://doi.org/10.1016/j.envint.2019.03.061. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 127 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector 15 Improving safe disposal of unused antimicrobials Improving antimicrobial disposal practices can direct unused antimicrobials from household settings to pharmacies or other safe disposal points. Improper disposal can result in dissemination of pharmaceuticals into the environment via trash, sewage, and manufacturing or other waste, potentially contaminating water systems. Uptake of safe disposal programs for all medicines was reviewed for evidence of effectiveness. The evidence base largely evaluates self- reported program awareness and participation. Several safe disposal programs have been trialed; however, outside of long-standing programs in Europe, many are relatively new. These newer programs vary in scope, have met with limited uptake, and have been established without broader systems in place. Case studies from Ghana, Malaysia, Kuwait, the Netherlands, and Turkey are presented. A systematic review of studies (n = 25) published between 2005 and 2015 reported that some countries used a pharmacy return program, with supervised incineration or recycling of medications 12 (Paut Kusturica et al. 2016). The highest return of unused medicines was reported from the Netherlands, estimated at 58 percent (Alnahas et al. 2020). In Ghana, the Disposal of Unused Medicines Program (DUMP) is operational but reported as limited in geographic scope (present 13 only in government-affiliated hospitals and clinics), with very low awareness of the program among participants (< 20 percent of participants). In Malaysia, the government offers a take-back program at hospitals and clinics. In Sabah, of patients (n = 244) at outpatient pharmacies, 54 14 percent had heard about the return program, and 26 percent reported they had used it (Yang et al. 2018); in Selangor, a survey of households (n = 103) found only 25 percent had utilized 15 the program (Ariffin and Zakili 2017). Several studies have tested collection via provision of special envelopes, with low reported return. In Kuwait, household participation in medication return was more successful in a small sample of households (n = 14) that received in-person 16 interviews and assistance, versus no uptake by households receiving only educational material and envelopes for pick-up (n = 200 households) (Abahussain and Ball et al. 2007). In Serbia, a study of patients (n = 800) visiting pharmacies in four cities found ~80 percent were likely or very likely to participate in a take-back program, but less than half would be willing to pay for collection (Paut Kusturica et al. 2020). In a workplace-based education and take-back campaign in Turkey (n = 1,112 participants), 28.6 percent of participants reported they had brought back medicine(s); there were also reports of increased proper at-home storage practices (Akici, Aydin, and Kiroglu 2018). The intervention appears feasible if centralized collection and destruction infrastructure is in place, but requires awareness, access, and clear designation of responsibility and financing for success. Public trust in programs is necessary; concern over resale of medicines has been suggested as a possible reason for low uptake. Program responsibility varies from the pharmaceutical industry to national agencies (e.g., health, drug enforcement), local governments, and communities (Barnett-Itzhaki et al. 2016; Lin et al. 2020). Studies indicate poor awareness of waste management by medical and dental professionals and students (e.g., Ranjan et al. 2016). Safe disposal relies on infrastructure to collect and properly dispose of antimicrobials, and on training and awareness to support participation. Supply-side interventions related to doses disbursed and treatment compliance, along with incentives (e.g., a voucher mechanism), could help to address the quantity and disposal of unused antimicrobials. Tracking sales data would provide a baseline. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 128 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices There are gaps in knowledge about safe disposal-seeking behaviors by patients with real or perceived future need for antimicrobials. Gaps are greater in settings with high rates of bacterial illness and/or low access to prescriptions. Safe disposal of antimicrobials remains important, but the evidence for the success of centralized medication take-back programs overall appears limited. Safe disposal may warrant consideration as a second-line priority once other interventions are in place, or may be paired with other investments such as public awareness to reduce demand, monitoring of antimicrobial use, and access to diagnostics. To ensure country-wide reach in LMICs, there is a need to develop programs that are connected to overall disposal systems and that are reinforced by uptake campaigns. References Abahussain, E. A., and D. E. Ball. 2007. “Disposal of Unwanted Medicines from Households in Kuwait.” Pharmacy World and Science 29 (4): 368–73. https://doi.org/10.1007/s11096- 006-9082-y. 12 Akici, A., V. Aydin, and A. Kiroglu. 2018. “Assessment of the Association between Drug Disposal Practices and Drug Use and Storage Behaviors.” Saudi Pharmaceutical Journal 26 (1): 7–13. https://doi.org/10.1016/j.jsps.2017.11.006. 13 Alnahas, F., P. Yeboah, L. Fliedel, A. Y. Abdin, and K. Alhareth. 2020. “Expired Medication: Societal, Regulatory and Ethical Aspects of a Wasted Opportunity.” International Journal 14 of Environmental Research and Public Health 17 (3): 787. https://doi.org/10.3390/ ijerph17030787. 15 Ariffin, M., and T. S. T. Zakili. 2019. “Household Pharmaceutical Waste Disposal in Selangor, Malaysia—Policy, Public Perception, and Current Practices.” Environmental 16 Management 64 (3): 509–19. https://doi.org/10.1007/s00267-019-01199-y. Barnett-Itzhaki, Z., T. Berman, I. Grotto, and E. Schwartzberg. 2016. “Household Medical Waste Disposal Policy in Israel.” Israel Journal of Health Policy Research 5 (1): 48. https://doi.org/10.1186/s13584-016-0108-1. Lin, L., X. Wang, W. Wang, X. Zhou, and J. R. Hargreaves. 2020. “Cleaning up China’s Medical Cabinet—An Antibiotic Take-back Programme to Reduce Household Antibiotic Storage for Unsupervised Use in Rural China: A Mixed-methods Feasibility Study.” Antibiotics (Basel) 9 (5): 212. https://doi.org/10.3390/antibiotics9050212. Paut Kusturica, M., S. Golocorbin-Kon, T. Ostojic, M. Kresoja, M. Milovic, O. Horvat, T. Dugandzija, N. Davidovac, A. Vasic, and A. Tomas. 2020. “Consumer Willingness to Pay for a Pharmaceutical Disposal Program in Serbia: A Double Hurdle Modeling Approach.” Waste Management 104: 246–53. https://doi.org/10.1016/j.wasman.2020.01.029. Ranjan, R., R. Pathak, D. K. Singh,M. Jalaluddin, S. A. Kore, and A. R. Kore. 2016. “Awareness about Biomedical Waste Management and Knowledge of Effective Recycling of Dental Materials among Dental Students.” Journal of International Society of Preventive & Community Dentistry 6 (5): 474–79. https://doi.org/10.4103/2231-0762.192941. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 129 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Yang, S. L., S. L. Tan, Q. L. Goh, and S. Y. Liau. 2018. “Utilization of Ministry of Health Medication Return Programme, Knowledge and Disposal Practice of Unused Medication in Malaysia.” Journal of Pharmacy Practice and Community Medicine 4: 07-11. 10.5530/ jppcm.2018.1.3. 12 13 14 15 16 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 130 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector 16 Monitoring presence of antimicrobial residues and antibiotic-resistant bacteria and genes in water and sanitation systems Monitoring of water and sanitation systems can generate data on the type of antimicrobials being used, as well as resistance patterns, helping to guide authorities on the appropriate actions to take. This information is important in the absence of reporting systems for AMU in humans and animals and can help determine potential for dissemination via shared or recycled water sources and the environment. Monitoring may detect concentration of residues (indicating presence of specific antimicrobial compounds, implying use) as well as antibiotic-resistant bacteria and antibiotic-resistant genes (Baquero, Martínez, and Cantón 2008). This review focused on effects of monitoring of antimicrobials (via residues) and antimicrobial resistance in water and sanitation systems on detection and disease investigation. There is good evidence that sampling at different points in the water and sanitation system, such as along WWTP processes, is effective in detecting antibiotics in the water 12 supply and informing where treatment enhancement is needed. Monitoring studies were conducted mainly for water and to a lesser extent for waste. Monitoring studies were reported from a variety of HIC and LMIC settings; it should be noted that the state of knowledge was 13 limited around ARG presence (e.g., Adesoji et al. 2015). Case studies are presented from Europe, Canada, Brazil, China, and Pakistan. A study conducted at WWTPs in seven European 14 countries reported that residues of 17 antibiotics out of the 53 screened for were found in final effluent (Rodriguez-Mozaz et al. 2020). The findings allowed for selection of a subset of residue monitoring targets for antibiotic pollution. Retrospective analysis examined reports of residues 15 from aquatic samples in 47 countries against concentration levels that are unlikely to result in development of resistance (“predicted no effect environmental concentration”) and found that 7.9 percent of antibiotic analyses exceed the level, with hospital and industrial wastewater 16 demonstrating antibiotic profiles of concern (Booth, Aga, and Wester 2020). In a study in three First Nation communities in Canada, bacterial contamination was found to occur post-treatment in storage and distribution infrastructure, with ARGs also detected (Mi et al. 2019). In Brazil, a monitoring study compared ARGs from urban and hospital wastewater, finding genes encoding for multidrug resistance in 33.3 percent of isolates (Zagui et al. 2020). Several studies also point to monitoring as a key component in outbreak investigation, such as sampling of drinking water from cases and control households in a ceftriaxone-resistant Salmonella Typhi outbreak in Pakistan (water samples ultimately revealed high contamination with E. coli, leading to an improvement of water chlorination and implementation of fecal sludge treatment processes) (Yousafzai et al. 2019). In some cases, monitoring has been conducted as part of wider water safety testing. A study in nonurban sewage treatment plants in China reported a significant association between the presence of ARGs and some heavy metals (Xu et al. 2017). In general, water and sanitation monitoring are feasible with standard technologies countries already have in place. Common methods include bacterial cultures and basic coliform testing, chromatography (chemical detection), and PCR- and qPCR-based methods (microbial and gene detection). Drug-resistant fecal coliform testing in WWTP effluent was conducted in 22 countries across five continents (Marano et al. 2020). Other methods typically require laboratory-based infrastructure. Water quality may affect detection (Pazda et al. 2019). Monitoring requires ongoing collection, reporting, and analysis to inform risk assessment and management. There may be a major gap in translating findings from monitoring into action if WASH infrastructure is lacking or poorly maintained. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 131 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The adequate scope for sampling and testing is a knowledge gap. Improved monitoring and comparison to background environmental data will support more precise monitoring needs (samples and sites and antibiotics, bacteria, and genes to screen for) and interpretation of findings. Understanding is also limited around the precise level of threat from residues and genes transmitted through waste and wastewater, including how community or individual-level behaviors may increase or decrease risk. Water monitoring appears to generate useful information in all settings. However, this intervention in particular requires a One Health approach to put findings from water monitoring into context about risk to humans and animals. It is likely to be synergistic with water treatment (and aquatic ecosystem protection), as well as regulatory interventions to address sources of contamination. It reinforces the importance of laboratory capacity and ongoing laboratory operations. References Adesoji, A. T., A. A. Ogunjobi, I. O. Olatoye, and D. R. Call. 2015. “Prevalence of Tetracycline Resistance Genes among Multi-drug Resistant Bacteria from Selected Water 12 Distribution Systems in Southwestern Nigeria.” Annals of Clinical Microbiology and Antimicrobials 14: 35. https://doi.org/10.1186/s12941-015-0093-1 [published correction appears in Annals of Clinical Microbiology and Antimicrobials 14 (2015): 41]. 13 Baquero, F., J. L. Martínez, and R. Cantón. 2008. “Antibiotics and Antibiotic Resistance in Water Environments.” Current Opinion in Biotechnology 19 (3): 260–65. 14 https://doi.org/10.1016/j.copbio.2008.05.006. Booth, A., D. S. Aga, and A. L. Wester. 2020. “Retrospective Analysis of the Global Antibiotic 15 Residues That Exceed the Predicted No Effect Concentration for Antimicrobial Resistance in Various Environmental Matrices.” Environment International 141: 105796. 16 https://doi.org/10.1016/j.envint.2020.105796. Marano, R. B. M., T. Fernandes, C. M. Manaia, O. Nunes , D. Morrison, T. U. Berendonk, N. Kreuzinger, et al. 2020. “A Global Multinational Survey of Cefotaxime-resistant Coliforms in Urban Wastewater Treatment Plants.” Environment International 144 : 106035. https://doi.org/10.1016/j.envint.2020.106035. Mi, R., R. Patidar, A. Farenhorst, Z. Cai, S. Sepehri, E. Khafipour, and A. Kumar. 2019. “Detection of Fecal Bacteria and Antibiotic Resistance Genes in Drinking Water Collected from Three First Nations Communities in Manitoba, Canada.” FEMS Microbiology Letters 366 (6): fnz067. https://doi.org/10.1093/femsle/fnz067. Pazda, M., J. Kumirska, P. Stepnowski, and E. Mulkiewicz. 2019. “Antibiotic Resistance Genes Identified in Wastewater Treatment Plant Systems: A Review.” Science of the Total Environment 697: 134023. https://doi.org/10.1016/j.scitotenv.2019.134023. Rodriguez-Mozaz, S., S. Chamorro, E. Marti, B. Huerta, M. Gros, A. Sànchez-Melsió, and J. L. Balcázar. 2020. “Antibiotic Residues in Final Effluents of European Wastewater Treatment Plants and Their Impact on the Aquatic Environment.” Environment International 140: 105733. https://doi.org/10.1016/j.envint.2020.105733. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 132 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Xu, Y. B., M. Y. Hou, Y. F. Li, L. Huang, J. J. Ruan, L. Zheng, Q. X. Qiao, and Q. P. Du. 2017. “Distribution of Tetracycline Resistance Genes and AmpC β-lactamase Genes in Representative Non-urban Sewage Plants and Correlations with Treatment Processes and Heavy Metals.” Chemosphere 170: 274–81. https://doi.org/10.1016/j. chemosphere.2016.12.027. Yousafzai, M. T., F. N. Qamar, S. Shakoor, K. Saleem, H. Lohana, S. Karim, A. Hotwani, A., et al. 2019. “Ceftriaxone-resistant Salmonella Typhi Outbreak in Hyderabad City of Sindh, Pakistan: High Time for the Introduction of Typhoid Conjugate Vaccine.” Clinical Infectious Diseases 68 (Supplement 1): S16–S21. https://doi.org/10.1093/cid/ciy877. Zagui, G. S., L. N. de Andrade, N. C. Moreira, T. V. Silva, G. P. Machado, A. L. da Costa Darini, and S. I. Segura-Muñoz. 2020. “Gram-negative Bacteria Carrying β-lactamase encoding Genes in Hospital and Urban Wastewater in Brazil.” Environmental Monitoring and Assessment 192 (6): 376. https://doi.org/10.1007/s10661-020-08319-w. 12 13 14 15 16 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 133 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multisector 17 Detecting and deterring substandard and falsified antimicrobials Tackling substandard and falsified (SF) antimicrobials requires interventions to improve detection and deterrence supported by regulatory action, including monitoring- based enforcement. Antimicrobials are among the most commonly reported SF medicines (WHO 2018). Although poorly quantified in relation to veterinary use, SF antimicrobials are a concern for both human and animal medicine. Detection and deterrence operations may involve traceability systems, quality screening, criminal justice and law enforcement, and regulatory standard setting. Potential results relevant for this intervention include reduction in rates of substandard and/or falsified products and improved treatment effectiveness. Studies involving detection interventions were reviewed for effects on SF product tracking, product quality, and enforcement. Overall, the evidence base is mixed for effectiveness in low-income countries, though some promising findings indicate the scale of the problem can be successfully reduced. The World Customs Organization (in partnership with WHO and others) has conducted recent capacity strengthening operations with customs officials to counter the flow of SF medicines. 26 Case studies are reported from Cambodia, Ghana, Kenya, Lao People’s Democratic Republic, and Nigeria. In Cambodia, a study using open surveyors and mystery clients to collect artemisinin-containing antimalarials (n = 291 samples) from drug outlets found no falsified medicines; all the medicines contained active pharmaceutical ingredients (although only 17 69 percent were reported to be of good quality). These findings indicated effectiveness of regulation, enforcement, education, and communication campaigns aimed at tackling poor- quality medicines in the country and addressing concern over antimalarial resistance (Yeung 18 et al. 2015). Several detection options have been trialed. Nigeria’s Mobile Authentication Service, initiated in 2010, uses a serialized code for immediate verification by consumers via text message (“OK” or “fake—don’t use”); the cost of the label is incurred by suppliers. Nigeria 19 has reported a reduction in counterfeit and substandard products (estimated at > 60 percent in 2001 compared to only 5 percent in 2012), though it is unclear what effect mobile authentication 20 had on this decrease (Spink, Moyer, and Rip 2016). Reliability of testing methods appears to vary. A blinded study for a specific antimalarial medication in Lao PDR found the US Food and Drug Administration’s CD3 device to be highly accurate (Tabernero et al. 2015). A comparison of three devices piloted in Ghana (the US Food and Drug Administration’s CD3+, the GPHF [Global Pharma Health Fund] Minilab, and the Thermo Scientific TruScan hand-held Raman spectrometer) found that detection/devices/methods for antimalarials varied in sensitivity and specificity (Batson et al. 2016). Paper analytical devices (PADs) for falsified antibiotics and antibiotic paper analytical devices (aPADs) for substandard antibiotics offer a simplified screening option. Based on the relatively low cost of PADs and aPADs (US$3) compared to standard high-performance liquid chromatography, a modeling study suggested a potential return of nearly US$15 million from potentially increased removal of SF amoxicillin to support effective treatment of childhood pneumonia (Chen et al. 2021). INTERPOL’s multicountry operations on substandard and falsified medicines and medical products have led to seizures, identification of suspects, and in some cases arrests. 26  For information about regional and global efforts to fight SF medical products, see the World Customs Organization website, https://www.wcoomd.org. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 134 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Feasibility largely rests on screening capabilities. A major challenge is the scale of SF medicines, which may require targeting of efforts to specific antimicrobials. Sourcing via manufacture in country versus via import may demand different approaches to interception as well as regional coordination. Limitations can include the need for multiple screening methods to examine both dosage and packaging validity, need for mobile signal and power reliability, and lack of connection to the product’s chain of custody. Field-based or local screening (e.g., via Minilab technologies) may help narrow down the quantity of samples for costly pharmacopeial confirmatory screening (Petersen et al. 2017). Constraints can negatively affect community pharmacist perceptions (see for example Oyetunde et al. 2019). Links between marketing and use in human health and animal health sectors should be considered, given the importance of regulatory capacity in human health and veterinary medicine (National Academies of Science, Engineering, and Medicine 2020). Knowledge gaps include suitable incentives to participate in SF screening, and reporting and removal from the market, at various points in the supply chain. Quality thresholds may be challenging to act on without sufficient alternatives, particularly where access is limited. This intervention is relevant for both human and animal medical products, and should be considered in tandem with suitable enforcement, deterrence, and incentives. The intervention could be AMR-sensitive or AMR-specific. Regulated supply in both human and animal medicine (and crop production) may also be a potential strategy for addressing SF medicines. References 17 Batson, J. S., D. K. Bempong, P.H. Lukulay, N. Ranieri, R. D. Satzger, and L. Verbois. 2016. “Assessment of the Effectiveness of the CD3+ Tool to Detect Counterfeit and 18 Substandard Anti-malarials.” Malaria Journal 15: 119. https://doi.org/10.1186/s12936- 016-1180-2. 19 Chen, H. H., C. Higgins, S. K. Laing, S. L. Bliese, M. Lieberman, and S. Ozawa. 2021. “Cost Savings of Paper Analytical Devices (PADs) to Detect Substandard and Falsified Antibiotics: Kenya Case Study.” Medicine Access @ Point of Care 5. https://doi. 20 org/10.1177/2399202620980303. National Academies of Sciences, Engineering, and Medicine; Health and Medicine Division. 2012. Ensuring Safe Foods and Medical Products through Stronger Regulatory Systems Abroad. Washington, DC: National Academies Press. Oyetunde, O. O., O. Ogidan, M. I. Akinyemi, A. A. Ogunbameru, and O. F. Asaolu. 2019. “Mobile Authentication Service in Nigeria: An Assessment of Community Pharmacists’ Acceptance and Providers’ Views of Successes and Challenges of Deployment.” Pharmacy Practice 17 (2): 1449. https://doi.org/10.18549/PharmPract.2019.2.1449. Petersen, A., N. Held, L. Heide, on behalf of the Difäm-EPN Minilab Survey Group. 2017. “Surveillance for falsified and substandard medicines in Africa and Asia by local organizations using the low-cost GPHF Minilab”. PLOS ONE 12(9): e0184165. https://doi.org/10.1371/journal.pone.0184165 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 135 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Spink, J., D. C. Moyer, and M. R. Rip. 2016. “Addressing the Risk of Product Fraud: A Case Study of the Nigerian Combating Counterfeiting and Sub-standard Medicines Initiatives.” Journal of Forensic Sciences and Criminology 4 (2): 201. Tabernero, P., M. Mayxay, M. J. Culzoni, P. Dwivedi, I. Swamidoss, E. L. Allan, M. Khanthavong, et al. 2015. “A Repeat Random Survey of the Prevalence of Falsified and Substandard Antimalarials in the Lao PDR: A Change for the Better.” American Journal of Tropical Medicine and Hygiene 92 (6 Supplement): 95–104. https://doi.org/10.4269/ ajtmh.15-0057. Yeung, S., H. L. S. Lawford, P. Tabernero, C. Nguon, A. van Wyk, N. Malik, M. DeSousa, et al. 2015. “Quality of Antimalarials at the Epicenter of Antimalarial Drug Resistance: Results from an Overt and Mystery Client Survey in Cambodia.” American Journal of Tropical Medicine and Hygiene 92 (6 Supplement), 39–50. https://doi. org/10.4269%2Fajtmh.14-0391. WHO (World Health Organization). 2018. “Substandard and Falsified Medical Products.” January 31, 2018. https://www.who.int/news-room/fact-sheets/detail/substandard-and- falsified-medical-products. 17 18 19 20 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 136 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multisector 18 Improving nutrition in humans and animals Nutrition is well recognized as playing a role in the incidence and burden of disease. Nutrition status can affect susceptibility to infection and the severity and duration of disease in humans and animals, while some infections affect the body’s ability to take up nutrients from food. Good nutrition is an important component in the management of HIV, for example, because it helps to maintain a strong immune system and supports absorption of medicines. In some food-producing animals, antimicrobials have been inappropriately used for growth promotion, and in humans antibiotics are routinely prescribed in the treatment of severe malnutrition and/or diarrheal disease, especially for children under five, contributing to a significant portion of AMU in some settings. Thus, improving nutrition is potentially important for action on AMR (Unger, Mark, and Pagliari 219; Moran 2019). Studies involving nutrition or food security improvements in humans and animals were reviewed for the effect of these improvements on AMU or AMR. There are few studies reporting on population-level nutrition interventions related to AMU and AMR specifically, across all settings. However, there is some evidence supporting an association between indicators related to improved nutrition in the form of nutrient supplementation or probiotics and AMR outcomes. Case studies are reviewed from the US, Germany, Bangladesh and Sweden, and Egypt. In the US, a year-long randomized controlled trial of vitamin supplementation in elderly residents (n = 617) at nursing homes found normal 17 levels of zinc were linked to lower pneumonia incidence and lower total antibiotic use compared to low zinc levels (Meydani et al. 2007). In Germany, a study of patients (n = 661) receiving parenteral (intravenous) nutrition in 82 hospital sites found that receiving higher levels (versus 18 a lower dosage) of omega-3 fatty acids was linked to a 26 percent lower antimicrobial demand (Heller et al. 2006). Cross-sectional studies have looked at factors linked to AMR that are potentially indicative of nutrition status, such as correlations between weight status and AMU 19 prevalence in the US National Health and Nutrition Examination Survey (Petersen et al. 2021). A systematic review of studies (n = 20) on probiotic-supplemented infant formulas reported 20 reduced antimicrobial prescriptions, though evidence was mixed and varied by probiotic strain (Skórka et al. 2017). A comparison of infant cohorts examined the association between Bifidobacterium levels with AMR in early life in Bangladesh (a cohort with relatively high levels) and Sweden (with lower levels), finding higher levels reduced ARGs; however, the effect was not sustained at age two, raising questions about relevance over the life course (Taft et al. 2018). In food production animals, nutrition interventions have involved dietary intake changes and supplementation (e.g., protein, fiber, acids, and other additives), varying by species (Smits et al. 2021). In Egypt, a controlled study on Bifidobacteria and Lactobacillus probiotics as alternatives to antimicrobials supported weight gain and reduced mortality in broiler chickens infected with Salmonella enterica (El-Sharkawy et al. 2020). Feasibility is likely to be limited by food insecurity, which affects access to and sustainment of nutrition resources. Detecting nutrition effects on clinically relevant AMR outcomes could require long-term monitoring. There are several possible indicators of nutrition for both humans and animal species (e.g., height, weight, dietary diversity, micronutrient intake); each target could involve different interventions. Food safety and water quantity and quality also play a role (Smits et al. 2021). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 137 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices There are key gaps in knowledge around community-based versus clinical nutrition interventions, as well as intervention scope. For example, improved nutrition efforts could range from counseling to direct provision of food supply. Additive effects with other interventions may be possible; a study on rates of infant diarrheal disease found nutrition incentives encouraged pickup of medicines at a collection location, a behavior that could affect nutrition and immune status as well as treatment compliance (Xue et al. 2010). Nutrition interventions could potentially help to reduce exposure to pathogens as well as antibiotic residues in the food supply, including through synergies with food safety initiatives. Overall, improvements in nutrition have important benefits, including for the prevention and management of infectious disease, but precise roles in AMR outcomes are unclear at present. Benefits of improved nutrition may be evident in animal production, particularly in replacement of existing AMU for some veterinary medical uses as well as nonveterinary medical uses (e.g., growth promotion). 27 References El-Sharkawy, H., A. Tahoun, A. M. Rizk, T. Suzuki, W. Elmonir, E. Nassef, M. Shukry, et al. 2020. “Evaluation of Bifidobacteria and Lactobacillus Probiotics as Alternative Therapy for Salmonella typhimurium Infection in Broiler Chickens.” Animals (Basel) 10 (6): 1023. Heller, A. R., S. Rössler, R. J. Litz, S. N. Stehr, S. C. Heller, R. Koch, and T. Koch. 2006. “Omega-3 Fatty Acids Improve the Diagnosis-related Clinical Outcome.” Critical Care Medicine 34 (4): 972–79. https://doi.org/10.1097/01.CCM.0000206309.83570.45. 17 Meydani, S. N., J. B. Barnett, G. E. Dallal, B. C. Fine, P.F. Jacques, L. S. Leka, and D. H. Hamer. 2007. “Serum Zinc and Pneumonia in Nursing Home Elderly.” American Journal of Clinical 18 Nutrition 86 (4): 1167–73. https://doi.org/10.1093/ajcn/86.4.1167. Moran, D. 2019. “A Framework for Improved One Health Governance and Policy Making for 19 Antimicrobial Use.” BMJ Global Health 4 (5): e001807. https://doi.org/10.1136/ bmjgh-2019-001807. 20 Petersen, M. R., S. E. Cosgrove, T. C. Quinn, E. U. Patel, M. K. Grabowski, and A. R. R. Tobian. 2021. “Prescription Antibiotic Use among the US Population 1999–2018: National Health and Nutrition Examination Surveys.” Open Forum Infectious Diseases 8 (7): ofab224. https://doi.org/10.1093/ofid/ofab224. Skórka, A., M. Pieścik-Lech, M. Kołodziej, and H. Szajewska. 2017. “To Add or Not to Add Probiotics to Infant Formulae? An Updated Systematic Review.” Beneficial Microbes 8 (5): 717–25. https://doi.org/10.3920/BM2016.0233. Smits, C. H. M., D. Li, J. F. Patience, and L. A. den Hartog, E. A. Bruno, and D. Battaglia. 2021. “Animal Nutrition Strategies and Options to Reduce the Use of Antimicrobials in Animal Production.” FAO Animal Production and Health, Paper 184. Food and Agriculture Organization of the United Nations. https://doi.org/10.4060/cb5524en. 27  WOAH uses the term “nonveterinary medical use” of antimicrobials to refer to use for any purpose other than to treat, control, or prevent disease. The terms “therapeutic” and “nontherapeutic” are used elsewhere in this Framework to make a general distinction between veterinary and nonveterinary medical use. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 138 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Taft, D. H., J. Liu, M. X. Maldonado-Gomez, S. Akre, M. N. Huda, S. M. Ahmad, C. B. Stephensen, and D. A. Mills. 2018. “Bifidobacterial Dominance of the Gut in Early Life and Acquisition of Antimicrobial Resistance.” mSphere 3 (5): e00441-18. https://doi.org/10.1128/ mSphere.00441-18. Unger, S. A., H. Mark, and C. Pagliari. 2019. “Nutrition: The Missing Link in the Battle against Microbial Resistance?” Journal of Global Health 9 (1): 010321. https://doi. org/10.7189%2Fjogh.09.010321. Xue, J., Z. Mhango, I. F. Hoffman, I. Mofolo, E. Kamanga, J. Campbell, G. Allgood, et al. 2010. “Use of Nutritional and Water Hygiene Packages for Diarrhoeal Prevention among HIV- exposed Infants in Lilongwe, Malawi: An Evaluation of a Pilot Prevention of Mother-to- child Transmission Post-natal Care Service.” Tropical Medicine & International Health 15 (10): 1156–62. doi: 10.1111/j.1365-3156.2010.02595. 17 18 19 20 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 139 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multisector 19 Expanding vaccination coverage in humans and animals Immunization is an indispensable tool in the protection against vaccine-preventable diseases in humans and animals. Expanding vaccination coverage is a priority goal to tackle vaccine-preventable illnesses in humans and animals, including those frequently treated by antimicrobials and more specifically those that lead to childhood deaths, such as pneumococcal disease, rotavirus, and Hib infection. 28 In addition to individual protection, vaccine strategies can provide indirect benefits; for example, animal vaccination can support herd protection, and some childhood vaccines have been linked to disease prevention in adults. Vaccination can also provide protective benefits where there is concern over development of AMR in pathogens with widespread distribution, as seen with increasing detection of extensively drug-resistant typhoid infections (Saha, Tabassum, and Saha 2021). The availability of vaccines varies for infections associated with high consumption of antimicrobials and potential for the development of resistance (WHO 2022). Studies were reviewed for effects of vaccination on AMU and AMR in humans and animal populations. Overall, there is evidence that vaccination (in addition to reducing vaccine-preventable infections) affects AMR outcomes, particularly AMU, in all settings, though effects are mixed and study quality and robustness vary. Studies have mainly examined the impact of disease-specific vaccination (e.g., influenza, pneumonia, or typhoid) on AMR-related outcomes, versus a multiple-vaccine strategy. A Cochrane Collaborative systematic review 17 (n = 96 randomized or observational studies) found evidence certainty varied by outcome, with high-certainty evidence that influenza vaccination reduces duration of antibiotic use in healthy adults (Buckley et al. 2019). Case studies are reviewed from the US, Lao PDR, Israel, the 18 Democratic Republic of Congo, and Belgium. In the US, an analysis of influenza vaccination and antibiotic prescribing between 2010 and 2017 found that for every 10 percentage point increase in vaccination, there was a 6.5 percent decrease in antibiotic use, with effects most pronounced in 19 pediatric and elderly populations (Klein et al. 2020). In terms of potential impact on the number of infections treated by antibiotics, a study of pneumococcal and rotavirus vaccines found that 20 over 37 million episodes of antibiotic-treated illness annually are prevented in children under five years in LMICs under current coverage, and that expanded coverage for all children ages 24–59 months in LMICs would result in additional prevention of nearly 22 million episodes (Lewnard et al. 2020). In Lao PDR, pneumococcal vaccination was found to be significantly associated with a reduction inantibiotic use in the preceding fortnight in children 12–23 months, from 46.1 percent down to 34.4 percent in pre-and-post cross-sectional surveys (Satzke et al. 2019). Studies have reported pneumococcal vaccination campaigns leading to both the elimination of resistant strains from circulation in Israel and the persistence or increase in resistant non-vaccine strains in the Democratic Republic of Congo (Ben-Shimol et al. 2018; Birindwa et al. 2018). Vaccination is a widely used animal health tool, though studies related to AMR outcomes in animals are often reported in combination with other interventions. A review reported that various bacterial and viral vaccines in animals have been linked to significant reductions in AMU (Hoelzer et al. 2018). In Belgium, herd action plans involving vaccination plus biosecurity intervention on pig farms (n = 61) found significant reduction—between 32 percent and 52 percent—in AMU for treatment incidences based on production system, including reduction in use of critically important antimicrobials (Postma et al. 2017). 28  Although infection with rotavirus is caused by a viral pathogen (and thus not treatable by antibiotics), antibiotics are commonly prescribed for the disease in some settings—driving unnecessary use of antimicrobials. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 140 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Implementation feasibility is likely to vary based on epidemiological, infrastructure (e.g., cold chain), economic, behavioral, and other factors. While vaccination reduces the burden of primary and secondary infections (including resistant infections), a key challenge for human and animal health is that vaccination is pathogen-specific—and thus may lead to continued antimicrobial prescribing in the absence of precise diagnosis. Vaccine licensing varies by country, and protection depends on effectiveness against circulating strains, so that ongoing monitoring for the appropriate selection of vaccines is required. Expanded vaccination is estimated to avert substantial AMR costs (e.g., Lu et al. 2021) but requires sustained investment. Gavi financing supports vaccine introduction, procurement, and use in low-income countries, but middle- income countries can lack resources to introduce vaccines that are needed after graduating from Gavi. While playing a crucial and potentially leading role, vaccination alone is unlikely to be successful in the eradication of diseases, as noted for typhoid (where challenges include asymptomatic transmission, environmental exposures, and achieving universal vaccination) (Stanaway et al. 2020), and given vaccine hesitance and access constraints more broadly. In animals, current feasibility varies by production type; for example, classical injection practices are impractical in aquaculture, and there is presently limited availability of commercial vaccines for some fish species (WOAH 2015). Some veterinary vaccines present safety issues (Hoelzer et al. 2018). Additional human and animal vaccines, including for resistant pathogens, are in various stages of development, but require a number of elements to facilitate their development and use (immunological factors, product development, access, and implementation). Generation of evidence for the value of vaccines in preventing AMR may be constrained by the many parameters that can affect AMR expansion; however, most economic analyses of vaccines do not consider effects on AMR, likely underestimating their potential value (Micoli et al. 2021). 17 Key knowledge gaps relate to epidemiological significance of reduced antimicrobial prescribing for specific diseases, as well as incentives for vaccine uptake and sustainment by the public sector and individuals (e.g., patients or farmers). Additionally, while benefits of 18 childhood immunization are broadly recognized, there are knowledge gaps around the utility of adult immunization in LMICs, including in relation to waning immunity and vaccine-preventable diseases linked to AMR in older adults (Sauer et al. 2021). In settings with limited access to 19 diagnostics, it is unclear what effect vaccination may have on AMU for nonspecific symptoms (fever, respiratory, or diarrheal illnesses). 20 Expanding vaccination is a promising intervention for vaccine-preventable diseases linked to high AMU or AMR. It likely requires working in tandem with prescribing policy and awareness or behavior change campaigns, plus pathogen detection infrastructure and animal biosecurity. References Ben-Shimol, S., N. Givon-Lavi, D. Greenberg, M. Stein, O. Megged, A. Bar-Yochai, S. Negari, R. Dagan, on behalf of the Israel Bacteremia and Meningitis Active Surveillance Group. 2018. “Impact of Pneumococcal Conjugate Vaccines Introduction on Antibiotic Resistance of Streptococcus Pneumoniae Meningitis in Children Aged 5 Years or Younger, Israel, 2004 to 2016.” Eurosurveillance 23 (47): 1800081. https://doi.org/10.2807/1560-7917.ES.2018.23.47.1800081. Birindwa, A. M., M. Emgård, R. Nordén, E. Samuelsson, S. Geravandi, L. Gonzales-Siles, B. Muhigirwa, et al. 2018. “High Rate of Antibiotic Resistance among Pneumococci Carried by Healthy Children in the Eastern Part of the Democratic Republic of the Congo.” BMC Pediatrics 18 (1): 361. https://doi.org/10.1186/s12887-018-1332-3. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 141 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Buckley, B. S., N. Henschke, H. Bergman, B. Skidmore, E. J. Klemm, G. Villanueva, C. Garritty, and M. Paul. 2019. “Impact of Vaccination on Antibiotic Usage: A Systematic Review and Meta-analysis.” Clinical Microbiology and Infection 25 (10): 1213–25. https://doi.org/10.1016/j.cmi.2019.06.030. Hoelzer, K., L. Bielke, D. P. Blake, E. Cox, S. M. Cutting, B. Devriendt, E. Erlacher-Vindel, et al. 2018. “Vaccines as Alternatives to Antibiotics for Food Producing Animals. Part 1: Challenges and Needs.” Veterinary Research 49 (1): 64. https://doi.org/10.1186/s13567-018-0560-8. Klein, E. Y., E. Schueller, K. K. Tseng, D. J. Morgan, R. Laxminarayan, and A. Nand. 2020. “The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010–2017.” Open Forum Infectious Diseases 7 (7): ofaa223. https://doi.org/10.1093/ofid/ofaa223. Lewnard, J. A., N. C. Lo, N. Arinaminpathy, I. Frost, and R. Laxminarayan. 2020. “Childhood Vaccines and Antibiotic Use in Low- and Middle-income Countries.” Nature 581 (7806): 94–99. https://doi.org/10.1038/s41586-020-2238-4. Lu, E. Y., H. H. Chen, H. Zhao, and S. Ozawa. 2021. “Health and Economic Impact of the Pneumococcal Conjugate Vaccine in Hindering Antimicrobial Resistance in China.” Proceedings of the National Academy of Sciences of the United States of America 118 (13): e2004933118. https://doi.org/10.1073/pnas.2004933118. Micoli, F., F. Bagnoli, R. Rappuoli, and D. Serruto. 2021. “The Role of Vaccines in Combatting Antimicrobial Resistance.” Nature Reviews Microbiology 19 (5): 287–302. https://doi.org/10.1038/s41579-020-00506-3. 17 Postma, M., W. Vanderhaeghen, S. Sarrazin, D. Maes, and J. Dewulf. 2017. “Reducing Antimicrobial Usage in Pig Production without Jeopardizing Production Parameters.” Zoonoses and 18 Public Health 64 (1): 63–74. https://doi.org/10.1111/zph.12283. 19 Saha, S. K., N. Tabassum, and S. Saha. 2021. “Typhoid Conjugate Vaccine—An Urgent Tool to Combat Typhoid, and Tackle Antimicrobial Resistance.” Journal of Infectious Diseases 224 (7 Supplement): jiab443. https://doi.org/10.1093/infdis/jiab443. 20 Satzke, C., E. M. Dunne, M. Choummanivong, B. D. Ortika, E. F. G. Neal, C. L. Pell, M. L. Nation, et al. 2019. “Pneumococcal Carriage in Vaccine-eligible Children and Unvaccinated Infants in Lao PDR Two Years Following the Introduction of the 13-valent Pneumococcal Conjugate Vaccine.” Vaccine 37 (2): 296–305. https://doi.org/10.1016/j. vaccine.2018.10.077. Sauer, M., P. Vasudevan, A. Meghani, K. Luthra, C. Garcia, M. D. Knoll, and L. Privor-Dumm. 2021. “Situational Assessment of Adult Vaccine Preventable Disease and the Potential for Immunization Advocacy and Policy in Low- and Middle-income Countries.” Vaccine 39 (11): 1556–64. https://doi.org/10.1016/j.vaccine.2021.01.066. Stanaway, J. D., P. L. Atuhebwe, S. P. Luby, and J. A. Crump. 2020. “Assessing the Feasibility of Typhoid Elimination.” Clinical Infectious Diseases 71 (Supplement 2): S179–S184. https://doi.org/10.1093/cid/ciaa585. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 142 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WOAH (World Organisation for Animal Health). 2015. “Report of the Meeting of the WOAH Ad Hoc Group on Prioritisation of Diseases for Which Vaccines Could Reduce Antimicrobial Use in Animals.” Paris, April 21–23, 2015. https://www.woah.org/app/uploads/2021/09/ahg- amur-vaccines-apr2015.pdf. WHO (World Health Organization). 2022. Bacterial Vaccines in Clinical and Preclinical Development: An Overview and Analysis. Geneva: World Health Organization. https://www.who.int/ publications/i/item/9789240052451. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 143 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Multisector 20 Using closed water systems in aquaculture Reducing the flow of waste to and from aquaculture farms is a potential way to limit the spread of pathogens and resistance. Effluent from aquaculture farms can be a source of environmental contamination by dispersing antibiotic residues and resistant pathogens and genes through surface water. Aquaculture production systems can produce significant changes in the structure of aquatic microbial populations (Zeng, Tian, and Wang 2017). Inputs from off- farm sources can also threaten fish health and production; for example, they may potentially introduce pathogens and other contaminants. Closed (or recirculating) systems limit the introduction and exit of water and waste to preserve water resources and reduce external contamination, typically filtering or treating contained water before reuse. Studies involving effects of closed aquaculture systems on AMR-related water treatment and water quality outcomes were reviewed. The evidence base is limited on the role of closed system interventions in AMR outcomes. Some interventions have been trialed in LMIC and HIC settings, though primarily in experimental studies and with widely varying approaches. Case studies are reviewed from the Czech Republic, Korea, and Thailand. In the Czech Republic, a treated wastewater pond–aquaculture pond system was compared to a control pond fed by river water to simulate water reuse in aquaculture. The study monitored 70 pharmaceutically active compounds, including antibiotics and antifungals, in both systems and concluded that treated water influent in the aquaculture 17 pond reduced ecotoxicological and antibiotic resistance water quality hazards (Fedorova et al. 2022). A study in Korea indicated that filter pore size affected how efficiently ARGs were removed from effluent (Kim et al. 2018). In Thailand, water from enclosed shrimp culturing ponds, which 18 represents an amplifying environment for resistant pathogens and genes, was treated with ferrate. Water quality (organic waste accumulation), antibiotic structure type, and pH acidity affected antibiotic removal effectiveness (Suyamud et al. 2021). 19 There are likely feasibility challenges with current technologies and practices in many settings. Integrated farming practices common in some regions involve the reuse of waste 20 products from poultry production as part of fish and vegetable production (Pruden et al. 2013). While closed systems are used at different scales (aquaria, commercial fish production), these are generally based on specialized and resource-intensive infrastructure (energy and cost). In settings where inland freshwater aquaculture is widespread, closed systems may be impractical. Although most systems are focused on land-based aquaculture, approaches vary. In marine pens, a major concern is invasion by wild fish that could lead to the introduction of pathogens and the type of genetic exchange that allows development of ARGs. Closed systems could potentially be integrated into biosecurity enhancements targeted to AMR outcomes. Knowledge gaps relate to types of systems, as well as the significance of partial removal of antimicrobial residues, pathogens, or ARGs. Since most wastewater treatment methods do not comprehensively remove ARGs, it is unclear what effect water recirculation has on ARG maintenance or degradation, and ultimately on fish populations. Incentives for farm investments in closed systems related to AMR are unclear, but could evolve with shifting demand (e.g., for low- AMU products). Potential additive effects of closed systems for reducing AMU in aquaculture— or of other measures to improve water quality, such as modifications in feeding practices and fish density—are not yet known. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 144 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices There is a limited evidence base for this intervention’s effects on AMR at present. At a farm level, there may be practical entry points as part of biosecurity enhancements in commercial operations. The technological methods used may vary widely by setting (from informal integrated systems to high-tech infrastructure); thus, utility should be considered in the specific context. Pairing this intervention with monitoring, specific guidance for use of antimicrobials in such systems, and farm-directed behavior change campaigns could help to shape its adoption. References Fedorova, G., R. Grabic, K. Grabicová, J. Turek, T. Van Nguyen, T. Randak, B. W. Brooks, and V. Zlabek. 2022. “Water Reuse for Aquaculture: Comparative Removal Efficacy and Aquatic Hazard Reduction of Pharmaceuticals by a Pond Treatment System During a One Year Study.” Journal of Hazardous Materials 421: 126712. https://doi.org/10.1016/j. jhazmat.2021.126712. Kim, Y. B., J. H. Jeon, S. Choi, J. Shin, Y. Lee, and Y. M. Kim. 2018. “Use of a Filtering Process to Remove Solid Waste and Antibiotic Resistance Genes from Effluent of a Flow-through Fish Farm.” Science of the Total Environment 615, 289–96. https://doi.org/10.1016/j. scitotenv.2017.09.279. Pruden, A., D. G. Larsson, A. Amézquita, P. Collignon, K. K. Brandt, D. W. Graham, J. M. Lazorchak, et al. 2013. “Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment.” Environmental Health Perspectives 121 (8): 878–85. https://doi.org/10.1289/ehp.1206446. 17 Suyamud, B., J. Lohwacharin, Y. Yang, and V. K. Sharma. 2021. “Antibiotic Resistant Bacteria and Genes in Shrimp Aquaculture Water: Identification and Removal by Ferrate(VI).” Journal 18 of Hazardous Materials 420: 126572. https://doi.org/10.1016/j.jhazmat.2021.126572. Zeng, Q., X. Tian, and L. Wang. 2017. “Genetic Adaptation of Microbial Populations Present in High- 19 intensity Catfish Production Systems with Therapeutic Oxytetracycline Treatment.” Scientific Reports 7 (1): 17491. https://doi.org/10.1038/s41598-017-17640-3. 20 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 145 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 4 Investing in AMR through World Bank Operations Summary 147 CHEVRON- Introduction 148 CHEVRON- Overview of the 2022 portfolio review 148 CHEVRON- Menu of options by sector 150 CHEVRON- Health sector approaches 151 CHEVRON- Agricultural and food sector approaches 157 CHEVRON- Water and environment sector approaches 161 CHEVRON- References 166 CHEVRON- A menu of options translating the list of intervention areas into World Bank operations can provide teams with scope to flexibly respond to the policy and lending dialogue in different contexts and in recognition that the intervention areas are a starting point, rather than a comprehensive list. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 146 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 4 Investing in AMR through World Bank Operations Chapter 4 summary This chapter describes how the 20 intervention areas identified in Chapter 3 can be translated into World Bank operations within and across the Health, Nutrition and Population (HNP), Agriculture and Food (AGF), and Water Global Practices (GPs). At the core of the World Bank’s support to addressing antimicrobial resistance (AMR) is the provision of concessional International Development Association (IDA) and International Bank of Reconstruction and Development (IBRD) lending to finance interventions. This chapter is intended to provide task teams and clients with a starting point for incorporating interventions to address AMR in World Bank operations, specifically Investment Project Financing (IPF), Development Policy Operations (DPOs), and Programs for Results (PforRs). It provides options for discussion, which can be developed by task and client teams so that approaches are aligned with specific situations and needs. This chapter begins by providing an overview of a 2022 portfolio review of World Bank lending; it then provides a menu of options for lending operations across the three sectors. At the time, the lending portfolio included 57 projects across 35 countries aiming at strengthening and developing agriculture, health, and water and sanitation systems that would prevent the emergence of diseases, reduce the need for antimicrobials, and limit the emergence and spread of resistance. The portfolio has since grown to more than 70 projects, and these have been drawn upon to inform the menu of options provided in this chapter. In addition, Appendix 3 provides detailed guidance on addressing the Environmental and Social Safeguards (ESS) considerations. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 147 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction This chapter provides guidance for task teams on how each of the following intervention areas can be translated into operations across the World Bank’s three primary lending instruments: IPFs, Development Policy Financing, and PforRs. At the core of the World Bank’s support to addressing AMR is the provision of concessional IDA and IBRD lending to finance interventions. With this in mind, Table 4 in Chapter 3 documented the intervention areas that have been identified across the HNP, AGF, and Water GPs, drawing on guidance from the United States Centers for Disease Control (CDC), the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO), and World Organisation for Animal Health (WOAH). Options for translating the list of interventions in Table 4 will be provided across sectors; however, the options will be broader than the areas covered in Chapter 3. This approach is meant to provide teams with scope to flexibly respond to the policy and lending dialogue in different contexts and in recognition that the intervention areas are a starting point, rather than a comprehensive list. This approach is also intended to respond to feedback from external partners on the range of areas that can be supported. For example, hand hygiene has proven to be an important and valuable infection prevention and control (IPC) measure through the COVID-19 pandemic. It is also an intervention that is amenable to continuation and scale-up in a range of different operations and to following on from COVID-19 operations focused on broader health and water sector reform. However, it is recognized that it is often part of a package of IPC and AMR stewardship interventions. Within HNP, and of relevance to all sectors, the intervention areas have been translated into specific investments at the local, regional, and national level and vary in complexity. For example, improving antibiotic prescribing guidelines for health care workers can include national- level interventions such as changes to curriculums for health workers, regional-level interventions such as trainings for health workers, and local-level interventions such as monitoring and auditing of local practices. In addition, the options provided also seek to recognize that clients will be in different stages of readiness to address AMR. For some the focus will need to be on establishing initial infrastructure—for example, improving sanitation in health facilities. For others the appropriate intervention may be in developing advanced laboratory capabilities. Overview of the 2022 portfolio review In January 2022 a rapid review of the World Bank’s IDA and IBRD lending was conducted to identify AMR investments, which were estimated to be approximately US$2 billion.29 At the time, the lending portfolio included 57 operations across 35 countries aiming at strengthening and developing agriculture, health, and water and sanitation systems that would prevent the emergence of diseases, reduce the need for antimicrobials, and limit the emergence and spread of resistance. Thirty-four of the operations were by the HNP GP (60 percent), 8 were led by the AGF GP (14 percent), and 15 were led by the Water GP (26 percent). The portfolio had a wide geographical spread, with 32 operations in the Africa region, eight in East Asia and Pacific, six in South Asia, five in Europe and Central Asia, five in the Middle East and North Africa, and one in Latin America and the Caribbean. The portfolio has since grown to more than 70 operations. Seventy-five percent of the portfolio was focused on human health investments. The review classified investments into three categories depending on whether they focused on human health, animal health, or both. Of the 57 operations, 43 operations (75 percent) include investments in human 29  In 2022 the World Bank’s AMR portfolio was estimated to be between US$0.62 billion and US$2.32 billion; US$0.6 billion in financing was clearly allocated for AMR investments and an additional US$1.7 billion was tagged as addressing AMR, but without a specific budget breakdown. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 148 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices health, six operations (11 percent) include investments in animal health, and eight operations (14 percent) include both. Out of 43 operations that focus on human health, six include investments to combat drug resistance related to tuberculosis (TB). Sixty-eight percent of the portfolio addresses AMR-sensitive interventions. The World Bank classifies investments into two types of interventions: (i) AMR-specific interventions, which have as their main purpose the reduction of AMR emergence and spread—for example, promulgating and enforcing regulations to ensure people can obtain antimicrobial medicines only with a valid prescription; and (ii) AMR-sensitive interventions, which have other primary purposes, such as improved animal husbandry or a reduction in disease incidence, but which contribute indirectly to addressing emergence and spread of AMR. Of the 57 operations in the portfolio, 15 (26 percent) address AMR-specific interventions (13 in HNP; two in AGF), while 39 (68 percent) address AMR- sensitive interventions (20 in HNP, 15 in Water, and four in AGF). Five percent of the operations address both types of interventions (one in HNP; two in AGF). The most common AMR interventions identified in the review were these: improvement of surveillance systems; strengthening of laboratory capacity; institutional and capacity building; water, sanitation, and hygiene (WASH) improvements in health care facilities; and prevention, detection, and treatment of TB. Operations focusing on TB have addressed AMR by including a component on the detection, treatment, and monitoring of drug-resistant TB. Operations focusing on animal health have usually addressed AMR indirectly through components addressing animal health and farm management, diagnostic and surveillance capacity, and livelihood support. Operations focusing on WASH in health care facilities indirectly address AMR through components on institutional WASH, health system strengthening, and improvement of health infrastructure. Operations have drawn on a wide range of indicators to assess and incentivize investments in AMR, and 33 operations include AMR-related indicators in their results framework. The majority of indicators focus on the incorporation of One Health platforms and approaches, AMR scorecards, reduction in the total use of antibacterial drugs, the number of TB drug susceptibility tests, improved farm management practices, and access to improved water and sanitation in health care facilities. Operations in the HNP GP have indicators on the successful establishment of One Health platforms, AMR scorecards, decrease in TB prevalence, increase in access to WASH in health care facilities, and health care waste management. Three operations focusing on One Health offer examples of investments aimed at improving animal and human health through the establishment of a regional One Health platform in West Africa (the Regional Disease Surveillance Systems Enhancement [REDISSE] Phases 1–3 [P154807, P159040, and P161163]. Another regional project in East Africa focuses on assessing and strengthening AMR testing in laboratories by deploying AMR scorecards (Africa CDC Regional Investment Financing Project in East Africa [P167916]). Five operations focus on decreasing drug resistance related to TB (AFR RI-East Africa Public Health Laboratory Networking Project [P111556], Emergency Tuberculosis Project in Papua New Guinea [P160947], Program Towards Elimination of Tuberculosis in India [P167523], Southern Africa Tuberculosis and Health Systems Support Project [P155658], and Burundi Public Health Laboratory Networking Project [P129551]). With regard to the TB operations’ intermediate results (IR) indicators, the regional project in East Africa and the operations in Papua New Guinea and India focus on drug susceptibility and culture conversion rates among TB patients; the operations in East Africa, Burundi, and Papua New Guinea focus on drug-sensitivity testing for multidrug-resistant TB; and lastly, the regional project in southern Africa focuses on harmonizing standard operating procedures for surveillance of multi-drug resistant TB (MDR-TB). Another project in Serbia offers an example of an IR indicator that directly focuses on reducing the total consumption of antibacterial drugs for systemic use (Additional Financing for Second Serbia Health Project [P166025]). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 149 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Operations in the AGF GP focus on improving animal health by decreasing the prevalence of diseases and improving breeding and management practices. Two operations in Mali and the Sahel offer an example of investments aimed at improving animal health through vaccination programs: Regional Sahel Pastoralism Support Project (P147674) and Mali Livestock Sector Development Support Project (PADEL-M) (P160641). Other operations focus on improving breeding and management practices—for example, the Kyrgyz Republic Integrated Dairy Productivity Improvement Project (P155412). With regard to IR indicators, in Mali, the indicators focus on reducing disease prevalence; in the Sahel, the focus is on vaccination rates. In the Kyrgyz Republic, the focus is on the number of dairy producers who have improved farm management practices. Operations from the Water GP focus on ensuring access to WASH in health care facilities, operations and maintenance of WASH facilities, and waste management. Four operations include indicators related to WASH facilities in health care facilities as Project Development Objective (PDO) indicators: Côte d’Ivoire Urban Water Supply Project Additional Financing (P170502); Results-Based Scaling Up Rural Sanitation and Water Supply Program in Vietnam (P152693); Rural Water Supply and Sanitation Project Tajikistan (P162637); and One WASH – Consolidated Water Supply, Sanitation and Hygiene Account Project Ethiopia (ONE WASH Phase II) (P167794). With regard to IR indicators, two operations include operations and maintenance of facilities: Burkina Faso Water Supply and Sanitation Program (P164345); and Haiti Sustainable Rural and Small Towns Water and Sanitation Project (P148970). One project includes antenatal programs, which are covered by hygiene- and sanitation-related behavior change communication (Vietnam); and another project, Angola Health System Performance Strengthening Project (P160948), includes municipalities implementing operational plans for medical waste management. Menu of options by sector To support task teams and clients in incorporating interventions into the design and implementation of future operations, this section provides a menu of options, organized by sector, for IPFs, DPOs, and PforRs. These options draw from the evidence review, preceding chapters, and existing and previous operations; however, they are intended to provide a starting point and recognize that interventions in AMR are often one part of an overall loan package, sectoral reform, or wider set of initiatives. Each of the components, performance-based conditions, and prior actions presented below should be seen as a starting point that task teams can adapt, through discussion, with client teams across ministries. In many cases, referencing the existing National Action Plan can help teams identify areas that could benefit from World Bank interventions and financing, and the components can be adjusted and developed further in recognition of a given context or based on consultation with Legal, Procurement, Finance, Environmental and Social, and other teams. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 150 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector approaches  COMPONENTS Strengthening infection prevention and control in clinical settings. This component focuses on a range of stewardship measures to reduce the emergence and spread of infections within hospital settings, and to limit the spread of highly resistant infections among infectious patients. This includes: » Hospital surveillance to detect drug-resistant pathogens. This includes laboratory equipment in regional, hospital, and local laboratories to support the detection of resistant pathogens and training of hospital-based health care and laboratory workers. » Health care waste management. This includes development and enforcement of clinical waste management protocols to safeguard patient safety and reduce the emergence and spread of infections within hospital settings. » Private sector and pharmaceutical retail. This includes the development of regulatory and enforcement mechanisms to facilitate citizens’ access to medication. It will include financing the development of regulatory assessments to inform legislative reforms and assessments to determine priorities for improving regulatory enforcement capacity. Strengthening the capacity to prevent and detect health emergencies at the local, regional, and national level. This component focuses on supporting activities that are needed in the health sector to keep public health threats and global health security threats like AMR from occurring, or keep them from spreading. Activities to improve prevention and detection encompass these activities at country and regional levels, as applicable: » Surveillance and collaborative intelligence of AMR at the local, regional, and national level. This includes providing laboratory equipment and routine consumables in regional, hospital, and local laboratories to support the detection of resistant pathogens, the appropriate use of antimicrobials for health conditions, and training of laboratory workers, microbiologists, physicians, and other health workers. » Training and capacity building programming to support health workers in detecting and preventing the spread of AMR. This includes training health workers on prescribing guidelines and appropriate use of antimicrobials, issuing national guidelines on appropriate use and prescription of antimicrobials (i.e., by using WHO’s Essential Medicines List AWaRe classifications 30), and conducting audits and monitoring to ensure adherence with national guidelines and to track antimicrobial use (AMU).31 This also includes reducing supply-side gaps, as logistics can ultimately affect prescribing practices. » Research into pathogens and other potential causes of AMR. This includes microbiological, social, and multisectoral initiatives that improve the understanding of the drivers and transmission patterns of AMR across community and health facility settings. 30  The classifications place antimicrobials in three stewardship groups: those to access (antimicrobials with broad uses and relatively lower resistance potential that are recommended for first- or second-line treatment), watch (to be prioritized as key targets of stewardship programs), or reserve (save for last-resort use). 31  Global standards have been established for reporting on two key areas of monitoring, which are collected via the Global Antimicrobial Resistance and Use Surveillance System (GLASS): (i) consumption of antimicrobials, and (ii) the presence or prevalence of antimicrobial-resistant pathogens, resistant genes, or antimicrobial residues. WHO GLASS proposes a master protocol to be used for the generation of reliable estimates of mortality attributable to AMR blood stream infections (BSIs), focused on the two AMR Sustainable Development Goal (SDG) indicators. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 151 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices » Community engagement, capacity building, trust building, and risk communication. Ensuring productive and efficient engagement from and with the community will require a combination of activities focused on capacity building, trust building, and clear risk communication to ensure that communities understand how risk levels ebb and flow and how communities can productively contribute to prevention and detection efforts. This will include working with private, public, and civil society actors and clinical bodies to support the development of information, education, and communication (IEC) messaging and materials. It also includes risk communication with specific subpopulations and will require close collaboration with other sectors dealing with animal husbandry and water and sanitation programs. » Strengthening and implementation of dis- and misinformation strategies. As the COVID-19 pandemic made clear, mitigating the emergence and spread of health threats (such as AMR) relies in part on providing clear, accurate, and easily digestible information about the drivers of epidemics to communities, health workers, and the general public. This includes programming to counter misinformation as well as communication campaigns and materials to build awareness and understanding of relevant risks and good practices. Guidelines and standards for AMR management. The component will support the development of consistent guidelines and standards for coordination between surveillance institutions, including provisions for sharing public health assets, transferring specimens, and sharing data on disease surveillance and outbreaks. It will provide finance for (i) developing consistent frameworks, standards, protocols, procedures, and guidelines (“standardized frameworks”); (ii) conducting country assessments and evaluating the establishment and performance of surveillance institutions for addressing AMR; (iii) developing protocols to facilitate and support the regional use of laboratories and other public health assets (“supportive protocols”); (iv) adapting regional protocols, frameworks, standards, and guidelines for addressing AMR to promote their adoption at the national level; (v) strengthening technical working groups; (vi) convening an annual conference on AMR surveillance and containment; and (vii) developing and disseminating multisectoral preparedness and response plans. Infection prevention and control in health care facilities. This component will finance an assessment of infection prevention and control needs in selected health care facilities. The assessment will cover the following areas: staffing needs, microbiology laboratory support, minor civil works that can improve ventilation and air flow, equipment needs, personal protective equipment and decontamination capabilities. Based on the assessment, the component will provide support to the Ministry of Health to develop national guidelines for all health care facilities, including guidelines for highly infectious patients with drug-resistant infections, and to develop and implement infection prevention and control programing in up to five health care facilities. At each of the facilities, the component will support the improved availability of isolation beds and IPC equipment and infrastructure at the point of care, training to support compliance with IPC measures, and audits and quarterly reporting on compliance with national guidelines on IPC practices. Prescribing guidelines. This component will support efforts to understand prescribing practices and design and implement stewardship programs to prompt a shift in prescribing toward rational prescription in health care facilities. These efforts will be based on an assessment of resistance patterns and clinical syndromes for institutions that do not have guidelines. It will finance equipment to enable the monitoring of antimicrobial use and support the Ministry of Health in conducting an assessment of key areas of irrational prescribing; based on this assessment, it will support the development of updated national prescribing guidelines for antimicrobials. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 152 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The stewardship program will focus on secondary/tertiary hospitals and will provide equipment to identify patterns of disease and resistance at each hospital and will provide support during regular ward rounds. It will also support prescription audits and monitoring, health worker training and prescribing consultations, a training program for managerial staff, and a pilot program to reduce surgical site infections in tertiary hospitals through a stewardship program on rational prophylaxis and treatment. Finally, the component will finance the procurement of information technology hardware and software to provide rapid, updated information and guidance on prescribing based on observed symptoms and basic patient medical information. Public awareness. This component will finance qualitative and quantitative assessments of patient and health worker beliefs about the appropriate use of antimicrobials in human health, and the assessments will consider socioeconomic factors, such as gender. The component will also finance technical assistance to support the design of a public awareness campaign, targeted at the community and health facility level, to change inaccurate beliefs about the use of antimicrobials . To support improvements in awareness at the community level, a classroom module will be developed for dissemination in schools and will be supported by a train-the-trainer teaching module, which will be developed in conjunction with behavior change experts. To target adult populations, the component will also support the development of a radio and billboard campaign highlighting the importance of prudent antimicrobial use and the consequences of irrational antimicrobial use. For the health facility level, public awareness campaigns will include posters, informational sessions, and health worker training. The component will also support dissemination through social media and religious platforms. Surveillance networks. This component will support the establishment of fit-for-purpose laboratories, transnational surveillance networks, rapid response mechanisms, and other health assets designed to manage AMR risks on a regional or continental scale. This will include the creation and integration of regional surveillance networks, including the creation of an integrated electronic network of regional surveillance platforms. The component will provide financing for (i) the development of a unified IT platform and infrastructure; (ii) technical workshops on selected public health challenges; (iii) transportation and processing of samples for testing at affiliated laboratories; and (iv) the procurement of reagents and specialized materials for sample testing. The subcomponent will also provide technical assistance for the piloting and rollout of a regional AMR scorecard at the national level. Laboratories. This component will finance (i) the design, construction, equipping, furnishing, and setup of a biosafety level 3 (BSL-3) national reference laboratory, including the establishment of a proficiency testing system and panel production center, a laboratory equipment maintenance center, a biobank center, and a central warehouse; (ii) the construction and equipping of selected reference BSL-2 laboratories at selected locations; and (iii) the equipping of selected BSL-2 regional reference laboratories. These laboratories will become Centers of Excellence in AMR prevention, preparedness, and detection. This component will finance (i) the development and dissemination of AMR tools and policies; (ii) the expansion of a regional AMR scorecard pilot at local and national level; and (iii) capacity building for an AMR network. The data management center will serve as a regional and national hub for data sharing, disease surveillance and reporting, integrated data analysis, evidence translation, and database development. Electronic information systems. This component will finance (i) the design and development of an electronic information platform and database for AMR intelligence; (ii) the implementation of an electronic distribution list to rapidly disseminate guidance to public health officials and health care providers on emerging threats; (iii) the development and distribution of a periodic Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 153 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices report that provides detailed analysis of AMR trends; and (iv) the development of multimedia information products designed to increase public awareness of disease risks and recommended health practices. Workforce training. The component will support the development of a diverse and skilled cadre of public health workers to fulfill a complex mandate and to ensure that the public health assets described above are fully utilized. The component will finance activities in three key areas: (i) the establishment of partnership agreements with health education institutions to support the development and implementation of AMR training programs; (ii) technical assistance for establishing and operationalizing an AMR fellowship program to build critical skills among entry-level, mid-career, and senior technical staff; and (iii) development and delivery of training for AMR staff on critical skills related to laboratory systems (including occupational health and safety and environmental and social safeguards), disease surveillance, outbreak investigation, emergency response, data management, and risk communication. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 154 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Health sector approaches  PERFORMANCE-BASED CONDITIONS AND PRIOR ACTIONS National strategic planning, budgeting, coordination, monitoring, etc. for AMR management in health care facilities and settings: » Adoption of a comprehensive/costed National Action Plan (NAP) for AMR (note: several countries have NAPs, but some have not finalized the approval, updating, or costing of the plan; for these countries, the revision and adoption of the national response plan can be a disbursement linked indicator (DLI) or prior action) » Completion of a Joint External Evaluation (JEE) » Number of quarterly operational reviews to identify threats and mitigation related to the spread and emergence of AMR, conducted across health care facilities » Government budgetary actions for AMR detection and mitigation through (i) contingency appropriations; (ii) expenditure reprioritization through reallocations and virements; or (iii) supplementary budgets » National regulation/legislation 32 to support the detection and mitigation of AMR (supported by budgetary action) Risk communication, community engagement, and social mitigation: » Number of behavior change campaigns aimed at health care workers that address the drivers of AMR in community settings » Improvement in people’s knowledge, behaviors, and attitudes related to AMR (using simple phone surveys to assess baselines and improvements thereafter) » Development and adoption of a national strategy for managing highly infectious patients, i.e., with infections that are drug resistant (e.g., MDR-TB, C. difficile, Vancomycin-resistant Enterococci [VRE], and Carbapenem-resistant Enterobacteriaceae [CRE]) » Number of high-risk persons benefiting from shielding/isolation interventions » Number of health facilities receiving material support for conducting risk communications Surveillance and diagnostics: » Number of AMR surveillance and detection teams established in hospital/ regional settings » Number of sentinel sites established for the detection and surveillance of AMR » Data platforms established—One Health, laboratory information, antibiotic use » Number of laboratories with appropriate equipment and staff to detect the top-three resistant pathogens for the country/region 32  A range of agencies may set regulations relevant to antimicrobial production, sale, or use, such as those with oversight of clinical practice, food and drug safety, commerce, imports and manufacturing, or environmental management. Regulations may span a range of issues, such as licensing of new antimicrobials (or alternatives), prescriber qualification requirements versus over-the-counter sale of antimicrobials, limits on the types and amounts of antimicrobials that may be used for certain purposes (including agriculture and aquaculture), quality and labeling requirements, or withdrawal periods after use of medicines in animals before processing for food. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 155 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Infection prevention and control: » Development of IPC guidelines 33 at the national level, which are disseminated to [X] percent of national hospitals » Number of health workers 34 trained in IPC for AMR prevention » Number of facilities with IPC monitoring mechanism for AMR detection and prevention » Number of facilities with WASH facilities 33  Guidelines often include hand hygiene and other WASH interventions, use of personal protective equipment, surface cleaning, waste management, injection safety, limitations on invasive procedures and nonessential inpatient stays, and facility capacity limits to ensure sufficient patient spacing (WHO 2016). 34  Including infection preventionists, who help to maintain a focus on IPC in health care facilities. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 156 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agricultural and food sector approaches  COMPONENTS Strengthening oversight and monitoring of antimicrobial use in livestock settings. This component will finance the development of prudent use guidelines for different audiences (government officials, professional associations, and facility-level actors). It will also provide support to the government, in particular the government’s ability to design and implement enforcement mechanisms, by financing equipment, infrastructure, and training to enable better oversight of AMU in selected settings and promote compliance with prudent use guidelines, such as the restricted use of antimicrobials in food-producing animals. In selected regions, where AMU oversight is weak, the component will finance a package of interventions designed to improve use and oversight. This will include equipment, training, and materials for increased vaccination and use of non-antibiotic feed additives. There will also be a pilot residue-monitoring program to assess compliance with and uptake of the package of interventions. Strengthening AMU and AMR monitoring in crop production. This component will support the government in establishing an initial infrastructure network to measure AMU and AMR in crop production. It will finance the equipment and materials to establish sentinel sites where crops can be screened for antimicrobial use. Monitoring of sales and use of antimicrobials in livestock settings. This component will support regulatory agencies in developing systems and infrastructure to better track the sale and use of antimicrobials in terms of class, volume, purpose, setting, and≈dosing to improve understanding of current practices, guide targeted interventions, and detect changes over time. It will provide equipment and training to collect, assess, and record data from samples of diseased animals, which will be screened for resistance at the national state veterinary diagnostic library. It will also support the government in complying with international regulations and initiatives and will enable pairing of resistance and consumption data in support of epidemiological analyses seeking to understand disease patterns. Assessments to support the development of behavior change campaigns. This component will finance interventions to support the government in efforts to improve understanding and rational use of antimicrobials among farmers, veterinarians, and paraveterinarians. It will finance qualitative and quantitative assessments that will be used to understand existing perspectives and to inform the approach to messaging and awareness campaigns, which will be disseminated through mass media channels. Early detection of disease outbreaks and laboratory confirmation of the etiologic agents/ pathogens. This component will support enhancement of national surveillance and reporting systems and their interoperability at the different tiers of the health systems, cross-border coordination in the surveillance of priority pathogens and diseases, and timely reporting of human public health and animal health emergencies in line with the International Health Regulations (IHR) 2005 and the WOAH Terrestrial Animal Health Code. This component will strengthen the linkages of surveillance and response processes at all levels of the health system. It will identify and/or establish networks of efficient, high-quality, accessible public health and veterinary laboratories and will also support the establishment of a regional networking platform to improve collaboration for laboratory investigations. It will contribute toward strengthening the capacities of national veterinary and public health laboratories in the areas of surveillance, pathology, diagnosis of priority infectious disease pathogens, and AMR. The four subcomponents of this component are (i) national and subnational surveillance system; (ii) health information and reporting systems; (iii) laboratory diagnosis capacity; and (iv) supply chain management systems. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 157 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Integrated disease surveillance infrastructure for cross-sectoral interoperability of surveillance and reporting systems at the country and regional level. This component will support investments in renovating and upgrading existing facilities, ensuring adequate supplies, and strengthening supply chain management. Networking of laboratories will be supported for (i) sharing of timely information across countries; and (ii) contributing to joint investigations of disease outbreaks. Networks will ensure improved capacity to diagnose diseases, identify public health threats, and conduct surveillance. Networks will also serve as effective platforms for learning and knowledge sharing. The component will support strengthening of specimen management, in part by (i) streamlining the laboratory specimen referral process, including through use of subnational laboratories rather than a central laboratory, where possible; and (ii) improving efficiency of specimen transport and disposal systems, including through use of private sector partnerships. Workforce development and incentives. This component is cross-cutting and aims to strengthen government capacity to plan, implement, and monitor human resource interventions. It will provide support to the development of institutional capacity for workforce training by leveraging existing training structures and programs in the region and other workforce training programs that address critical human/veterinary health needs. It will support analysis to improve the incentive environment within which public health and veterinary health workers operate. This analysis will consider creating incentives that seek to draw those with relevant skills into the public sector and also improve staff motivation and retention, considering gender differences within the health workforce. Viable options will be explored under this component to ensure a centrally coordinated and efficient process for retaining a skilled workforce (in both animal and human health) that is available for routine surveillance and rapid deployment for case detection, laboratory confirmation of suspected cases, vaccine distribution logistics, and delivery of primary health care for common illnesses as part of outbreak response. Strengthening capacity of national veterinary services. This component strengthens the capacity of national veterinary services to perform their core public good mandate (primarily to prevent and control contagious animal diseases), thereby benefiting all herders and especially pastoralists and agropastoralists. The component will (i) support veterinary services workforce development by regularly updating training plans based on identified gaps in human resources, helping to implement training plans by sponsoring veterinary masters and doctoral degrees and continuing education programs, and establishing private veterinary clinics to provide animal health care services in strategic areas; (ii) support construction or upgrade of essential infrastructure and equipment for veterinary services; field veterinary units or pharmacies, border inspection posts, and vaccination pens; and provide critical equipment; and (iii) improve the management of staff, material resources, disease information, and data collection and analysis by strengthening and maintaining digital databases and tools. Support to harmonized surveillance and control of priority contagious animal diseases. This component will support (i) the regular updating of National Strategic Plans against these diseases, in line with global and regional strategies and based on respective national capacities and financing available; (ii) the cofinancing of nationwide mass vaccination campaigns, surveillance programs, and necessary equipment needed to reach the highest possible level of protection against priority diseases in the livestock population (based on disease National Strategic Plans); (iii) surveillance and capacity-building programs for other important transboundary animal diseases, including climate-sensitive and zoonotic diseases such as Rift Valley fever and foot and mouth disease; and (iv) laboratory capacity strengthening for the testing and treatment of contagious animal diseases. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 158 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Support to control veterinary medicines. To help address growing concerns over the misuse of veterinary medical products (VMPs), particularly antimicrobials, which have wide negative impacts on animal and human health and economies, this component will (i) support the development or improvement and initial implementation of a National Strategic Plan on VMPs, as well as a National Action Plan on AMR, consistent with the global WHO/FAO/WOAH strategy; (ii) help to finance the implementation of surveillance and monitoring plans to ensure the quality of VMPs and reduce antimicrobial resistance (in slaughterhouses, marketplaces, and farms), and (iii) establish more regular inspection campaigns to reduce illegal sales of VMPs, which are virtually unchecked. These plans will include extensive communication activities to increase awareness of these issues in the general population (herders in particular). Improving livestock producers’ access to animal health services. The component will build on the results from the WOAH evaluation under the Performance of Veterinary Services (PVS) Pathway to enhance the long-term capacity of the country to sustainably reduce livestock mortality and other losses caused by animal diseases, thereby increasing livestock productivity and reducing inappropriate reliance on and misuse of antimicrobials. It will improve farmers’ access to efficient animal health services provided by both public and private veterinary services under their respective responsibilities (including the “sanitary mandate” for private veterinarians). The component will finance (i) vaccine purchase and delivery as well as vaccination campaigns; (ii) the implementation of a mass communication and sensitization campaign to reach all targeted beneficiaries; (iii) studies on disease prevalence through the National Livestock Laboratory; (iv) rehabilitation of one regional laboratory; (v) strengthening of the National Livestock Laboratory’s capacity to assess and advise on AMR and drugs residues; (vi) technical assistance to the General Directorate of Veterinary Services to develop or update animal disease control strategies for dissemination to field veterinarians (prioritizing foot and mouth disease, Newcastle disease, fowl pox, sheep and goat plague (PPR), and contagious bovine pleuropneumonia); and (vii) strengthening of national veterinary services, specifically of surveillance systems, to ensure early reporting, notification, and effective response to disease outbreaks. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 159 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Agricultural and food sector approaches  PERFORMANCE-BASED CONDITIONS AND PRIOR ACTIONS National strategic planning, budgeting, coordination, monitoring, etc. for AMR management in health care facilities and settings: » Adoption of a multisectoral comprehensive/costed NAP for AMR (note: several countries have NAPs, but some have not finalized the approval, updating, or costing of the plan; for these countries, the revision and adoption of the national response plan can be a disbursement linked indicator (DLI) or prior action) » Completion of a PVS evaluation » Number of quarterly operational reviews to identify threats and mitigations related to the spread and emergence of AMR, conducted across network of agriculture sentinel sites » Government budgetary actions for AMR detection and mitigation through (i) contingency appropriations; (ii) expenditure reprioritization through reallocations and virements; or (iii) supplementary budgets » National regulation/legislation to support the detection and mitigation of AMR (supported by budgetary action), including phasing out of nontherapeutic use of antimicrobials, and banning the use of the highest priority/critically important antimicrobials in animal and plant health Risk communication, community engagement, and social mitigation: » Number of behavior change campaigns aimed at agricultural producers/workers that address the drivers of AMR in community settings » Improvement in people’s knowledge, behaviors, and attitudes related to AMR (using simple phone surveys) » Development and adoption of a national strategy for managing antibiotic-resistant bacterial diseases in agriculture and aquaculture » Number of agriculture advisory offices/programs receiving material support for conducting risk communications Surveillance and diagnostics: » Number of agriculture AMR surveillance and detection teams established in regional settings » Number of sentinel sites established for the detection and surveillance of AMR » Number of laboratories with appropriate equipment and staff to detect the top resistant pathogens that pose potential threats to people Infection prevention and control: » Development of IPC guidelines at the national level, which are disseminated to [X] percent of agricultural producers » Number of agricultural health workers trained in IPC for AMR prevention » Number of facilities with IPC monitoring mechanism for AMR detection and prevention » Number of facilities with WASH facilities Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 160 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector approaches  COMPONENTS Strengthening water and sanitation infrastructure for health emergency preparedness and response. This component will support preparedness, response, and recovery related to health and disease threats by focusing targeted investments in WASH facilities and waste management in public institutions such as schools and health care facilities and in public places such as markets, transport hubs, etc. It will finance assessments to understand gaps in existing infrastructure, civil works, and renovations so that existing infrastructure can be upgraded in compliance with an appropriate standard and that annual audits can ensure that infrastructure is properly maintained. Strengthening water, sanitation, and hygiene in health care facilities. This component will support improved infrastructure and the provision of equipment in health care facilities. It will finance interventions to ensure access to minimum water supply, sanitation, and hygiene standards through construction or rehabilitation of infrastructure and efforts to ensure continuity of services. The component will provide equipment and supplies (including water containers) as well as water service (where it does not currently exist) utilizing trucks or carts for water delivery (small containers, sachets, or other pre-packaged water) and water tankers (including adequate water storage for service operators). It will also provide basic sanitation, including construction of latrine blocks equipped with handwashing facilities and a cabin dedicated to hygienic menstrual management in health care facilities. Finally, it will provide support to strengthen medical waste management and disposal systems, including the purchase of an incinerator and training for health care workers and staff on risk communication, proper handwashing, and hygiene and waste management practices for IPC, with dedicated training modules on the safe disposal of antimicrobials. It will also finance the purchase of alcohol-based hand rubs, relevant cleaning and disinfectant materials, sanitation supplies, and IPC/ WASH kits. Strengthening water, sanitation, and hygiene in health care facilities for patients and health care workers with disabilities. This component will support infrastructure investments for the construction, upgrading, and rehabilitation of water, sanitation, and hygiene facilities in health care facilities as per standard guidelines, with special considerations for gender, disability, inclusion, and climate change adaptation in design of WASH facilities. This component will ensure (i) water supply within the compound of the facility; (ii) improved sanitation facilities that are usable with at least one toilet dedicated for staff, at least one sex-separated toilet, and at least one toilet accessible for people with limited mobility; (iii) functional handwashing facility, with water and soap or alcohol-based hand rubs available at point of care and within five meters of toilets, and with appropriate accommodations for patients with disabilities; (iv) health care waste management facilities for safe treatment and disposal of sharp and infectious waste (incinerator, placenta pit, waste disposal pit), (v) water treatment and safe water storage; and (vi) promotion of hygienic practices in health facilities. Additionally, this component will focus on capacity building through technical assistance to support creation of operation and maintenance plans for constructed facilities as well as development of sanitation service chains. It will also provide capacity building and training to personnel and health care workers and seek the harmonization of WASH information systems across all key participating institutions. Finally, this component will provide support in procurement and contract management for proposed infrastructure to address substandard construction quality. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 161 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Strengthening water, sanitation, and hygiene infrastructure in community settings during emergencies and for vulnerable populations. This component will support (i) provision of safe water, targeting the most vulnerable (elderly, refugees/internally displaced people); (ii) promotion of the existing electronic payment systems for water bills to reduce risks of disease transmission; (iii) provision of water and basic supplies (such as soap, personal hygiene products, and other toiletries) to vulnerable people and families; and (iv) emergency support to water supply and sanitation utilities to ensure continuity of water supplies. The component will also support civic authorities in strengthening the availability of WASH stations in business areas and areas of public need such as stations, libraries, and markets; and it will support strategies and partnerships with the private sector to incentivize increased production and provision of hygiene materials. Strengthening water, sanitation, and hygiene infrastructure in schools. The activity will support schools with essential measures to ensure the safety of pupils, including (i) provision of low-cost water, sanitation, and hygiene equipment, such as water tankers and portable handwashing stations, at all public primary and secondary schools; (ii) provision of hygiene kits, disinfectants, and sanitizers; and (iii) support for school infirmaries, including training on good hygiene practices and prevention measures for infirmary staff. Strengthening water, sanitation, and hygiene in schools for children and educational staff with disabilities. This component supports infrastructure investments to support the construction, upgrading, and rehabilitation of WASH facilities in schools as per standard guidelines, with special consideration for gender, disability, inclusion, and climate change adaptation in design of WASH facilities. The project will support the construction of toilets in schools in the project area and will coordinate with Ministry of Education to ensure proper maintenance of facilities in schools. School toilets will consist of separate facilities for students: males (one urinal and one toilet for 70 boys) and females (one toilet per 35 to 40 girls and features to support menstrual hygiene management), and separate facilities for teachers. Unlined pit latrines in schools will be converted to energy-efficient dry latrines with regular sludge removal for reuse as fertilizer, thereby contributing to greenhouse gas emission reduction and improving latrine emptying and waste containment and management. Running water will be made available in the toilet, together with handwashing facilities with soap. This component will focus on capacity building through technical assistance to support creation of long-term operation and maintenance plans to finance and maintain WASH services. It will also provide capacity building and training to personnel and teachers and seek the harmonization of WASH information systems across all key participating institutions. Finally, this component will provide support in procurement and contract management for proposed infrastructure to address substandard construction quality. Community engagement and risk communication. This component will finance a comprehensive behavior change and risk communication intervention by working with private, public, and civil society actors to develop messaging and materials. This component will finance (i) the development of reporting tools; (ii) training for community health workers and volunteers; (iii) the development and testing of messages and materials; and (iv) activities related to the identification and advocacy of key influencers (i.e., religious leaders, celebrities, etc.). Construction and rehabilitation of WASH facilities and handwashing stations in schools, health facilities, and public places. This component supports increasing access to water supply, sanitation, hygiene, and waste management services for schools, health centers, and other public spaces. The activities to be financed include a full inventory of existing schools and health centers and their current WASH service levels, as well as construction and/or rehabilitation of WASH facilities. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 162 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Construction and rehabilitation of WASH facilities in agricultural and fisheries/aquaculture settings. This component will ensure proper WASH infrastructure and practices are in place aboard fishing vessels, landing sites, aquaculture operations, processing plants, and markets so as to protect fish health, provide safe fish and fish products, and reduce the spread of AMR. This component will include provision of safe water supply by ensuring that fisheries and aquaculture workers have access to potable water for drinking, and that water used for ice production is potable water or purified seawater. It will also provide improved sanitation by ensuring access to improved sanitation facilities, with separate facilities for women and girls that are affixed with a lock on the inside and are regularly cleaned, disinfected, and in good working order. Sanitation facilities will also include disposal containers for menstrual management materials, and soap and water for washing. Finally, the component will ensure that (i) a cleaning and disinfection protocol is available and implemented, with materials for cleaning and disinfection available, (ii) handwashing facilities with access to soap and water are available, and staff are trained on procedures for personal hygiene; and (iii) there is proper treatment and management of waste and wastewater. Strengthening water, sanitation, and hygiene in agricultural settings. This component will ensure that farm owners and workers have adequate access to WASH services with special consideration given to gender, disability, inclusion, and climate change adaptation in design of WASH services. This will include support for (i) clean water; (ii) improved sanitation to reduce the occurrence of open defecation, which includes separate sanitation facilities for women and girls; (iii) handwashing facilities with soap and promotion of good hygiene behaviors to support workers’ health, well-being, and productivity; (iv) provision of sanitary and disinfection material; (v) pest prevention and control; and (vi) agricultural wastewater treatment to control pollution from confined animal operations and from surface runoff that may be contaminated by chemicals in fertilizer, pesticides, animal slurry, crop residues, or irrigation water. Sewerage and wastewater treatment. This component includes activities related to institutional support for sanitation service delivery, alternative sanitation technologies, construction of fecal sludge treatment plants, and more effective wastewater treatment. The objective of this component is to improve wastewater collection and treatment in the project areas and finance all infrastructure works related to wastewater collection and treatment. The component will develop a comprehensive response to the on-site sanitation challenges and support on-site sanitation services and systems in priority areas. In areas where sewers are not feasible or where there are tenurial barriers, such as in low-income settlements, this component will provide alternative sanitation services, including (i) improved sanitation and septage management through upgrading of unimproved toilets in poor households; (ii) construction of a number of Decentralized Wastewater Treatment Systems (DEWATS); (iii) communal septic tanks; (iv) provision of septage services (emptying, transport, and treatment, including leasing of emptying and transport equipment from private operators and a support fund for on-site sanitation facilities); (v) support for the development of fecal sludge management infrastructure and service providers; and (vi) sanitation marketing and hygiene promotion to influence sanitation behaviors. This component will also support capacity building of the water and sewerage utility, including its capacity to respond to climate risks and related impacts and contribute to climate change adaptation actions; this aspect strengthens the social compact between the utility and its users, reduces barriers to the use of communal sanitation facilities among women and girls in tandem with establishing on-site sanitation, increases billing and collection, and supports potential national water sanitation and supply reform initiatives. In addition, disaster planning and response for water and wastewater infrastructure and services will be strengthened through the elaboration of emergency preparedness plans. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 163 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Sewerage and wastewater treatment investments to specifically address AMR. This component will establish a national program to improve water, sanitation, and hygiene issues with the focus on improving approaches to addressing AMR, through the following subcomponents: » Assessments of the need for on-site and sewered solutions. This subcomponent will finance a national assessment of context-specific, geographical, and social and economic conditions in high-priority locations and sites for sewered and on- site solutions, to determine the urgency and feasibility of potential investments to address AMR. » On-site sanitation solutions. This subcomponent will finance on-site sanitation interventions in areas where open defecation rates and access gaps are still high and will provide equipment and infrastructure to increase access to toilets and on- site sanitation. It will also finance septic tanks and systems for the effective removal, transport, and treatment of waste. » Sewerage networks. This subcomponent will finance improved connections to existing sewerage networks and to effective treatment in wastewater treatment plans, with primary/secondary/tertiary/advanced treatment levels. 35 » Last-mile sludge treatment and disinfection. To address trace levels of antimicrobials and evidence of resistant bacteria in treated sewage sludge, this subcomponent will finance assessments to determine approaches to the highest-risk areas, once safely managed sanitation is achieved, and will then finance equipment and infrastructure investments to support disinfection to remove trace antimicrobials. » Wastewater treatment for highest-risk areas. This subcomponent will finance advanced treatment solutions for critical municipal wastewater treatment plans and pretreatment solutions for hospitals or antibiotic manufacturing facilities. » Surveillance. This subcomponent will support surveillance and monitoring of AMR and antimicrobial-resistant gene (ARG) levels at sentinel sites to support the government in identifying the effectiveness of sanitation solutions and the need for adjustments. Nature-based solutions for wastewater treatment. This component supports a range of nature-based solutions, including conventional and high-end constructed wetlands, 36 river re-naturalization, and restoration of wetlands that provide secondary/tertiary treatment of wastewater, enabling removal of contaminants and leading to dispersal of AMR in the environment. Hygiene behavior change. This component will finance behavior change and communication campaigns at the community level and for farming and aquaculture workers. » Behavior change and communication in communities. This subcomponent will finance a comprehensive behavior change intervention in communities by working with private, public, and civil society actors to support the development of information, education, 35  Wastewater treatment plants are effective at eliminating many pathogens, but they are not typically designed to remove antimicrobial residues or resistant organisms, and so, task and client teams will need to discuss the resulting trade-off—that is to weigh the goal of reducing AMR contaminants (urgency) against the goal of ensuring affordable operating and management costs (feasibility). The higher the goal of removing AMR contaminants, the higher will be the costs and the need for specialized operators. 36  Constructed wetlands can efficiently remove aqueous ARGs, but there is also a risk that they can act as reservoirs for specific ARGs. There is evidence that some ARGs can accumulate in constructed wetland sediments, which can then later be released from sediments to water. In some settings, this type of intervention will be better than no treatment, but evaluating the specifics of the intervention in the proposed setting will be important for the relevant task and client teams. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 164 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices and communication (IEC) messaging and materials. This will include (i) nationwide campaigns promoting and marketing handwashing, through various communication channels such as mass media and social media; (ii) information and communication activities to increase the attention and commitment of government, private sector, civil society, community leaders, and religious leaders, and to increase awareness, knowledge, and understanding among the general population; and (iii) development of reporting tools. » Hygiene and behavior change in farming and aquaculture workers. This component will finance a comprehensive behavior change intervention in fishing vessels, landing sites, aquaculture operations, processing plants, markets, and fishing communities. The component will promote hygiene behaviors through campaigns, short workshops, and IEC materials. Workshops will be conducted on seafood hazards and on fishery product quality and quality measurement, contamination, and waste management, and will include good hygiene practice requirements for washing, cleaning, handling, and storing fish. Workshops will be supplemented by campaigns and IEC material on personal hygiene, handwashing, and menstrual health and hygiene. » Hygiene and behavior change in agriculture. This component will finance a comprehensive behavior change intervention in farms and agricultural communities. It will support the development of IEC messaging and materials. Trainings will be conducted on basic cleaning and disinfection, isolating animals to prevent spread of infectious germs, pest prevention and control, and waste management and disposal. This will be supplemented by campaigns and IEC material on personal hygiene, handwashing, and menstrual health and hygiene. Strengthening AMR surveillance and monitoring in wastewater systems. This component will build local capacity to perform wastewater testing for AMR. The main activities will focus on building capacity for sample analysis, improving data management, and building capacity for surveillance. This component will include the following subcomponents: » Providing support to water and sanitation utilities to implement routine surveillance, detection, and reporting of AMR » Strengthening laboratory capacity to perform wastewater testing; establishing networks of efficient, high-quality, accessible public health, veterinary, and private laboratories for the diagnosis of AMR and infectious human and animal diseases; and establishing a regional networking platform to improve collaboration for laboratory investigation » Improving data management by (i) strengthening the competencies of laboratory personnel to analyze and use laboratory surveillance data; (ii) strengthening laboratory data management systems to report more effectively; and (iii) achieving interoperability between data management systems, where possible » Training and capacity building, including training to develop human resource capacity in surveillance, preparedness, and response Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 165 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector approaches  PERFORMANCE-BASED CONDITIONS AND PRIOR ACTIONS Risk communication, community engagement, and social mitigation: » Number of (district/community level) WASH officers trained on the drivers of AMR in community settings » Number of people reached with hygiene behavior change campaigns for IPC Surveillance and diagnostics: » Number of wastewater treatment plants implementing routine surveillance, detection, and reporting of AMR » Number of water utilities implementing routine surveillance, detection, and reporting of AMR » Reporting mechanism for AMR in water and sanitation systems established and in use Infection prevention and control: » National program on water supply and sanitation developed to improve access to water supply, sanitation, and hygiene in communities, schools, and health care facilities » National hygiene awareness and behavior change campaign developed » Number of people provided with access to improved water supply, sanitation, and handwashing facilities under the project » Number of health care facilities with functioning water, sanitation, hygiene, and waste management services » Development of medical waste management and disposal guidelines at the national level, which are disseminated to [X] percent of health care facilities/water and sanitation utilities » Issuance of regulations/legislation on treatment requirements, including disinfection for public water systems that prevent pathogens from contaminating drinking water and wastewater » Issuance of regulations/legislation on treatment and disposal of sewage and wastewater to mitigate spread of AMR References WHO (World Health Organization). 2016. Guidelines on Core Components of Infection Prevention and Control Programmes at the National and Acute Health Care Facility Level. Geneva: World Health Organization. Guidelines on core components of infection prevention and control programmes at the national and acute health care facility level (who.int). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 166 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 5 Implementation Guidance for Investing in Interventions to Address AMR through World Bank Operations Summary 168 CHEVRON- Introduction 169 CHEVRON- National institutional arrangements 171 CHEVRON- Regional institutional arrangements 174 CHEVRON- Takeaways 178 CHEVRON- References 179 CHEVRON- Three implementation case studies 180 CHEVRON- Case Study 1: Indonesia 180 CHEVRON- Case Study 2: Tanzania 192 CHEVRON- Case Study 3: Nigeria 202 CHEVRON- Early and detailed attention to implementation arrangements is beneficial for the success of interventions to address AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 167 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 5 Implementation Guidance for Investing in Interventions to Address AMR through World Bank Operations Chapter 5 summary Early and detailed attention to implementation arrangements is beneficial for the success of interventions to address antimicrobial resistance (AMR), and this two-part chapter draws on World Bank operations and other projects and country experiences. Implementing interventions to address AMR can be challenging, not least because they can involve collaboration across multiple organizations and sectors. The first part of this chapter draws on experiences from World Bank operations within and across sectors to provide examples of different implementation arrangements that task teams and countries can adopt. The second part goes beyond the World Bank’s engagement through three country case studies, which explore successes and challenges in addressing the AMR agenda in Indonesia, Tanzania, and Nigeria. As of 2023, the World Bank had more than 60 operations addressing AMR, and these provide a range of experiences to support the design and implementation of new operations. Many projects have strengthened national coordination bodies, which allow for multiple agencies—within a sector and across sectors—to be informed and have a stake in a project’s success. Identifying senior advocates and high-level supporters from presidential and prime ministerial offices has also benefited implementation, by ensuring that the AMR agenda is elevated and prioritized, and by providing neutrality between ministries. In addition, given that AMR is not confined by geographical boundaries, projects have drawn on regional mechanisms, both to support technical delivery and to receive and coordinate financing and project management. The three case studies in the second part of the chapter exemplify multisectoral and single-sector implementation initiatives using a One Health approach to build AMR surveillance and laboratory capacity. They likewise offer important examples for AMR stakeholders. Indonesia has adopted an AMR National Action Plan (NAP) and is collaborating with international organizations to strengthen its surveillance and laboratory capacity, though it still faces challenges such as lack of coordinated multisector working groups and limited laboratory capacity and expertise. In Tanzania, the AfyaData project, which includes an app for data collection, a web-based server for mapping and analysis, and a disease-prediction and decision-making repository, has been successful in building community-led AMR surveillance capacity. Despite facing various challenges, Nigeria is implementing a national AMR surveillance network, leveraging partnerships and international collaborations, involving multiple sectors, and utilizing community-led surveillance to generate real-time data on AMR. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 168 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction Mechanisms can be adopted to support regional and national coordination of efforts to address AMR; such coordination helps ensure that initiatives benefit from strong technical guidance and that implementation approaches draw together relevant parties. Institutional and implementation setups for addressing AMR vary across diverse regional and national environments, but a common challenge concerns the level of coordination required (Box 5). To help address this, client and task teams have drawn on several mechanisms to support coordination at the regional and national levels. This chapter provides examples from World Bank operations implementing AMR-sensitive interventions—the Regional Sahel Pastoralism Support Project (PRAPS), the East Africa Public Health Laboratory Networking Project, the Africa Centres for Disease Control and Prevention (CDC) Regional Investment Financing Project, and the Regional Disease Surveillance Systems Enhancement (REDISSE) project (Phases 1–4)—and draws on key themes and guidance from previous and current task team leaders. Box 5. Common Challenges for Multisectoral Implementation on AMR Diversity of stakeholders: Multisectoral collaboration involves bringing together stakeholders from various sectors, such as health care, agriculture, veterinary, environmental, and policy making. Coordinating and aligning their interests and priorities can be complex. Fragmentation: Different sectors may have their own strategies, policies, and regulations regarding AMR. Overcoming fragmentation and establishing cohesive approaches can be challenging. Communication and language barriers: Experts from different sectors may use jargon and language specific to their field, making communication difficult. Effective communication and understanding between sectors are crucial for success. Power imbalance: Certain sectors may have more influence or resources than others, leading to power imbalances that can hinder effective collaboration and decision-making. Conflicting priorities: Each sector may have its own pressing issues and priorities, which could compete with AMR initiatives for attention and resources. Policy and regulatory differences: Sectors might have different regulatory frameworks and policies that can create conflicts when implementing joint strategies to combat AMR. Data sharing and privacy concerns: Sharing data across sectors is vital for a holistic understanding of AMR, but concerns over data privacy and confidentiality can hinder cooperation. Resource constraints: Some sectors, especially in low- and middle-income countries (LMICs), may lack adequate resources, infrastructure, and capacity to actively participate in multisectoral efforts. Resistance to change: Adapting to new ways of working and collaborating can be met with resistance from institutions accustomed to working within their sector’s boundaries. Accountability and responsibility: Determining responsibility and accountability in a multisectoral setting can be challenging when issues arise or when measuring the impact of interventions. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 169 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Time and coordination: Multisectoral efforts require substantial time and effort to coordinate and align strategies, which may slow down decision-making and implementation. Monitoring and evaluation: Establishing common monitoring and evaluation frameworks to assess the impact of multisectoral interventions can be complex, especially given the diverse nature of involved sectors. Political will and leadership: Multisectoral efforts often require strong political will and leadership at the highest levels to overcome challenges and ensure sustained commitment. Long-term sustainability: Ensuring the continuity of multisectoral collaboration beyond short-term initiatives is crucial for effectively combating AMR over time. Source: Joshi et al 2021. For multicounty operations, project design has often drawn on guidance from the Independent Evaluation Group (IEG). According to current and previous task team leaders, important project enablers include drawing on and strengthening existing implementation structures and clearly defining roles and responsibilities. To facilitate project success, the IEG advises that projects rely on “national institutions for execution and implementation of program interventions at the country level, and on regional institutions for supportive services that cannot be performed efficiently by national agencies, such as coordination, data gathering, technical assistance, dispute resolution, and monitoring and evaluation” (IEG 2007, 34). This guidance is reflected in implementation experience across projects, and task team leaders have noted that multisectoral efforts were much more likely to achieve their aims if implementation arrangements were anchored in existing structures. Similarly, soliciting leadership from existing networks or mechanisms is more likely to result in sustained action. Many project examples also demonstrate that clearly defining institutional roles and responsibilities within projects has helped participating institutions to understand how project activities interact with their own mandates as well as other regional and national development priorities. Many projects have also used Memoranda of Understanding (MoUs), terms of reference, and technical and subsidiary agreements to provide entities with clear expectations when embarking on shared agendas. MoUs can help ensure that all parties rely on the established conditions to cooperate effectively, provide any agreed financial or human resources, and share information. Projects have shown that these agreements are useful for setting out an agreed approach for cooperation on research, implementation, and stakeholder engagement, as well as for establishing a regular, efficient flow of data and data analysis. For multicountry projects, these agreements have typically been drawn up between the regional-level agencies and participating countries, as well as between stakeholders at the national level. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 170 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices National institutional arrangements National coordination mechanisms can be helpful for enabling collaboration within and across sectors. The Regional Sahel Pastoralism Support Project, for example, draws on multiple national coordination mechanisms. It provides US$248 million in financing across five components: (i) animal health improvement, (ii) natural resource management enhancement, (iii) market access facilitation, (iv) pastoral crisis management, and (v) project management and institutional support. At the national level, PRAPS has several institutional arrangements, including National Steering Committees (NSCs) and Technical Committees (TCs), National Project Coordination Units (N-PCUs), and Results Monitoring and Evaluation Arrangements. Each participating country has established an NSC and TC to serve as monitoring bodies for exchange, guidance, and implementation. Relevant line ministries (particularly those aligned with the livestock agenda of the country) participate in the NSC/TC; they advise on strategic planning and implementation and engage in supervision at the national level. N-PCUs have been established within selected ministries in each country to support the implementation of project activities, and the Committee for Drought Control in the Sahel (CILSS) is responsible for coordinating the monitoring and evaluation (M&E) function. Box 6 provides further details. Box 6. Regional Sahel Pastoralism Support Project Regional Sahel Pastoralism Support Project Project overview Sahel Belt The Regional Sahel Pastoralism Support Project is a multifunctional initiative to strengthen the resilience of pastoralists in the Sahel. With a focus on productivity improvements and the sustainability and resilience of assets for pastoral existence, PRAPS has brought together the private sector, pastoral organizations, advanced research institutes, and national, regional, and international stakeholders to collaborate on a range of coordinated solutions. Since 2014, the project has been implemented in the six countries of the western Sahel belt (Burkina Faso, Chad, Mali, Mauritania, Niger, and Senegal). Program implementation for PRAPS is coordinated regionally by the Permanent Interstate Committee for Drought Control in the Sahel (CILSS), under the political leadership of the Economic Community of West African States (ECOWAS) and the West African Economic and Monetary Union (WAEMU). Through its project oversight and coordinating role, CILSS has responsibility for executing strategic decisions to ensure the continued coherence between the program support priorities and sector development and regional pastoralism development priorities. Overview of institutional arrangements • Regional Steering Committee (RSC). A Regional Steering Committee was established to replace the project’s initial Regional Task Force on Pastoralism. The RSC is in charge of coordinating and facilitating cross-boundary interventions; it provides a platform for technical assistance, M&E, training, knowledge sharing, and communication, and it supports policy dialogue with countries for regional alignment and harmonization. The RSC comprises representatives of technical ministries, civil society organizations, and the CILSS. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 171 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices • National Steering Committees and Technical Committees. Each participating country has established an NSC and a TC to serve as bodies for exchange, guidance, and implementation monitoring. Relevant line ministries (particularly those aligned with the livestock agenda of the country) participate in the NSC/TC, advise on strategic planning and implementation, and engage in supervision at the national level. • National Project Coordination Units. In each country, N-PCUs have been established within selected ministries to support implementation of project activities. N-PCUs also have responsibility for implementation supervision, proposal preparation, project financial management and procurement, M&E, and reporting. • Results monitoring and evaluation arrangements. Monitoring and evaluation for PRAPS is structured to take place at both the regional and country levels. The CILSS has the overall responsibility for coordinating the M&E function, including the design and implementation of data collection efforts and a data quality assurance mechanism, the review of evaluation and progress reports from participating countries, and facilitation of cross-country learning. At the national level, countries produce monitoring data against established targets, generate information on project progress, and document and disseminate key lessons. Source: World Bank 2015. The East Africa Public Health Laboratory Networking Project is another project that has drawn on national and regional mechanisms. It provides US$113.66 million in financing through three components: (i) laboratory networking for specialized diagnostic services and disease surveillance preparedness; (ii) training and regional capacity building to undertake specialized tests to diagnose tuberculosis (TB) and communicable diseases; and (iii) joint operational research and knowledge- sharing activities. It is implemented by the East, Central and Southern African Health Community (ECSA-HC), which is based in Arusha, Tanzania. ECSA-HC has overall responsibility for coordinating activities under the project; at the country level, the responsible entity is the Burundi Ministry of Public Health. Additional institutional arrangements include the National Steering Committee, Project Management Unit, and Results Monitoring and Evaluation Arrangements, which aim to ensure effective implementation, oversight, and monitoring of the project. Box 7 provides further details. Box 7. East Africa Public Health Lab Networking Project: Burundi East Africa Public Health Lab Networking Project: Burundi Project overview The East Africa Public Health Lab Networking Project was established to support the development of a network of high-quality cross-country public health laboratories within East African Community member states to serve as surveillance sites to monitor disease transmission. Specifically, the laboratory network aims to enhance access to diagnostic services, contribute to disease surveillance, and serve as a platform for training, research, and knowledge sharing. One component of the project aims to strengthen capacities for the diagnosis and surveillance of TB and other communicable diseases. Burundi The East, Central and Southern African Health Community (ECSA), based in Arusha, has overall responsibility for coordinating activities under the project. At the country level, the Burundi Ministry of Public Health has responsibility for the project. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 172 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Overview of institutional arrangements • Regional Advisory Panel (RAP). ECSA-HC put in place a Regional Advisory Panel to serve as a platform for multicountry and multistakeholder expert engagement and dialogue. The RAP is a forum for the participating countries and their implementing partners to report on overall program progress and to share scale-up experiences and lessons. The RAP reviews periodic reports from technical partners—including the World Health Organization (WHO), TB Union, the US Centers for Disease Control and Prevention, and the Tuberculosis Control Assistance Program of the United States Agency for International Development (TB-CAP/ USAID)—that offer ongoing technical support, program coordination, and regional learning. RAP also provides support for the establishment of working groups in each thematic area. It comprises officials from each participating country, the East African Community chair, and representatives of WHO, USAID, and other implementing partners. • National Steering Committee. Under the guidance of the permanent secretary of the Ministry of Public Health of Burundi, an NSC was established to review and approve implementation plans. The NSC comprises the head of surveillance and representatives from the National Reference Laboratory of the National Institute of Public Health, WHO, and other implementing partners. • Project Management Unit. The Project Management Unit is housed within the Ministry of Health, and contributes to the preparation of consolidated technical and financial reports quarterly and annually. Burundi’s minister of public health has overall responsibility for the project, while the permanent secretary is responsible for its technical oversight. Project activities are undertaken by a team consisting of a project manager, an epidemiologist, a microbiologist, and an accountant. • Results monitoring and evaluation arrangements. Like other countries participating in the East Africa Public Health Lab Networking Project, Burundi has relied on a common framework for monitoring performance of the project, which is regionally coordinated by ESCA-HC. At the national level, Burundi’s Ministry of Health designates an M&E specialist responsible for overseeing data collection and quality assurance processes. The specialist also participates in technical reviews, as well as the review of consultant reports or analytical products for M&E. Source: World Bank 2012. In many instances, coordination across the human health, animal health, and environment sectors has proven to be challenging. To mitigate these challenges, countries can establish interagency coordination committees (or AMR or One Health committees) composed of representatives from relevant ministries and institutions, particularly those with links to the country’s health security agenda. These committees can play a role in making multisectoral decisions on strategic planning and implementation and can guide the development of standard operating procedures, as well as conduct the review of M&E plans and structures. These committees often meet two to four times a year. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 173 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The ministries and institutions participating in the National Steering Committee vary; however, commonly participating ministries and institutions include the ministries of health, agriculture, forestry, and food security as well as environment, with support from partners such as the Food and Agriculture Organization of the United Nation (FAO), WHO, and the US CDC. Among the participating ministries and institutions, the ministry that oversees implementation often takes the role of an anchor ministry; it acts as secretariat to the national coordination committee and engages various stakeholders, including development partners, civil society organizations, and technical experts, among others. Projects can achieve stronger political commitment and convening power if they can draw upon a high-level official, such as the minister of the anchor ministry or a representative from presidential or prime ministerial offices or cabinet secretariat, to serve as the chair for the National Steering Committee. Some World Bank operations have used effectiveness conditions to secure appropriate implementation arrangements. These conditions have required that countries pass legislation or put in place processes to establish or support an overarching entity or agency that will guide implementation at the national level. These entities often reflect the structure of a public health institute and have been housed in an anchor ministry (such as the ministry of health), with close collaboration with other relevant ministries working on the AMR agenda. The agency has responsibility for coordinating the implementation of various project components by sectoral ministries (agriculture, livestock, health, environment, etc.), nongovernmental organizations, and other stakeholders. The implementing agency comprises National Project Coordination Units and Project Implementation Units that take on cross-cutting functions, including working across sectors to improve efficiency and alignment in the implementation of project activities, transferring and monitoring the use of funds by other implementing ministries and partners, and handling procurement, cross-stakeholder communication, and M&E, as well as generating national progress reports. Given the granularity of project implementation, some projects have put in place subnational coordination mechanisms to support and monitor implementation at field level. Regional institutional arrangements Many projects use established regional agencies to guide regional implementation and to coordinate and communicate on important actions in line with the regional agenda. Regional implementing agencies have provided regional oversight and have supported the execution of project components. Projects have typically created regional implementation units that have responsibility for day-to-day administration of regional activities, procurement, financial management, and programming as well as monitoring and evaluation. To help ensure that regional bodies are well positioned for this role, several projects have sought to strengthen the implementation capacity and processes of regional implementing agencies. Projects have also provided technical and investment support to enhance expertise across the project management cycle. Options for regional governance (such as regional steering committees) can leverage One Health structures to ensure the participation, leadership, and representation of the human, animal, and environmental health sectors of participating countries. These mechanisms have been anchored in regional implementing agencies through their roles as project secretariats. Steering bodies are typically tasked with shaping, overseeing, and monitoring AMR-related activities across countries and sectors for systematic and comprehensive implementation, and reflect multidisciplinary and cross-sectoral action. These mechanisms have also leveraged technical working groups with clear terms of reference to provide technical oversight during implementation, and they are responsible for the review and finalization of operational plans that include priority activities, implementation arrangements, detailed budgeting and costing, data collection timelines, and reporting methods. These steering bodies have also served as platforms for multicountry and multistakeholder engagement, dialogue, and information sharing. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 174 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The Africa CDC Project is a US$200 million project that includes activities to address AMR and that draws on coordination mechanisms to enable progress across its three implementing agencies. The project provides financing through five components: (i) governance, advocacy, and operational frameworks; (ii) public health assets; (iii) human resource development; (iv) project management support; and (v) a Contingent Emergency Response Component (CERC) for Ethiopia and Zambia. Its three implementing agencies are the Africa CDC and the Ethiopian and Zambian governments. In addition, the Ethiopia Public Health Institute and the Zambia National Public Health Institute serve as dedicated national-level institutions for coordinating public health interventions. Box 8 provides an overview of the institutional arrangements. Box 8. Africa CDC Regional Investment Financing Project Africa CDC Regional Investment Financing Project Project overview The Africa Centres for Disease Control and Prevention Regional Investment Financing Project was established to strengthen continental and regional infectious disease detection and response systems. The Africa CDC provides all 55 African Union (AU) member states with training and legal and administrative support to facilitate a harmonized and cooperative approach to disease surveillance and response across countries. In addition to the CERCs for Ethiopia and Zambia, the Africa CDC provides project-funded emergency assistance during disease outbreaks by facilitating the shipment of samples to project-supported laboratories in Ethiopia. Overview of institutional arrangements • Ethiopian and Zambian Ministries of Health (MoHs) and National Public Health Institutes (NPHIs). The Ethiopian and Zambian MoHs are the primary implementation agencies; the NPHIs serve as technical entities for coordination and implementation. In each country, the NPHI also provides technical and financial reports to the MoH and the World Bank. In Ethiopia, the state minister for programs is responsible for the execution of project activities, and the Ethiopian Public Health Institute reports directly to the state minister. In Zambia, the permanent secretary for administration and the permanent secretary for technical services are responsible for managing project activities. • Project Implementation Units (PIUs). PIUs were established at the Africa CDC and the Zambian MoH to carry out the day-to-day project activities. The PIUs include technical staff and operational staff for the management of fiduciary responsibilities and compliance with legal, environmental, and social safeguards. In Ethiopia, the Grant Management Unit (GMU) of the MoH’s Partnership and Cooperation Directorate is responsible for the day-to- day management of activities. The PIUs and GMU have the flexibility to recruit specialized technical staff as needed, and some activities may be outsourced to third parties through contract agreements acceptable to the World Bank. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 175 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices • The Project Technical Steering Committee. The Project Technical Steering Committee includes the director of the Africa CDC, the heads of the Ethiopian and Zambian NPHIs, and representatives of the agriculture and livestock sector, as well as representatives of regional projects such as REDISSE. The committee also draws on experts and specialists on an ad hoc basis. It meets at least twice a year to review and finalize annual work plans, review implementation progress, provide technical guidance to the implementing agencies, and share information among relevant stakeholders. Representatives from the agriculture and livestock sectors as well as other regional projects—such as the East Africa Public Health Laboratory Networking Project, Southern Africa Tuberculosis and Health Systems Support Project, and REDISSE—participate in the annual meetings to ensure coordination and harmonization among the continent’s various regional projects on surveillance and laboratory networks. The Africa CDC serves as the secretariat, and the committee’s activities are guided by terms of reference that clearly define its functions, responsibilities, and collaboration with the Africa CDC, Southern Africa Regional Collaborating Centre, and NPHIs from both countries. • Country Steering Committees (CSCs). In each country, a CSC oversees implementation of the project subcomponents for which the country is responsible. The CSCs include representatives from the ministries of health, agriculture, livestock, and finance as well as from academia and civil society. The composition of the CSC in each country reflects country circumstances and preferences. The primary mandate of the CSCs is to monitor the functions of the implementing agencies at the country level, review annual work plans and implementation progress, provide technical guidance, support the MoHs and NPHIs, and facilitate information exchange among project stakeholders. Technical working groups, subcommittees, and other standing or ad hoc groups have been put in place at the MoH and NPHI level to carry out activities within particular areas of the project operations. • Results monitoring and evaluation arrangements. In each country, monitoring against the results framework is conducted by the PIUs at the country level. PIUs have collected and compiled data related to the Project Development Objective and intermediate indicators, and have produced progress reports on a monthly, quarterly, semiannual, and annual basis—with a semiannual report produced for the World Bank. For each country, an external independent evaluation to assess overall outcomes and effectiveness is planned for 2026. Source: World Bank 2019. The Regional Disease Surveillance Systems Enhancement project has used steering committees to facilitate collaboration across countries. Over seven years, US$657 million in financing has been structured through five components: (i) surveillance and health information; (ii) laboratory capacity strengthening; (iii) preparedness and emergency response; (iv) human resource management for effective disease surveillance and preparedness for epidemics; and (v) institutional capacity building, project management, and coordination and advocacy. In Central Africa, these components of REDISSE have been expanded to include (i) strengthening of surveillance and laboratory capacities to rapidly detect epidemics; (ii) strengthening of emergency planning and management capacities to respond quickly to epidemics; (iii) human capacity development in public health for effective disease surveillance and epidemic preparedness; and (iv) institutional capacity building, project management, coordination, and advocacy. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 176 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Program implementation is coordinated at the regional level by the West African Health Organization (WAHO), an affiliate institution of the Economic Organization of West African States (ECOWAS) that also serves as the program secretariat. WAHO has established agreements with the WHO Regional Office for Africa, the World Organisation for Animal Health, the Regional Animal Health Center, the Centre for International Cooperation in Health and Development, and Fondation Merieux to assist with regional-level activities and provide technical support to participating countries. In Central Africa, the Economic Community of Central African States (ECCAS) Commission is the primary implementing agency. Box 9 provides more details on the implementation arrangements. Box 9. Regional Disease Surveillance Systems Enhancement Project: Phases 1–4 REDISSE Project overview The REDISSE project supports the development of regional platforms and country-specific operations for disease surveillance and response capacity in West and Central Africa. REDISSE has been designed as an interdependent series of projects and is being implemented in phases. Since 2016, four REDISSE projects have provided WAHO with financing for regional West coordination and regional activities, and they have provided 16 ECOWAS and ECCAS member Central states with country-specific financing. Overview of institutional arrangements • Project Coordination Units (PCUs). Existing or newly created PCUs in participating countries’ ministries of health have responsibility for the technical and fiduciary execution of the project and the day-to-day coordination, implementation, and communication of project components and results. In most participating countries, the PCUs have comprised a project coordinator, an accountant, a social safeguard specialist, an environment specialist, an M&E specialist, and a procurement specialist. • Regional Steering Committee. A Regional Steering Committee was established to oversee overall project governance. The RSC includes representatives of participating country ministries. The RSC meets twice a year and has primary responsibility for the technical coordination of REDISSE projects. Within the RSC, a regional implementation unit was created to oversee day-to-day administration of regional activities, procurement, financial management, and programming as well as M&E at the regional level. • National Steering Committees. In each country, multisectoral One Health National Steering Committees have been created to oversee implementation of country-level activities, as well as to review annual work plans and budgets, monitor project progress, and approve annual project reports. The NSCs include representatives from the ministries of livestock, economy and finance, education, agriculture, security, environment and sustainable development, and communications, and from local, regional, and global partners. The NSCs meet twice a year to define project implementation strategies and validate annual work plans and budgets. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 177 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices • Results monitoring and evaluation arrangements. M&E is undertaken at the regional level by implementing agencies; at the country level it will be undertaken in conjunction with external partners such as WHO, US CDC, and WOAH. WAHO and ECCAS have overall responsibility for coordinating the M&E function of REDISSE projects in West and Central Africa, including the design and implementation of data collection efforts that are best done at the regional level; they are also responsible for the provision of technical backstopping on M&E at the country level. Other coordination functions include the development of data quality assurance mechanisms, the collection of data, and facilitation of cross- country learning. Source: World Bank 2016. Takeaways Early and detailed attention to implementation arrangements can be beneficial given the complexities of addressing AMR within and across sectors and across national boundaries. The projects reviewed for this section offer some important lessons on how task and client teams can establish effective approaches for new operations. Multisectoral and intersectoral actions for AMR-related projects such as the Regional Sahel Pastoralism Support Project demonstrate that coordination must take place horizontally across sectors as well as vertically at regional, national, subnational/subregional, and local levels. This includes clearly defining roles, responsibilities, and accountability at all levels. For leveraging capacity, minimizing costs, and accounting for established relationships, drawing on existing institutions and reporting structures has many benefits. In the reviewed projects, institutional capacity building has comprised a primary component of implementation support provided by the World Bank. In addition to investments to enhance implementing agencies’ capacity for financial and project management, efforts have also been directed at understanding the political ecosystem, managing relationships and conflicts between stakeholders, distributing leadership, and providing incentives for institutions and individuals to collaborate. For AMR, these efforts may require a clear understanding of the types of political settlements that are in place, as well as the policy change required over time. Promoting greater awareness and ownership of the AMR agenda among influential stakeholders could help consolidate multisectoral action and ensure adequate resourcing within current institutional arrangements. Anchoring the AMR agenda within supra-sectoral bodies such as the Office of the President or Office of the Prime Minister may present avenues for promoting greater ownership of the AMR agenda through key stakeholders and political champions. This is also a way to enhance mechanisms for transparency and accountability. Implementation can benefit when decisions are made and activities are carried out at the highest relevant geographic level. The PRAPS and REDISSE projects have highlighted the use of the subsidiarity principle, a mechanism for guiding the appropriateness of and responsibility for activity implementation within the optimum geographic context—at the subnational, national, or regional level. Under this guiding principle, participating countries were responsible for delegating regional- level activities to the regional implementing agency and for defining activities they deemed most suitable for the country level. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 178 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Successful projects have simplified their monitoring and evaluation arrangements and processes to the extent possible. In establishing baselines and targets, project results frameworks could benefit from early focus on and adequate consideration of country contexts. Projects such as the PRAPS call for monitoring and evaluation to be streamlined and realistic. References IEG (Independent Evaluation Group). 2007. The Development Potential of Regional Programs: An Evaluation of World Bank Support of Multicountry Operations. Washington, DC: World Bank. https://ieg.worldbankgroup.org/sites/default/files/Data/reports/regional_program_ evaluation.pdf. Joshi, M. P., T. Hafner, G. Twesigye, A. Ndiaye, R. Kiggundu, N. Mekonnen, N. Kusu, et al. 2021. “Strengthening Multisectoral Coordination on Antimicrobial Resistance: A Landscape Analysis of Efforts in 11 Countries.” Journal of Pharmaceutical Policy and Practice 14: 27. https://doi.org/10.1186/s40545-021-00309-8. World Bank. 2012. “East Africa Public Health Lab Networking Project: Burundi.” Project Information Document 6952, World Bank, Washington, DC. https://documents1.worldbank.org/curated/ en/683031468008448305/pdf/Project0Inform0t0000Appraisal0Stage.pdf. World Bank. 2015. “Regional Sahel Pastoralism Support Project.” Project Appraisal Document 1091, World Bank, Washington, DC. https://documents1.worldbank.org/curated/ en/250471468000282631/pdf/PAD1091-PAD-P147674-IDA-R2015-0106-1-Box391422B- OUO-9.pdf. World Bank. 2016. “Regional Disease Surveillance Systems Enhancement Project.” Project Appraisal Document 1752, World Bank, Washington, DC. https://documents1.worldbank.org/ curated/en/965001467305866621/pdf/PAD1752-PAD-P154807-OUO-9-IDA-R2016-0154-1- Box396265B.pdf. World Bank. 2019. “Africa CDC Regional Investment Financing Project.” Project Appraisal Document 3217, World Bank, Washington, DC. https://documents1.worldbank.org/curated/ en/550521576292519493/pdf/Africa-Union-Ethiopia-and-Zambia-Africa-Centres-for- Disease-Control-and-Prevention-Regional-Investment-Financing-Project.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 179 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Three implementation case studies This part of the chapter examines how three countries, in partnership with various organizations, have tackled AMR through surveillance, training, and technology. The case studies present the implementation experiences of Indonesia, Tanzania, and Nigeria, highlighting the unique challenges and approaches taken in each country. They provide an overview of current AMR circumstances within each country, specific challenges being addressed, and actions being taken to respond to AMR. The case studies also outline implementation arrangements, enablers of progress, challenges, and barriers to success. Key takeaways for the benefit of teams and other countries planning to implement similar or related interventions are also included. Indonesia: Supporting the development of a One Health surveillance system for AMR Case Study 1 Indonesia Summary Over the past decade, increasing levels of drug-resistant infections made it urgent for countries in Asia to address antimicrobial resistance via a multisector collaboration. Indonesia has adopted a One Health approach focused on understanding the burden of drug- resistant infections and their impact on livelihoods. The country has focused on building its AMR surveillance and laboratory capacity across the human, animal, and environmental sectors. This effort has been executed through engagement with international stakeholders and organizations, such as WHO and the Fleming Fund, and through coordinated action across several Indonesian ministries. This case study provides an overview of current AMR circumstances within the country, specific challenges being addressed, and actions being taken to respond to AMR. Existing surveillance implementation arrangements, such as the Tricycle Project, are described, along with factors that have enabled progress and factors that have been a barrier to success. Key takeaways for the benefit of other teams planning to implement similar or related interventions are also included. Country context Indonesia is the largest economy in Southeast Asia (Index Mundi 2021) and has reduced poverty by investing in health care and public health provisions, including provisions to address AMR. Indonesia is poised to lead the way in addressing AMR, in particular AMR surveillance and laboratory capacity issues, following its G20 2022 presidency and plans to focus efforts on two priority issues, Global Health Architecture and Digital Transformation. 37 The first Indonesian AMR National Action Plan was implemented in 2017 (Rencana Aksi Nasional 2017-2019), and focused on the need for more robust and coordinated surveillance efforts throughout the country (Dewi et al. 2021; Gani and Budiharsana 2019; Chua et al. 2021; Sivaraman and Parady 2018). In 2021, building on the work achieved during NAP 2017–2019, 37  G20, “G20 Presidency of Indonesia–Issue Priorities,” https://g20.org/g20-presidency-of-indonesia/#priorities. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 180 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Indonesia approved a new AMR NAP for 2020–2024. 38 The draft was developed in consultation with multiple sectors, represented by the Ministry of Health, Ministry of Defense, National Agency of Drug and Food Control, Ministry of Agriculture, Ministry of Marine and Fisheries, Ministry of Environment and Forestry, professional and community organizations, and private stakeholders. According to the 2021 Tripartite AMR Country Self-Assessment Survey, or TrACSS, Indonesia ranks its NAP progress with the highest rating possible. 39 The country has strived to secure a budget for AMR NAP implementation and develop functional multisector working groups that are actively and jointly responsible and accountable for addressing common AMR objectives with a One Health Case Study 1 Indonesia approach. During the first wave of COVID-19, the unprecedented demand for laboratory testing saw an expansion of the COVID-19 referral laboratory network to include 685 laboratories in 34 provinces. The successful scale-up was made possible due to cross-ministerial collaborations that brought together expertise and capacity to respond to the health emergency. Although much of the information regarding AMR levels in Indonesia is still limited to a patchwork of areas with laboratory capacity and expertise, the infrastructures and multisector working collaborations initiated during the pandemic have undoubtedly laid the foundations for the future response to AMR in the country. In a bid to strengthen surveillance efforts across all sectors, Indonesia was selected by WHO to participate in the Tricycle Project. The global integrated survey on extended-spectrum beta- lactamase (ESBL)-producing E. coli, or the Tricycle Project, aims to strengthen AMR surveillance systems and to promote integrated surveillance across human, animal, and environmental sectors. In 2019, Indonesia enrolled in the Global Antimicrobial Resistance and Use Surveillance System (GLASS) and by 2020 had established at least 20 surveillance sites, 16 of which regularly provide data to GLASS (WHO 2021b). Implementation of antimicrobial stewardship programs and multidisciplinary antibiotic awareness campaigns have also become more widespread, and some tangible policies have been enacted. Such projects will inform ongoing activities in Indonesia to assess the AMR burden and to continue developing surveillance capacity. Specific challenges The development of the initial Indonesia AMR NAP was supported by a situation analysis conducted in 2016, which highlighted the multisector collaboration within Indonesia as well as several gaps and challenges (Parathon et al. 2017). Misuse and overuse of antimicrobials were identified as the driving forces of AMR across several sectors, including human health, livestock, and the environment, while several interventions have been implemented to tackle the issue (Table 6). Indonesia has national guidelines on empirical antimicrobial therapy and has established a process of hospital accreditation, which includes the requirement for a hospital-based AMR control committee. The country has also banned over-the-counter sales of antimicrobials (i.e., without prescription) and the use of antibiotics for growth promotion in animal agriculture, including any use of the antibiotic colistin in livestock. Despite these guidelines and regulations, multiple reviews have identified practices that continue to contribute to the misuse and overuse of antimicrobials. The drivers of such inappropriate antibiotic dispensing are complex and interwoven, ranging from a lack of basic knowledge about antibiotics and AMR, to the desire for financial gain (e.g., incentives are offered to maximize drug sales and animal production), to regulatory/enforcement circumstances across a geographically diverse country. The research collaboration known as PINTAR (Protecting Indonesia 38  Indonesia AMR National Action Plan (RENCANA AKSI NASIONAL PENGENDALIAN RESISTENSI ANTIMIKROBA TAHUN 2020- 2024) (accessed January 3, 2022), https://cdn.who.int/media/docs/default-source/searo/indonesia/20221115_nap-on-amr. pdf?sfvrsn=20f27da3_1&download=true. 39  See the Global Database for the Tripartite Antimicrobial Resistance (AMR) Country Self-Assessment Survey (TrACSS) (accessed January 3, 2022), http://amrcountryprogress.org/. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 181 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices from the Threat of Antibiotic Resistance) has highlighted issues at community pharmacies, which dispense antibiotics without any input from trained physicians or pharmacists (Ferdiana et al. 2021; Karuniawati et al. 2020; Limato et al. 2021). The project is working to address behavior change and to incorporate best practices from the handling of the COVID-19 pandemic into the design of interventions. Antibiotics intended for use in livestock can also be purchased at pharmacies or feed shops without prescription, and they frequently are inappropriately used (without input from trained veterinary practitioners). As a result, high levels of resistance have been found in several pathogens, such as E. coli and K. pneumonia, both from human patients and animals or animal products Case Study 1 Indonesia (Hedman, Vasco, and Zhang 2020; Sivaraman and Parady 2018; Karuniawati et al. 2021). The Joint Programming Initiative on Antimicrobial Resistance, or JPIAMR, is an international collaboration helping Indonesia to curb AMR. Through its COINCIDE project, JPIAMR is working to determine what will result from the ban on colistin use in animals; the intent is to help governments and clinicians safeguard colistin use for when it is needed. More investments are needed to allow for routine surveillance of pathogens and resistant genes in the environment, particularly in wastewater from hospitals, animal and food production facilities, and municipalities. To strengthen the capacity to monitor the effects of environmental pollutants on human health, and to develop water treatment plants that are fit for the context, innovative solutions are necessary. Research projects will inform ongoing activities in Indonesia to assess the AMR burden and continue development of surveillance capacity. To address AMR, appropriate policies must be implemented, and a system must be built that can financially support those policies and allow for systematic surveillance of resistant infections’ burden (Table 6). Like many low- and middle-income countries (LMICs), Indonesia still has limited information on antimicrobial use (AMU) and rates of resistant infections. Increasing AMR and AMU surveillance capabilities through a systemic collection of data will inform the knowledge base about AMR and drive appropriate AMU among prescribers and those who dispense or administer antimicrobial drugs. Table 6. Addressing AMR across Sectors: Challenges and Existing Interventions  Antibiotic use in humans CHALLENGES EXISTING INTERVENTIONS • Antibiotics are inappropriately dispensed at • Over-the-counter sales of antimicrobials community pharmacies. without prescription are banned. • There is a high rate of empirical use of • National guidelines exist on empirical broad-spectrum antibiotics in hospitals. antimicrobial therapy. • According to the WHO AWaRe classification, • Hospital accreditation requires a hospital- watch antibiotics accounted for 67.4 percent based AMR control committee. of hospital prescriptions; access for 28.0 • Surveillance is routinely performed under percent; and reserve for 2.4 percent. the guidance of the Ministry of Health. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 182 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices  Antibiotic use in animals CHALLENGES EXISTING INTERVENTIONS • Antibiotics for livestock can be purchased • Use of antibiotics for growth promotion and at pharmacies and feed shops. colistin use in livestock are banned. • There is a lack of trained veterinary • Veterinarians or technical staff are required Case Study 1 Indonesia practitioners on farms. on farms to administer antibiotics. • Antibiotics are used prophylactically. • Surveillance for AMR and AMU is performed under the guidance of the Ministry of Agriculture and Directorate General of Livestock and Animal Health Services (DGLAHS).  Antibiotics in the environment CHALLENGES EXISTING INTERVENTIONS • Bacteria and antibiotic residues from • Wastewater treatment plants are present food, animal production, and hospital for municipal systems, hospitals, and wastewaters are found in the environment abattoirs, though routine surveillance is not and in wild fauna. currently performed.  Policy implementation CHALLENGES EXISTING INTERVENTIONS • Greater awareness and stewardship of • A PINTAR study aims at improving antibiotic antimicrobials are needed. sales practices. • There is no national surveillance and data • The Fleming Fund strengthens surveillance collection and reporting system. and laboratory capacity with One Health focus. • The diverse geographic area made up of multiple islands is not coordinated. • The Tricycle Project aims at establishing cross-sectoral surveillance capacity. • The country is enrolled in GLASS and has established surveillance sites. Source: World Bank. Note: AMU = antimicrobial use; AWaRe = access, watch, reserve; GLASS = Global Antimicrobial Resistance and UseSurveillance System; PINTAR = Protecting Indonesia from the Threat of Antimicrobial Resistance; WHO = World Health Organization. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 183 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Actions taken to respond to AMR and enablers of progress Indonesia has followed a stepwise approach to implementing AMR plans, with the long-term goal of developing an operational AMR containment program that has a sustainable funding mechanism and that incorporates functional monitoring and evaluation. The development of the initial Indonesia AMR NAP was supported by a situation analysis conducted in 2016, followed by the assessment of AMR programs by the WHO Southeast Asia Regional Office (SEARO) in 2017 (Kakkar, Sharma, and Vong 2017). In the same year, the FAO Assessment Tool for Laboratory and Case Study 1 Indonesia Antimicrobial Resistance (FAO_ATLASS) was launched in Indonesia, reinforcing the country’s planned implementation of a national AMR surveillance system. That was followed by efforts to further build the surveillance capacity of the country with the start of the Tricycle Project, the enrollment into GLASS, and the receipt of funding from the Fleming Fund (Figure 2). Figure 2. Timeline of Key Steps to Address AMR Assessment of AMR programs through SEARO 1st NAP published Colistin use banned in livestocks FOA ATLASS launched NAP budgeting tool piloted 2016 2018 2020 2017 2019 2021 Situation analysis PINTAR Fleming Fund starts starts GLASS enrollment Tricycle Project starts Source: World Bank. Note: FAO-ATLASS = FAO Assessment Tool for Laboratory and Antimicrobial Resistance; GLASS = Global Antimicrobial Resistance and Use Surveillance System; NAP = National Action Plan; SEARO = World Health Organization Southeast Asia Regional Office. Indonesia’s progress toward AMR containment has been enabled through three levels of commitment: community, national, and international. Table 7 shows the initiatives aimed at fulfilling AMU and AMR stewardship policy and program goals, along with how activities were implemented—that is, carried out within communities across the country, enabled through national policies, or enabled as part of larger international programs. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 184 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 7. Actions Taken and the Enablers of Progress IMPLEMENTATION LEVEL INTERNATIONAL COMMUNITY NATIONAL Case Study 1 Indonesia ENABLER OF PROGRESS INTERVENTION/ACTION National political Situational analysis report and Indonesia NAP commitment are issued. ☑ Minister of Agriculture bans the use of antibiotics for growth promotion. ☑ Directorate General of Livestock and Animal Health Services (DGLAHS) bans colistin. ☑ National AMR Coordination Committee and AMR focal point are established. ☑ Surveillance sites are established; country is enrolled in GLASS. ☑ ☑ WHO Southeast Asia Regional Office tool to assess AMR programs is piloted. ☑ International FAO Assessment Tool for Laboratory and Antimicrobial aid & support Resistance (ATLASS) is launched. ☑ Fleming Fund strengthens surveillance capacity and aids NAP implementation. ☑ ☑ WHO pilots the AMR financing and budgeting tool for NAP implementation. ☑ ☑ Multi-Partner Trust Fund makes investment to improve AMR awareness, optimize antimicrobial use, and ☑ ☑ strengthen surveillance. WHO launches the Tricycle Project. ☑ ☑ ☑ Cross-country PINTAR study is undertaken. ☑ collaboration Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) is undertaken. ☑ Source: World Bank. Note: GLASS = Global Antimicrobial Resistance and Use Surveillance System; NAP = National Action Plan; PINTAR = Protecting Indonesia from the Threat of Antibiotic Resistance; WHO = World Health Organization. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 185 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Strengthening surveillance capacity across all sectors: The Tricycle Project In November 2018, the WHO Tricycle Project, using ESBL-producing E. coli as an AMR indicator, was piloted in Jakarta to promote and strengthen integrated surveillance across human, animal, and environmental sectors. The project brought together national political bodies (ministries), international organizations (WHO and the Fleming Fund), and regional centers (hospitals and research institutions) to collect data; this effort has not only provided AMR indicators Case Study 1 Indonesia of the spread of resistance nationally, but has also contributed to defining the burden of AMR globally (Table 8). The High-Level Inter-Ministerial Steering Committee (IMSC), formed by the Ministry of Health, Ministry of Agriculture, and Ministry of Environment and Forestry, coordinated the pilot, while the National AMR Coordination Committee (NARCC) implemented it nationally. Initial results were reported in 2021 and revealed a very high proportion of ESBL-producing E. coli in sample types across all sectors (Puspandari et al. 2021). The protocol in Indonesia also featured an added module, called EpiX (Puspandari et al. 2021), which expanded the epidemiological data collection and analysis to demonstrate the epidemiological interconnectedness between humans, animals, and the environment. The first phase of implementation included training of the local researchers in data management and analysis and in use of the WHONET software. Trainings were held in 2017 in the Netherlands and Jakarta. Monitoring visits were also conducted at Rumah Sakit Persahabatan Hospitals, Health Center Jatinegara, slaughterhouses/markets, canals, the microbiology laboratory in the Indonesian National Institute of Health Research and Development (NIHRD), and the microbiology laboratory in the Ministry of Environment and Forestry. Findings and feedback from the visits revealed that the country had well-established surveillance systems for the human and animal sectors, but still had limited capacity to monitor AMR in the environment; this was also corroborated by the Joint External Evaluation (JEE) of the International Health Regulations (IHR) (GHS Index 2021). While local researchers within the regional centers and the ministerial coordinating committees have showed a high level of commitment to implementing the Tricycle Project, there is still limited capacity to analyze epidemiological data. The AMR data currently collected originate primarily from the Java region. Although there were plans in place to establish laboratory networks across other regions, COVID-19 significantly slowed down the further rollout of the Tricycle Project and other programs. The Fleming Fund has been pivotal in supporting Indonesia, helping to build surveillance laboratory capacity for priority pathogens, train researchers and health care professionals in microbiology, and carry out sample collection and analysis. The Fleming Fund has also assisted with overall coordination across sectors, regional centers, and government bodies by supporting the implementation of coordinating mechanisms such as IMSC and NARCC. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 186 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 8. Tricycle Pilot: Partners and Implementation Arrangements IMPLEMENTING INSTITUTIONS PARTNERS INVOLVED MAIN RESPONSIBILITIES International Fleming Fund • Surveillance laboratory organizations capacity building • Training of researchers and clinicians Case Study 1 Indonesia • Implementation support for national AMR committees US CDC • Surveillance laboratory capacity building WHO • Training of researchers and clinicians • Coordination of AMR activities National High-Level Inter-Ministerial Steering Overall governance for AMR strategy ministries and Committee (IMSC) coordinated by in Indonesia research centers • Ministry of Health • Provides political commitment • Ministry of Defense • Supports national • Ministry of Agriculture containment efforts • Ministry of Foreign Affairs • Links to the international global health community National AMR Coordination Implementation agency for the Committee (NARCC) coordinated by Indonesian NAP • Different ministries • Provides the platform and • Governmental and structure for program planning nongovernmental agencies (e.g., and implementation civil society, media) • Oversees technical working • International agencies (WHO, groups for each of the individual FAO, WOAH, MPTF) NAP strategic objectives Indonesian National Institute Coordination of national of Health Research and surveillance and sample analysis Development (NIHRD) Balai Besar Laboratorium National Reference Laboratories Kesehatan (BBLK) (human samples) • Surabaya • Jakarta Ministry of Environment Microbiology laboratories (animal and Forestry and environmental samples) Community • Rumah Sakit Sample collection centers Persahabatan Hospital • Health Center Jatinegara • Slaughterhouses/markets • Canals Source: World Bank. Note: FAO = Food and Agriculture Organization of the United Nations; MPTF = Multi-Donor Trust Fund; NAP = National Action Plan; WHO = World Health Organization; WOAH = World Organisation for Animal Health. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 187 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Ongoing challenges and barriers to success Economic circumstances and the COVID-19 pandemic continue to impact Indonesia’s efforts to address AMR. A recent WHO costing and budgeting workshop noted that, until 2019, the budget allocations for AMR were low, and there was a lack of coordination (or ability to coordinate) across sectors (WHO 2021a). Additionally, the COVID-19 pandemic has brought unexpected challenges, slowing down the country’s economic growth with the most significant drop since 1998 and pushing Indonesia’s gross domestic product ranking from upper-middle income to lower-middle income in Case Study 1 Indonesia 2021.40 The pandemic has also delayed the formal approval of the draft 2020–2024 Indonesia NAP on AMR that was completed in 2019 (WHO 2021a), in turn affecting progress on the Tricycle Project and its expansion to other regions. Ensuring the long-term sustainability of the Indonesia NAP and the Tricycle Project will require financial plans that improve national laboratory networks. In 2021, a new Country Partnership Framework (2021–2025) was published, which prioritizes medium-term development plans and economic recovery from the COVID-19 pandemic (World Bank, IFC, and MIGA 2021). With funding from the Fleming Fund coming to an end in Indonesia, it is important to ensure that there are mechanisms in place for the long-term sustainability of the achievements made to date. Like other LMICs, Indonesia faces challenges with diagnostic laboratory readiness and even distribution of resources. As a result, laboratories, staff, equipment, and consumable capacities are concentrated within Java Island. With the bulk of the work still carried out by single research institutions or laboratories supported by independent grants, many other provinces are unable to meet demand for laboratory diagnosis. The geographical fragmentation of the country represents a real challenge, the experience with the scale-up of diagnostic laboratories during the COVID-19 pandemic has shown that equally distributed capacity and efficient cross-sector collaborations are needed. Additionally, systematic data collection, analysis, and sharing of surveillance data across the laboratory network are needed to draw a clear picture of the burden of AMR and to implement appropriate interventions based on need. Takeaways for the benefit of other teams planning to implement similar or related interventions A strong political drive, combined with international aid and willingness to collaborate internationally with key stakeholders in global health, has allowed Indonesia to exponentially grow its technical capacity to monitor the spread of resistant infections. As noted in the JEE of IHR Core Capacity, as of 2018 Indonesia already had sufficient laboratory capacity to conduct surveillance of relevant zoonotic diseases in the human sector (WHO 2018). Since 2019, the Fleming Fund has made significant investments in laboratory infrastructure enhancement, human resource strengthening, workforce reforms, surveillance system strengthening and data use, and rational use of antimicrobials. The Fleming Fund has enabled progress in implementation of NAP, the establishment of NARCC and the AMR focal point, and the rollout of the Tricycle Project. This work represents the first step toward the long-term sustainability of AMR containment interventions. Most recently, Indonesia received further investments from the Multi-Partner Trust Fund (MPTF), equal to US$1 million, to improve AMR awareness, optimize antimicrobial use, and further strengthen surveillance capacity across all sectors. The government of the Netherlands has also provided extra funds to build veterinary surveillance capacity as part of the expansion of the Tricycle Project. 40  See World Bank, “The World Bank in Indonesia,” https://www.worldbank.org/en/country/indonesia. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 188 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The establishment of funding partnerships that support local leaders in driving the AMR agenda, both within the community and in government, has been critical to the success seen in Indonesia. Such partnerships allow for a bottom-up approach that leverages existing structures and local capabilities alongside international expertise and technical training to advance in-country capacity. The key steps that Indonesia has taken to address AMR to date are presented below. These might prove useful as recommendations to other teams or countries working toward the implementation of AMR containment activities. 1. Case Study 1 Indonesia Political action to ensure support for AMR. Indonesia has actively engaged with external stakeholders such as the Fleming Fund and the US CDC to strengthen its AMR operational capacity. Most recently, the government has further formalized its interest in actively tackling global health challenges by signing a Memorandum of Understanding on health cooperation and antimicrobial resistance surveillance with the United Kingdom. Furthermore, it has formally established national AMR committees in charge of implementing and monitoring AMR action. 2. Accountability of local actors and capacity building through active support of local research communities. Local experts and Fleming Fellows have supported the coordination of AMR projects across the country in collaboration with ministries. In particular, training of local staff has ensured that knowledge and expertise are retained within the country, paving the way to self-sustainability. Additionally, collaborations with international research stakeholders have contributed to strengthening the local technical capacity to conduct surveillance and stewardship of antimicrobials. 3. Translation of political will into resources, including funding through multisector resource mobilization. Partnerships with the Fleming Fund, MPTF, and others have translated into tangible resources (financial and operational) aimed at strengthening AMR surveillance capacity and increasing AMR awareness and responsible use of antimicrobials. The implementation of the WHO budgeting tool, which is also underway, will further strengthen the prioritization and availability of financial resources for the implementation of AMR NAP activities in the country. 4. Use of strategic information to drive input by performing country-level AMR situation analysis to understand progress and bottlenecks. This step could include use of the WHO budgeting tool and participation in activities to implement NAP; conduct of a situation analysis and testing of others’ tools to determine how AMR programs are faring and to identify challenges that are specific to the context and country; and participation in the WHO GLASS and Tricycle Project to expand national surveillance capacity across human, animal, and environmental sectors. 5. Better policies through improved dissemination and uptake of global policies. This step involves support for WHO in the dissemination and uptake of policies and guidelines through regular engagement and meetings. For instance, Indonesia has worked closely with WHO and other international stakeholders to develop and implement guidelines for the responsible use of antimicrobials in farming, in the community, and in hospitals. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 189 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Bibliography Chua, Alvin Qijia, Monica Verma, Li Yang Hsu, and Helena Legido-Quigley. 2021. “An Analysis of National Action Plans on Antimicrobial Resistance in Southeast Asia Using a Governance Framework Approach.” The Lancet Regional Health: Western Pacific 7 (January): 100084. https://doi.org/10.1016/j.lanwpc.2020.100084. Dewi, Aisyah N., Chyntia A. Mayadewi, Gayatri Igusti, Logan Manikam, Wiku Adisasmito, and Zisis Case Study 1 Indonesia Kozlakidis. 2021. “Laboratory Readiness and Response for SARS-Cov-2 in Indonesia.” Frontiers in Public Health 9. https://doi.org/10.3389/fpubh.2021.705031. Ferdiana, Astri, Marco Liverani, Mishal Khan, Luh Putu Lila Wulandari, Yusuf Ari Mashuri, Neha Batura, Tri Wibawa, et al. 2021. “Community Pharmacies, Drug Stores, and Antibiotic Dispensing in Indonesia: A Qualitative Study.” BMC Public Health 21 (1): 1800. https://doi.org/10.1186/ s12889-021-11885-4. Gani, Ascobat, and Meiwita P. Budiharsana. 2019. “The Consolidated Report on Indonesia Health Sector Review 2018.” https://www.unicef.org/indonesia/media/621/file/Health%20 Sector%20Review%202019-ENG.pdf%20.pdf. GHS (Global Health Security) Index. 2021. “Country Score Justifications and References Indonesia.” https://www.ghsindex.org/wp-content/uploads/2021/12/Indonesia.pdf. Government of Indonesia. 2017. “National Action Plan on Antimicrobial Resistance Indonesia 2017– 2019.” https://ncdc.gov.ng/themes/common/docs/protocols/56_1510840387.pdf. Hedman, Hayden D., Karla A. Vasco, and Lixin Zhang. 2020. “A Review of Antimicrobial Resistance in Poultry Farming within Low-Resource Settings.” A nimals: An Open Access Journal from MDPI 10 (8): 1264. https://doi.org/10.3390/ani10081264. Index Mundi. 2021. “Indonesia Economy – Overview – Economy.” September 18, 2021. https://www.indexmundi.com/indonesia/economy_overview.html. Kakkar, Manish, Anuj Sharma, and Sirenda Vong. 2017. “Developing a Situation Analysis Tool to Assess Containment of Antimicrobial Resistance in South East Asia.” BMJ 358 (September): j3760. https://doi.org/10.1136/bmj.j3760. Karuniawati, Hidayah, Mohamed Azmi Ahmad Hassali, Wan Ismahanisa Ismail, Taufik, and Sri Suryawati. 2021. “Antibiotic Use in Animal Husbandry: A Mixed-Methods Study among General Community in Boyolali, Indonesia.” International Journal of One Health 7 (1): 122–27. https://doi.org/10.14202/IJOH.2021.122-127. Karuniawati, Hidayah, Mohamed Azmi Ahmad Hassali, Sri Suryawati, Wan Ismahanisa Ismail, Taufik, and Anis Wiladatika. 2020. “Public Practices towards Antibiotics: A Qualitative Study.” Clinical Epidemiology and Global Health 8 (4): 1277–81. https://doi.org/10.1016/j. cegh.2020.04.027. Limato, Ralalicia, Erni J. Nelwan, Manzilina Mudia, Justin de Brabander, Helio Guterres, Enty, Ifael Y. Mauleti, et al. 2021. “A Multicentre Point Prevalence Survey of Patterns and Quality of Antibiotic Prescribing in Indonesian Hospitals.” JAC-Antimicrobial Resistance 3 (2). https://doi.org/10.1093/jacamr/dlab047. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 190 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Parathon, Harry, Kuntaman Kuntaman, Tri Hesty Widiastoety, Bayu T. Muliawan, Anis Karuniawati, Mariyatul Qibtiyah, Zunilda Djanun, et al. 2017. “Progress towards Antimicrobial Resistance Containment and Control in Indonesia.” BMJ 2017 (358): j3808. https://doi.org/10.1136/bmj. j3808. Puspandari, Nelly, Sunarno, Tati Febrianti, Dwi Febriyana, Ratih Dian Saraswati, Indri Rooslamiati, Novi Amalia, et al. 2021. “Extended Spectrum Beta-Lactamase-Producing Escherichia Coli Surveillance in the Human, Food Chain, and Environment Sectors: Tricycle Project (Pilot) in Case Study 1 Indonesia Indonesia.” One Health 13 (December): 100331. https://doi.org/10.1016/j.onehlt.2021.100331. Sivaraman, S., and Vida Parady. 2018. “Antibiotic Use in Food Animals: Indonesia Overview.” ReAct Asia-Pacific, Tamil Nadu, India. https://www.reactgroup.org/wp-content/uploads/2018/11/ Antibiotic_Use_in_Food_Animals_Indonesia_Overview_LIGHT_2018_web.pdf. WHO (World Health Organization). 2018. Joint External Evaluation of IHR Core Capacities of the Republic of Indonesia. Geneva: World Health Organization. https://www.who.int/publications-detail- redirect/WHO-WHE-CPI-REP-2018.9. WHO (World Health Organization). 2021b. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2021. Geneva: World Health Organization. https://www.who.int/ publications/i/item/9789240027336. WHO (World Health Organization). 2021a. “Country Case Study: Indonesia WHO Costing and Budgeting Tool for National Action Plans on Antimicrobial Resistance.” https://www.who.int/ publications/m/item/country-case-study-indonesia. World Bank, IFC (International Finance Corporation), and MIGA (Multilateral Investment Guarantee Agency). 2021. “Country Partnership Framework for the Republic of Indonesia for the Period FY21–FY25.” Strategy Document. World Bank, Washington, DC. https://openknowledge. worldbank.org/handle/10986/35559. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 191 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Tanzania: Building community-led AMR surveillance capacity through mobile technology Summary Case Study 2 Tanzania This case study describes key findings from Tanzania’s work to establish cross-border relationships and a sustainable technology infrastructure for community-based infection, outbreak, and antimicrobial resistance (AMR) surveillance. Over the past decade, partnerships between Tanzanian and international agencies have built training and software development programs that aim to empower community members in One Health infectious disease surveillance, while building relationships and promoting shared decision-making between community data reporters and national government officials. Tanzania’s collaborative and technology-driven work culminated in 2018 with the launch of AfyaData, a mobile application that allows community members to collect, report, analyze, and receive feedback on AMR and infectious disease data. The use of AfyaData to respond to infectious disease outbreaks garnered investment from Tanzania’s national Ministry of Health (MoH), and the app was deployed to measure drug resistance in community-acquired urinary tract infections (UTIs), which country officials have identified as a significant driver of inappropriate antibiotic prescribing that is possibly increasing drug resistance. A pilot study made possible by close collaboration between the community, the national government, and international agencies indicated that multidrug- resistant (MDR) strains of bacteria were a prevalent cause of UTI in the community. Findings laid the groundwork for guidelines on community UTI prescribing (currently in development) and affirmed the importance of technology-based, community-focused AMR surveillance as part of a national and cross-border infectious disease strategy. The context and specific challenges being addressed More is known about antibiotic use than about AMR in Tanzania. Data are scarce on the burden of AMR in Tanzania. More is known about the prevalence of inappropriate antimicrobial prescribing or purchasing, which is a known contributor to increases in drug resistance. Investigative studies have found that antibiotics to treat fever—most commonly ampicillin, tetracyclines, and ciprofloxacin— are frequently sold without a prescription and in suboptimal doses if the purchaser is unable to afford the entire dose (Makoye 2021; Mbwasi et al. 2020). Tanzania is focused on implementing National Action Plan strategies for AMR surveillance and measurement. Tanzania participates in the WHO Global Antimicrobial Resistance and Use Surveillance System. As of 2022, the country reports AMR data on bloodstream infections and UTIs to GLASS (WHO 2022). Tanzania’s MoH adopted a National Action Plan on AMR in 2017, establishing priorities for the control of AMR and antimicrobial use in human and veterinary health through 2022 (MoH 2017). NAP implementation is overseen by an AMR focal point—the Pharmaceutical Services Unit, which sits within MoH. The NAP identifies improvement of surveillance systems as one of five urgent goals, and calls the lack of health care resources and programs to improve public awareness and education a key weakness that may inhibit achievement of the NAP’s objectives (Frumence et al. 2021). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 192 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Governance and committee structures outlined in the NAP have the capability to promote AMR surveillance at the national level, but communities’ capacity for testing for AMR and knowledge about AMR vary significantly. Tanzania’s Multi-Sectoral Coordinating Committee is co- chaired by the chief medical officer and the WHO representative to Tanzania and comprises a diverse membership drawn from national human health, agriculture, horticulture, food, and environment agencies, as well as from the Africa Centres for Disease Control and Prevention and international health and development agencies. The committee supervises all surveillance implementation activities, although the country’s AMR surveillance framework primarily focuses on antimicrobial use Case Study 2 Tanzania in hospital and agricultural settings. As of 2021, nine laboratories across the country were equipped to perform antimicrobial susceptibility testing, and 63 sites—45 of them larger facilities that provide acute and outpatient care—contributed data to the national surveillance system. Though promotion of various NAP activities has been underway at the national government level for years, capacity for carrying out AMR work at the local level varies by region and setting. A 2020 survey found that most Tanzanian clinicians were not aware of the NAP; only 23 percent had software to collect and store data on AMR, and 15 percent had access to policies and guidelines for appropriate antibiotic treatment (Sangeda et al. 2020). A lack of AMR surveillance in the community and misuse or lack of access to appropriate antibiotics have raised questions about how common infections, such as UTIs, contribute to AMR burden within the community. UTI is one of the most common bacterial infections globally and is usually diagnosed and treated with antibiotics based on the presence of symptoms (fever, urinary pain) in primary care settings. If medical care is not available, it may be treated by waiting for symptoms to resolve, antibiotic self-prescription, or traditional healing practices. Drug-resistant UTIs in the community can be a risk factor for bloodstream infection and the development of MDR infections and hard-to-treat infections (Madut et al. 2020), and Tanzania has recently documented an increased spread of MDR pathogens outside of hospitals (Moremi 2022). In Tanzania, UTI is the second most common reason for seeking health care among people ages five and older and the most common reason among children younger than five. A gap analysis conducted by the Southern African Centre for Infectious Disease Surveillance (SACIDS) across four East African countries, including Tanzania, identified numerous issues contributing to antibiotic overprescription for UTIs and the risk of rising AMR, including a shortage of trained prescribers and laboratory staff, the lack of clear empirical prescribing guidelines for UTI, the fact that existing surveillance structures do not collect community AMR or UTI data, and the lack of infrastructure and guidelines to carry out AMR susceptibility testing on community urine samples (Silago et al. 2022). Actions taken to respond to AMR Local health training formed the basis of Tanzania’s community AMR surveillance plans. In 2010, with funding from the Rockefeller Foundation and the goal of moving from paper-based to technology-guided infectious disease surveillance, SACIDS began training the staff of primary health care facilities across Tanzania on infectious disease data collection and analysis with the open source EpiCollect and Open Data Kit apps. Funding from the Canadian International Development Research Centre replaced Rockefeller Foundation support in 2013 and sustained the training program through 2017 (Karimuribo et al. 2017), after which numerous international foundations funded specific training and technology development projects. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 193 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices An EpiHack event brought the importance of accessible technology to the forefront of community surveillance efforts.41 The EpiHack in AMR surveillance generated significant awareness of the importance of contributions from primary health care physicians, pharmacists, laboratory professionals, and health care administrators to national infection surveillance. In 2014, funding from the Skoll Global Threats Fund allowed SACIDS to host EpiHack Tanzania, an event that brought together 66 software developers and health professionals from Africa, Asia, and North and South America. The EpiHack fostered discussions between developers and health experts on pressing infectious disease challenges that could be simplified by a technology-based intervention Case Study 2 Tanzania (Karimuribo et al. 2017). The Enhancing Community-Based Disease Outbreak Detection and Response in East and Southern Africa (DODRES) project provided infrastructure, training, and technology that enabled community-led surveillance. The EpiHack was followed in 2015 by a training session to identify ideas and practices aligned with the Global Health Security agenda that could be implemented by SACIDS’s community-centered One Health Security Initiative. SACIDS again hosted the workshop, which was funded by the Skoll Global Threats Fund and the Bill and Melinda Gates Foundation and which included members of the Mekong Basin Disease Surveillance Foundation. The Mekong Basin group was instrumental in guiding discussions around using mobile technology for cross-border partnerships and One Health surveillance near waterways. The major outcome of the workshop was the formation of the DODRES project, which was ongoing as of 2022. Community-led AMR surveillance initiatives worked across East African borders from the outset. DODRES sought to develop infectious disease surveillance tools that could be used within communities, shared information easily with the national Integrated Disease Surveillance and Response System, and strengthened cross-border knowledge and partnerships in East Africa. The formation of DODRES, funded by Ending Pandemics and the Skoll Global Threats Fund, involved close collaboration between SACIDS, the Tanzanian National Institute for Medical Research, the Kenyan Medical Research Institute, Morogoro Municipal and Ngorongoro District Councils in Tanzania, the Narok County government in Kenya, and officials from ministries for health and livestock development in both Tanzania and Kenya. Collaborations and technological groundwork laid the basis for the creation of three app-based AMR surveillance tools. The Techno-Health Innovative Laboratory, established in 2015 at Morogoro Regional Hospital in Tanzania, provided a base for a DODRES design team made up of information and communication technology experts and programmers. The team received mentorship and training from the US-based organization Innovative Support to Emergencies, Diseases, and Disasters. The laboratory chose to use the theory-of-change framework to evaluate its efforts to develop technologic approaches that could be used in and by communities, and in 2016 it issued the first TechnoHealth Surveillance newsletter, which connected partners and the general public to the work being led by DODRES. One of the major activities initiated by DODRES was the creation of three app- based tools; after pilot-testing the prototypes in the laboratory’s urban district and at a cross-border site in Tanzania and Kenya, the tools were packaged together in 2018 as the AfyaData infectious disease surveillance mobile application (Karimuribo et al. 2017). Table 9 highlights the actions taken to develop the AfyaData app and improve awareness of AMR and infectious disease surveillance in Tanzania since 2013, along with the different actors involved in each project. 41  An EpiHack, or epidemiology hackathon, is a gathering of health professionals and software developers intended to develop low-cost and open source technology for public health projects. For more information, see the EpiHack website at https://epihack.org/. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 194 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 9. Actions Taken to Respond to AMR in Tanzania: 2013–2018 IMPLEMENTING INSTITUTIONS PARTNERS INVOLVED MAIN RESPONSIBILITIES International • Rockefeller Foundation Providing financial support to organizations • Canadian International the EpiHack, training programs, Development Research Centre launch of DODRES, and • Skoll Global Threats Fund AfyaData development Case Study 2 Tanzania • Bill and Melinda Gates Foundation • Ending Pandemics • Mekong Basin Disease Providing technical assistance Surveillance Foundation and advice on cross-border • Government officials from and One Health infectious Kenya’s Narok County disease surveillance • Officials from Kenya’s Ministry of Health and Ministry of Agriculture, Livestock, Fisheries, and Cooperatives • Kenya Medical Research Institute • Innovative Support to Providing training and mentorship Emergencies, Diseases, on the use of information and Disasters technology for AMR surveillance National • SACIDS Providing training to community ministries and health workers on app-based research centers infectious disease surveillance • SACIDS Forming a community-based • Ending Pandemics infectious disease outbreak surveillance program based on identified priorities • SACIDS Establishing a resource hub to meld • Ending Pandemics technology, design, and infectious • Tanzanian National Institute for disease surveillance priorities Medical Research and communication • SACIDS Creating the AfyaData app • Ending Pandemics for infectious disease and • Tanzanian National Institute for AMR surveillance Medical Research • Morogoro Municipal Council Guiding technology-based • Ngorongoro District Council surveillance interventions • Morogoro Regional Hospital through advocacy for infectious disease priorities Community • Community health workers Attending training and ongoing groups and local • Members of the public communication efforts for infectious organizations disease surveillance projects Source: World Bank. Note: DODRES = Enhancing Community-Based Disease Outbreak Detection and Response in East and Southern Africa; SACIDS = Southern African Centre for Infectious Disease Surveillance. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 195 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Implementation arrangements The AfyaData mobile app enables data collection, analysis, feedback, and outbreak prediction.42 SACIDS launched the AfyaData mobile app in 2018, along with a training initiative to ensure that AfyaData was usable in communities and across human health and veterinary settings in Tanzania. The AfyaData package comprises (i) an app for data collection; (ii) a web-based server to map, analyze, and provide feedback on surveillance data; and (iii) a disease-prediction and decision- making repository developed by the DODRES team and the Tanzanian National Institute for Medical Case Study 2 Tanzania Research through extensive consultation with health experts. Communication between community reporters and national government officials enabled the national government to stay up to date with AMR and infectious disease issues. Community users of the AfyaData app who were trained to report AMR data and potential outbreaks, along with MoH officials, could receive feedback on submitted data through the AfyaData server, and often used WhatsApp to share best practices and challenges of the One Health approach (Karimuribo et al. 2017). Table 10 summarizes the activities that contributed to the launch and use of AfyaData and the app’s implementation at the MoH level, at the nonprofit and academic level in Tanzania (e.g., SACIDS), across country borders, in collaboration with international nonprofits (e.g., Ending Pandemics), and in community settings with trained primary health care providers and members of the general public. Table 10. AfyaData Implementation Activities across Tanzania and Neighboring Countries IMPLEMENTATION LEVEL INTERNATIONAL INTERNATIONAL (Tanzania MoH) HEALTH CARE AND PRIMARY [e.g., SACIDS]) COMMUNITY (government) NATIONAL NATIONAL (nonprofit) (nonprofit IMPLEMENTATION ACTIVIT Y Launch of AfyaData mobile app’s three interactive modules AfyaData module 1: Android-based client app for offline data collection ☑ AfyaData module 2: Web-based app/server that maps the geographic distribution of infectious disease reports and handles the life cycle of ☑ surveillance data AfyaData module 3: One Health Knowledge Repository that serves as an infectious disease and ☑ ☑ outbreak-prediction and decision-making system Initial AfyaData training and implementation in Tanzania Training of government officials and community reporters to use AfyaData for cholera surveillance ☑ ☑ ☑ across 10 Tanzanian districts 42  For more information, see the SACIDS AfyaData website at http://afyadata.sacids.org/. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 196 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices IMPLEMENTATION LEVEL INTERNATIONAL INTERNATIONAL (Tanzania MoH) HEALTH CARE AND PRIMARY [e.g., SACIDS]) COMMUNITY (government) NATIONAL NATIONAL (nonprofit) (nonprofit IMPLEMENTATION ACTIVIT Y Case Study 2 Tanzania Use of WhatsApp to conduct training, enable feedback on submitted data to community reporters, and share best practice and ☑ ☑ ☑ outbreak warnings Ebola outbreak response Deployment of AfyaData to the Democratic Republic of Congo to enable community- focused surveillance during the 2018–2020 Kivu ☑ ☑ ☑ Ebola outbreak Training of Democratic Republic of Congo health ministry officials and community reporters on ☑ ☑ ☑ ☑ potential uses of AfyaData for Ebola surveillance Protocol for surveillance of MDR community-acquired UTI Gap analysis of needs and opportunities for the development of shared surveillance protocols ☑ ☑ across Malawi, Tanzania, Uganda, and Zambia Development of a study protocol to understand the magnitude and drivers of MDR community- acquired UTI and formulate an AMR control ☑ ☑ ☑ ☑ strategy in the community, while gathering information to strengthen the NAP Use of AfyaData to collect and analyze clinical and demographic information on patients presenting with UTI symptoms in primary care clinics in ☑ ☑ ☑ Mwanza and Dar es Salaam Susceptibility testing through partnerships with national laboratories and via the WHONET ☑ ☑ microbiology laboratory database software Identification of next steps, including translation of the protocol and study methods to other countries and use of the data to inform the development of ☑ ☑ ☑ ☑ UTI prescribing guidelines and policy Source: World Bank. Note: MDR = multidrug-resistant; NAP = National Action Plan; SACIDS = Southern African Centre for Infectious Disease Surveillance; UTI = urinary tract infection. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 197 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The next step in using AfyaData for AMR surveillance was to draw on the collected data to inform antibiotic guidelines. Community reporters and health officials needed guidance in integrating community surveillance with antimicrobial stewardship while also using data to inform national AMR policies and evaluation of the NAP. A UK Fleming Fund grant to Ending Pandemics supported SACIDS in developing and implementing a community-based AMR surveillance protocol on UTI. The protocol was built to understand the dynamics of MDR community-acquired UTI and incorporated (i) case definitions for UTI categories of infection and demographics assembled across several published studies, (ii) national standard operating procedures for urine sample collection, Case Study 2 Tanzania and (iii) Clinical & Laboratory Standards Institute (CLSI) breakpoints and the WHONET microbiology laboratory database software for susceptibility testing and reporting (Silago et al. 2022). The identification of a high prevalence of MDR community-acquired UTI led a pilot study to become a case study for guideline and policy implementation. A study of patients seen for UTI symptoms in two Tanzanian primary care clinics found that more than half of 143 Escherichia coli isolates were resistant to more than three classes of antibiotics (Silago et al. 2022). Despite the limited nature of a pilot study, the finding of pervasive MDR pathogens prompted researchers to develop a project to create empirical antibiotic prescribing guidelines and a national-level community surveillance program. Enablers of progress Several enablers of progress allowed AfyaData to grow from an idea about community-led surveillance into a tool that provides information on drug-resistant UTI in the community— information that formed the basis for the development of empirical antibiotic prescribing guidelines: (i) the value it demonstrated during a cholera outbreak; (ii) constant communication between the community and government leaders; and (iii) a commitment by stakeholders to use data to build needed prescribing guidelines and fight AMR. Each of these is discussed below. A cholera outbreak demonstrated the value of community-led surveillance to national MoH officials. One of the most important factors in connecting community-focused surveillance work to involvement and investment from the MoH was a 2015–2016 outbreak of cholera. Government officials attributed the long duration of the epidemic to the fact that community-level data were not available to the paper-based national surveillance system at the outset. In 2016, as cholera cases continued to mount, a Tanzanian government official recommended that the MoH consult with SACIDS to deploy an early form of AfyaData in five Tanzanian districts; the purpose was both to conduct epidemic surveillance and build a structure for technology-based community reporting into the national infectious disease surveillance system (Ending Pandemics 2017). Ongoing app-based conversations were essential to providing the community with feedback on submitted data and helping government officials use data to meet AMR goals. The One Health Knowledge Repository and the problem-solving community formed on WhatsApp gave community reporters access to valuable real-time feedback from officials about the meaning or implications of data they submitted. Because of this link with the national government and health experts, community reporters had access to knowledge that could lead to protective action against a possible outbreak or to identification of drug-resistant bacteria. Health Ministry officials, in turn, were able to integrate community-level data on AMR into the national surveillance system (Karimuribo et al. 2017; Ending Pandemics 2017). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 198 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Stakeholder commitment to app development and training was integral to informing clinical guidelines. Interviews with national AMR focal point officials helped to reveal the extent of inappropriate empirical prescribing for UTIs. In addition, Tanzania’s National Public Health Laboratory (NPHL) ensured the quality of data submitted via AfyaData by community reporters throughout the UTI study. Data were sent to the NPHL via the WHONET software, a process that offered an opportunity to successfully test how well the national urine collection protocol conformed to global susceptibility reporting structures. Ongoing support for the project and feedback to reporters from the National Institute for Medical Research and MoH within the AfyaData app was invaluable and Case Study 2 Tanzania was built over years through an understanding that community surveillance could help achieve local prescribing improvements and national AMR goals at the same time. Challenges and barriers to success Many of the challenges and barriers to success involved a lack of information and infrastructure for community data collection. Addressing a lack of information meant not only collecting data but also demonstrating that community data could change existing policies and further national AMR goals. Growing investment from national officials was integral to ensuring that community- led AMR surveillance became a key piece of Tanzania’s health infrastructure. Table 11 highlights several barriers to the success of a community-led AMR surveillance approach, along with the factors contributing to these challenges and potential solutions or interventions. Table 11. Barriers and Solutions to Community-Led AMR Surveillance in Tanzania CHALLENGES AND BARRIERS CONTEXT FOR THE INTERVENTIONS OR TO SUCCESS CHALLENGES POTENTIAL SOLUTIONS Lack of • AMR surveillance data come • AfyaData demonstrated that information on primarily from hospitals, where community data used to alert the usefulness data can more easily inform health officials to potential or design of changes in protocols. outbreaks, such as cholera, can community-based be used to track AMR. • Published studies on data tools community AMR in Tanzania • A common surveillance are lacking, and the few protocol for UTI can that exist focus on specific support the translation of populations, such as pregnant or community surveillance into immunocompromised people. evidence-informed guidelines. Lack of • The national surveillance • AfyaData built a structure infrastructure system focuses on collecting for collecting, analyzing, for community- hospital-based data. and responding to based infectious community-level data. • Many communities do not have disease data access to laboratory testing, • Partnerships with the national collection making it difficult to understand laboratory and the use of the burden of AMR. WHONET software ensured that community isolates could be tested for resistance. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 199 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Limited • WHO guidelines do not • Community data can guide applicability of recommend screening physicians when susceptibility global guideline for extended-spectrum and ESBL testing are needed, to local beta-lactamases (ESBLs) especially when laboratory circumstances in community-acquired UTI testing is unavailable. caused by Enterobacterales. Source: World Bank. Case Study 2 Tanzania Note: UTI = urinary tract infection; WHO = World Health Organization. Takeaways for the benefit of One Health teams planning to implement similar or related interventions Tanzania’s experience of developing a tool and a network for community-based surveillance of infections, outbreaks, and AMR could help other teams planning a similar community-based project. Key elements of Tanzania’s success include the following: 1. Iterative, step-by-step process. Rather than focus on the long-term sustainability of the project at the outset, SACIDS took an iterative approach to the development of AfyaData, seeking out diverse funding sources that would enable one clear step of the project. This approach allowed SACIDS the freedom to build a tool and foster a community that arose from relevant infectious disease surveillance needs; the approach also empowered shared leadership for different aspects of the project, and allowed the tools to be tested in real-life surveillance situations. 2. Relevance to clinical guidelines and policy. AfyaData’s use for community-led surveillance provided a digital platform for timely data collection and rapid understanding of Tanzanian UTI pathogens and antibiograms, which facilitated the creation of rational empirical therapy guidelines still in development. 3. Diverse networks. Learning from South and Southeast Asian projects about infectious disease surveillance in river basins and across national borders via the Mekong Basin Disease Surveillance Foundation helped to build a more sustainable project, one that concentrated on human health but incorporated a One Health focus and methodology. 4. Collaboration between community and government. Relationships built on knowledge exchange and feedback between health officials and community members broadened the national surveillance focus to include disease and drug resistance occurring outside of hospitals. 5. Training and mentorship. Training programs on infectious disease and AMR surveillance and reporting promoted a participatory relationship between community members, government officials, clinicians, and laboratory staff, creating the potential for harmonized work during a public health crisis and community involvement in developing in-progress prescribing guidelines. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 200 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices References Ending Pandemics. 2017. “The DODRES Project: Revolutionizing Human and Animal Disease Surveillance in Tanzania.” http://endingpandemics.org/wp-content/uploads/2017/04/ EP_DODRES_CaseStudy.pdf. Frumence G., L. E. G. Mboera, C. Sindato, B. Z. Katale, S. Kimera, E. Metta, A. Durrance-Bagale, et al. 2021. “The Governance and Implementation of the National Action Plan on Antimicrobial Case Study 2 Tanzania Resistance in Tanzania: A Qualitative Study.” Antibiotics (Basel) 10 (3): 273. https://www.mdpi.com/2079-6382/10/3/273. Karimuribo E. D., E. Mutagahywa, C. Sindato, L. Mboera, M. Mwabukusi, M. K. Njenga, S. Teesdale, J. Olsen, and M. Rweyemamu. 2017. “A Smartphone App (AfyaData) for Innovative One Health Disease Surveillance from Community to National Levels in Africa: Intervention in Disease Surveillance.” JMIR Public Health and Surveillance 3 (4). https://publichealth.jmir. org/2017/4/e94. Madut D. B., M. P. Rubach, N. Kalengo, M. Carugati, M. J. Maze, A. B. Morrissey, B. T. Mmbaga, et al. 2020. “A Prospective Study of Escherichia coli Bloodstream Infection among Adolescents and Adults in Northern Tanzania.” Transactions of the Royal Society of Tropical Medicine & Hygiene 114 (5). https://academic.oup.com/trstmh/article/114/5/378/5671604. Makoye, Kizito. 2021. “Antibiotic Misuse Drives Drug-Resistant Bacteria in Tanzania.” Anadolu Agency. September 24, 2021. https://www.aa.com.tr/en/africa/antibiotic-misuse-drives-drug- resistant-bacteria-in-tanzania/2373815. Mbwasi, R., S. Mapunjo, R. Wittenauer, R. Valimba, K. Msovela, B. J. Werth, A. M. Khea, et al. 2020. “National Consumption of Antimicrobials in Tanzania: 2017–2019.” Frontiers in Pharmacology 11. https://www.frontiersin.org/articles/10.3389/fphar.2020.585553/full. MoHCDGEC (Ministry of Health, Community Development, Gender, Elderly and Children). 2017. “The National Action Plan on Antimicrobial Resistance 2017–2022.” https://www.who. int/publications/m/item/united-republic-of-tanzania-the-national-action-plan-on- antimicrobial-resistance. Moremi, N. 2022. “Tanzania AMR Surveillance: Fleming Fund Regional Grant Pilot Study.” Research presented for an Ending Pandemics and Fleming Fund seminar (online). January 17, 2022. Sangeda R. Z., J. Kibona, C. Munishi, F. Arabi, V. P. Manyanga, K. D. Mwambete, and P. G. Horumpende. 2020. “Assessment of Implementation of Antimicrobial Resistance Surveillance and Antimicrobial Stewardship Programs in Tanzanian Health Facilities a Year after Launch of the National Action Plan.” Frontiers in Public Health. https://www.frontiersin.org/ articles/10.3389/fpubh.2020.00454/full. Silago, V., Moremi, N., Mtebe, M., Komba, E., Masoud, S., Mgaya, et al. 2022. “Multidrug-Resistant Uropathogens Causing Community Acquired Urinary Tract Infections among Patients Attending Health Facilities in Mwanza and Dar es Salaam, Tanzania.” Antibiotics (Basel, Switzerland), 11(12). https://pubmed.ncbi.nlm.nih.gov/36551375/ WHO (World Health Organization). 2022. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 2022. Geneva: World Health Organization. https://www.who.int/ publications/i/item/9789240062702. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 201 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Nigeria: Strengthening laboratory capacity for antimicrobial resistance Summary Case Study 2 Nigeria Limitations in laboratory capacity hinder the prompt identification of pathogens and the antibiotic susceptibility testing needed to mitigate the spread of antimicrobial-resistant pathogens in Nigeria through optimal surveillance. The Nigerian National Action Plan highlights the existence of too few quality-assured microbiology laboratories as a major challenge in the fight against AMR in the country. A lack of trained personnel with the requisite skills to man these laboratories, along with difficulties in procuring supplies needed to ensure their smooth operation, poses another challenge. Strengthening laboratory systems in Nigeria will be important for generating the high-quality data needed to inform actions and policies that curtail the spread of AMR. Together with international partners, Nigeria is currently implementing interventions as part of a multiphase AMR program aimed at strengthening diagnostic stewardship in major health care facilities. Strengthened laboratory facilities, efficient pre-analytic clinical processes, and the timely use of quality-assured laboratory data play a crucial role in supporting patient care, AMR surveillance, and diagnostic stewardship. This case study describes two initiatives that aim to build resilient health systems and a trained workforce in order to better address AMR. The two partnerships highlighted in this case study are the Diagnostic Stewardship subproject of the Capacity Development for Preparedness and Response for Infectious Diseases (NiCaDe) project and the Regional Disease Surveillance Systems Enhancement (REDISSE) project. The case study outlines implementation arrangements, enablers of progress, challenges and barriers to success, and takeaways to support the implementation of similar interventions in other countries. The context and specific challenges being addressed The paucity of high-quality AMR data and absence of a robust national AMR surveillance system are challenges for Nigeria. Nigeria’s NAP highlights too few quality-assured microbiology laboratories as a challenge. To better manage infectious diseases and the associated AMR, the generation of high-quality microbiological and clinical data is essential. Nigeria has made some progress in strengthening health systems and infrastructure but still faces significant gaps in equipment availability, laboratory reagents, and trained personnel needed to perform standard blood cultures in secondary health care facilities (Federal Ministries of Agriculture, Environment, and Health 2017a). Some of the challenges facing laboratories in Nigeria are also linked to broader country-specific infrastructural challenges, such as poor power supply. In addition, limited data capture systems, local manufacturing of equipment, and the use of low-quality or substandard reagents may also affect laboratory results. These challenges have created gaps that increase the use of broad-spectrum antibiotics, and that could, in turn, lead to the spread of more resistant pathogens. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 202 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The national surveillance program in Nigeria has not effectively captured information on AMR. AMR diagnostics that currently support national surveillance are primarily undertaken by a few teaching hospitals and private laboratories in universities in the context of multiple ongoing research projects with international academic and research institutions. The National Reference Laboratory (NRL) currently supports only limited AMR activities because of insufficient materials, infrastructure, and clinical bacteriology expertise for quality assurance. Without a robust and representative national AMR surveillance program, generating reliable data to inform treatment guidelines or policy is difficult. Case Study 2 Nigeria Actions taken to respond to AMR and implementation arrangements Nigeria has made substantial progress in response to AMR. It has AMR-specific national action plans and an ongoing collaboration with international partners to improve the AMR surveillance system and strengthen laboratory capacity within the country. The Implementation activities and actions taken to respond to AMR across Nigeria are summarized in Table 12. The Nigeria Centre for Disease Control (NCDC) coordinates prevention, response, and control activities across the human, animal, and environmental sectors in line with the One Health approach articulated in the NAP for AMR. As the central coordinating body and AMR focal point, the NCDC led Nigeria’s situation analysis in 2016, the development of Nigeria’s 2017–2022 NAP (Federal Ministries of Agriculture, Environment, and Health 2017b; NCDC 2018), and the One Health Strategic Plan 2019–2023 (Federal Republic of Nigeria 2019), where AMR was considered a major focus for One Health actions. These documents were developed in collaboration with key stakeholders from the Federal Ministry of Agriculture and Rural Development (FMARD), the Federal Ministry of Health (FMOH), and the Federal Ministry of Environment (FMOE), with support from Global Antibiotic Resistance Partnership (GARP) Nigeria. With the formation of the national Antimicrobial Resistance Coordination Committee (AMRCC) to shape, oversee, and monitor AMR-related activities across sectors for systematic and comprehensive implementation, the governance structure for implementing the initiatives above was intended to reflect multidisciplinary and sectoral integration. The operational aspect of the national AMR activities in Nigeria is overseen by the national AMR Technical Working Group (ATWG). This working group has representation from the government ministries, departments, and agencies across One Health sectors, including academia and the private sector. This structure facilitates intersectoral coordination at the national level and serves as a governance template that can be replicated at the lower levels and in line with Nigeria’s tiered political and health systems. The NCDC is supported by a range of partnerships with public health institutes and nongovernmental organizations. The AMR coordinating center at the NCDC has also built a network with sentinel sites (designated AMR centers selected from across the country) and secondary health care facilities for AMR surveillance. Through existing government funds and support from development partners, the NCDC has overseen the establishment of the NRL to support pathogen surveillance and has made substantial progress in strengthening public health infrastructure in Nigeria. In addition, AMR testing has been incorporated into other existing systems, such as the laboratories of the National Institute of Pharmaceutical Research and Development (NIPRID), the National Veterinary Research Institute (NVRI), and other regional laboratories supported with funding from the Fleming Fund and other partners.43 However, the NRL currently does not support many AMR activities due to gaps in the availability of materials for quality assurance, infrastructure, and clinical bacteriology expertise. The main activities in bacteriology have been limited to the surveillance of cerebrospinal meningitis and cholera. 43  For information on the Nigeria grant, see Fleming Fund, “Nigeria Country Grant,” https://www.flemingfund.org/grants/nigeria- country-grant/. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 203 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR diagnostics are primarily undertaken by teaching hospitals and private laboratories in universities in the context of multiple ongoing research projects with international academic and research institutions. In addition, resistant TB surveillance programs are in place within the country. The Global Fund currently supports an existing resistant TB detection program in Nigeria public hospitals. The national AMR surveillance system was established in 2017 with 19 laboratories (11 human health and 8 animal health laboratories) to strengthen diagnostic capabilities and epidemiological data collection. The Fleming Fund has been instrumental in establishing and Case Study 2 Nigeria maintaining these laboratories. There is also improved coordination of AMR activities in the country and synergy between the NCDC and relevant ministries and agencies. NVRI was recently designated as the NRL for animal health and oversees the surveillance of AMR in food systems, livestock, poultry, aquaculture, and other related sectors. This One Health and interdisciplinary approach is critical for ensuring functional infection prevention and control (IPC) systems within farms and health facilities. Capacity was scaled up in response to the COVID-19 pandemic, especially in molecular surveillance of viral diseases across sectors. Cumulatively, there is increased capacity for clinical, laboratory, and research staff, and the country is slowly taking greater ownership of the AMR response. The World Bank REDISSE project (World Bank 2020) has helped to build capacity for zoonotic disease surveillance, laboratories, outbreak preparedness, human resources, and institutional capacity in Nigeria (Box 10). The project fosters One Health competencies that are AMR-sensitive and helps to address the public health challenges that might arise from the interaction between humans, animals, and the environment, including those associated with AMR. The World Bank’s US$200 million intervention in the COVID-19 pandemic positioned Nigeria and other African countries participating in the REDISSE project to mount an early and effective response to COVID-19. Box 10. REDISSE Project in Nigeria REDISSE Project in Nigeria The World Bank launched the REDISSE project in 2016 to respond to the challenge of infectious diseases and help protect countries from current epidemic threats like Ebola and from any future epidemics. The project became effective in Nigeria on February 13, 2018, and is jointly implemented by the NCDC, FMOH, and FMARD. As the COVID-19 pandemic escalated, the REDISSE project provided more than US$200 million for the response in 13 countries in West and Central Africa. By working closely with the German Robert Koch Institute (RKI), the NCDC is improving diagnostic and antibiotic stewardship programs in many health care facilities in Nigeria. So far, IPC training guidelines have been developed with support from RKI and the US Centers for Disease Control and Prevention. The RKI diagnostic stewardship project (GHPP 2021) serves as a proof-of-principle diagnostic stewardship intervention; it provides technical and material support to improve the generation of quality-assured microbiologic data, which are needed to inform clinical antimicrobial therapy in preselected model secondary hospitals and as part of AMR surveillance nationally. The program promotes patient-centered interdisciplinary communication strategies through the NiCaDe project. Some of the resources and capacity provided also supported diagnostics of SARS-Cov-2 as part of the national response to the COVID-19 pandemic. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 204 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The efforts of various professional bodies and agencies have helped to increase the general public’s awareness of AMR. Professional bodies—such as the Veterinary Council of Nigeria (VCN), the Medical Laboratory Science Council of Nigeria (MLSCN), and the Nigeria Medical and Dental Association—integrate AMR education into their continuing education programs and conferences to raise awareness directly among professionals and indirectly among the general public. Agencies, including the National Agency for Food and Drug Administration and Control (NAFDAC) and National Primary Health Care Development Agency (NPHCDA), also carry out education and awareness activities on hand hygiene and WASH (water, sanitation, and hygiene) among health care workers Case Study 2 Nigeria and within communities and schools. These campaigns are aimed as contributory but foundational strategies to reduce the burden and spread of diseases and, thus, the need for antimicrobials. Establishment of the national One Health Antimicrobial Resistance/Antimicrobial Use Community of Practice (COP) by the government of Nigeria, with support from development partners, has enhanced and continues to ensure the exchange of ideas to support and improve AMR activities and stewardship in the country through a One Health approach. For example, as part of World Antimicrobial Awareness Week 2021, a National Awareness Walk was held in the nation’s capital to create public awareness of responsible antibiotic use. Nigeria has been enrolled in the WHO GLASS surveillance network for AMR since April 2017. The collection, analysis, and sharing of AMR data by countries are increasingly standardized through GLASS. As a result, Nigeria and other participating countries can now better monitor and compare resistance patterns and use the data to inform policy. Veterinary clinicians are also encouraged to follow the WOAH guidelines on antimicrobial agents for use in animals. The establishment of the Field Epidemiology and Laboratory Training Program (FELTP) in Nigeria with the support of the US CDC is also important for outbreak preparedness and response.44 Complementary but specific to the AMR response is the Fleming Fund’s public health leadership program that trains fellows from across the One Health spectrum to support AMR programs and surveillance activities. The fellows from Nigeria constitute a trained workforce team with enhanced capacity, increasingly leading the implementation and taking national ownership of national strategies. The WHO Tricycle surveillance project is a more recent One Health intervention strengthening surveillance of ESBL Escherichia coli in animals, humans, and the environment (WHO 2021). The project’s implementation in Nigeria and other countries uses a WHO-approved protocol that compares the local and regional evidence base to advance strategies for combatting AMR. 44  TEPHINET (Training Programs in Epidemiology and Public Health Interventions Network), “Nigeria Field Epidemiology and Laboratory Training Program,” https://www.tephinet.org/training-programs/nigeria-field-epidemiology-and-laboratory-training-program. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 205 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 12. Implementation Activities and Actions Taken to Respond to AMR across Nigeria IMPLEMENTING INSTITUTIONS ACTIVIT Y OR ACTION PARTNERS INVOLVED International Financial support • Public Health England organizations (Fleming Fund) • Robert Koch Institute • US CDC Case Study 2 Nigeria • World Bank • Canadian Foundation for Infectious Diseases • WHO Technical assistance in activity planning and • WHO implementation (AMR surveillance, diagnostic • African Field and antimicrobial stewardship, IPC, One Epidemiology Health, epidemic preparedness, and advice Network (AFENET) on cross-border and One Health infectious • Africa CDC disease surveillance • US CDC • Public Health England Digitalization of sentinel sites for • Robert Koch Institute AMR surveillance National Regulatory activities • Federal Ministries of ministries and • AMR coordinating body Health, Agriculture, research centers established at NCDC and Environment • NCDC • AMR national surveillance coordinating • National universities body formed • National Agency • One Health AMR Technical Working for Food and Drug Group formally inaugurated at NCDC to Administration conduct situation analysis on AMR; Nigeria and Control enrolled in GLASS • FMARD • Development of NAP for AMR • National AMR policy ongoing • Strengthening of import regulations to assure drug quality • Update of national drug policy to include AMR and antimicrobial stewardship • Draft of the national antimicrobial stewardship plan • Adoption of WHO AWaRe (access, watch, reserve) classification and update of essential drug lists and standard treatment guidelines Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 206 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Capacity-building activities • NCDC • AMR awareness raising through education • Federal Ministries of information and training Health, Agriculture, and Environment • Strengthening of AMR surveillance system • WHO for human health by equipping laboratories • Robert Koch Institute and training workers in quality assurance • Fleming Fund for AMR detection and surveillance and by Case Study 2 Nigeria enrolling more laboratories in GLASS • Implementation of antibiotic stewardship programs at all levels • Implementation of IPC committee in designated health facilities • Tricycle One Health surveillance • Mobilization of stakeholders and communities by COP to improve awareness, build capacity, and advocate for AMR • Support by FMARD for the World Organisation for Animal Health (WOAH) Performance of Veterinary Services Follow-up Mission (report from this mission is publicly available and has also been circulated with relevant stakeholders) Research centers Targeted research studies • NCDC • Point Prevalence Survey on • Local researchers Antimicrobial Use • Various international partners • National Antimicrobial Stewardship work plan according to NAP and Joint External Evaluation benchmark • Antimicrobial stewardship needs assessment • Antimicrobial consumption surveillance in pharmacies across many states in Nigeria Community Targeted awareness raising and education • University of Ibadan groups and local by student and university groups, especially • Africa One Health organizations during World Antibiotic Awareness Week Network (AfOHNet) Webinars, policy advisory Private organizations Source: World Bank. Note: CDC = Centers for Disease Control and Prevention; COP = Community of Practice; FMARD = Federal Ministry of Agriculture and Rural Development; GLASS = Global Antimicrobial Resistance and Use Surveillance System; IPC = infection prevention and control; NCDC = Nigeria Centre for Disease Control; WHO = World Health Organization. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 207 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Enablers of progress International partnerships allow for the mobilization of resources, technical exchange, collaborative project implementation, and institutional capacity building to strengthen laboratories and consequently improve patient care, AMR surveillance, and diagnostic stewardship. The implementation of action plans to address AMR depends on the efforts of many actors within the country and on the support of several international organizations, especially in the animal and human health sector (e.g., the Fleming Fund and the WHO). The focus here will be Case Study 2 Nigeria on the remarkable contributions of the RKI’s NiCaDe project and the World Bank’s REDISSE project, in addition to some in-country efforts. Through the NiCaDe project, the RKI has supported NCDC by strengthening laboratory capacity in selected secondary hospitals through pilot models for diagnostic stewardship. This multiyear project supports structures and processes to enhance quality assurance in AMR diagnostics, surveillance, multidisciplinary communication, data digitalization, and equipment and material procurement. The project was co-conceived by both partners, but NCDC led the implementation of the project to accommodate predefined local priorities and to contribute knowledge of the local context. This approach has facilitated the achievement of the expected project  outputs so far. The project also funded guest residency of Nigerian AMR program managers and senior laboratory staff at the RKI Berlin. They gained the required knowledge and skills to support national AMR control efforts further. This clear identification of partners’ strengths promotes mutual respect and the overall success of the ongoing projects.45 The World Bank–funded REDISSE project supports the One Health framework in Nigeria by building capacity for disease surveillance and epidemic preparedness. The REDISSE project funds the development of high-quality public health and veterinary laboratories to facilitate emergency disease response. This component of the project has strengthened systems, laboratory capacity, and disease response in Nigeria. Nigeria’s involvement in the REDISSE project is also generating data on animal health activities necessary for policy implementation and intervention designs. Highly committed local institutions, and strong and stable leadership at the NCDC in particular, have strengthened local institutional capacity for AMR. Aside from cross-sectoral governance and capacity building led by the NCDC, the National AMR Coordination Committee and Animal Health Technical Working Group are in place to support AMR activities. NCDC continues to organize training and education opportunities for laboratory, clinical, and animal health staff locally and in the context of international scientific partnership. In particular, FELTP brings together medical, animal, and environmental science professionals who continue to provide personnel to support AMR field activities. The recent designation of NVRI as the NRL for animal health that oversees surveillance of AMR in food systems, livestock, poultry, aquaculture, and other related sectors is a step in the right direction for addressing AMR and a sign of progress. The Nigerian NAP for AMR has provided a clear framework for implementing AMR activities and links strongly with the Global Action Plan’s five core work packages (awareness creation, surveillance, antimicrobial stewardship, infection prevention, and research) (WHO 2015). The Global Action Plan was endorsed by the World Health Assembly in May 2015 to tackle the growing problems of antimicrobial resistance globally. The Nigeria NAP, however, highlights the strengths, weaknesses, opportunities, and threats of the AMR situation in Nigeria and outlines the governance structure from within the Nigerian ecosystem that oversees AMR-related activities and interventions. 45  Details about and insight into the RKI-funded NiCaDe project in Nigeria are from Dr. Olaniyi Ayobami of the Robert Koch Institute, Germany. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 208 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices This clear roadmap of action plans allows for strategies that will prevent, reduce, or slow down the spread of resistant pathogens in the country and facilitate a strong alignment of locally identified priorities with external resources and technical support. A review of the Nigeria NAP (2017–2022) is currently ongoing to assess progress and determine next steps for the subsequent edition of the Nigeria NAP. A variety of institutions and agencies have contributed to increased AMR awareness among human and animal health professionals by engaging these professionals in AMR and One Health Case Study 2 Nigeria activities, such as World Antimicrobial Awareness Week. The NCDC also coordinates a National One Health Antimicrobial Resistance/Antimicrobial Use COP with the support of the Fleming Fund. The COP is meant to provide a social learning platform for formal and informal stakeholders who work in human, animal, and environmental health who wish to collaborate, share ideas, and find solutions to the challenges of AMR. In Nigeria, the human resource base for One Health is also increasing as the dangers of reducing antibiotics’ effectiveness become more evident and as opportunities for training on AMR proliferate. Challenges and barriers to success Political commitment and funding are still a major barrier to pushing forward AMR prevention and control activities in Nigeria. A strong political commitment can guarantee adequate funding and the requisite legislative actions to address AMR across sectors. This is true in a socially complex setting with several structural and systemic weaknesses in governance and law enforcement. The Nigerian government still needs to make a significant investment and allocate a substantial part of its budget to strengthen the country’s laboratories and health systems. The current budgetary allocation to health in Nigeria (about 7 percent as of 2021) is not enough to cater for the ever-growing Nigerian population. It falls short of the Abuja Declaration of 2001 that requires governments to allocate 15 percent of their budget to the health sector. The poor political commitment has stifled the mobilization of adequate funds, especially given the competing demand for limited resources and the dwindling government revenue. With the decreasing revenue from oil sales, the government is actively seeking other sources of revenue while cutting down funding in some sectors that are most in need of sustained funding. Dependence on donors thus becomes unavoidable in the absence of significant local funding. One of the main issues behind the low funding of AMR projects in Nigeria is that there could be inadequate economic case models for investment in AMR. Such models are needed to capture the AMR burden and convey its impact on AMR-related productivity losses affecting the country’s economy. Political will—demonstrated via tailored engagements and innovative financing through local financing instruments—is important to get the message through and stimulate action. Socioeconomic realities of poverty and unemployment present an ethical dilemma for strict enforcement of regulated antibiotic use that is critical to counter the emergence of resistant infections in the community. Many people in urban and rural communities access antibiotics through open markets and poorly regulated patent medicine vendors. The nonprescription use of antibiotics is a widespread driver of selective pressure. The nonprescription sale of antibiotics is poorly regulated, though it remains part of the economic life of many local communities, where it is a common source of livelihood. This situation points to the need for stronger law enforcement around the sale and use of medicines in Nigeria, along with economic initiatives addressing poverty and unemployment. An additional challenge is the lack of access to antimicrobials—especially second- line antibiotics—when the first-line antibiotic is ineffective. This drives the emergence and spread of resistant infections. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 209 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices As in most LMICs, weak health systems are another challenge; a resilient health system is needed to sustainably confront AMR, as resistant infections exert organizational and financial pressures that are resource intensive. The Nigerian health system is bedeviled with perennial challenges of weak funding, weak governance, and a rural-urban disparity in human resources, made worse by the surging brain drain in recent years. According to estimates in the 2017 NCDC situation analysis on antimicrobial use and AMR, only about 6 percent of the public health facilities in Nigeria have functional laboratories, while only one-third of these laboratories have qualified personnel to handle diagnostic tasks (Federal Ministries of Agriculture, Environment, and Health 2017a). Few Case Study 2 Nigeria personnel are trained in AMR laboratory surveillance, and the infrastructure to support genomic surveillance of emerging and circulating resistant infections is limited. Setting up such laboratory systems and infrastructure to ensure quality assurance is expensive and usually beyond the reach of low-resource countries without innovative strategies to leapfrog the adoption of these emerging diagnostic technologies. It is imperative to take actionable steps to address this challenge; these should include increasing laboratory capacity, securing a supply chain to ensure availability of laboratory reagents for priority AMR pathogens detection, and establishing AMR trainings to support in-country AMR surveillance programs. Sectoral integration and standardization of methods are inadequate; the animal, human, and environmental health sectors are traditionally fragmented, and the individual disciplines employ different strategies. Policy planning and coordination are conducted with the stakeholders in the FMOE and FMARD, but at the operational level, the majority of the AMR projects the NCDC superintends are in the human health sectors. The animal and environmental sectors in Nigeria are yet to benefit from adequate funding for AMR-related projects. The insufficient inclusion of the environmental and agricultural sectors might be linked to poor awareness of the contributions of these sectors in mitigating the spread of AMR, to lack of tools, or to risk-mapping standards. In many respects, data sharing on surveillance methods is not yet standardized or integrated. In addition, there are still challenges with defining roles for the major players in the FMOE regarding surveillance and control of AMR pathogens. Shifting emphasis from a human-centric approach to a true One Health approach will require sustained engagement, standardization of methods, and new tools. Data-related challenges are pervasive; there are particular challenges with quality-assured AMR data and its linkage with clinical data on the one hand and its interoperability on the other. The available data are limited and suffer from quality challenges, including bias, duplication, lack of timeliness, and lack of intersectoral linkages, thereby limiting the potential of the available data for greater impact across sectors. Specific challenges include the dearth of data on antimicrobial use across sectors but especially in the animal sector; multiple factors are responsible for this situation, including a poor or absent regulatory framework and limited coordination with the private sector, livestock owners, and crop farmers. A lack of standards and tools compounds the problem. Other sector-specific challenges include the absence of a national animal identification and traceability system, which leaves livestock farming practices and ownership unregulated. There is also poor delineation of roles and responsibilities in subsectors like the food systems, where multiple agencies still have overlapping responsibilities and sometimes work at cross-purposes. Without coordination of and support for AMR researchers under a defined local AMR research agenda, it will be challenging to bridge data gaps and build the evidence needed to engage policy makers and galvanize public health actions. To address this challenge, much more needs to be done to improve data capture, storage, and use through modern technologies and information systems in laboratories and hospitals in the human, animal, and environmental sectors. This may also include developing standard operating procedures for verification and identifying an external quality assessment provider for the NRL. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 210 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Takeaways for the benefit of other teams planning to implement similar or related interventions To achieve improved population health outcomes, especially in low- and middle-income countries, health policies and strategies must address locally determined priorities in a way that also addresses the sociocultural underpinnings of the issue, and policies and strategies must be implemented in a way that ensures impact and sustainable ownership. For other teams planning to implement an intervention similar to the REDISSE or RKI project, the following Case Study 2 Nigeria recommendations might prove helpful: 1. Align the intervention with predefined local action plans and strategies. This is important to ensure that priority activities are funded and implemented so as to promote resource efficiency and achieve expected outputs and impact on population health. RKI keyed into defined priorities of the NCDC in addressing gaps in AMR surveillance and antimicrobial stewardship. By doing so, it was able to align the historical competencies of RKI in AMR surveillance with the desire of the NCDC leadership to strengthen the national surveillance system for high-quality and representative AMR data. This strategic mutual interest has fostered the needed cooperation and continuous exchange at the highest level of health sector leadership in Nigeria and Germany. 2. Consider building sustainability strategies. The REDISSE project has ensured its sustainability in part by including the government, practitioners, communities, and other stakeholders at the conception and planning stages of the project. It also established a sustainable plan that thinks beyond the funding cycle by empowering, training, and supporting the recipient country to take ownership and lead the project. Also relevant is the scientific cooperation between RKI and NCDC, which provides funding to the NCDC to manage the staff recruitment, material procurement, and the project’s field implementation. At the same time, RKI offers technical support for research, tools development, and overall project implementation. The laboratories in model sites are being designed to serve as hubs to provide high-quality microbiological services to other catchment hospitals in a defined geographical range; the goal is to pool finances for regular procurement of consumables and other low-level logistics sustainably beyond project lifespan. Furthermore, to complement external support, promote sustainability, and lessen dependence on donor funding, local communities (individuals and organizations) should be engaged to mobilize local resources beyond government funding. The NCDC-RKI diagnostic stewardship project identified many local experts, including those from the selected hospitals, to lead training where appropriate. 3. Promote local research and professional bodies (such as medical associations and other allied professional societies) to engage policy and actions. Locally generated evidence is needed to engage policy makers, develop solutions, prioritize interventions, and allocate resources for impact. Where possible, teams can support or fund proofs-of-concept that are adapted to contextual realities and that provide templates for scaling up and wider adoption. Opportunities must be provided to share learning experiences across sectors with communities and policy stakeholders through dissemination feedback and policy briefs. Where feasible, international partnerships should support knowledge translation and incorporate existing structures and processes beyond the national level to include regional and local health systems. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 211 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices References Federal Ministries of Agriculture, Environment, and Health. 2017a. “Antimicrobial Use and Resistance in Nigeria: Situation Analysis and Recommendations.” https://ncdc.gov.ng/themes/common/ docs/protocols/56_1510840387.pdf. Federal Ministries of Agriculture, Environment, and Health. 2017b. “National Action Plan for Antimicrobial Resistance 2017–2022.” http://www.ncdc.gov.ng/themes/common/docs/ Case Study 2 Nigeria protocols/77_1511368219.pdf. Federal Republic of Nigeria. 2019. “One Health Strategic Plan.” https://ncdc.gov.ng/themes/common/ docs/protocols/93_1566785462.pdf. GHPP (Global Health Protection Programme). 2021. “Nigeria Centre for Disease Control: Capacity Development for Preparedness and Response for Infectious Diseases (NiCaDe).” https://ghpp.de/en/projects/nicade/. NCDC (Nigeria Centre for Disease Control). 2018. “National Action Plan for Health Security 2018–2022.” https://ncdc.gov.ng/themes/common/files/establishment/5e88f9e22d2b4e4563b527005 c8a0c43.pdf. WHO (World Health Organization). 2015. “Global Action Plan on Antimicrobial Resistance.” https://apps.who.int/iris/handle/10665/193736. WHO (World Health Organization). 2021. “The Tricycle Project: WHO Integrated Global Surveillance on ESBL Producing E. coli Using ‘One Health’ Approach.” March 16, 2021. https://www.who.int/ publications/i/item/who-integrated-global-surveillance-on-esbl-producing-e.-coli-using-a- one-health-approach. World Bank. 2020. “Epidemic Preparedness and Response.” October 12, 2020. https://www.worldbank. org/en/results/2020/10/12/epidemic-preparedness-and-response. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 212 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 6 Tools to Support the Design and Implementation of Operations Summary 214 CHEVRON- Introduction 215 CHEVRON- Phase 1: Project Identification, Preparation and Appraisal 216 CHEVRON- Phase 2: Implementation 218 CHEVRON- Phase 3: Completion and Evaluation 220 CHEVRON- Tools 222 CHEVRON- Costing and Implementing AMR Interventions, including NAPs 240 CHEVRON- References 241 CHEVRON- Costing and financing have been identified as a challenge to addressing AMR in low- and middle-income countries…a range of tools exist that can be used to support the prioritization and leadership of sectors in mobilizing investments. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 213 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Chapter 6 Tools to Support the Design and Implementation of Operations Chapter 6 summary In 2021, the World Bank published a Landscape Analysis of Tools to Address Antimicrobial Resistance (AMR). This chapter draws on that work to provide task teams and clients with guidance on the range of tools that can be used to support project design and implementation. The Landscape Analysis of Tools identified over 90 tools for supporting investments in AMR. This chapter organizes the tools in terms of the project cycle across three categories: project identification, preparation, and appraisal; implementation; and completion and evaluation. Costing and financing have been identified as a challenge to addressing AMR in low- and middle-income countries (LMICs), and this chapter highlights tools that can be used for costing interventions. In 2020, the World Health Organization (WHO) found that only 20 percent of National Action Plans (NAPs) were fully funded, and 40 percent had a budgeted operational plan (WHO 2021c). Successive Joint External Evaluation (JEE) reports have also highlighted a gap in financing for health security, particularly for AMR. This chapter therefore highlights a range of tools that can be used to support the prioritization and leadership of sectors in mobilizing investments. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 214 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Introduction The World Bank’s (2021) Landscape Analysis of Tools to Address AMR identified over 90 tools for supporting investments in AMR. The review identified six domains for actions and interventions focused on AMR: (i) awareness raising; (ii) antimicrobial stewardship; (iii) sur-veillance; (iv) infection prevention and control (IPC) in human and animal health; (v) the reduction of pathogen spread in the environment; and (vi) development of a national research agenda. These domains cut across human, animal, and environ¬mental health and key sectors—health, agriculture, environment and water, sanitation, and hygiene—that are all part of a multisectoral approach. Certain domains were well covered by the tools identified in the review, including surveillance interventions (46 out of the 90 tools), IPC (34 out of 90), and stewardship policies and intervention options (34 out of 90). In contrast, only 13 tools considered the spread of pathogens in the environment; five of these looked at the issue in detail, and the remaining eight looked at broader concerns related to the issue. This chapter aims to provide task teams and clients with guidance on the range of tools that are available and offer suggestions about how they might be drawn upon in the design and implementation of operations. The Quadripartite organizations—WHO, World Organisation for Animal Health (WOAH), and Food and Agriculture Organization of the United Nations (FAO)—along with the United Nations Environment Programme (UNEP) and other institutions have developed a wide range of global, regional, and country-level tools that are designed to support countries in addressing AMR. At the relevant points in the project cycle, these tools can ensure that sector- and country-specific actions to target AMR are integrated appropriately into World Bank–financed projects. The chapter provides a list of the tools (updated since the Landscape Analysis in 2021). To support task teams and clients in selecting from among available tools, it organizes the tools into three categories related to the project cycle: identification, preparation, and appraisal; implementation; and completion and evaluation (see Table 14). The chapter also highlights certain tools across each project category to assist countries and implementers in leveraging the most essential tools from the range of options and in streamline their decision-making processes. Project identification, preparation, and appraisal Implementation PHASE 1 PHASE 3 PHASE 2 Completion and evaluation PHASE 3 Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 215 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Project identification, preparation, and appraisal PHASE 1 PHASE 2 PHASE 3 Phase 1: Project identification, preparation, and appraisal Tools in this grouping can be used for project identification—specifically to assess the technical, economic, social, and environmental aspects of a proposed project, to outline project theories of change, and to assess project feasibility. Box 11 provides a snapshot of “first- line” or highlighted tools in this category. The revised International Health Regulations (IHR) require all IHR State Parties to evaluate minimum national core capacities for surveillance and response as specified in the IHR, and to develop a plan of action to ensure that these capacities are functional and up to date. In the human health and animal health sectors, functions associated with early detection, proper management, and early response to public health emergencies of international concern (PHEICs) rely on the health security framework laid out under the IHR. Tools such as the Joint External Evaluation and the Performance of Veterinary Services (PVS) Pathway reports can help clients to assess capacities in the human and animal sectors, and to outline gaps, operational weaknesses, and strengths. Where there is appetite for a multisectoral approach, bringing the results of the JEE and the PVS together in a bridging workshop can help countries prioritize investments and plan for collaborative implementation at an early stage. Box 11. Highlighted Tools within the Project Identification, Preparation, and Appraisal Category Highlighted Tools within the Project Identification, Preparation, and Appraisal Category The JEE has been deployed as a tool to assess a country’s capacity to prevent, detect, and rapidly respond to public health risks (WHO 2023). The JEE tool helps countries self- identify critical gaps within their human and animal health systems to prioritize opportunities for enhanced preparedness and response, and to match gaps with resources. The tool is designed to be implemented by host country governments in collaboration with national experts and external teams of international subject matter experts. The tool assesses 19 technical areas divided among four categories and using 49 underlying indicators. The PVS Pathway is a voluntary, multistage, continuous process that uses a set of complementary tools to help veterinary services improve their capacity to undertake their animal health, veterinary public health, and other regulatory functions in closer compliance with the international standards of the WOAH codes (WOAH 2019). The PVS Pathway advances a strong systems approach and supports the strengthening of the multisectoral capacities needed for the control of zoonoses, food safety, and AMR. The PVS Pathway assesses the performance of a country’s veterinary services and their compliance with the WOAH intergovernmental standards on the quality of veterinary services. It reviews all aspects relevant to the Terrestrial Code and the quality of veterinary services according to the WOAH’s definition. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 216 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The WOAH’s List of Antimicrobials of Veterinary Importance was developed to safeguard the efficacy and availability of veterinary antimicrobial products for animal diseases where there are few or no alternatives (WOAH 2018). The list’s additional aims are to help veterinarians in their choice of the appropriate therapeutic agent, to complement the WOAH guidelines for responsible and prudent use of antimicrobial agents, and to serve as a useful information base to support science-based risk assessment of antimicrobial resistance. The FAO Assessment Tool for Laboratories and AMR Surveillance Systems (FAO-ATLASS) helps countries evaluate their AMR surveillance systems and build surveillance capacity (FAO 2020a). The tool maps the national AMR surveillance systems along five pillars— laboratory capacity and network, epidemiology unit, governance, communication, and sustainability. The tool consists of two modules—laboratory and surveillance—that include features of FAO’s Laboratory Mapping Tool (LMT) and Surveillance Evaluation Tool (SET), focusing on AMR. FAO-ATLASS provides recommendations for improving the systems, measures progress relative to the FAO Global Action Plan, and provides evidence for action and advocacy. The Methodology for the Analysis of AMR-Relevant Legislation in the Food and Agriculture Sector (Guidance Document for Regulators)46 is a tool that allows countries and regional organizations to identify, analyze, assess, and potentially improve their regulatory frameworks to better meet their AMR objectives (FAO 2020c; see also FAO 2020b).a It addresses (i) regulation of antimicrobials, including veterinary medicinal products and pesticides; (ii) protection of food and the environment against antimicrobial and AMR contamination; and (iii) prevention of AMR through healthier and more resilient ecosystems. The methodology has been used in more than 26 countries and by a regional organization. It will be upgraded with a One Health AMR Legal Assessment Tool (currently under development by FAO, WHO, and the WOAH) that will assess the status of legislation on AMR and outline gaps in governance of AMR. The WHO AWaRe Tool47 aims to promote the use of narrow-spectrum antibiotics for common infections and to reserve broad-spectrum antibiotics for the most challenging infections.b This tool provides recommendations on appropriate antibiotic choices for 21 common infections. It categorizes antibiotics into three groups. The access category comprises the preferred narrow-spectrum antibiotics for the most common infections. The majority of antibiotics in this group are β-lactams (52.63 percent), followed by aminoglycosides (15.78 percent), macrolides (5.26 percent), and tetracyclines (5.26 percent). The watch category comprises antibiotics that are reserved for specific and limited indications and are more susceptible to antibiotic resistance. They are preferred over access antibiotics in the treatment of severe infections. The largest share of antibiotics in the watch group are β-lactams (54.54 percent), followed by macrolides (18.18 percent), aminoglycosides (9.09 percent), and carbapenems (9.09 percent). The reserve category includes antibiotics that should be used sparingly or as a last resort when other antimicrobial options have failed. The reserve group primarily consists of polymyxin (28.57 percent), followed by β-lactams (14.28 percent) and aminoglycosides (14.28 percent). a. The selection of the cited tools as a focus was also validated in 2021 consultation with FAO. b. World Health Organization, “WHO Antibiotic Categorization,” https://aware.essentialmeds.org/groups. 46  Food and Agriculture Organization of the United Nations, “Containment of Antimicrobial Resistance in Terrestrial and Aquatic Food Production Systems, under the One Health Approach in Latin America,” https://www.fao.org/antimicrobial-resistance/projects/completed/ project-6/en/; see also FAO (2020b). The selection of these tools as tools for focus was also validated in the recent consultation with FAO. 47  World Health Organization, “WHO Antibiotic Categorization,” https://aware.essentialmeds.org/groups. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 217 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Implementation PHASE 1 PHASE 2 PHASE 3 Phase 2: Implementation Tools in this grouping can inform implementation support (including the supervision of timelines, actions, and monitoring mechanisms). They can also inform assessments of progress toward the achievement of project objectives as well as measures for course correction. More broadly, they can facilitate the application of practical global, regional, and national lessons garnered at the human-animal-environment implementation interface. Box 12 provides a snapshot of first- line or highlighted tools in this group, which include the PVS Gap Analysis Tool, FAO’s Progressive Management Pathway for AMR (FAO-PMP-AMR), FAO Legal Methodology tool, and National Action Plans on AMR. Box 12. Highlighted Tools within the Implementation Category Highlighted Tools within the Implementation Category The Global Action Plan on AMR (WHO 2015) is a comprehensive framework developed by the World Health Organization to address the growing threat of antimicrobial resistance worldwide. The plan guides countries in implementing effective strategies to combat AMR across human health, animal health, and the environment. It emphasizes the importance of strengthening surveillance systems, promoting appropriate use of antimicrobials, enhancing IPC measures, and fostering research and innovation. The Global Action Plan serves as a critical roadmap for countries, fostering global collaboration on efforts to preserve the effectiveness of antimicrobial drugs and protect public health for future generations. Notably, the “Monitoring and Evaluation of the Global Action Plan on AMR” toolkit (WHO, FAO, and WOAH 2019) offers countries guidance in selecting and utilizing core indicators to effectively measure progress toward the Global Action Plan’s objectives. The Strategy on AMR and the Prudent Use of Antimicrobials (WOAH 2021) focuses on promoting responsible and judicious use of antimicrobials in animal health to minimize the emergence and spread of AMR. WOAH emphasizes the importance of surveillance, monitoring, and reporting of antimicrobial use in animals, along with implementing appropriate veterinary practices, including disease prevention and control measures. By advocating for the prudent use of antimicrobials in animals, the WOAH strategy aims to safeguard animal health and welfare along with public health, thereby contributing to global efforts to combat AMR and preserve the effectiveness of antimicrobial treatments for both humans and animals. The FAO (2016) Action Plan on Antimicrobial Resistance was formulated to address the significant challenges posed by AMR in the agricultural sector. The plan focuses on promoting responsible and sustainable practices in animal and plant production systems, aquaculture, and crop farming. It emphasizes the need for improved surveillance systems, Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 218 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices increased awareness, and capacity building to ensure the prudent use of antimicrobials in agriculture. The plan also advocates for enhanced biosecurity measures, improved animal welfare practices, and the development of alternatives to antimicrobials in animal production. By implementing the FAO Action Plan on AMR, countries can help mitigate the risks associated with AMR in the agricultural sector and protect human health, animal health, and the environment. For the agriculture and food sectors, the Progressive Management Pathway for AMR (FAO-PMP-AMR) offers a staged process for guiding activities and interventions on AMR in the four focus areas of the FAO Action Plan and in alignment with the AMR Global Action Plan.a The FAO-PMP-AMR helps countries develop and operationalize the main food and agriculture components of their NAPs, ranging from small-scale, targeted interventions to national-level interventions. The process brings together public and private stakeholders to self-assess the level of NAP implementation in their country and agree on actions to escalate AMR management to a higher stage, as required. During FAO-PMP-AMR workshops, countries are assisted and guided in undertaking concrete steps toward implementing a multisector One Health NAP on AMR in line with the Global Action Plan. At the end of the workshop, progress in implementing the NAP is determined within the different focus areas and stages of the FAO-PMP-AMR; the capacities of the key national stakeholders on AMR management are strengthened, and the FAO-PMP-AMR tool is finalized for validation by the relevant stakeholders. Countries own the information generated from the workshops, and the assessment is maintained as confidential—that is, the tool is not meant for cross-country comparison. The FAO-PMP-AMR also complements other tools of the Tripartite organizations, such as the JEE, GLASS, PVS Pathway, and FAO-ATLASS. The WHO (2022) AMR National Action Plan Implementation Handbook provides comprehensive stepwise guidance for implementing NAPs within the human health sector. It collates and summarizes existing WHO tools and resources to support countries with readiness assessments, governance and multisectoral coordination, activity prioritization, implementation tools across the Global Action Plan’s strategic objectives, costing and budgeting of NAPs, resource mobilization, and monitoring and evaluation. The modular WHO (2021c) National Action Plan costing and budgeting tool helps countries estimate costs and plan budgets for the prioritized activities outlined in their NAPs, with a specific focus on addressing AMR. This tool enables users to identify funding flows, assess budget gaps, and leverage user-friendly dashboards to advocate for additional resources as needed. The tool is complemented by a user guide, a comprehensive training package, and a web-based help desk, which foster collaboration and participation across multiple sectors. Having undergone successful piloting in Sierra Leone, Somalia, Jamaica, and Paraguay, the tool is now being rolled out on a broader scale and to a wider range of countries and regions. The Tailoring Antimicrobial Resistance Programmes (TAP) Quick Guide (WHO 2021b) offers a step-by-step, practical approach to designing and implementing projects that address AMR in human and animal health through targeted behavior change. TAP is a behavioral change methodology developed to modify the behaviors that drive AMR. It aims to identify both barriers to proper behavior and incentives that drive certain behaviors. Accompanying the Quick Guide is a TAP Toolbox with exercises and tools to assist in each stage of project development. a. See Food and Agriculture Organization of the United Nations, “FAO Progressive Management Pathway for Antimicrobial Resistance (FAO-PMP-AMR),” https://www.fao.org/antimicrobial-resistance/resources/tools/fao- pmp-amr/en/. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 219 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Completion and evaluation PHASE 1 PHASE 2 PHASE 3 Phase 3: Completion and evaluation Tools in this grouping can help to align information sharing and reporting with wider operational processes. Box 13 provides a snapshot of first-line or highlighted tools that have been included in this category; a more inclusive list of 100 tools is in Table 13. Tools such as TrACSS (the Tripartite AMR Country Self-Assessment Survey) and TISSA (Tripartite Integrated Surveillance System on AMR/ AMU [antimicrobial use]) platform can help to document the results achieved, the problems encountered, the lessons learned, and the knowledge gained from carrying out projects. The tools in this section can also inform the description and evaluation of final project outcomes, and they can help countries determine what additional measures and capacity improvements are needed to sustain the outputs derived from a project. For example, a tool like TrACSS—a multisectoral self-assessment questionnaire—helps to capture country information on capacity, coverage, and performance on key aspects of the AMR Global Action Plan. The Tripartite is also in the process of developing a mechanism for collecting multisectoral AMR data in an integrated system for surveillance, where data on antimicrobial use and resistance are integrated with data from the human health, animal health, plant, food, and environment sectors. Box 13. Highlighted Tools in the Completion and Evaluation Category Highlighted Tools in the Completion and Evaluation Category The Tripartite Integrated Surveillance System on AMR/AMU is an integrated surveillance system that is being developed to monitor AMR and AMU/AMC (antimicrobial consumption) across the human-animal-plant-food-environment interface.a TISSA will link and reference current initiatives for AMR and AMU/AMC surveillance data across sectors at the regional and global levels. It will also leverage data from country surveillance and monitoring systems to capture and report AMR and AMU/AMC data in humans, animals, plants, food, and the environment. The Tripartite Monitoring and Evaluation Framework and Recommended Indicators for implementation of the Global Action Plan (WHO, FAO, and WOAH 2019) aims to generate data to assess the delivery of the Global Action Plan’s objectives and inform operational and strategic decision-making on AMR for the next five years. The framework is designed to assess the effectiveness of efforts to implement the Global Action Plan, including monitoring of results and evaluation of impact on various aspects of AMR action. TrACSS is aligned with the indicators of the framework and is delivered on an annual basis. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 220 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The Global Antimicrobial Resistance and Use Surveillance System (GLASS) (WHO 2020) was developed as a standardizing mechanism to identify indicators and set targets to monitor progress toward the AMR Global Action Plan across human health, animal health, and agriculture. Through the AMR module, GLASS provides a standardized approach for collection, analysis, interpretation, and sharing of data by countries, and monitors the status of existing and new national surveillance systems. GLASS has been updated to include a new component on AMC surveillance at the national level. GLASS now also includes a One Health module, based on the extended spectrum β-lactamase (ESBL) E. coli Tricycle project, which as of 2021 had been piloted in six countries. GLASS reports summarized data reported to WHO in the previous year. They include data on AMC surveillance and AMR data on laboratory-confirmed infections reported by surveillance sites in countries globally. The reports also describe developments related to GLASS and other AMR surveillance programs led by WHO, including resistance to anti-HIV and anti-TB medicines and antimalarial drug efficacy. The FAO (2017) Surveillance Evaluation Tool addresses AMR surveillance in the agricultural sector. This tool serves as a valuable resource for countries seeking to assess and enhance their surveillance systems for AMR in animal and plant production, aquaculture, and crop farming. The FAO surveillance evaluation tool provides a standardized framework to evaluate the effectiveness, efficiency, and quality of AMR surveillance activities. It helps countries identify gaps in their surveillance systems, improve data collection and analysis, and strengthen their capacity for timely reporting. Countries can monitor the prevalence of AMR, track trends, and make informed decisions to mitigate the risks associated with AMR in agriculture, thereby safeguarding human and animal health and promoting sustainable agricultural practices. a. See Arno Muller, “Tissa: The Tripartite Integrated System for Surveillance of AMR/AMU,” slide presentation, https://www.ivi.int/wp-content/uploads/2022/04/Day_1_Arno_Muller_The_Tripartite_Integrated_System_ for_Surveillance_of_AMR_AMU.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 221 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 13. List of Tools YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 1. Global Action Plan on AMR Benchmark tool that enables World Health 2015 (GAP-AMR) countries to devise a context- Organization (WHO) View ARROW-RI specific national action plan on AMR 2. Strategy on AMR and Presents a top-level WOAH-specific Organisation for 2016 the Prudent Use of strategy on actions to combat AMR Animal Health View ARROW-RI Antimicrobials (WOAH) 3. FAO Action Plan on FAO-specific plan to support the Food and 2016 Antimicrobial Resistance food and agriculture sectors in Agriculture implementing GAP-AMR Organization of View ARROW-RI the United Nations (FAO) 4. FAO Assessment Tool Assesses laboratories and FAO 2018 for Laboratories and antimicrobial resistance surveillance View ARROW-RI Surveillance Systems (FAO- systems at national and regional ATLASS) levels 5. Progressive Management Self-assessment tool that provides FAO 2019 Pathway for AMR (FAO- guidance for countries in developing View ARROW-RI PMP-AMR) and implementing a multisector One Health national action plan 6. FAO Surveillance Developed by FAO to provide FAO 2017 Evaluation Tool countries with a comprehensive and standardized way to evaluate animal View ARROW-RI disease surveillance systems, including for zoonoses 7. FAO Laboratory Mapping Assesses the functionality of FAO 2015 View ARROW-RI Tool (LMT) veterinary laboratories 8. WHO AMR Stewardship Provides guidance on core elements WHO 2019 Programmes in Health- and structures that need to be in Care Facilities and LMICs place at the national and facility View ARROW-RI Toolkit level in low-resource countries to establish and support antimicrobial stewardship interventions 9. Global Antimicrobial Developed to facilitate and WHO 2015; 2021 Resistance and Use encourage a standardized approach update Surveillance System to AMR surveillance globally and in View ARROW-RI (GLASS) tool and One turn support the implementation Health module of the Global Action Plan on antimicrobial resistance Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 222 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 10. AWaRe tool Classifies antibiotics into three WHO 2019 groups —access, watch, and reserve—and categorizes antibiotics in terms of common and serious View ARROW-RI infections, availability in the health care system, and sparing or last- resort use 11. AWaRe Campaign: “Adopt Accompanying advocacy material WHO 2019 AWaRe. Handle antibiotics to AWaRe tool for implementers and View ARROW-RI with care.” policy makers 12. Antibiotic Prescribing and Report on awareness of AMR and WHO, Antimicrobial 2017 Resistance: Views from knowledge of antibiotics within Resistance Centre at Low- and Middle-Income prescribing and dispensing settings the London School View ARROW-RI Prescribing and Dispensing across low- and middle-income of Hygiene and Professionals (LMIC) contexts Tropical Medicine 13. AMR Framework for Aims to support and accelerate the Interagency 2017 Action Supported by the implementation of the GAP-AMR Coordination Group Interagency Coordinating on Antimicrobial View ARROW-RI Group on Antimicrobial Resistance Resistance (IACG) 14. WHO Situation Analysis Provides an analysis of initiatives WHO 2015 currently being implemented to View ARROW-RI combat AMR in all six WHO regions 15. Antimicrobial Resistance: Enables countries to devise a WHO, FAO, and 2016 A Manual for Developing context-specific National Action WOAH View ARROW-RI National Action Plans Plan on AMR 16. Country Progress on the Collects data on GAP-AMR WHO, FAO, and 2018 Implementation of the and National Action Plan WOAH Global Action Plan on implementation progress View ARROW-RI Antimicrobial Resistance: WHO, FAO, and WOAH global tripartite database 17. WHO Competency AMR-related reference guide on WHO, FAO, and 2018 Framework for Health training, skills, and knowledge for WOAH Workers’ Education and health professionals View ARROW-RI Training on Antimicrobial Resistance 18. Strategic Research Agenda: Platform for the coordination of Joint Programming 2018 Joint Programming programming research on AMR Initiative on AMR View ARROW-RI Initiative on Antimicrobial Resistance Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 223 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 19. Technical Brief on Water, Provides information on WASH WHO, FAO, and 2020 Sanitation, Hygiene and wastewater management for WOAH (WASH) and Wastewater infection prevention View ARROW-RI Management to Prevent Infections and Reduce the Spread of AMR 20. Guidelines on Core Provides guidance to policy makers WHO 2016 Components of Infection and facility-level administrators Prevention and Control on IPC programs and infection View ARROW-RI Programmes at the prevention in clinical settings National and Acute Health Care Facility Level 21. FAO Resource Package on Set of resources that provide FAO 2020 Good Hygiene Practices prescriptive guidance on good View ARROW-RI hygiene practices across food production sectors 22. FAO Good Practices for Describes biosecurity risks in FAO 2010; 2015 Biosecurity in the Pig developing countries and measures update Sector that can be taken to mitigate these View ARROW-RI risks along pig production and marketing chains 23. Antimicrobials in Paper proposes three broad Review on 2015 Agriculture and the interventions to reduce the use of Antimicrobial Environment: Reducing antibiotics in food production and Resistance View ARROW-RI Unnecessary Use and curtail the consequential dispersion Waste of resistant bacteria (through animal waste) into the environment 24. Monitoring and Evaluation Aims to provide a manageable WHO, FAO, and 2019 of the Global Action system that can facilitate the WOAH Plan on Antimicrobial generation, collection, and analysis Resistance: Framework of standardized data to assess the and Recommended success of the GAP-AMR and inform View ARROW-RI Indicators operational and strategic decision- making on AMR for the next 5–10 years at the national and global levels 25. Tripartite AMR Country Collects data on GAP-AMR WHO, FAO, and Annual Self-Assessment Survey and National Action Plan WOAH View ARROW-RI (TrACSS) implementation progress 26. FAOSTAT System for collecting data on food FAO 2015 View ARROW-RI and agriculture Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 224 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 27. FAOLEX A comprehensive and up-to-date FAO Database legislative and policy database; one of the world's largest electronic collections of national laws, View ARROW-RI regulations, and policies on food, agriculture, and natural resources management 28. FAO Methodology to Provides guidance for legislators FAO 2021 Analyze AMR-Relevant seeking to identify and analyze Legislation in the Food existing legislation relevant to AMR View ARROW-RI and Agriculture Sectors in a national legal system; highlights a list of regulatory areas with an impact on AMR 29. WHO Benchmarks for Lists benchmarks and WHO 2019 International Health corresponding actions to improve Regulations (IHR) IHR capacities for health security Capacities and integrate multisectoral View ARROW-RI concerns at subnational (local and regional/provincial) and national levels 30. Global Analysis and Provides policy makers and WHO 2019 Assessment of Sanitation decision-makers with a reliable, and Drinking-Water easily accessible, comprehensive, (GLAAS) and global analysis of relevant View ARROW-RI investments and enabling environment so they can make informed decisions on sanitation, drinking water, and hygiene 31. AMR Benchmark A benchmark to rank and guide Access to Medicines Annual pharmaceutical company action Foundation View ARROW-RI on drug resistance 32. WHO/UNICEF Joint Global portal for global WASH data WHO, United Database Monitoring Programme for Nations Children’s View ARROW-RI Water Supply, Sanitation Fund (UNICEF) and Hygiene 33. WHO Hand Hygiene Self- Enables a situation analysis of WHO Annual Assessment Framework hand hygiene promotion and and WHO Infection practices within an individual health Prevention and Control care facility, according to a set of View ARROW-RI Assessment Framework indicators; acts as a diagnostic tool, identifying key issues requiring attention and improvement Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 225 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 34. WOAH PVS Pathway Toolkit for the sustainable WOAH Cyclical improvement of national veterinary services; provides a comprehensive View ARROW-RI understanding of services’ strengths and weaknesses using a globally consistent methodology 35. STAR-IDAZ International Platform that coordinates animal International 2016 Research Consortium health research globally to Research View ARROW-RI accelerate delivery of disease Consortium on control tools and strategies Animal Health 36. W HO Model Lists of Report on the recommendations WHO 2019 Essential Medicines (20th of the WHO Expert Committee on list) the Selection and Use of Essential View ARROW-RI Medicines for the 2019 Essential Medicines Lists 37. ReAct Online Toolbox for Resource package to support ReAct Annual National Action Plans countries in the development and implementation of National View ARROW-RI Action Plans, utilizing a One Health approach 38. Declaration by the Declaration signed by 85 companies International 2016 Pharmaceutical, and 9 industry associations on Federation of Biotechnology and priority actions against drug Pharmaceutical View ARROW-RI Diagnostics Industries on resistance, including creation Manufacturers’ Combating Antimicrobial of sustainable antibiotic market Associations (IFPMA) Resistance models 39. Tackling Antimicrobial Paper on potential actions (and G7/ OECD (Organisation 2017 Resistance: Ensuring G20 roles) to amplify sustainable for Economic Sustainable R&D research and development for Co-operation and View ARROW-RI antimicrobial therapies Development), WHO, FAO, and WOAH 40. World Antibiotic Report on the country and regional WHO Annual Awareness Week: level outcomes of the 2018 World View ARROW-RI Monitoring & Evaluation Antibiotic Awareness Week Report 41. Guidelines for the Global guidelines for the prevention WHO 2017 Prevention and Control and control of carbapenem- of Carbapenem-Resistant resistant Enterobacteriaceae, Enterobacteriaceae, Acinetobacter baumannii, and View ARROW-RI Acinetobacter baumannii Pseudomonas aeruginosa, which and Pseudomonas are emerging causes of health care– aeruginosa in Health Care acquired infections Facilities Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 226 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 42. Global Framework Outlines the current AMR situation WHO 2017 for Development & and options for establishing a global Stewardship to Combat framework on the development, View ARROW-RI Antimicrobial Resistance: control, and use of antimicrobial Draft Roadmap medicines, diagnostics, and other interventions 43. WASH in Health Care Presents eight practical actions WHO 2019 Facilities: Practical Steps that governments can take at the to Achieve Universal national and subnational levels to View ARROW-RI Access to Quality Care improve WASH services in health care facilities 44. WASH in Health Care Establishes national, regional, and WHO, UNICEF 2019 Facilities: Global Baseline global baseline estimates for WASH View ARROW-RI Report services in health care facilities 45. Progress on Drinking Paper presents estimates of WHO, UNICEF 2017 Water, Sanitation and population with access to “safely View ARROW-RI Hygiene: 2017 Update and managed” drinking water and SDG Baselines sanitation services 46. Library of National Action A library of existing, publicly WHO 2015 Plans available National Action Plans on View ARROW-RI antimicrobial resistance 47. AMR National Action Plan Resource materials for the WHO 2015 Support Tools development and implementation View ARROW-RI of National Action Plans 48. Global Priority List of Outlines a global priority pathogen WHO 2017 Antibiotic-Resistant list of antibiotic-resistant bacteria Bacteria to Guide as a useful input for research on View ARROW-RI Research, Discovery, and development of antibiotic and Development of New treatments Antibiotics 49. Diagnostic Stewardship: A A GLASS companion tool to support WHO 2016 Guide to Implementation microbiological diagnosis, including View ARROW-RI in Antimicrobial Resistance antimicrobial susceptibility testing Surveillance Sites 50. Africa CDC Antimicrobial Africa-specific regional approach to Africa Centres for Resistance Surveillance surveillance that aims to improve Disease Control and Network (AMRSNET) mechanisms to monitor and delay Prevention (CDC) View ARROW-RI AMR emergence and limit AMR transmission 51. Africa Regional Strategy on Africa - specific regional approach FAO, WHO, WOAH, 2021 AMR Communication and to advocacy and communication UNEP, African Union View ARROW-RI Advocacy on AMR, particularly on prudent use and animal husbandry practices Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 227 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 52. Estimating the Economic Global economic burden study on RAND Corporation, 2014 Costs of Antimicrobial the costs and direct and indirect Independent Review View ARROW-RI Resistance: Model and impacts of AMR on AMR Results 53. Antibacterial Agents in Annual review of the alignment of WHO 2017 Clinical Development: the clinical antibacterial pipeline to An Analysis of the the WHO priority pathogens list View ARROW-RI Antibacterial Clinical Development Pipeline, Including Tuberculosis 54. PVS Gap Analysis Tool Companion planning and costing WOAH Cyclical tool for the PVS Pathway tool (launched View ARROW-RI in 2013) 55. Resistance Map Collection of charts and maps that Center for Disease Up-to-date: summarize national and subnational Dynamics, 2023 View ARROW-RI data on antimicrobial use and Economics and resistance globally Policy 56. Health Workers’ AMR-related curricula guide on WHO 2019 Education and Training on training, skills, and knowledge for View ARROW-RI Antimicrobial Resistance: health professionals Curricula Guide 57. The Structured Program on AMR being UNICEF, 2019 Operational Research and implemented in 36 operational United Nations Training IniTiative (SORT research studies in five countries Development IT) on AMR, coordinated by (Ghana, Uganda, Sierra Leone, Programme (UNDP), View ARROW-RI the Special Programme for Myanmar, and Nepal) World Bank, WHO Research and Training in Tropical Diseases (TDR) 58. Integrated Surveillance of Guidance document on efforts WHO 2017 Antimicrobial Resistance to minimize the impact of AMR View ARROW-RI associated with the use of antimicrobials in food animals 59. The 6th Annual WOAH Annual report on global data on WOAH Annual Report on Antimicrobial the use of antimicrobial agents in View ARROW-RI Agents Intended for Use in animals Animals 60. Tackling Antimicrobial Paper outlining gender and equity WHO 2018 Resistance Together: considerations as countries Working Paper 5.0: address AMR View ARROW-RI Enhancing the Focus on Gender and Equity Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 228 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 61. S ummary Report of Report outlining scientific FAO, WHO 2018 the FAO/WHO Expert advice on the transmission of Meeting on Foodborne antimicrobial-resistant bacteria View ARROW-RI Antimicrobial Resistance: from environmental sources to Role of Environment, Crops foods and feeds of plant and and Biocides aquatic animal origin 62. The Environment as Platform for coordinated research Centre for Antibiotic 2019 a Driver of Antibiotic on AMR and the environment Resistance (CARe), Resistance focused on sources and drivers and University of View ARROW-RI on mitigation Gothenburg, Swedish Research Council 63. Frontiers 2017: Emerging Report on key emerging issues, United Nations 2017 Issues of Environmental including the environmental Environment View ARROW-RI Concern dimension of AMR Programme (UNEP) 64. Preventing the Next Report on the root causes of UNEP 2020 Pandemic – Zoonotic emergence and spread of zoonoses View ARROW-RI Diseases and How to Break the Chain of Transmission 65. Reframing Resistance Toolkit on impact communications Wellcome Trust 2020 for AMR (for experts, View ARROW-RI communicators, and practitioners) 66. Gulf–Middle East–North Middle East and North Africa– British Society 2020 Africa Antimicrobial specific educational platform for for Antimicrobial View ARROW-RI Stewardship Network antimicrobial stewardship and Chemotherapy related resources 67. Tackling Antimicrobial Practical guidance on establishing WHO 2018 Resistant Together: and sustaining multisectoral View ARROW-RI Working Paper 1.0: coordination in the implementation Multisectoral Coordination of National Action Plans for AMR 68. An Analysis of the Animal Report outlines antimicrobial use Fleming Fund, 2016 Human Interface with a and AMR in livestock and farmed Wellcome Trust Focus on Low- and Middle- aquatic species in LMICs; includes View ARROW-RI Income Countries recommendations for surveillance and research 69. Joint External Evaluation Tool assesses country capacities WHO Cyclical (JEE) tool and reports and capabilities relevant to the 19 technical areas of JEE; provides baseline data and View ARROW-RI recommendations to improve public health security and comply with the IHR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 229 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 70. Global Research on Facilitates the generation of University of 2017 Antimicrobial Resistance accurate and timely evidence on Oxford Big Data (GRAM) Project AMR burden globally Institute–Institute for Health Metrics View ARROW-RI and Evaluation (IHME) Strategic Partnership 71. I nternational Book by the Tripartite organizations WHO, FAO, and 2020 Instruments on the use of providing an overview and analysis WOAH Antimicrobials across the of international instruments that View ARROW-RI Human, Animal and Plant outline standards related to the use Sectors of antimicrobials across the human, animal, and plant sectors 72. US CDC Laboratory Laboratory assessment tool for use US Centers for 2020 Assessment of AMR Testing in clinical bacteriology laboratories Disease Control and Capacity (LAARC) in LMICs; helps laboratories identify Prevention (CDC) View ARROW-RI and correct laboratory practices that contribute to inaccurate antibiotic resistance data 73. Guidelines for the Outlines a three-step approach to WHO 2018 Development of National help countries plan and implement Action Plan for Health priority actions to attain health Security security; builds on and refers to all existing policies, agreements, View ARROW-RI strategies, and frameworks at the national, regional, and global levels; designed to be used by countries to facilitate multisectoral National Action Plans 74. I ndustry Alliance against A snapshot of the life sciences AMR Industry Annual AMR Progress Report industry’s collective efforts and Alliance leadership in tackling AMR—in View ARROW-RI the areas of research and science, access, appropriate use, and environmental manufacturing 75. T he Industry Roadmap for Lays out key commitments for International 2016 Progress on Combating combatting AMR and consolidating Federation of Antimicrobial Resistance stewardship of antibiotics Pharmaceutical View ARROW-RI Manufacturers and Associations 76. Time is Running Out Outlines UNICEF’s AMR-related UNICEF 2019 Technical Note programming and related View ARROW-RI partnerships with governments and other stakeholders Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 230 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 77. WOAH Data Collection Template for collecting data on WOAH 2020 Template and Related antimicrobial agents intended for View ARROW-RI Guidance use in animals 78. Core Elements of Human Provides a template (core elements) US CDC 2019 Antibiotic Stewardship to optimize antibiotic prescription View ARROW-RI Programs in Resource- in resource-limited hospital settings Limited Settings 79. ACORN (Clinically-Oriented Project aims to develop an Wellcome Trust, 2020 Antimicrobial Resistance efficient clinically orientated AMR University of Oxford View ARROW-RI Surveillance Network) surveillance system, implemented View ARROW-RI alongside routine clinical care in hospitals in LMIC settings 80. AMR Surveillance in Tool aims to facilitate AMR Fleming Fund 2016 Low- and Middle-Income surveillance and participation Settings: A Roadmap for in GLASS for LMICs; outlines Participation in the Global an approach that allows the View ARROW-RI Antimicrobial Surveillance independent development of each System (GLASS) component of surveillance to build a comprehensive system 81. Critically Important Publication issued by WHO Advisory WHO 2019 Antimicrobials for Human Group on Integrated Surveillance of Medicine: 6th Revision Antimicrobial Resistance (AGISAR) every two years; reviews and updates the WHO List of Critically View ARROW-RI Important Antimicrobials for Human Medicine; ranks medically important antimicrobials for risk management of antimicrobial resistance due to nonhuman use 82. WHO Guide for the Offers practical guidance to improve WHO 2017 Stepwise Laboratory laboratory services, infrastructure, Improvement Process and quality assurance, with a focus View ARROW-RI Towards Accreditation in on the African region the African Region 83. WHO Global Guidelines on Lists 29 evidence-based WHO 2018 the Prevention of Surgical recommendations for patients and View ARROW-RI Site Infection health systems to address health care–associated infections 84. Infection Control in Provides information and US CDC 2019 Healthcare Personnel: recommendations for health Infrastructure and Routine care professionals on preventing View ARROW-RI Practices for Occupational transmission of infectious diseases Infection Prevention and among health care personnel Control Services and patients Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 231 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 85. WHO Guidelines on Use Guidelines on use of medically WHO 2017 of Medically Important important antimicrobials in food- Antimicrobials in Food- producing animals; recommends Producing Animals that farmers and the food industry View ARROW-RI stop routine use of antibiotics to promote growth and prevent disease in healthy animals 86. WHO Costing and Modular tool to support countries WHO 2021 Budgeting Tool for with costing and budgeting of National Action Plans on prioritized activities in National Antimicrobial Resistance Action Plans; allows decision- View ARROW-RI makers to identify different funding flows and budget gaps, and to use dashboards to advocate for additional resources where needed 87. WHO Implementation Provides comprehensive stepwise WHO 2022 Handbook for National guidance for National Action Action Plans on Plan implementation within the Antimicrobial Resistance human health sector; collates and summarizes existing WHO tools and resources to support countries View ARROW-RI with readiness assessments, governance and multisectoral coordination, activity prioritization, and implementation of tools across the strategic objectives of the Global Action Plan on AMR 88. FAO Situation Analysis of Designed by the FAO Regional FAO 2021 AMR Risks in the Food and Office for Latin America and the Agriculture Sectors Caribbean to help LMICs organize their baseline information on AMR and associated risks and gaps; View ARROW-RI allows countries to define mitigation measures with a multisectoral approach, coordinated between actors from animal health, public health, and the environment 89. Tailoring Antimicrobial Provides a step-by-step, practical WHO 2021 Resistance Programmes approach to designing and (TAP) Quick Guide implementing targeted behavior View ARROW-RI change interventions that address drivers of AMR in human and animal health Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 232 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 90. T ailoring Antimicrobial Accompanies the TAP Quick Guide WHO 2021 Resistance Programmes with exercises and tools to assist in View ARROW-RI (TAP) Toolbox each stage of project development 91. Tripartite Integrated A global web-based repository WHO, FAO, and TBD System for Surveillance of of antimicrobial resistance and WOAH AMR/AMU (TISSA) use data across human health, View ARROW-RI animal health, and food and agriculture sectors 92. WASH in Health Care Describes national, regional, WHO, UNICEF 2020 Facilities: Global Progress and global progress on WASH View ARROW-RI Report 2020 services in health care facilities 93. I nfection Prevention and Outlines multimodal improvement WHO 2021 Control: Guidance to strategies to implement IPC Action Tools interventions; includes standard and transmission-based precautions according to national View ARROW-RI guidelines or standard operating procedures and under the coordination of the national IPC focal point/team 94. Understanding Barriers Describes an approach for WHO 2021 to Quality of Care: An conducting a national situational Approach for Conducting analysis of WASH as a basis for a Situational Analysis of improving quality of care View ARROW-RI Water, Sanitation and Hygiene (WASH) and Quality in Health Care Facilities 95. WHO Policy Guidance on Outlines policy guidance on how WHO 2021 Integrated Antimicrobial to facilitate the implementation Stewardship Activities of national AMS activities in an View ARROW-RI integrated and programmatic approach 96. Antimicrobial Stewardship Describes 10 common stewardship WHO 2021 Interventions: A Practical interventions (and evidence behind Guide them) to promote optimal use of antimicrobials at health care View ARROW-RI facilities; describes implementation considerations, particularly for low- resource settings Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 233 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices YEAR ISSUED/ TOOL DESCRIPTION ORGANIZATION L AUNCHED SOURCE 97. African Union Framework Describes the African Union’s African Union 2020 for Antimicrobial priorities on AMR for the Resistance Control 2020– forthcoming five years; aim is 2025 to improve surveillance, delay View ARROW-RI emergence, limit transmission, and mitigate harm from antimicrobial resistance 98. Joint Risk Assessment Supports countries in assessing WHO, FAO, and 2020 Operational Tool risks, including AMR, at the human– WOAH View ARROW-RI animal–environment interface 99. Global Repository of Based on a 2018 survey by World World Veterinary 2019 Available Guidelines Veterinary Association and WOAH; Association, WOAH for Responsible Use of lists 102 guidelines, action plans, Antimicrobials In Animal and promotional material on View ARROW-RI Health prudent use of antimicrobials, covering large number of countries, languages, veterinary aspects, and animal species 100. Strengthening Infection Aims to support those working in WHO 2021 Prevention and Control in primary care to strengthen IPC; Primary Care: A Collection informed by existing WHO IPC View ARROW-RI of Existing Standards, guidance and implementation Measurement and resources Implementation Resources Source: Adapted from World Bank 2021. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 234 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 14. Tools Organized by Project Phase Project PHASE 1: identification, Completion preparation, and appraisal Project identification, preparation, PHASE 2: Implementation 3: evaluation PHASE and and appraisalPHASE 1 PHASE Implementation 2 and supervision PHASE Completion and 3 evaluation FAO Assessment Tool for Laboratories Global Action Plan on AMR (GAP-AMR) Tripartite Integrated Surveillance and Surveillance Systems (FAO- System on AMR/AMU (TISSA) ATLASS) FAO Laboratory Mapping Tool (LMT) Strategy on AMR and the Prudent Use Global Antimicrobial Resistance and of Antimicrobials Use Surveillance System (GLASS) and One Health module AWaRe tool FAO Action Plan on Antimicrobial Country Progress on the Resistance Implementation of the Global Action Plan on Antimicrobial Resistance: WHO, FAO, and WOAH Global Tripartite Database The AWaRe Campaign: “Adopt AWaRe. Progressive Management Pathway for Industry Alliance against AMR Progress Handle Antibiotics with Care.” AMR (FAO-PMP AMR) Report Antibiotic Prescribing and Resistance: WHO AMR Stewardship Programmes Tripartite AMR Country Self- Views from Low- and Middle- in Health-care Facilities and LMICs Assessment Survey (TrACSS) Income Prescribing and Dispensing Toolkit Professionals WHO Situation Analysis AMR Framework for Action Supported FAOSTAT by the IACG Antimicrobial Resistance: A Manual for WHO Competency Framework for The 4th Annual WOAH Report on Developing National Action Plans Health Workers’ Education and Antimicrobial Agents Intended for Training on Antimicrobial Resistance Use in Animals WHO Benchmarks for IHR Capacities Strategic Research Agenda: World Antibiotic Awareness Week 2018: Joint Programming Initiative on Monitoring & Evaluation Report Antimicrobial Resistance Global Analysis and Assessment of Technical Brief on Water, Sanitation, Africa CDC Antimicrobial Resistance Sanitation and Drinking-Water (GLAAS) Hygiene (WASH) and Wastewater Surveillance Network (AMRSNET) Management to Prevent Infections and Reduce the Spread of Antimicrobial Resistance (AMR) AMR Benchmark Guidelines on Core Components of FAO Surveillance Evaluation Tool Infection Prevention and Control Programmes at the National and Acute Health Care Facility Level WHO Hand Hygiene Self-Assessment FAO Resource Package on Good WASH in Health Care Facilities: Global Framework, and the WHO Infection Hygiene Practices Progress Report 2020 Prevention and Control Assessment Framework Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 235 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices PHASE 1: Project identification, preparation, PHASE 2: PHASE 3: and appraisal Implementation and supervision Completion and evaluation WOAH PVS Pathway FAO Good Practices for Biosecurity in Integrated Surveillance of the Pig Sector Antimicrobial Resistance STAR-IDAZ International Research Antimicrobials in Agriculture and the Monitoring and Evaluation of the Consortium Environment: Reducing Unnecessary Global Action Plan on Antimicrobial Use and Waste Resistance: Framework and Recommended Indicators WHO Model List of Essential Medicines: AMR National Action Plan Support 20th List Tools ReAct Online Toolbox for National ReAct Online Toolbox for National Action Plans Action Plans WASH in Health Care Facilities: Global Summary Report of the FAO/WHO Baseline Report 2019 Expert Meeting on Foodborne Antimicrobial Resistance: Role of Environment, Crops and Biocides Progress on Drinking Water, Sanitation Declaration by the Pharmaceutical, and Hygiene: 2017 Update and SDG Biotechnology and Diagnostics Baselines Industries on Combating Antimicrobial Resistance Joint External Evaluation Tackling Antimicrobial Resistance: Ensuring Sustainable R&D US CDC Laboratory Assessment of AMR Guidelines for the Prevention and Testing Capacity (LAARC) Control of Carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa in Health Care Facilities Guidelines for the Development Global Framework for Development & of National Action Plan for Health Stewardship to Combat Antimicrobial Security Resistance: Draft Roadmap WHO AMR Stewardship Programmes in WASH in Health Care Facilities: Healthcare Facilities and LMICs Toolkit Practical Steps to Achieve Universal Access to Quality Care Technical Brief on Water, Sanitation, Global Research on Antimicrobial Hygiene (WASH) and Wastewater Resistance (GRAM) Project Management to Prevent Infections and Reduce the Spread of Antimicrobial Resistance (AMR) Guidelines for the Prevention and WHO/UNICEF Joint Monitoring Control of Carbapenem-resistant Programme for Water Supply, Enterobacteriaceae, Acinetobacter Sanitation and Hygiene baumannii and Pseudomonas aeruginosa in Healthcare Facilities Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 236 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices PHASE 1: Project identification, preparation, PHASE 2: PHASE 3: and appraisal Implementation and supervision Completion and evaluation PVS Gap Analysis Tool WOAH Data Collection Template and Related Guidance International Instruments on the Use Diagnostic Stewardship: A Guide to of Antimicrobials across the Human, Implementation in Antimicrobial Animal and Plant Sectors Resistance Surveillance Sites WHO Global Guidelines on the ASEAN Regional Strategy on AMR Prevention of Surgical Site Infection Communication and Advocacy WHO Guidelines on Use of Medically Estimating the Economic Costs of Important Antimicrobials in Food- Antimicrobial Resistance: Model and Producing Animals Results FAO Surveillance Evaluation Tool Antibacterial Agents in Clinical Development: An Analysis of the Antibacterial Clinical Development Pipeline, Including Tuberculosis Monitoring and Evaluation of the PVS Gap Analysis Tool Global Action Plan on Antimicrobial Resistance: Framework and Recommended Indicators WOAH Data Collection Template and Resistance Map Related Guidance WHO/UNICEF Joint Monitoring Health Workers' Education and Programme for Water Supply, Training on Antimicrobial Resistance: Sanitation and Hygiene Curricula Guide Global Research on Antimicrobial The Structured Operational Resistance (GRAM) Project Research and Training IniTiative on AMR, Coordinated by the Special Programme for Research and Training in Tropical Diseases (TDR) The 4th Annual WOAH Report on Integrated Surveillance of Antimicrobial Agents Intended for Use Antimicrobial Resistance in Animals Resistance Map Tackling Antimicrobial Resistance Together (Working Paper 5.0): Enhancing the Focus on Gender and Equity Reframing Resistance The Environment as a Driver of Antibiotic Resistance Global Priority List of Antibiotic- Frontiers 2017: Emerging Issues of Resistant Bacteria to Guide Research, Environmental Concern Discovery, and Development of New Antibiotics Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 237 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices PHASE 1: Project identification, preparation, PHASE 2: PHASE 3: and appraisal Implementation and supervision Completion and evaluation Preventing the Next Pandemic: Preventing the Next Pandemic: Zoonotic Diseases and How to Break Zoonotic Diseases and How to Break the Chain of Transmission the Chain of Transmission Frontiers 2017: Emerging Issues of Reframing Resistance Environmental Concern FAO Methodology to Analyze AMR- Gulf–Middle East–North Africa relevant legislation in the food and Antimicrobial Stewardship Network agriculture sectors FAOLEX Tackling Antimicrobial Resistance Together (Working Paper 1.0): Multisectoral Coordination African Union Framework for An Analysis of the Animal/Human Antimicrobial Resistance Control Interface with a Focus on Low- and 2020–2025 Middle-Income Countries Tailoring Antimicrobial Resistance The Industry Roadmap for Progress on Programmes (TAP) Toolbox Combating Antimicrobial Resistance WASH in Health Care Facilities: Global Core Elements of Human Antibiotic Progress Report 2020 Stewardship Programs in Resource- Limited Settings Understanding Barriers to Quality of International Instruments on the Use Care: An Approach for Conducting of Antimicrobials across the Human, a Situational Analysis of Water, Animal and Plant Sectors Sanitation and Hygiene (WASH) and Quality in Health Care Facilities Global Priority List of Antibiotic- ACORN (Clinically-Oriented Resistant Bacteria to Guide Research, Antimicrobial Resistance Surveillance Discovery, and Development of New Network) Antibiotics WHO Situation Analysis Time Is Running Out Technical Note Health Workers' Education and AMR Surveillance in Low- and Training on Antimicrobial Resistance: Middle-Income Settings: A Roadmap Curricula Guide for Participation in the Global Antimicrobial Surveillance System (GLASS) Estimating the Economic Costs of WHO Policy Guidance on Integrated Antimicrobial Resistance: Model and Antimicrobial Stewardship Activities Results Critically Important Antimicrobials for Infection Prevention and Control: Human Medicine: 5th Revision Guidance to Action Tools Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 238 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices PHASE 1: Project identification, preparation, PHASE 2: PHASE 3: and appraisal Implementation and supervision Completion and evaluation Critically Important Antimicrobials for WHO Guide for the Stepwise Human Medicine: 5th Revision Laboratory Improvement Process Towards Accreditation in the African Region Joint Risk Assessment Operational WHO Global Guidelines on the Tool Prevention of Surgical Site Infection WHO Policy Guidance on Integrated Infection Control in Healthcare Antimicrobial Stewardship Activities Personnel: Infrastructure and Routine Practices for Occupational Infection Prevention and Control Services Library of National Action Plans WHO Guidelines on Use of Medically Important Antimicrobials in Food- Producing Animals WHO Global Guidelines on the WHO Costing and Budgeting Tool for Prevention of Surgical Site Infection National Action Plans on Antimicrobial Resistance WHO Guidelines on Use of Medically Draft WHO Implementation Handbook Important Antimicrobials in Food- for National Action Plans on Producing Animals Antimicrobial Resistance Global Repository of Available Draft FAO Situation Analysis of AMR Guidelines for Responsible Use of Risks in the Food and Agriculture Antimicrobials in Animal Health Sectors Antimicrobial Stewardship Interventions: A Practical Guide Tailoring Antimicrobial Resistance Programmes (TAP) Quick Guide Strengthening Infection Prevention and Control in Primary Care: A Collection of Existing Standards, Measurement and Implementation Resources Source: World Bank compilation. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 239 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Costing and implementing AMR interventions, including NAPs The JEEs and the TrACSS data have shown that costing and securing financing are widespread challenges in addressing AMR in LMICs. National Actions Plans translate the WHO’s Global Action Plan on AMR into local priorities. As of 2020, TrACSS found that only 20 percent of NAPs were fully funded and 40 percent had a budgeted operational plan (WHO 2021c). Successive JEE reports have also highlighted a gap in financing for health security and AMR. This section focuses on costing tools for AMR interventions, including NAPs. Donors and development partners have key roles in facilitating action on AMR and supporting activities that are excluded from government plans and budgets. However, country case studies undertaken by WHO on NAP implementation show the difficulty of identifying sources of donor support, and note the lack of tools that could help LMICs find and access financial and technical support from donors. In these circumstances, a well-designed and costed NAP is a useful tool for raising awareness, coordinating across stakeholders and sectors, fostering ownership, promoting accountability, and monitoring and evaluating actions on AMR in the country. Costed NAPs are decision tools that allow countries to identify the activities that are easiest to scale up, most cost-effective, or potentially able to provide the greatest impact; this information in turn enables governments to prioritize activities and allocate resources effectively and efficiently. Costed NAPs can also enable stakeholders to pinpoint resource gaps as well as existing or potential bottlenecks and optimize alignment with other policy processes and priorities. Increasingly, costing tools are being developed to identify and allocate the resources required to build and sustainably implement NAPs for AMR. There has previously been a limited evidence base for countries wishing to select and implement appropriate costing strategies, particularly for AMR. Currently, the inventory of costing tools relevant to AMR actions can be categorized as follows: (i) tools that target AMR-specific activities that are new or focused on antimicrobial resistance only; (ii) tools that target AMR-sensitive activities that are contained within existing programs; and (iii) tools that target AMR activities linked to the wider health system. Building on costing approaches for implementation of the IHR, two broad methodologies (detailed or action-based) have been outlined for strategic costing of capacity assessment processes, such as the JEE, to prevent, detect, and respond to AMR and other public health threats (Mghamba et al. 2018). NAP costing refers to the process of assigning cost to each activity in the plan. Costing is the first step toward developing a NAP budget and should be accompanied by identifying the relevant sources of funding for each activity. NAP costing strategies can be either detailed (i.e., can aggregate the individual components of country-defined activities to generate an overall cost estimate) or action-based (i.e., estimate costs for a set of predefined actions based on country capacity levels). The following AMR-relevant costing tools have been developed for the purposes of costing and resource planning. The WHO (2021c) NAP Costing and Budgeting Tool is a modular tool to support countries with the costing and budgeting of prioritized activities included in their NAPs, and it is relevant for AMR-specific activities. It allows users to identify funding flows and budget gaps and to use dashboards to advocate for additional resources, where needed. Accompanied by a user guide, a training package, and a web-based help desk, the tool is designed to support multisectoral participation and collaboration. It has been piloted in Africa (Sierra Leone and Somalia) and Latin America and the Caribbean (Jamaica and Paraguay) and is being rolled out more widely. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 240 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The WHO (2021a) NAP Costing and Budgeting Tool, the Costing Tool for IHR, and the Priority Actions Costing Tool can target AMR-sensitive activities that are contained within existing programs. The National Action Plan for Health Security (NAPHS) is a process developed by WHO to create capacity-building plans based on recommendations from the International Health Regulations Monitoring and Evaluation Framework,48 country risk assessments, and other assessments. The NAPHS includes activities that are developed to address gaps identified by the IHR Monitoring and Evaluation Framework, as well as activities from other national plans, including those for antimicrobial resistance and influenza pandemic preparedness. The output of the NAPHS process includes a cost envelope of the actions required to increase preparedness for health emergencies, which can be used to develop specific annual implementation plans, allocate domestic budgets, and mobilize resources from bilateral and multilateral partners (Katz et al. 2012). The Costing Tool for IHR implementation (Global Health Security Index 2019) was developed in collaboration between WHO and the George Washington, Emory, and Australian National Universities, and is organized by IHR Core Capacities and public health core functions. Estimated costs are calculated using a template to identify inputs—for example, personnel compensation, travel and per diem, meeting costs—that can be systematically applied to appropriate public health actions necessary to fulfill each IHR attribute with appropriate multipliers such as the number of districts. The Priority Actions Costing Tool (PACT) (Lee et al. 2020) was developed by the US Centers for Disease Control and Prevention and is designed to quickly generate cost estimates for priority actions outlined from a country’s JEE report. Priority actions consist of three to four recommendations provided by the external assessment team for each technical area and are based on the strengths and weaknesses identified through the JEE process. The tool is based on key actions required for the attainment of improved JEE scores. The Avenir OneHealth Tool is an example of a tool that targets AMR activities linked to the wider health system.49 The OneHealth Tool links strategic objectives and targets of disease control and prevention programs to outlined investments in health systems. It provides planners with a single framework for scenario analysis, costing, health impact analysis, budgeting, and financing of strategies for all major diseases and health system components. It is primarily intended to inform sector-wide national strategic health plans and policies. WHO provides technical oversight to the development of the tool, facilitates capacity building, and provides technical support to policy makers to inform national planning and resource needs estimates. The first official version of the OneHealth Tool was released in May 2012. The tool has since been applied in over 55 countries, mostly in Sub-Saharan Africa. References FAO (Food and Agriculture Organization of the United Nations). 2016. “FAO Action Plan on AMR.” http://www.fao.org/3/a-i5996e.pdf. FAO (Food and Agriculture Organization of the United Nations). 2017. “FAO Surveillance Evaluation Tool.” https://www.fao.org/3/i9143en/I9143EN.pdf. FAO (Food and Agriculture Organization of the United Nations). 2020a. “FAO Assessment Tool for Laboratories and AMR Surveillance Systems (FAO-ATLASS).” https://www.fao.org/ antimicrobial-resistance/resources/tools/fao-atlass/en/. 48  World Health Organization, “IHR Monitoring and Evaluation Framework,” https://extranet.who.int/sph/ihr-monitoring-evaluation. 49  See Avenir Health, “OneHealth Tool,” https://www.avenirhealth.org/software-onehealth.php; World Health Organization, “One Health Tool,” https://www.who.int/tools/onehealth. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 241 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices FAO (Food and Agriculture Organization of the United Nations). 2020b. “FAO Highlights Its Four Tools That Help Mitigate AMR.” November 11, 2020. http://www.fao.org/antimicrobial-resistance/ news-and-events/news/news-details/en/c/1333178/ Global Health Security Index. 2019. “Georgetown International Health Regulations (IHR) Costing Tool.” https://www.ghsindex.org/ar/georgetown-international-health-regulations-ihr-costing- tool/. Katz, Rebecca, Vibhuti Haté, Sarah Kornblet, and Julie E. Fischer. 2012. “Costing Framework for International Health Regulations (2005).” Emergency Infectious Disease 18, no. 7: 1121–27. DOI: 10.3201/eid1807.120191. Lee, C. T., R. Katz, S. Eaneff, M. Mahar, and O. Ojo. 2020. “Action-Based Costing for National Action Plans for Health Security: Accelerating Progress toward the International Health Regulations (2005).” Health Security 18, no. S1: S-53–S-63. https://doi.org/10.1089/hs.2019.0063. Mghamba, J. M., A. O. Talisuna, L. Suryantoro, G. E. Saguti, M. Muita, M. Bakari, N. Rusibamayila, et al. 2018. “Developing a Multisectoral National Action Plan for Health Security (NAPHS) to Implement the International Health Regulations (IHR 2005) in Tanzania.” BMJ Global Health 3, no. 2: e000600. doi:10.1136/ bmjgh-2017-000600. WOAH (World Organisation for Animal Health). 2018. “List of Antimicrobial Agents of Veterinary Importance.” https://www.woah.org/app/uploads/2021/06/a-oie-list-antimicrobials- june2021.pdf. WOAH (World Organisation for Animal Health). 2019. “Performance of Veterinary Ser¬vices (PVS) Pathway.” https://www.woah.org/en/what-we-offer/improving-veterinary-services/ pvs-pathway/. WOAH (World Organization for Animal Health). 2021. “Strategy on Antimicrobial Resistance and the Prudent Use of Antimicrobials.” https://www.woah.org/app/uploads/2021/03/en-amr- strategy-final.pdf. WHO (World Health Organization). 2015. “Global Action Plan on Antimicrobial Resistance.” World Health Organization, Geneva. https://apps.who.int/iris/handle/10665/193736. WHO (World Health Organization). 2020. Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report: Early Implementation 2020. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789240005587. WHO (World Health Organization). 2021a. “NAPHS Planning and Costing Tool.” https://extranet.who. int/sph/naphs-planning-and-costing-tool. WHO (World Health Organization). 2021b. “The TAP Quick Guide: A Practical Handbook for Implementing Tailoring Antimicrobial Resistance Programmes.” https://apps.who.int/ iris/bitstream/handle/10665/341631/9789289055673-eng.pdf?sequence=1&isAllowed=y | https://www.euro.who.int/en/health-topics/disease-prevention/antimicrobial-resistance/ publications/2021/the-tap-quick-guide-a-practical-handbook-for-implementing-tailoring- antimicrobial-resistance-programmes-2021. WHO (World Health Organization). 2021c. WHO Costing and Budgeting Tool for National Action Plans on Antimicrobial Resistance: User Guide. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789240036901. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 242 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices WHO (World Health Organization). 2022. WHO Implementation Handbook for National Action Plans on Antimicrobial Resistance: Guidance for the Human Health Sector. Geneva: World Health Organization. https://www.who.int/publications/i/item/9789240041981. WHO (World Health Organization). 2023. Joint External Evaluation Tool: International Health Regulations (2005). 3rd ed. Geneva: World Health Organization. https://iris.who.int/ bitstream/handle/10665/357087/9789240051980-eng.pdf?sequence=1. WHO (World Health Organization), FAO (Food and Agriculture Organization of the United Nations), and WOAH (World Organisation for Animal Health). 2019. “Monitoring and Evaluation of the Global Action Plan on Antimicrobial Resistance: Framework and Recommended Indicators.” https://apps.who.int/iris/handle/10665/325006. World Bank Group. 2021. “Landscape Analysis of Tools to Address Antimicrobial Resistance.” World Bank, Washington, DC. https://thedocs.worldbank.org/en/doc/e9d15ce04da6b28e0013 dfca2cd2426f-0140012021/original/Landscape-Analysis-of-Tools-to-Address-AMR- Circulation-Copy-May-13-2021.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 243 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Appendices Appendix 1: An Overview of the World Bank Project Cycle and Instruments 245 CHEVRON- Appendix 2: Further details on the methodology for the Evidence Review of Interventions 249 CHEVRON- Appendix 3: Environmental and Social Safeguards Guidance 271 CHEVRON- Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 244 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Appendix 1 An Overview of the World Bank Project Cycle and Instruments The World Bank provides financing and services to low- and middle-income countries to support development and change, including the development of health, agriculture, and water and sanitation systems. Development projects are implemented by borrowing countries following certain rules and procedures to guarantee that the money reaches its intended target. The project cycle is the framework used to design, prepare, implement, and supervise projects. The duration of the project cycle is long by commercial standards. It is not uncommon for a project to last more than four years from the time it is identified until the time it is completed. A World Bank project consists of six stages: Identification, Preparation, Appraisal, Negotiation/Approval, Implementation/Support, and Completion/Evaluation (as shown in Figure 3). Figure 3. The World Bank Project Cycle Country Partnership Framework (CPF) 6 1 5 2 4 3 Source: World Bank, “The World Bank Project Cycle,” https://www.worldbank.org/en/projects-operations/ products-and-services/brief/projectcycle. Note: IEG = Independent Evaluation Group; PAD = Project Appraisal Document. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 245 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices In the Identification stage, the World Bank works with a borrowing country’s government and other stakeholders to determine how financial and other assistance can be designed to have the largest impact. After analytical work is conducted, the borrower and the World Bank Group produce a strategy, called the Country Partnership Framework, to identify the country’s highest priorities for reducing poverty and improving living standards. Identified projects can range across the economic and social spectrum, from infrastructure, to education or health, to government financial management. The World Bank and the government agree on an initial project concept and its beneficiaries, and the World Bank’s project team outlines the basic elements in a Project Concept Note. This document identifies proposed objectives, imminent risks, alternative scenarios, and a likely timetable for the project approval process. Two other World Bank documents are generated during this phase. The Project Information Document outlines the scope of the intended project and contains useful public information for tailoring bidding documents to the proposed project, and the publicly available Integrated Safeguards Data Sheet identifies key issues related to the World Bank’s safeguard policies for environmental and social issues. In the Project Preparation stage, the borrower government and its implementing agency or agencies are responsible for preparing the project. It can take several years to conduct feasibility studies and prepare engineering and technical designs, to name only a few of the work products required. The government contracts with consultants and other public sector companies for goods, works, and services, if necessary, not only during this phase but also later in the project’s implementation phase. Beneficiaries and stakeholders are also consulted now to obtain their feedback and ensure the project meets their needs. Given the time, effort, and resources involved, the government’s full commitment to the project is vital. During the preparation phase, the World Bank generally takes an advisory role and offers analysis and advice when requested. However, it does assess the relevant capacity of the implementing agencies at this point in order to reach agreement with the borrower about arrangements for overall project management, such as the systems required for financial management, procurement, reporting, and monitoring and evaluation. Earlier screening by World Bank staff may have determined that a proposed project could have environmental or social impacts that are included under the World Bank’s Safeguard Policies. If necessary, the borrower now prepares an Environmental Assessment Report that analyzes the planned project’s likely environmental impact and describes steps to mitigate possible harm. In the event of major environmental issues in a country, the borrower’s Environmental Action Plan describes the problems, identifies the main causes, and formulates policies and concrete actions to deal with them. To understand a project’s potentially adverse social impacts, various studies may be undertaken to analyze its effects on the health, productive resources, economies, and cultures of indigenous peoples. An Indigenous Peoples Plan identifies the borrower’s planned interventions in indigenous areas with the objective of avoiding or lessening potential negative impacts on the people. These plans are integrated into the design of the project. Projects supported through the Investment Project Financing instrument are governed by operational policies and procedures designed to ensure that the projects are economically, financially, socially, and environmentally sound. The World Bank Environmental and Social Framework (ESF), approved by the World Bank Board on August 4, 2016, expands protections for people and environments in World Bank–financed projects. The new requirements took effect in 2018 and apply to new investment projects for which a concept note is issued. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 246 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The Project Appraisal stage gives stakeholders an opportunity to review the project design in detail and resolve any outstanding questions. The government and the World Bank review the work done during the Identification and Preparation phases and confirm the expected project outcomes, intended beneficiaries, and evaluation tools for monitoring progress. Agreement is reached on the viability of all aspects of the project at this time. The World Bank team confirms that all aspects of the project are consistent with the requirements of all World Bank operations and that the government has institutional arrangements in place to implement the project efficiently. All parties agree on a project timetable and on public disclosure of key documents, and they identify any unfinished business that must be addressed for final World Bank approval. The final steps are assessment of the project’s readiness for implementation and agreement on conditions for effectiveness (actions agreed upon prior to implementation). The Project Information Document is updated and released when the project is approved for funding. Project Approval takes place once all project details are negotiated and accepted by the government and the World Bank: the project team prepares the Project Appraisal Document (for Investment Project Financing) or the Program Document (for Development Policy Financing), along with other financial and legal documents, for submission to the World Bank’s Board of Executive Directors for consideration and approval. When funding approval is obtained, conditions for effectiveness are met, and the legal documents are accepted and signed, the implementation phase begins. Project Implementation takes place when the borrower government implements the development project with funds from the World Bank. With technical assistance and support from the World Bank’s team, the implementing government agency prepares the specifications for the project and carries out all procurement of goods, works, and services needed, as well as any environmental and social impact mitigation set out in agreed-upon plans. Financial management and procurement specialists on the World Bank’s project team ensure that adequate fiduciary controls on the use of project funds are in place. At this phase all components are ready, but project delays and unexpected events can sometimes prompt the restructuring of project objectives. Once underway, the implementing government agency reports regularly on project activities. The government and the World Bank also join forces twice a year to prepare the Implementation Status and Results Report, which is a review of project progress. The project’s progress, outcomes, and impact on beneficiaries are monitored by the government and the World Bank throughout the implementation phase to obtain data used to evaluate and measure the ultimate effectiveness of the operation and the project’s results. Project Completion refers to the stage when a project is completed and closed at the end of the loan disbursement period, a process that can take anywhere from 1 to 10 years. At this point the World Bank and the borrower government document the results achieved, the problems encountered, the lessons learned, and the knowledge gained in carrying out the project. A World Bank operations team compiles this information and data in an Implementation Completion and Results Report, using input from the implementing government agency, co‑financiers, and other partners/stakeholders. The report describes and evaluates final project outcomes. The final outcomes are then compared to expected results. The information gained during this exercise is also often used to determine what additional government measures and capacity improvements are needed to sustain the benefits derived from the project. The evaluation team also assesses how well the entire operation complied with the World Bank’s operations policies and accounts for the use of World Bank resources. The knowledge gained from this results measurement process is intended to benefit similar projects in the future. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 247 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Evaluation may be carried out by the Independent Evaluation Group (IEG), which assesses the performance of roughly one project out of four (about 70 projects a year). Evaluations measure outcomes against the original objectives, sustainability of results, and institutional development impact. From time to time, IEG also produces Impact Evaluation Reports to assess the economic worth of projects and the long-term effects on people and the environment against an explicit counterfactual. All project and bidding documents are made available to public. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 248 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Appendix 2 Methodology for the Evidence Review of Interventions To identify potential interventions and assess the weight of the evidence for possible antimicrobial resistance (AMR) investment priorities, a literature review was conducted in two stages (Figure 4). First, a list of multisectoral interventions was developed (see Table 17); second, 20 interventions were selected for evidence review. The review was primarily web-based, relying on searches of websites and scholarly literature, and it was informed by several stages of expert consultation. Figure 4. Overview of Methodology Source: World Bank. A comprehensive list of interventions with the potential to address AMR in low- and middle-income countries (LMICs) was developed across health, water, agriculture, and the environment. As shown in Table 15, the basis for the selection of interventions was AMR “drivers,” which provide a practical starting point for identifying major causal pathways or conditions creating AMR risk and impact. While broad and sometimes co-occurring, drivers provide a basis for identifying more proximal and specific issues shaping outcomes and informing plausible interventions. Global‑level reports and scientific papers on AMR were reviewed from partner websites and Google search engines to determine relevant drivers, key issues and context factors, and potential interventions (see Table 15 for key sources reviewed). This approach ensured that the selection of Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 249 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices potential interventions took stock of existing knowledge, calls for action, and terminology. While the literature review was grouped by sector-specific entry points, it provided an overall understanding and identification of shared issues and interventions across sectors. This result was used to compile a list presented by (i) drivers, (ii) issues, (iii) plausible interventions (sensitive and specific), and (iv) context. As interventions are aligned to drivers, some interventions were listed multiple times. The primary sector of relevance was identified. The list was distilled down to 20 intervention areas for in-depth literature review and consultations with World Bank experts and external organizations. Table 15. Key Background Literature for Intervention List, by Drivers, Issues, Context, and Possible Interventions DRIVERS PRIMARY SECTOR a ISSUES, CONTEXT, AND INTERVENTIONS Interagency Coordinating Group WASH UNEP (United Nations Environment Programme). 2017. on Antimicrobial Resistance. 2019. and environment “Frontiers 2017: Emerging Issues of Environmental “No Time to Wait.” Concern.” UNEP, Nairobi. https://www.unep. https://www.who.int/docs/ org/resources/frontiers-2017-emerging-issues- default-source/documents/no- environmental-concern. time-to-wait-securing-the-future- WHO (World Health Organization), FAO (Food and from-drug-resistant-infections-en. Agriculture Organization of the United Nations), pdf?sfvrsn=5b424d7_6. and WOAH (World Organisation for Animal Health). Iskandar, K., L. Molinier, S. Hallit, 2020. “Technical Brief on Water, Sanitation, M. Sartelli, F. Catena, F. Coccolini, Hygiene and Wastewater Management to Prevent T. C. Hardcastle, C. Roques, and Infections and Reduce the Spread of Antimicrobial P. Salameh. 2020. “Drivers of Resistance.” https://www.who.int/publications/i/ Antibiotic Resistance Transmission item/9789240006416. in Low- and Middle-Income Wellcome Trust. 2018. “Initiatives for Addressing Countries from a ‘One Health’ Antimicrobial Resistance in the Environment: Perspective: A Review.” Antibiotics Current Situation and Challenges.” https://wellcome. (Basel) 9 (7): 372. doi:10.3390/ ac.uk/sites/default/files/antimicrobial-resistance- antibiotics9070372. environment-report.pdf. Holmes, A. H., L. S. Moore, A. Hendriksen, R. S., P. Munk, P. Njage, B. van Bunnik, Sundsfjord, M. Steinbakk, S. Regmi, L. McNally, O. Lukjancenko, and T. Röder, et al. 2019. A. Karkey, P. J. Guerin, and L. J. “Global Monitoring of Antimicrobial Resistance Piddock. 2016. “Understanding Based on Metagenomics Analyses of Urban Sewage.” the Mechanisms and Drivers of 2019. Nature Communications 10: 1124. https://doi. Antimicrobial Resistance.” Lancet org/10.1038/s41467-019-08853-3. 387 (10014): 176–87. doi: 10.1016/ S0140-6736(15)00473-0. Fouz, N., K. N. A. Pangesti, M. Yasir, A. L. Al-Malki, E. I. Azhar, G. A. Hill-Cawthorne, and M. A. El Ghany. 2020. Laxminarayan, R., A. Duse, C. “The Contribution of Wastewater to the Transmission Wattal, A. K. Zaidi, H. F. Wertheim, of Antimicrobial Resistance in the Environment: N. Sumpradit, E. Vlieghe, et al. 2013. Implications of Mass Gathering Settings.” Tropical “Antibiotic Resistance: The Need for Medicine and Infectious Disease 5 (1): 33. doi: 10.3390/ Global Solutions.” Lancet Infectious tropicalmed5010033. Diseases 13 (12): 1057–98. doi: 10.1016/S1473-3099(13)70318-9. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 250 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices DRIVERS PRIMARY SECTOR a ISSUES, CONTEXT, AND INTERVENTIONS Agriculture and WOAH (World Organisation for Animal Health). 2020. food safety WOAH Standards, Guidelines and Resolutions on Antimicrobial Resistance and the Use of Antimicrobial Agents. Paris: WOAH. https://www.WOAH.org/app/ uploads/2021/03/book-amr-ang-fnl-lr.pdf. FAO (Food and Agriculture Organization of the United Nations). 2020. “Understanding Antimicrobial Resistance in Aquaculture.” Asian Fisheries Society. http://www.fao.org/documents/card/en/c/cb2601en. FAO (Food and Agriculture Organization) and WHO (World Health Organization). 2021a. “Code of Practice to Minimize and Contain Foodborne Antimicrobial Resistance.” CXC 61-2005. Adopted 2005; revised 2021. Codex Alimentarius Commission. CXC_061e.pdf (directoriolegislativo.org). FAO (Food and Agriculture Organization) and WHO (World Health Organization). 2011. “Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance.” Cac/Gl 77-2011. Adopted 2011. Codex Alimentarius Commission. http://www.fao.org/fao-who- codexalimentarius/thematic-areas/antimicrobial- resistance/en/. Van Boeckel, Thomas P., João Pires, Reshma Silvester, Cheng Zhao, Julia Song, Nicola G. Criscuolo, Marius Gilbert, Sebastian Bonhoeffer, and Ramanan Laxminarayan. 2019. “Global Trends in Antimicrobial Resistance in Animals in Low- and Middle-Income Countries.” Science 365 (6459): eaaw1944. https://doi. org/10.1126/science.aaw1944. Schar, D., E. Y. Klein, R. Laxminarayan, Marius Gilbert, and Thomas P. Van Boeckel. 2020. “Global Trends in Antimicrobial Use in Aquaculture.” Scientific Reports 10: 21878. https://doi.org/10.1038/s41598-020-78849-3. Taylor, P., and R. Reeder. 2020. “Antibiotic Use on Crops in Low and Middle-Income Countries Based on Recommendations Made by Agricultural Advisors.” CABI Agriculture and Bioscience 1 (1). https://doi. org/10.1186/s43170-020-00001-y. Marshall B. M., and S. B. Levy. 2011. “Food Animals and Antimicrobials: Impacts on Human Health.” Clinical Microbiology Reviews 24 (4): 718–33. doi: 10.1128/ CMR.00002-11. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 251 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices DRIVERS PRIMARY SECTOR a ISSUES, CONTEXT, AND INTERVENTIONS Health WHO (World Health Organization). 2015. “Global Action Plan on Antimicrobial Resistance.” WHO, Geneva. https://apps.who.int/iris/bitstream/ handle/10665/193736/9789241509763_eng. pdf?sequence=1. WHO (World Health Organization). 2015. “Worldwide Country Situation Analysis: Response to Antimicrobial Resistance.” https://iris.who.int/bitstream/ handle/10665/163468/9789241564946_eng. pdf;sequence=1. https://apps.who.int/iris/bitstream/ handle/10665/163468/9789241564946_eng. pdf;sequence=1. WHO (World Health Organization). 2018. “Antimicrobial Resistance and Primary Health Care. https://www. who.int/docs/default-source/primary-health-care- conference/amr.pdf?sfvrsn=8817d5ba_2. WHO (World Health Organization). 2019. Antimicrobial Stewardship Programs in Health-Care Facilities in Low- and Middle-Income Countries. A WHO Practical Toolkit. Geneva: WHO. https://apps.who.int/iris/ handle/10665/329404. UNICEF. 2019. “Time Is Running Out: Technical Note on Antimicrobial Resistance.” https://www.unicef. org/documents/amr-urgent-threat-drug-resistant- infections. Sartelli, M., C. Hardcastle, F. Catena, A. Chichom- Mefire, F. Coccolini, S. Dhingra, M. Haque, et al. 2020. “Antibiotic Use in Low and Middle-Income Countries and the Challenges of Antimicrobial Resistance in Surgery.” Antibiotics (Basel) 9 (8): 497. doi:10.3390/ antibiotics9080497. Source: World Bank compilation. a. Some sources informed issues, context, and intervention in multiple sectors. WASH = water, sanitation, and hygiene. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 252 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Drawing on existing reviews where available, a high-level summary of the evidence base was developed for 20 interventions to provide an indication of the state of knowledge. For this stage, the team utilized a broad search strategy on PubMed for quick screening of titles of topical relevance and for full-text review of all results (see Table 16). In select cases, Google Scholar was also used to broaden the search; these results were sorted by relevance, and only the first 250 results were reviewed for feasibility. While targeted searches were conducted for each intervention or group of interventions, relevant evidence found incidentally for another intervention was included. The Cochrane Library was also searched (title abstract keyword, Reviews only). Titles and abstracts were scanned for relevance. The primary review of literature was conducted in May and June 2021, unless otherwise specified. Preference was given to evidence generated in the past 10 years to best reflect current AMR challenges and knowledge. Literature was reviewed in English. Snowball sampling from reviewed papers provided a source of additional programs and references, as did grey literature obtained through key websites reporting on interventions and evidence (e.g., ReAct and the AMResilience Intervene database). While reports on dedicated interventions were the focus, cross- sectional studies and topic reviews provided crucial background that broadly illuminated scope, types of impacts to beexpected, feasibility, and gaps. For each intervention, the review reported on intervention scope; the state of knowledge and indications of effectiveness, with country case studies; feasibility considerations; gaps in knowledge; and key takeaways. Given the range of implementation approaches, metrics, sample sizes, and formats (e.g., systematic reviews, grey literature), meta-analysis was not conducted. Intervention evidence criteria were selected and an assessment was conducted to group intervention areas by likelihood of success for investments. Consultations with World Bank staff and external experts were held as part of iterative evidence gathering, analysis, and prioritization of interventions. This outreach sought to validate findings and assumptions and identify any gaps in intervention scope as well as available evidence, particularly for unpublished and negative findings. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 253 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Search terms Table 16. Search Strategy for Intervention Reviews Health sector TOPIC SEARCH TERM RESULT RESULTS 1 Improving infection prevention and control in health care settings Improving infection ("infection prevention and control" OR "IPC") AND ("intervention" PubMed 503 prevention OR "pilot" OR "upgrade" OR "improve" OR "facility" OR and control "community") AND ("antibiotic resistance" OR "antimicrobial resistance" OR "antibiotic use") 2 Improving prescribing practices through guidelines for health care workers Prescribing guidelines "stewardship" AND "rational prescribing " AND (antibiotic resistance PubMed 1,113 OR antimicrobial resistance) AND (LMICs OR LMIC OR "low-and- middle income " OR "Africa" OR Asia OR Afghanistan OR Albania OR Algeria OR Angola OR "Antigua and Barbuda" OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR "Bosnia and Herzegovina" OR Botswana OR Brazil OR "Burkina Faso" OR Burundi OR "Cabo Verde" OR Cambodia OR Cameroon OR "Central African Republic" OR Chad OR China OR Colombia OR Comoros OR "Democratic Republic of Congo" OR Congo OR "Cook Islands" OR "Costa Rica" OR "Côte d'Ivoire" OR Cuba OR Djibouti OR Dominica OR "Dominican Republic" OR Ecuador OR Egypt OR "El Salvador" OR "Equatorial Guinea" OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR "Guinea-Bissau" OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR "Democratic People's Republic of Korea" OR Kosovo OR Kyrgyzstan OR Lao People's Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR "Former Yugoslav Republic of Macedonia" OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR "Marshall Islands" OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR Paraguay OR Peru OR Philippines OR Rwanda OR "Saint Helena" OR Samoa OR "São Tomé and Príncipe" OR Senegal OR Serbia OR Sierra Leone OR "Solomon Islands" OR Somalia OR "South Africa" OR "South Sudan" OR "Sri Lanka" OR "Saint Lucia" OR "Saint Vincent and the Grenadines" OR Sudan OR Suriname OR Swaziland OR "Syrian Arab Republic" OR Tajikistan OR Tanzania OR Thailand OR "Timor-Leste" OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR "Wallis and Futuna" OR "West Bank and Gaza Strip" OR Yemen OR Zambia OR Zimbabwe) Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 254 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS 3 Conducting public awareness campaigns Public awareness “public awareness” OR “awareness” AND “antimicrobial resistance” PubMed 225 campaign/ AND (LMICs OR LMIC OR “low-and-middle income “ OR “Africa” intervention OR Asia OR Afghanistan OR Albania OR Algeria OR Angola OR “Antigua and Barbuda” OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR “Bosnia and Herzegovina” OR Botswana OR Brazil OR “Burkina Faso” OR Burundi OR “Cabo Verde” OR Cambodia OR Cameroon OR “Central African Republic” OR Chad OR China OR Colombia OR Comoros OR “Democratic Republic of Congo” OR Congo OR “Cook Islands” OR “Costa Rica” OR “Côte d’Ivoire” OR Cuba OR Djibouti OR Dominica OR “Dominican Republic” OR Ecuador OR Egypt OR “El Salvador” OR “Equatorial Guinea” OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR “Guinea-Bissau” OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR “Democratic People’s Republic of Korea” OR Kosovo OR Kyrgyzstan OR Lao People’s Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR “Former Yugoslav Republic of Macedonia” OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR “Marshall Islands” OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR Paraguay OR Peru OR Philippines OR Rwanda OR “Saint Helena” OR Samoa OR “São Tomé and Príncipe” OR Senegal OR Serbia OR Sierra Leone OR “Solomon Islands” OR Somalia OR “South Africa” OR “South Sudan” OR “Sri Lanka” OR “Saint Lucia” OR “Saint Vincent and the Grenadines” OR Sudan OR Suriname OR Swaziland OR “Syrian Arab Republic” OR Tajikistan OR Tanzania OR Thailand OR “Timor-Leste” OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “Wallis and Futuna” OR “West Bank and Gaza Strip” OR Yemen OR Zambia OR Zimbabwe) 4 Increasing human health laboratory capacity and access to diagnostics Laboratory capacity “rapid diagnosis” OR “laboratory capacity” AND “antimicrobial PubMed 273 resistance” AND (LMICs OR LMIC OR “low-and-middle income “ OR “Africa” OR Asia OR Afghanistan OR Albania OR Algeria OR Angola OR “Antigua and Barbuda” OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR “Bosnia and Herzegovina” OR Botswana OR Brazil OR “Burkina Faso” OR Burundi OR “Cabo Verde” OR Cambodia OR Cameroon OR “Central African Republic” OR Chad OR China OR Colombia OR Comoros OR “Democratic Republic of Congo” OR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 255 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS OR Congo OR “Cook Islands” OR “Costa Rica” OR “Côte d’Ivoire” OR Cuba OR Djibouti OR Dominica OR “Dominican Republic” OR Ecuador OR Egypt OR “El Salvador” OR “Equatorial Guinea” OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR “Guinea-Bissau” OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR “Democratic People’s Republic of Korea” OR Kosovo OR Kyrgyzstan OR Lao People’s Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR “Former Yugoslav Republic of Macedonia” OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR “Marshall Islands” OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR Paraguay OR Peru OR Philippines OR Rwanda OR “Saint Helena” OR Samoa OR “São Tomé and Príncipe” OR Senegal OR Serbia OR Sierra Leone OR “Solomon Islands” OR Somalia OR “South Africa” OR “South Sudan” OR “Sri Lanka” OR “Saint Lucia” OR “Saint Vincent and the Grenadines” OR Sudan OR Suriname OR Swaziland OR “Syrian Arab Republic” OR Tajikistan OR Tanzania OR Thailand OR “Timor-Leste” OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “Wallis and Futuna” OR “West Bank and Gaza Strip” OR Yemen OR Zambia OR Zimbabwe) Rapid diagnostics (“rapid diagnostic” OR “rapid test” OR “point of care” OR “point- PubMed 107 of-care” OR “bedside” OR “near-patient”) AND (“access” OR [Conducted for papers “availability”) AND (“antimicrobial resistance” OR “AMR” OR published through “antimicrobial use” OR “antibiotic use” OR “antibiotic prescribing”) 2022] 5 Strengthening surveillance of antimicrobial use (AMU) and AMR in human populations Surveillance “surveillance” AND (antibiotic resistance OR antimicrobial resistance) AND (LMICs OR LMIC OR “low-and-middle income “ OR “Africa” OR Asia OR Afghanistan OR Albania OR Algeria OR Angola OR “Antigua and Barbuda” OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR “Bosnia and Herzegovina” OR Botswana OR Brazil OR “Burkina Faso” OR Burundi OR “Cabo Verde” OR Cambodia OR Cameroon OR “Central African Republic” OR Chad OR China OR Colombia OR Comoros OR “Democratic Republic of Congo” OR Congo OR “Cook Islands” OR “Costa Rica” OR “Côte d’Ivoire” OR Cuba OR Djibouti OR Dominica OR “Dominican Republic” OR Ecuador OR Egypt OR “El Salvador” OR “Equatorial Guinea” OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR “Guinea-Bissau” OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 256 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR PubMed 3,232 Kiribati OR “Democratic People’s Republic of Korea” OR Kosovo OR Kyrgyzstan OR Lao People’s Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR “Former Yugoslav Republic of Macedonia” OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR “Marshall Islands” OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR Paraguay OR Peru OR Philippines OR Rwanda OR “Saint Helena” OR Samoa OR “São Tomé and Príncipe” OR Senegal OR Serbia OR Sierra Leone OR “Solomon Islands” OR Somalia OR “South Africa” OR “South Sudan” OR “Sri Lanka” OR “Saint Lucia” OR “Saint Vincent and the Grenadines” OR Sudan OR Suriname OR Swaziland OR “Syrian Arab Republic” OR Tajikistan OR Tanzania OR Thailand OR “Timor-Leste” OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “Wallis and Futuna” OR “West Bank and Gaza Strip” OR Yemen OR Zambia OR Zimbabwe) Agriculture and food sector TOPIC SEARCH TERM RESULT RESULTS 6 Increasing oversight of AMU by veterinarians Veterinary prescribing (animal OR veterinar*) AND prescribing AND (guideline OR PubMed 102 regulation) AND (antimicrobial OR antibiotic) AND (global OR LMICs OR LMIC OR “low-and-middle income countries” OR “developing countries” OR “Latin America” OR Africa OR Asia OR “South America” OR “Central America” OR Afghanistan OR Albania OR Algeria OR Angola OR “Antigua and Barbuda” OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR “Bosnia and Herzegovina” OR Botswana OR Brazil OR “Burkina Faso” OR Burundi OR “Cabo Verde” OR Cambodia OR Cameroon OR “Central African Republic” OR Chad OR China OR Colombia OR Comoros OR “Democratic Republic of Congo” OR Congo OR “Cook Islands” OR “Costa Rica” OR “Côte d’Ivoire” OR Cuba OR Djibouti OR Dominica OR “Dominican Republic” OR Ecuador OR Egypt OR “El Salvador” OR “Equatorial Guinea” OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR “Guinea-Bissau” OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR “Democratic People’s Republic of Korea” OR Kosovo OR Kyrgyzstan OR Lao People’s Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR “Former Yugoslav Republic of Macedonia” OR Madagascar OR Malawi OR Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 257 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS Malaysia OR Maldives OR Mali OR “Marshall Islands” OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR “Papua New Guinea” OR Paraguay OR Peru OR Philippines OR Rwanda OR “Saint Helena” OR Samoa OR “São Tomé and Príncipe” OR Senegal OR Serbia OR Sierra Leone OR “Solomon Islands” OR Somalia OR “South Africa” OR “South Sudan” OR “Sri Lanka” OR “Saint Lucia” OR “Saint Vincent and the Grenadines” OR Sudan OR Suriname OR Swaziland OR “Syrian Arab Republic” OR Tajikistan OR Tanzania OR Thailand OR “Timor-Leste” OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “Wallis and Futuna” OR “West Bank and Gaza Strip” OR Yemen OR Zambia OR Zimbabwe) Veterinary prescribing veterinary prescribing guideline AND ("antibiotic use" OR Google 6,850 "antimicrobial use") Scholar (First 250 results reviewed) 7 Monitoring of AMU, surveillance of AMR, and increasing oversight in plant/crop production Crop production (“monitoring” OR “regulation” OR “supervision” OR “prescribing” OR PubMed 845 “guideline”) AND (“intervention” OR “reduc*”) AND (“antimicrobial” OR “antibiotic” OR “resistance” OR “AMR”) AND (“crop” OR “orchard” OR “fruit production”) 8 Improving animal husbandry practices and biosecurity Animal husbandry (animal OR livestock OR farm) AND (hygiene OR biosecurity OR PubMed 303 practices and "animal health" OR welfare) AND (improvement OR enhance biosecurity OR intervention) AND (infection OR disease OR treatment) AND ("antimicrobial use" OR "antibiotic use") 9 Monitoring sales and use of antimicrobials and surveillance of AMR in animals Monitoring of (“monitoring system” OR “reporting system” OR database) PubMed 266 sales and use of AND (antibiotic OR antimicrobial) AND (sales OR use OR usage) antimicrobials AND (animal OR veterinary OR livestock OR farm) AND (“growth promoter” OR “critically important” OR trend OR track OR pattern) Surveillance of AMR in (“monitoring system” OR “reporting system” OR “database” OR PubMed 1,415 animals “surveillance”) AND (“antibiotic resistance” OR “antimicrobial resistance” OR “AMR” OR “resistant”) AND (“case” OR “incidence” [Conducted for papers OR “outbreak” OR “prevalence”) AND (animal OR veterinary OR published through livestock OR farm) 2022] Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 258 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS 10 Promoting behavior change campaigns in animal production Behavior change (farmer OR veterinarian OR extension OR "animal production") PubMed 193 AND ("antibiotic use" OR "antimicrobial use" OR antibiotics) AND ("behavior change" OR prudent OR "change in") 11 Increasing veterinary laboratory capacity and access to diagnostics Increasing veterinary (“laboratory capacity” OR “diagnosis” OR “field-based” OR “mobile PubMed 395 laboratory capacity laboratory” OR sensitivity OR susceptibility OR quality) AND (“animal” OR “livestock” OR “veterinary”) AND (infection OR disease OR treatment) AND (“antimicrobial use” OR “antibiotic use”) AND (treatment OR prescribing) Water and environment sector TOPIC SEARCH TERM RESULT RESULTS 12 Improving infrastructure to provide access to water and sanitation in health care centers Improving (“water” OR “sanitation” OR “hygiene” OR “WASH” OR “water, PubMed 287 infrastructure to sanitation and hygiene” OR “IPC” OR “infection prevention” OR provide access to “infection control” OR “infection prevention and control”) AND water and sanitation (piping OR piped OR pipe OR running OR infrastructure) AND (“in in health centers hospital” OR “hospital setting” OR “clinic” OR “health center” OR “health care center” OR “health facility” OR “healthcare facility” [Conducted for papers OR “healthcare facilities”) AND (infection OR antimicrobial OR published through antibiotic OR burden OR resistance OR resistant OR “hand hygiene” 2022] OR “water quality”) 13 Implementing effective treatment and disposal of sewage and wastewater Treatment and (pharmaceutical manufacturing OR hospital OR urban OR PubMed 86 disposal of sewage municipal) AND (tertiary OR advanced) AND treatment AND (waste and wastewater OR effluent) AND (antimicrobial OR antibiotic) AND (gene OR residue OR pathogen) Treatment and (wastewater OR waste) AND "advanced treatment" AND antibiotic Google 7,110 (First disposal of sewage Scholar 250 results and wastewater reviewed) 14 Improving waste management practices in agricultural and aquaculture production/processing Waste management (“waste management” OR “manure treatment” OR “effluent PubMed 141 practices in treatment”) AND (intervention OR program) AND (agriculture agricultural and OR aquaculture OR “on farms”) AND (resistance OR resistant OR aquaculture residue) production/ processing Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 259 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS 15 Improving safe disposal of unused antimicrobials Safe disposal "take back" AND (antibiotic OR medication) PubMed 147 Safe disposal (“safe disposal” OR “take back”) AND (antibiotic OR medication) PubMed 103 AND (global OR LMICs OR LMIC OR “low-and-middle income countries” OR “developing countries” OR “Latin America” OR Africa OR Asia OR “South America” OR “Central America” OR Afghanistan OR Albania OR Algeria OR Angola OR “Antigua and Barbuda” OR Argentina OR Armenia OR Azerbaijan OR Bangladesh OR Belarus OR Belize OR Benin OR Bhutan OR Bolivia OR “Bosnia and Herzegovina” OR Botswana OR Brazil OR “Burkina Faso” OR Burundi OR “Cabo Verde” OR Cambodia OR Cameroon OR “Central African Republic” OR Chad OR China OR Colombia OR Comoros OR “Democratic Republic of Congo” OR Congo OR “Cook Islands” OR “Costa Rica” OR “Côte d’Ivoire” OR Cuba OR Djibouti OR Dominica OR “Dominican Republic” OR Ecuador OR Egypt OR “El Salvador” OR “Equatorial Guinea” OR Eritrea OR Ethiopia OR Fiji OR Gabon OR Gambia OR Georgia OR Ghana OR Grenada OR Guatemala OR Guinea OR “Guinea-Bissau” OR Guyana OR Haiti OR Honduras OR India OR Indonesia OR Iran OR Iraq OR Jamaica OR Jordan OR Kazakhstan OR Kenya OR Kiribati OR “Democratic People’s Republic of Korea” OR Kosovo OR Kyrgyzstan OR Lao People’s Democratic Republic OR Lebanon OR Lesotho OR Liberia OR Libya OR “Former Yugoslav Republic of Macedonia” OR Madagascar OR Malawi OR Malaysia OR Maldives OR Mali OR “Marshall Islands” OR Mauritania OR Mauritius OR Mexico OR Micronesia OR Moldova OR Mongolia OR Montenegro OR Montserrat OR Morocco OR Mozambique OR Myanmar OR Namibia OR Nauru OR Nepal OR Nicaragua OR Niger OR Nigeria OR Niue OR Pakistan OR Palau OR Panama OR “Papua New Guinea” OR Paraguay OR Peru OR Philippines OR Rwanda OR “Saint Helena” OR Samoa OR “São Tomé and Príncipe” OR Senegal OR Serbia OR Sierra Leone OR “Solomon Islands” OR Somalia OR “South Africa” OR “South Sudan” OR “Sri Lanka” OR “Saint Lucia” OR “Saint Vincent and the Grenadines” OR Sudan OR Suriname OR Swaziland OR “Syrian Arab Republic” OR Tajikistan OR Tanzania OR Thailand OR “Timor- Leste” OR Togo OR Tokelau OR Tonga OR Tunisia OR Turkey OR Turkmenistan OR Tuvalu OR Uganda OR Ukraine OR Uzbekistan OR Vanuatu OR Venezuela OR Vietnam OR “Wallis and Futuna” OR “West Bank and Gaza Strip” OR Yemen OR Zambia OR Zimbabwe) Safe disposal antibiotic AND (disposal OR "take back") AND (intervention OR Google 18,700 program) Scholar (First 250 results reviewed) Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 260 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices TOPIC SEARCH TERM RESULT RESULTS 16 Monitoring presence of antimicrobial residues and antibiotic-resistant Monitoring in water (monitoring OR surveillance OR detection) AND (“antimicrobial” PubMed 257 and sanitation OR “antibiotic” OR “antibiotic-resistant bacteria” OR “antibiotic systems resistant”) AND (“water system” OR “sanitation system” OR “water and sanitation system”) Multisectoral TOPIC SEARCH TERM RESULT RESULTS 17 Detecting and deterring substandard and falsified antimicrobials (customs/law enforcement/health/ agriculture) Detecting and "counterfeit" OR "falsified" OR "substandard" AND ("medicine" OR PubMed 1,342 deterring substandard "antibiotics" OR "antimicrobials" OR "resistance") and falsified antimicrobials 18 Improving nutrition in humans and animals (health/agriculture) Improving nutrition in ("AMR" OR "antimicrobial resistance" OR "antibiotic resistance" PubMed 280 humans and animals OR "antimicrobial use" OR "antibiotic use") AND ("nutrition" OR "nutrient" OR "food security") AND ("reduction" OR "reduce") 19 Expanding vaccination coverage in humans and animals (health/agriculture) Expanding vaccination ("AMR" OR "antimicrobial resistance" OR "antibiotic resistance" PubMed 474 coverage in humans OR "antimicrobial use" OR "antibiotic use") AND ("vaccination" OR and animals "vaccine") AND ("reduction" OR "reduce") 20 Using closed water systems in aquaculture (agriculture/environment) Closed water systems ("AMR" OR "antimicrobial resistance" OR "antibiotic resistance" PubMed 45 in aquaculture OR "antimicrobial use" OR "antibiotic use") AND ("aquaculture" OR "fish") AND ("waste") AND ("integrated system" OR "closed system" OR "recirculating" OR “recirculate” OR "management" OR "treatment" OR "removal") Source: World Bank. Note: Several topic searches included terms for income level, region, or country, using a set listing from the protocol by Pinto and Chandler (2020). This approach was used to narrow searches in cases where literature was extensive and appeared to be dominated by findings from high-income countries (primarily for health sector interventions); the goal was a more representative sample for review. Most searches were conducted in 2021 (specific exceptions are noted). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 261 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 17. Long List of Interventions Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Health; law Substandard and Poor quality • Supply chain management/ • Testing antimicrobials upon import Approach depends on enforcement falsified antibiotics (counterfeit, traceability, including upon import • Antimicrobial registration portion/type of antibiotics degraded, • Closed drug distribution laws, • Monitoring, regulation, and imported vs. produced in mislabeled, expired) rescheduling, and elimination of enforcement infrastructure to detect country off-label use and deter substandard or falsified • Drug manufacturer antibiotics in the supply chain authenticity partnerships (e.g., labeling, blockchain) Health; Availability of Poor quality • Drug prescribing and sales laws • Antimicrobial prescribing and Settings with high consumer agriculture antibiotics over the (counterfeit and enforcement sales laws and enforcement (e.g., demand for antibiotics and counter or degraded); • Improved access to/utilization of registration of sellers) high burden of infections; inappropriate use formal health care system • Point of sale instruction on use low health care or • Education of dispensers diagnostic access • Incentive programs for changing sales practices (stewardship) Health/ Limited public High demand; poor • Overall health literacy enhancement • Compliance support to Settings with a high burden education awareness and compliance in • Integrated approaches as part patients (e.g., phone of TB, malaria knowledge of use and improper of prevention/control of sexually call/telehealth/SMS reminders) Frequent users of antibiotics and disposal transmitted infections, vector- • Centralized collection (e.g., via antimicrobials (for personal antibiotic resistance borne diseases (e.g., malaria), and town halls, community health use or occupation) livestock diseases: allows for targeted workers, etc.) messaging to practitioners, sellers, • KAP studies and behavior and the public change initiatives • Compliance support • Consumer/public outreach (e.g., school-based, social media) Health Limited availability or Susceptibility to • Community vaccination campaigns Settings with a high burden uptake of vaccines vaccine-preventable • R&D investment in of vaccine-preventable disease accessible vaccines disease Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 262 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Health Overprescribing/non- Limited tracking • Clinical guidelines on treatment • Stewardship campaigns (e.g., Several different contexts: prudent use and awareness • Clinical protocols to inform rational prescribing, facility or settings with a high burden by providers; differential diagnosis (e.g., provider prescribing audits, of endemic disease (e.g., limited health care intake history) education/awareness campaigns, malaria, typhoid); low access/ treatment • Clinical decision support tools incentive campaigns) continuity of care options; incentives • Practitioner buy-in and engagement • Patient education on the importance and demand; not in stewardship of treatment completion completing the full • Possible AWaRe categorization • Pharmaceutical industry restrictions treatment course on antibiotic marketing • Antibiotic labeling Agriculture; Inadequate food Overuse of • Food safety improvement measures • Regulations on AMU and residues in Settings with inadequate food safety safety regulations, antimicrobials and controls (identification food production and supply food storage (e.g., cold monitoring, and and additives; of responsible authority, • Harmonization to international chain) controls limited traceability legislation, proper human and standards, such as Codex across the volume financial resources) Alimentarius, specifically TFAMR of trade and • Hygiene measures in food • Standard treatment guidelines number of outlets; preparation and storage (e.g., for prophylaxis, contamination along (pasteurization, improved packaging, metaphylaxis, treatment) the food chain, or cold storage) • Regulations, training, and including spoilage • Monitoring of risk and enforcement for withdrawal periods pharmaceutical use in the • Pathogen and/or residue testing of food system foods on import and other points in the market chain • AMR monitoring in food animal handlers • Product (or farm) certification Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 263 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Agriculture Inappropriate volume High volume of AMU; • Awareness and uptake of good • Regulation of AMU in animal Production system type (animal of antibiotics used non-judicious use; husbandry and welfare practices production (regulatory change, (e.g., intensive, extensive, production) to grow livestock, use of medically • Nature-based solutions for pest training, enforcement) integrated): affects the flow poultry, and aquatic important antibiotics or pathogen control to reduce • Standard treatment (prescribing) of inputs and outputs animals (e.g., colistin, disease burden guidance and essential medicines aminoglycosides, • Biosecurity/husbandry practices list for veterinary practice and animal macrolides, production use penicillins, • Regulation on AMU in animal quinolones, production for prophylaxis and sulfonamides, growth promotion tetracyclines); • Training of practitioners perceived benefits in (veterinarians/paraveterinarians, animal production farmer associations, and/or consumers) on appropriate use (storage, dosing, application) • Resistant breeds • Product (or farm) certification • Public information campaigns (for veterinarians, farmers, or consumers) Agriculture (crop  Inappropriate volume High volume of • Nature-based solutions for pest and • Regulation of AMU in crop Production system production) of antibiotics used AMU; nontargeted pathogen control to reduce disease production, including use type (e.g., organic vs. to grow crops; poor application allowing burden (e.g., polycultures) of medically important nonorganic); used for farm hygiene for environmental • Use of local crop varieties with antibiotics (regulatory change, bacterial/fungal concerns dissemination; a natural resistance against training, enforcement) and pest insects; typically contamination of pathogens and pests • Training of farmers on appropriate certain fruit production (e.g., crops by pests use (storage, dosing, application) apple, pear) • Resistant crop variants • AMU tracking • Market-based incentives for reduced AMU • Surveillance for residues in soil and handlers and on fruit Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 264 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Agriculture Need to intensify High-density animal • Improved livestock and • Regulation of AMU in animal Transitional production (animal animal production production; low agricultural productivity production, including use systems where disease production) to meet increasing drug absorption • Improved biosecurity and overall of medically important spread potential is likely to demand by animals; slow good practices to reduce disease antibiotics (regulatory change, change as density increases; clearance of active risk (e.g., stock rates, appropriate training, enforcement) climate-related effects on pharmaceutical husbandry, vaccination) • Alternatives to antibiotics: e.g., prevalence of water- and ingredients; dietary • Treatment (chemical, biological) of herbal therapy, phages vector-borne pathogens; transitions (nutrition influent and effluent varying nutrition status and improvement, wild to • Improved disease diagnosis to access to animal protein domestic, excess) support improved targeting of alternatives disease control measures • Reduced demand for excess protein (education, alternatives) Agriculture Household sharing Infections from • WASH interventions to reduce • Restriction of AMU (human only, Smallholder production (animal habitat with poultry animal-human potential for contamination animal only) to protect efficacy of systems production) and livestock exposures • Biosecurity measures medically important antibiotics in animal and farmers Water/ Sharing of surface Potential for bacterial • WASH interventions to reduce • Pathogen and/or residue testing Low biosecurity; reliance on environment waters by humans infections potential for contamination of water, source traceback, and open water sources and animals treatment or contamination control measures Agriculture Limited access or Susceptibility to • Improved provision of vaccines and • Training of prescribers and farmers Settings without required (animal uptake of veterinary vaccine-preventable vaccine uptake nudges through on appropriate AMU and disease vaccination; rural setting production) vaccines diseases; poor veterinary services reporting with limited infrastructure access to differential • Improved storage and administration • Education of farmers for vaccine cold storage/ diagnostics practices to promote efficacy distribution Agriculture; Food consumption Pathogen exposures; • Cooking to address pathogen risks • Labeling with recommendations Low consumer awareness food safety behaviors and antimicrobial residue • Improved animal production and on preparation of food and its and limited risk preferences (i.e., exposures preparation practices to reduce intended use communication raw or undercooked pathogen load and AMU meat) • Community education/awareness raising on safe food consumption, food-related risk Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 265 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Agriculture Absence of farm Potential for • Development of agricultural • AMU training provided directly to Limited access to veterinary biosecurity and contamination; lack extension networks farmers and/or farming associations services; informal/ frameworks for of awareness • Training on biosecurity • Regulations and reporting system for inadequate existing training farmers AMU by farms biosecurity infrastructure Environment High levels of Susceptibility- • Soil/other environmental • Restrictions on AMU Weak environmental environmental weakened immune remediation • Effluent/waste treatment services/governance contamination with system (e.g., • Policy/legislative interventions requirements for antimicrobial antibiotic residues, pesticide exposures); (e.g., restrictions on use and release residues and synergistic heavy metals, and multi-resistance of contaminants) contaminants prior to release into biocides development to • Waste management in/around environment heavy metals and ecotourism sites antibiotics; AMU to treat symptoms from toxicant exposures Agriculture Behaviors relating Food safety and • Overall waste management practices • Education of farmers on the law, Settings with limited access (animal to the slaughter and waste disposal issues, in agricultural production/processing enforcement of the regulations to extensions services production) processing of food including bacterial • Food safety legislation and • Strengthening of veterinary services animals contamination; enforcement at slaughterhouses/ and extension services dissemination of abattoirs • Training at community level; training ARGs • Improved husbandry (legislation, for farmers and paraprofessionals training, infrastructure, certification) • WASH interventions to reduce potential for contamination (e.g., in abattoirs) Agriculture; Irrigation with Bacterial • Wastewater treatment to address • Wastewater treatment for residues Settings with limited access/ water untreated wastewater contamination pathogen risks and ARGs prior to use water shortages Agriculture Use of untreated Infection with • Treatment of animal waste prior • Animal waste treatment for residues animal waste for a antimicrobial- to use as fertilizer to address and ARGs prior to use variety of purposes, resistant pathogens pathogen risks e.g., as fertilizer due to antibiotics in waste; contamination of land and water sources Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 266 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Agriculture Use of poultry Bacterial • Closed systems: treatment of influent • Reduction of unnecessary (e.g., waste as feed in contamination; and effluent nontherapeutic) AMU in poultry aquaculture persistence of • Non-integrated • Treatment of poultry waste resistant genes poultry-aquaculture operations prior to use in environmental • Where use has been widespread, may reservoirs need to target ARGs persistent in environment Water Untreated Dissemination • Regulation on active pharmaceutical • Regulations on effluent management wastewater into environment, ingredient manufacturing and audits • Regulations on antimicrobial originating from including into • Waste treatment waste management throughout pharmaceutical waterways • Controlled entry of effluent into manufacturing, use, and industries, hospitals, broader environment (e.g., surface disposal spectrum markets, manure, and water, rivers, agricultural plots, etc.) • Monitoring for residues, pathogens, sewage runoff and genes • Waste treatment for residues, pathogens, and genes Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 267 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Health; water Overcrowding and High potential for • Other IPC and WASH measures • Waste/wastewater treatment from Health care settings poor sanitation and bacterial infections; in hospitals (improved cleaning, health care facility for residues, lacking designated areas hygiene (health care uncontrolled cross- toilet facilities, waste management, pathogens, and ARGs for patients at high risk, or facilities) contamination equipment sharing and • Availability of handwashing/ those with infectious illness in overcrowded sanitation, IPC training, protocol • disinfection wards; poor contact implementation, monitoring and • “Offensive” and “defensive” infection precautions; easy evaluation by IPC practitioners/ control SOPs (managing standardized spread of resistant trained health workers) practice such as contact precautions strains • Staff education on equipment and post-diagnosis; protocol for infection hand hygiene prevention—i.e., prevention of • Increase in segmented areas for surgical site contamination through patients with varying comorbidities equipment contamination) • Isolation wards • Implementation of contact • IPC training, protocol precautions and isolation procedures implementation, monitoring and for patients with high-consequence evaluation by IPC practitioners/ AMR infections trained health workers • New or upgraded facilities designed to limit infection spread (e.g., ventilation) Water; urban Overcrowding and Prophylactic use; • WASH interventions to reduce overall • Centralized toilet facilities with waste Informal settings; reliance poor sanitation and poor access to disease burden in community and treatment for residues and/or genes on surface water; facilitated/ hygiene (community) trained medical household settings (e.g., schools) • Sewage monitoring for increased contamination providers; exposure • Safe childhood play areas free of pathogens and ARGs due to flooding; exacerbated to animals/animal waste contamination • Waste treatment for risk due to displacement waste; high potential pathogens and ARGs from climate change and for bacterial conflict situations infections; easy spread of resistant strains/conditions for mutations Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 268 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Agriculture; Liquid waste from Contamination of • Improved waste management • AMR monitoring of wastewater and/or Live animal markets where water markets (blood, water sources before reuse liquid waste slaughter occurs, local feces, wastewater) • Off-site animal slaughter to culture disposed into centralize treatment of point municipal drains source contamination through direct washout Health; social Scarce data on the Low detection/ • Improved population-level detection • Improved population-level detection development magnitude and tracking of impacts; and reporting and reporting economic burden of few safety nets; • Vulnerability and impact • Vulnerability and impact assessments AMR in humans minimal data on assessments (e.g., climate-sensitive, • Improved institutional governance number of individuals food or water insecurity) and safety nets to mitigate per household • Reduced vulnerability to and impact vulnerability and cope with of infections overall AMR impacts • Increased monitoring of local human migration patterns (i.e., rainy season causing influx into inland cities) Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 269 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Issues Contextual Primary sector Drivers (more specific AMR-sensitive intervention AMR-specific intervention considerations (main sector able (broad factors or proximal (broader initiatives that can reduce (initiatives that have AMR reduction (relevance for a given to take action) linked to risk) contributing factors) AMR risk or impact a co-benefit) as their main purpose) country) Health; Weak surveillance, Poor detection, • Clinical protocols to inform • Regulatory requirement for reporting Setting with limited agriculture laboratory, and diagnosis, and differential diagnosis of infections of antimicrobial use (prescribing governance, monitoring (animal health) epidemiological epidemiological (e.g., intake history) or sales) and AMR—at health care infrastructure, and capacity (and lack of understanding; • Point of care diagnostics (e.g., rapid facilities, points of sale, prescribers, multisectoral coordination resourcing) unaffordable testing; diagnostic tests) farms, etc. in AMR monitoring and poor monitoring • Monitoring of pharmaceutical • Susceptibility testing (individual action planning; limited of use trends and drug use (clinical and veterinary or patient-level) to inform existing guidance, lab, and pathogens circulating prescribing) and sales antimicrobial prescribing surveillance capacities and • Practitioner audits of prescribing • AMR outbreak monitoring and regulations; substandard history and behavior tracking, including contact tracing to and falsified veterinary • Laboratory capacity for quality of optimize which patients to test in the medicinal products veterinary medicinal products event of low testing supplies • Quality assurance of and reporting back on surveillance information • Low-cost, high-yield surveillance strategies (e.g., in sewage systems; whole genome sequencing for point source detection) Source: World Bank compilation. Note: This list is adapted from previous lists of drivers and expert input (see Table 15). Drivers do not represent equal risk or lead to equal impacts, and their relevance is context-specific for any given country. The scope is focused on issues pertinent to low- and middle-income countries. ARG = antimicrobial-resistant gene; AMU = antimicrobial use; AWaRe = access, watch, reserve; IPC= infection prevention and control; KAP = knowledge, attitudes, and practices; SOP = standard operating procedure; TB = tuberculosis; TFAMR = Ad Hoc Codex Intergovernmental Task Force on Antimicrobial Resistance; WASH = water, sanitation, and hygiene. References Pinto, C., and C. I. R. Chandler. 2020. “WASH and Biosecurity Interventions for Reducing Burdens of Infection, Antibiotic Use and Antimicrobial Resistance: A One Health Mixed Methods Systematic Review.” London School of Hygiene and Tropical Medicine, et al. https://researchonline.lshtm.ac.uk/id/eprint/4657795/1/ Pinto-Chandler-2020_WASH_and_biosecurity%20interventions_review.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 270 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Appendix 3 Environmental and Social Safeguards Guidance Introduction This appendix explains how the Environmental and Social Framework (ESF) can help client countries address antimicrobial resistance (AMR) through managing the environmental and social (E&S) risks and impacts of Investment Project Financing (IPF). The E&S policies and the 10 E&S Standards (ESSs) apply to all projects financed by the World Bank through IPF. The ESSs outline specific requirements for client countries to address in areas such as labor conditions, resource efficiency, community health, and natural resource management (see Box 14). The World Bank will support only those projects 50 that meet the requirements of the ESS in a manner and time frame acceptable to the World Bank. Box 14. Overview of the Environmental and Social Standards Overview of the Environmental and Social Standards The ESF comprises 10 Environmental and Social Standards: • ESS1: Assessment and Management of Environmental and Social Risks and Impacts • ESS2: Labor and Working Conditions • ESS3: Resource Efficiency and Pollution Prevention and Management • ESS4: Community Health and Safety • ESS5: Land Acquisition, Restrictions on Land Use and Involuntary Resettlement • ESS6: Biodiversity Conservation and Sustainable Management of Living Natural Resources • ESS7: Indigenous Peoples/Sub-Saharan African Historically Undeserved Traditional Local Communities • ESS8: Cultural Heritage • ESS9: Financial Intermediaries • ESS10: Stakeholder Engagement and Information Disclosure 50  “Project” refers to the activities for which the World Bank provides support. Projects may include new facilities or activities and/or existing facilities or activities, or a combination of these. Projects may also include subprojects (World Bank 2017). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 271 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices The Framework for Action describes 20 interventions across agriculture, the environment, health, and water; investments in these areas can support low- and middle-income countries in strengthening and developing agriculture, health, and water and sanitation systems that prevent the emergence of diseases and thus reduce AMR (see Table 18). Application of the ESSs in IPF operations can provide entry points for these interventions and appropriate mitigations. Recommendations for mitigation measures should be tailored to the specific type of risks identified for the specific intervention and its given context. This guidance will provide a systematic approach to the identification, assessment, and mitigation of related risks with clearly defined roles for both client country and the World Bank. Table 18. Intervention Areas for Addressing AMR, by Sector Health Water and environment 1 Improving infection prevention and 12 Improving infrastructure to provide control in health care settings access to water and sanitation in health care centers 2 Improving prescribing practices through guidelines for health care workers 13 Implementing effective treatment and disposal of sewage and wastewater 3 Conducting public awareness campaigns 14 Improving waste management practices 4 Increasing human health laboratory in agricultural and aquaculture capacity and access to diagnostics production/processing 5 Strengthening surveillance of 15 Improving safe disposal of unused antimicrobial use (AMU) and AMR in antimicrobials human populations 16 Monitoring presence of antimicrobial residues and antibiotic-resistant bacteria Agriculture and food and genes in water and sanitation systems 6 Increasing oversight of AMU by veterinarians Multisectoral 7 Monitoring AMU, surveillance of 17 Detecting and deterring substandard AMR, and increasing oversight in and falsified antimicrobials (customs/law plant/crop production enforcement/health/agriculture) 8 Improving animal husbandry practice 18 Improving human and animal nutrition and biosecurity (health/agriculture) 9 Monitoring sales and use of antimicrobials 19 Expanding vaccination coverage in and surveillance of AMR in animals humans and animals (health/agriculture) 10 Promoting behavior change campaigns in 20 Using closed water systems in animal production aquaculture (agriculture/environment) 11 Increasing veterinary laboratory capacity and access to diagnostics Source: World Bank. Note: AMU = antimicrobial use. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 272 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Objectives and scope ESS1 (Assessment and Management of Risks) and ESS10 (Stakeholder Engagement) set out client countries’ responsibility for assessing, managing, and monitoring E&S risks. ESS1 provides for an E&S assessment of the proposed project, engagement with stakeholders, disclosure of appropriate information, development of an Environmental and Social Commitment Plan (ESCP), and assessment, monitoring, and reporting on the performance of the project against the ESSs. ESS10 on stakeholder engagement must be read in conjunction with ESS1—that is, it should be recognized that effective stakeholder engagement can improve environmental and social sustainability of projects, enhance project acceptance, and make a significant contribution to successful project design and implementation. ESS10 includes a systematic approach to enabling stakeholders’ views to be considered in project design and environmental and social performance. The primary objective of this guidance is to support World Bank staff, including E&S specialists and task teams, in engaging with client countries to manage risks related to the identified AMR-related interventions. Section 1 focuses on understanding E&S risks and conducting E&S assessments. Section 2 discusses potentially significant AMR-related risks and impacts on gender. Section 3 describes approaches to stakeholder engagement. Section 4 guides actions for mitigation required for meeting the ESSs. Section 1. Environmental and social assessment of AMR projects The client country’s E&S assessment includes environmental risks and impacts, such as those related to community safety, climate change, and ecosystem services, as well as social risks and impacts, such as the risk that a project disproportionately and negatively affects disadvantaged or vulnerable individuals or groups. Resistant microorganisms occur not only in people and animals, but also in contaminated food and water sources and more broadly in the environment. Resistant microorganisms and genes can be transmitted through various pathways, such as person-to-person contact, person-to-animal contact, consumption of contaminated foods, and contact with human and agricultural wastes. The environmental dimension of AMR has received comparatively less focus than AMR in human or animal health. However, evidence indicates that the release of antimicrobial compounds into the environment, coupled with direct contact between natural bacterial communities and discharged resistant bacteria, is driving bacterial evolution and the emergence of more resistant strains (UNEP 2017). A Review on Antimicrobial Resistance (2016) report highlights the need to reduce antibiotic pollution of the environment through three pathways: (i) municipal and industrial wastewater, such as from households, health care facilities, manufacturing, and pharmacies; (ii) land spreading of animal manure and sewage sludge from animal production; and (iii) aquaculture. ESS1, ESS2, ESS3, ESS4, ESS6, and ESS10 are relevant to AMR and related risks to humans, animals, and the environment. Table 19 aims to support the E&S assessment of 20 AMR-related interventions by identifying risks and impacts of each intervention as well as options for mitigating them. The table should help World Bank staff identify good practices/mitigation measures aligned with these and similar interventions. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 273 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices These ESSs provide entry points for the control of AMR; for projects supporting livestock and aquaculture production, health care facilities (HCFs), and WASH (water, sanitation, and hygiene) services, impact assessment and mitigation should consider risks such as the introduction of resistant microbes into natural ecosystems. Addressing the impact of ecosystems on AMR spread and emergence, and vice versa, as well as the impact of AMR on certain individuals and groups, will be relevant in complying with the ESSs, including the selection of stakeholders and preparing the ESCP. Mitigation measures and good practices are tailored to the level of risk and project specificities and can be summarized within five main groupings of interventions: (i) infection prevention and control, (ii) policy and guidelines for limiting use of antimicrobials, (iii) waste and wastewater management, (iv) surveillance and monitoring, and (v) quality testing of antimicrobials for use. Each of the groupings includes interventions that can be applied across different sectors. Strong infection prevention and control measures are considered the most effective and cost-efficient way of controlling the spread of AMR. The most effective intervention is to improve hygiene in health centers, schools, and other public facilities, in part through promotion of hand hygiene and better hospital hygiene. Preventing and controlling infections on farms entails use of biosecurity measures, including better hygiene, records of farm visitors, and disinfection of vehicles entering the farm area. Policy and guidelines for limiting use of antimicrobials include public awareness campaigns and antimicrobial guidelines, including vaccination strategies, stewardship, and changing regulations around prescribing and reimbursement. Waste and wastewater management practices can reduce the risk of introducing antimicrobial-resistant bacteria and genes into the environment. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 274 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Table 19. Environmental and Social Assessment of AMR Projects Health sector AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Limited access to WASH facilities or • Poor access to diagnostics, vaccines, • Hold regular training sessions. 1 Improving infection important components of hygiene and and affordable medicines (ESS4) prevention and • Ensure prior design of HCF by experienced health care sanitation kits, such as soap (ESS2, • Poor design and layout of HCFs, which design engineer. control in health ESS3, ESS4) impedes separation of clean/ sterilized • Develop and include adequate disinfection/sterilization care settings • Poor infection and disease prevention and dirty/ contaminated materials and procedures and facilities. control in health care facilities people flows (ESS1, ESS2, ESS3, ESS4) • Select HCF-appropriate HVAC systems that provide (ESS2, ESS4) isolation and protection from airborne infections. • Select easily cleaned building materials that do not promote microbiological growth. • Limited access to trained health care • Absence of the well-functioning • Develop prescribing guidelines that consider access to 2 Improving prescribing workers and antimicrobials (ESS1, diagnostics system needed to improve health care facilities and health care workers. practices through ESS2, ESS4) patient outcomes (ESS4) guidelines for health care workers 3 Conducting public • Limited health literacy, which results • Lack of outreach to areas with the most • Develop education materials that are nondiscriminatory in increased demand for and use of limited health literacy (ESS4, ESS10) and provide equal opportunities for behavior change. awareness campaigns antimicrobials (ESS4, ESS10) • Engage stakeholders to provide insights into what would lead to behavioral changes among different groups. • Laboratory capacity that is limited • Lack of trained personnel for out- • Improve monitoring of antimicrobial use and surveillance 4 Increasing human and not in compliance with of-date equipment, electricity of emergence of AMR by strengthening laboratory health laboratory international standards (ESS2, ESS4) failures, and stock-out of laboratory capacity and developing systems for gathering capacity and access consumables (ESS2) data on how the public health sectors access and to diagnostics • Lack of integrated waste management use antimicrobials. systems in health care and hence no • Improve rapid diagnostic methods for infectious diseases processes for minimizing, reusing, and in humans, including susceptibility testing, to target recycling waste to implement source appropriate treatments and determine specifically if reduction and waste toxicity reduction, antimicrobials are appropriate. or to provide adequate on-site handling, • Ensure that HCFs establish, operate, and maintain health collection, storage, and transport of care waste management systems adequate for the scale waste (ESS3, ESS4) and type of activities and identified hazards. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 275 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Lack of information on amounts • Lack of surveillance and • Implement a surveillance, monitoring, and risk 5 Strengthening of antimicrobials sold in informal monitoring systems communication system that can be accessed by all surveillance of markets (ESS4) • Lack of risk communication systems, relevant parties. antimicrobial use • Lack of a baseline to measure the so that resources put into early • Establish national targets for the reduction of (AMU) and AMR in reduction of antimicrobial use (ESS4) detection will not support investigations antimicrobial use in livestock, especially for human populations of outbreaks (ESS1, ESS2, ESS4) nontherapeutic usages; assist countries in presenting • Lack of public or private standards for antimicrobial registration, annual progress reports to the Tripartite AMR country manufacturing, distribution, or sales self-assessment survey of the WHO/FAO/WOAH. and use (ESS2, ESS4) • Provide an enabling environment by strengthening public and private standards for the registration, manufacture, distribution, sale, and use of antimicrobials throughout the supply chain, including implementation and enforcement of standards. Agriculture and food sector AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Use of veterinary medicinal products • Spread of infectious diseases, such as • Develop viable alternatives for farmers to transition away 6 Increasing in the wrong circumstances or in foot and mouth disease or African swine from reliance on antimicrobials. oversight of AMU manner not in accordance with fever, by animal health workers working • Strengthen education, training, and communication by veterinarians prescribed conditions or dosages, across a community (ESS2, ESS3, ESS4) at national levels, with particular focus on veterinary leading to increased drug resistance in • Addition of antimicrobials to feed education and the role of veterinarians and veterinary animals and food contamination due for growth promotion or other para-professional standards in governing the use of to drug residues; use of substandard nontherapeutic use (ESS3, ESS4, ESS6) antimicrobials in livestock. and falsified antimicrobials, also • Identify production systems that are heavily reliant on contributing to the emergence of AMR drugs and critical points in animal life cycles where the (ESS3, ESS4, ESS6) use of antimicrobials is highest, to provide entry points for interventions. • Implement national targets for reducing or banning the use of antimicrobials for growth promotion and promote the use of probiotics, prebiotics, organic acids, or zeolites as alternatives. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 276 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Lack of information on amounts • Lack of surveillance and monitoring • Implement a surveillance, monitoring, and risk 7 Monitoring AMU, of antimicrobials sold in informal systems that can distinguish potential communication system that can be accessed by all surveillance of markets (ESS4) sources of antimicrobial contamination relevant parties. AMR, and increasing • Lack of a baseline to measure the in crop production • Establish national targets for the reduction of oversight in plant/ reduction of antimicrobial use • Lack of suitable alternatives antimicrobial use in crop production, especially for crop production (ESS4, ESS6) nontherapeutic usages; assist countries in presenting • Limited understanding of the direct • Lack of public or private standards epidemiological relevance of residue annual progress reports to the Tripartite AMR country for antimicrobial registration, detection and AMR in crops for self-assessment survey of the WHO/FAO/WOAH. manufacturing, distribution, or sales human health • Provide an enabling environment by strengthening public and use (ESS2, ESS4) • Lack of risk communication systems, so and private standards for the registration, manufacture, that resources put into early detection distribution, sale, and use of antimicrobials throughout will not support investigations of the supply chain, including implementation and outbreaks (ESS1, ESS2, ESS4) enforcement of standards. • Poorly designed farms leading to • Absence of waste treatment on farms • Investigate field conditions to identify ways to redesign 8 Improve animal increased incidence of disease that are intensifying production, production systems and animal husbandry practices husbandry practice and poor animal welfare (ESS3, leading to increase in risks related to that rely less on antimicrobials, including upgrading and biosecurity ESS4, ESS6) pollution, such as water contamination of housing, genetic selection, vaccination strategies, • A high density and concentration by farm effluents, which can become dietary adjustments, improved hygiene procedures, and of animals favoring the emergence a transmission channel of AMR (ESS3, staff training. and spread of infectious diseases, ESS4, ESS6) • Improve biosecurity and access to vaccines. including zoonotic diseases (ESS3, • Undertake economic and feasibility studies to identify ESS4, ESS6) how to adjust production systems to reduce the use of • Poor welfare in animals, impacting antimicrobials without compromising food supply or their ability to provide expected animal health and welfare. services or production (ESS3, ESS6) • Raise awareness of, and educate professionals • Reliance on management practices and livestock owners to better understand, how that induce poor welfare of animals antimicrobials function, the potential adverse (ESS1, ESS3, ESS4, ESS6) consequences of inappropriate use, and possible alternatives to their use. • Develop appropriate vaccines and vaccination strategies with the specific objective of reducing the use of antimicrobials in livestock. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 277 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Lack of information on amounts • Absence of risk communication systems, • Establish national targets for the reduction of 9 Monitoring sales and of antimicrobials sold in informal implying that resources put into early antimicrobial use in livestock, especially for use of antimicrobials markets (ESS3, ESS4, ESS6) detection will not support investigations nontherapeutic usages; assist countries in presenting and surveillance of • Lack of a baseline to measure the of outbreaks (ESS1, ESS2, ESS4) annual progress reports to the Tripartite AMR country AMR in animals reduction of antimicrobial use self-assessment survey of the WHO/FAO/WOAH. (ESS4, ESS6) • Provide an enabling and regulatory environment by • Lack of public or private standards strengthening public and private standards for the for antimicrobial registration, registration, manufacture, distribution, sale, and use of manufacturing, distribution, sales, or antimicrobials throughout the supply chain, including use (ESS2, ESS4, ESS6) implementation and enforcement of standards. • Limited knowledge of alternatives • Lack of outreach to areas with the most • Develop education materials that are nondiscriminatory 10 Promote behavior to antimicrobial use, resulting in limited health literacy (ESS2, ESS4, and provide inclusive opportunities for behavior change. change campaigns in increased demand for and use of ESS6, ESS10) animal production antimicrobials (ESS4, ESS10) • Laboratory capacity that is limited • Lack of trained personnel (ESS2) • Improve monitoring of antimicrobial use and surveillance 11 Increase veterinary and not in compliance with of emergence of AMR by strengthening laboratory laboratory capacity international standards (ESS2, capacity and developing systems for gathering data and access ESS3, ESS4) on how national livestock sectors access and use to diagnostics antimicrobials, including identification, traceability, and measurement of antimicrobial residues in livestock food products. • Improve rapid diagnostic methods for infectious diseases in livestock, fish, and crops, including susceptibility testing, to target appropriate treatments and determine specifically if antimicrobials are appropriate. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 278 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Water and environment sector AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Lack of access to adequate water and • Diversified access in terms of city- or • Include wastewater composition analysis in the design of 12 Improving sanitation in a high-volume setting, village-wide water system improvement advanced wastewater treatment interventions. infrastructure to potentially leading to infection and (ESS3, ESS4, ESS6) • Ensure that water systems can provide adequate supplies provide access to onward transmission of disease • Other sources of infection (e.g., at of potable water to reduce risks of exposure to Legionella water and sanitation (ESS3, ESS4, ESS6) home), which likely diminish the and other waterborne pathogens. in health care centers potential benefits of infrastructure improvements in schools and other communal settings (ESS3, ESS4, ESS6) • Untreated effluent and dissemination • Poor understanding of how different • Include wastewater composition analysis in the design of 13 Implementing of residues and resistant pathogens technologies and practices across advanced wastewater treatment interventions. effective and genes from hospital effluent production systems may potentially • Use proper waste management practices. treatment and and other sources, which presents increase or decrease presence and disposal of sewage potential risks of dissemination via dissemination of resistant pathogens and wastewater drinking water, irrigation, and aquatic on the ground (ESS3, ESS4, ESS6) environments, including through surface water contamination (ESS3, ESS4, ESS6) • Absence of waste treatment on farms • Poor understanding of how different • Undertake economic and feasibility studies to identify 14 Improving waste that are intensifying production, technologies and practices across how to adjust production systems to reduce the use of management practices leading to increase in risks production systems may potentially antimicrobials without compromising food supply or in agricultural related to pollution, such as water increase or decrease presence and animal health and welfare. and aquaculture contamination by farm effluents, dissemination on the ground (ESS3, • Use proper waste management in agriculture production/processing which can become a transmission ESS4, ESS6) and aquaculture. channel of AMR (ESS2, ESS3, • Educate farmers on optimal use of waste treatment ESS4, ESS6) technologies to support implementation success. • Limited knowledge of the precise • Community- or individual-level • Review uptake of safe disposal programs for all 15 Improving safe level of threat from residues and behaviors, which may increase or medicines for evidence of effectiveness. disposal of genes transmitted through waste and decrease risk (ESS3, ESS4, ESS6) • Increase public awareness to reduce demand; unused antimicrobials wastewater (ESS3, ESS4, ESS6) monitor antimicrobial use, access to diagnostics, and proper dosage. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 279 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Lack of knowledge of AMR exposure • Community- or individual-level • Improve monitoring and comparison to background 16 Monitoring presence routes and transmission channels behaviors, which may increase or environmental data to support more precise monitoring of antimicrobial (ESS3, ESS4, ESS6) decrease risk (ESS3, ESS4, ESS6) needs (samples and sites; antibiotics, bacteria, and genes residues and to screen for) and better interpretation of findings. antibiotic-resistant bacteria and genes in water and sanitation systems Multisector AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION Detecting • Use of falsified antimicrobials, which • Absence of risk communication systems, • Register and test antimicrobials, including upon import. 17 can reduce effective treatment implying that resources put into early • Monitor, regulate, and enforce infrastructure to detect and deterring for both humans and animals detection will not support investigations and deter substandard or falsified antibiotics in the substandard (ESS3, ESS4) of outbreaks (ESS1, ESS2, ESS4) supply chain. and falsified • Establish drug manufacturer authenticity partnerships antimicrobials (e.g., for labeling). Improving human and • Limited knowledge of alternatives • Community- or individual-level • Investigate field conditions to identify ways to redesign 18 to antimicrobial use in animal behaviors, which may increase or production systems and animal husbandry practices animal nutrition production, such as improved decrease risk (ESS3, ESS4, ESS6) that rely less on antimicrobials, including upgrading animal nutrition as an alternative to • Food insecurities that affect access to of housing, genetic selection, vaccination strategies, antimicrobials for growth promotion and sustainment of nutrition resources dietary adjustments, improved hygiene procedures, and (ESS4, ESS10) (ESS3, ESS4, ESS6) staff training. • Poor access to nutritional resources • Develop campaign materials that are nondiscriminatory due to lack of food safety or food and provide inclusive opportunities for behavior change. security (ESS3, ESS4, ESS6) • Establish national targets for the reduction of antimicrobial use in livestock, especially for nontherapeutic usages, and assist countries in identifying improved animal nutrition as an alternative to their use. • Implement food and feed safety compliance systems to help reduce exposure to pathogens and antibiotic residues in the food supply. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 280 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR INTERVENTION ENTRY POINTS IN ESS RISK TO AMR INTERVENTION OPTIONS FOR MITIGATION TO AMR INTERVENTION • Poor access to diagnostics, • Lack of infrastructure (e.g., cold chain) to • Investigate field conditions to identify ways to redesign 19 Expanding vaccines, and affordable medicines distribute vaccines (ESS4) production systems and animal husbandry practices vaccination coverage (ESS3, ESS4) • Vaccine hesitancy in populations (ESS4) that rely less on antimicrobials, including upgrading in humans and of housing, genetic selection, vaccination strategies, animals dietary adjustments, improved hygiene procedures, and staff training. • Develop campaign materials that are nondiscriminatory and provide inclusive opportunities for behavior change. • Provide an enabling environment for the distribution, sale, and use of vaccines throughout the supply chain. • Lack of knowledge of AMR exposure • Poor understanding of how different • Investigate field conditions to identify ways to redesign 20 Using closed routes and transmission channels technologies and practices across production systems and animal husbandry practices water systems in (ESS3, ESS4, ESS6) production systems may potentially that rely less on antimicrobials, including upgrading aquaculture • Absence of waste treatment on farms increase or decrease presence and of housing, genetic selection, vaccination strategies, that are intensifying production, dissemination on the ground (ESS3, dietary adjustments, improved hygiene procedures, leading to increase in risks ESS4, ESS6) and staff training. related to pollution, such as water • Provide water systems to reduce wastewater pollution. contamination by farm effluents, which can become a transmission channel of AMR (ESS2, ESS3, ESS4, ESS6) Source: World Bank. Note: ESS = Environmental and Social Standard; FAO = Food and Agriculture Organization of the United Nations; HCF = health care facilities; HVAC = heating, ventilation, and air conditioning; WASH = water, sanitation, and hygiene; WHO = World Health Organization; WOAH = World Organisation for Animal Health. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 281 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Section 2. AMR-related risks to and impacts on gender and vulnerable groups The World Bank’s overall approach to gender is guided by the World Bank Gender Strategy and OP4.20: Gender and Development. The ESF addresses gender risks in both the process and methodology of the E&S assessment; the aim is to assess the potential risks and impacts of the project that may fall disproportionately on the disadvantaged or vulnerable and to identify any prejudice or discrimination toward such groups in providing access to development resources and project benefits. ESS1, ESS2, ESS4, and ESS10 set standards for gender equality and inclusion to be addressed by client countries. To ensure that interventions addressing AMR are effective, it is important to understand how both AMR and AMR interventions can present a risk to men and women as well as vulnerable groups. The choice of gender-responsive mitigation activities will depend on a good understanding of the context in which a project is intended to operate, derived from a detailed analysis of gender roles, responsibilities, and power relations. Table 20 presents examples of gender-responsive activities, approaches, and actions in AMR interventions. Table 20. Examples of Activities to Integrate Gender and Vulnerable Groups in AMR Projects AMR considerations (WHO 2018; ReAct 2020) Vulnerable group AMR intervention Gender-responsive activities by ESS Risk during pregnancy, Women • Improving hand hygiene in • Assess risk that any harm caused by abortion, and childbirth: health care settings projects falls disproportionately on the Increasing AMR may raise • Improving infrastructure disadvantaged or vulnerable; assess women’s risk of exposure to provide access to WASH any prejudice or discrimination toward to AMR during pregnancy, in HCF, schools, and such groups in providing access to abortion, and cThildbirth, other facilities development resources and project especially where these • Improving infection benefits (ESS1). events take place in health prevention and control • Avoid or minimize the potential for care settings without safe or • Improving prescribing community exposure to diseases that hygienic conditions. guidelines for health could result from project activities care workers (including waterborne, water-based, • Strengthening surveillance of water-related, and vector-borne AMR in human populations diseases and both communicable and • Increasing human health noncommunicable diseases), taking laboratory capacity into consideration differentiated exposure and higher sensitivity of vulnerable groups (ESS4). • Identify the disadvantaged or vulnerable (ESS10). • Describe in the Stakeholder Engagement Plan what measures will be used to remove obstacles to participation, and how the views of differently affected groups will be captured (ESS10). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 282 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR considerations (WHO 2018; ReAct 2020) Vulnerable group AMR intervention Gender-responsive activities by ESS • Provide stakeholders with access to the information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these (ESS10). Urinary tract infections Elderly men and • Improving hand hygiene in • Assess risk that any harm caused by (UTIs): An increasing number women (UTIs health care settings projects falls disproportionately on the of antibiotic-resistant strains are eight times • Improving infrastructure disadvantaged or vulnerable; assess combined with expansion of more common for to provide access to WASH any prejudice or discrimination toward efforts to tackle AMR is making women) in HCF, schools, and such groups in providing access to the effective treatment of UTIs other facilities development resources and project more complicated. • Improving infection benefits (ESS1). prevention and control • Avoid or minimize the potential for • Improving prescribing community exposure to diseases that guidelines for health could result from project activities care workers (including waterborne, water-based, • Strengthening surveillance of water-related, and vector-borne AMR in human populations diseases and both communicable and • Increasing human health noncommunicable diseases), taking laboratory capacity into consideration differentiated exposure and higher sensitivity of vulnerable groups (ESS4). • Identify the disadvantaged or vulnerable (ESS10). • Describe in the Stakeholder Engagement Plan what measures will be used to remove obstacles to participation, and how the views of differently affected groups will be captured (ESS10). • Provide stakeholders with access to information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these (ESS10). Gonorrhea: With close to 80 Men who have • Improving infection • Assess risk that any harm caused by million new cases every year, sex with men, prevention and control projects falls disproportionately on the gonorrhea is one of the most indigenous people, • Improving prescribing disadvantaged or vulnerable; assess common sexually transmitted women guidelines for health any prejudice or discrimination toward diseases. Gonorrhea has over care workers such groups in providing access to time developed resistance to • Strengthening surveillance of development resources and project each of the antibiotics used for AMR in human populations benefits (ESS1). treatment, and some cases of • Increasing human health • Evaluate and address project’s risks for gonorrhea are now untreatable laboratory capacity and impacts on the health and safety or nearly so. • Conducting public of the affected communities, including awareness campaigns the vulnerable, during the project life cycle (ESS4). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 283 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR considerations (WHO 2018; ReAct 2020) Vulnerable group AMR intervention Gender-responsive activities by ESS • Detecting and deterring • Identify the disadvantaged or substandard and vulnerable (ESS10). falsified antimicrobials • Describe in the Stakeholder Engagement Plan what measures will be used to remove obstacles to participation, and how the views of differently affected groups will be captured (ESS10). • Provide stakeholders with access to the information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these (ESS10). Health care workers: Women Women, health care • Improving infection • Assess risk that any harm caused by globally make up 67 percent workers prevention and control projects falls disproportionately on the of health care workers and • Improving prescribing disadvantaged or vulnerable; assess have a vital role in addressing guidelines for health any prejudice or discrimination toward AMR, both through appropriate care workers such groups in providing access to prescribing and dispensing of • Conducting public awareness development resources and project antimicrobial medicines and campaigns benefits (ESS1). through ensuring clean care for • Improving infrastructure • Provide appropriate measures of all patients. to provide access to WASH protection and assistance to address in HCF, schools, and the vulnerabilities of project workers, other facilities including women (ESS2). • Improving safe disposal of • Evaluate and address project’s risks for unused antimicrobials and impacts on the health and safety of the affected communities, including the vulnerable, during the project life cycle (ESS4). • Identify the disadvantaged or vulnerable (ESS10). • Describe in the Stakeholder Engagement Plan what measures will be used to remove obstacles to participation, and how the views of differently affected groups will be captured (ESS10). • Provide stakeholders with access to information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these (ESS10). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 284 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices AMR considerations (WHO 2018; ReAct 2020) Vulnerable group AMR intervention Gender-responsive activities by ESS Workers in livestock and fish Farmers, farmer’s • Improving the quality • Assess risk that any harm caused by farming or manufacturing: families and friends, of veterinary medicinal projects falls disproportionately on the People employed in farming of veterinarians products and their use under disadvantaged or vulnerable; assess livestock and fish as well as in supervision by veterinarians any prejudice or discrimination toward manufacturing companies may • Improving animal such groups in providing access to be more exposed than others husbandry practice development resources and project to animals carrying resistant • Conducting behavior change benefits (ESS1). bacteria. campaigns and providing • Ensure the projects do not alternatives in animal inadvertently compromise existing production legitimate rights for land and natural • Increasing veterinary resource tenure and use, and laboratory capacity that they do not have unintended • Improving infection consequences (ESS1). prevention and control • Provide appropriate measures of • Improving infrastructure protection and assistance to address to provide access to WASH the vulnerabilities of project workers, in HCF, schools, and including women (ESS2). other facilities • Avoid or minimize the potential for community exposure to diseases that could result from project activities (including waterborne, water-based, water-related, and vector-borne diseases and both communicable and noncommunicable diseases), taking into consideration differentiated exposure and higher sensitivity of vulnerable groups (ESS4). • Identify the disadvantaged or vulnerable (ESS10). • Describe in the Stakeholder Engagement Plan what measures will be used to remove obstacles to participation, and how the views of differently affected groups will be captured (ESS10). • Provide stakeholders with access to information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these (ESS10). Source: World Bank. Note: ESS = Environmental and Social Standard; HCF = health care facilities; WASH = water, sanitation, and hygiene. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 285 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Section 3. Stakeholder engagement and AMR projects ESS10 provisions on stakeholder engagement and disclosure of information are essential elements of AMR projects that are shaped by actions in multiple sectors. ESS10 highlights the importance of open and transparent engagement between the client country and relevant stakeholders to improve the environmental and social sustainability of projects. Depending on the significance and context of the E&S risks and impacts, comprehensive analysis and design of the engagement process can involve independent third-party specialists. The type of stakeholders 51 who should be engaged as part of the assessment and management of E&S risks and impacts can vary significantly depending on the type of intervention (see Table 21). Table 21. Examples of Possible Stakeholders by Sector Health: Improving prescribing Agriculture: WASH: guidelines for health care Improving animal husbandry Improving safe disposal of Type of stakeholder workers practice unused antimicrobials Affected by project Health care workers, patients, Pastoralists, farmers, herders, Health care workers, patients, women’s groups, pharmaceutical women farmers, farmer groups, women’s groups, pharmaceutical companies, pharmacies, etc. veterinarians, fish farmers, etc. companies, pharmacies, pastoralists, farmers, herders, women farmers, farmer groups, animal health workers, etc. Interested in project Patient organizations, Community members, Community members, animal youth, researchers, traders, slaughterhouse workers, welfare groups, nongovernmental nongovernmental organizations, traders, faculties and students organizations, civil society civil society organizations in veterinary colleges, women’s organizations, traders groups, patient groups Source: World Bank Stakeholder engagement can help improve resonance and engagement with important actors from different sectors that are relevant to tackling AMR, in part by shaping messages and identifying gaps and entry points for AMR interventions. As resistant microorganisms can be transmitted through various pathways, such as person-to-person contact, person-to-animal contact, consumption of contaminated foods, and contact with human and agricultural wastes, projects addressing AMR will have a wide range of stakeholders who will be either directly or indirectly affected by both AMR and the interventions addressing AMR. 51  In accordance with ESS10, stakeholders are individuals and groups that are affected or likely to be affected by the project or may have an interest in the project (World Bank 2017). Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 286 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices Section 4. Guidance on actions for mitigation Before project approval, the client country develops an ESCP that sets out the actions for mitigation that will enable the project to meet the ESSs over a specific time frame. The ESCP forms part of the legal agreement, and the client country is obligated to support the implementation of the ESCP. AMR-informed projects can be better designed and monitored by referencing activities that positively impact the global stewardship of antimicrobials and measures that aim to systematically mitigate, adapt, and innovate regarding AMR. A good approach involves a combination of country or regional institutional support, such as a gap analysis regarding national standards or guidelines, legislation, or training, and promotion of good practices at HCF and livestock and aquaculture production facilities. Table 22 aims to support the capacity of project implementation units by providing examples of measures that can be included in the ESCP per relevant ESS and relating these to specific AMR interventions, measures, and actions. Table 22. Material Measures and Actions for a Selection of AMR Interventions, by ESS INTERVENTION TO ADDRESS AMR MATERIAL MEASURE AND ACTION ESS1: Assessment and Management of Environmental and Social Risks and Impacts • Improve the quality of veterinary medical products • Carry out a study to identify the project’s impact and their use under supervision by veterinarians on legitimate rights for land and natural resource • Improve antibiotic prescribing guidelines for health tenure and use (including collective rights, care workers subsidiary rights, and the rights of women) and • Strengthen surveillance of AMR and AMU in other unintended consequences. human populations • Improve antibiotic prescribing guidelines for health • Provide appropriate measures of protection care workers and assistance, including training and capacity • Improve the quality of veterinary medical products building, to ensure impacts of the project are and their use under supervision by veterinarians equally distributed among all relevant groups and • Strengthen surveillance of AMR in stakeholders, including vulnerable groups. human populations • Improve infection prevention and control • Monitor sales and use of antimicrobials in animals • Implement public and private standards for the • Strengthen surveillance of AMR and AMU in human registration, manufacture, distribution, sale, and populations and in animals, aquaculture, and crops use of antimicrobials throughout the supply chain. • Detect and deter substandard and falsified antimicrobials ESS2: Labor and Working Conditions • Improve hand hygiene in health care settings • Provide appropriate measures of protection • Increase human health laboratory capacity and assistance, including training, to address • Improve animal husbandry practice for livestock the vulnerabilities of project workers, including and aquaculture specific groups of workers such as women, people • Promote behavior change campaigns and the with disabilities, migrant workers, and children of provision of alternatives in animal production working age. • Increase veterinary laboratory capacity Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 287 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION TO ADDRESS AMR MATERIAL MEASURE AND ACTION • Improve the quality of veterinary medical products • Strengthen education, training, and and their use under supervision by veterinarians communication at national and professional level • Improve antibiotic prescribing guidelines for health in governing the use of antimicrobials care workers • Improve animal husbandry practice for livestock and aquaculture • Strengthen surveillance of AMR in human populations • Promote behavior change campaigns and the provision of alternatives in animal production • Increase veterinary laboratory capacity • Improve safe disposal of unused antimicrobials • Detect and deter falsified antimicrobials • Improve infection prevention and control ESS3: Resource Efficiency and Pollution Prevention and Management • Improve hand hygiene in health care settings • Establish, operate, and maintain waste • Increase human health laboratory capacity management systems adequate for the scale and • Improve infrastructure to provide access to water type of activities and identified hazards. and sanitation in HCF, schools, and other facilities • Improve safe disposal of unused antimicrobials • Monitor antimicrobial use and antibiotic-resistant bacteria in water and sanitation systems • Use closed water systems in aquaculture • Improve infrastructure to provide access to water • Carry out a wastewater composition analysis to and sanitation in HCF, schools, and other facilities identify wastewater treatment interventions. • Monitor antimicrobial use and antibiotic residues, resistant bacteria, and resistant genes in water and sanitation systems • Improve waste management practices in agriculture and aquaculture production/processing ESS4: Community Health and Safety • Improve hand hygiene in health care settings • Carry out a study on community exposure to • Increase human health laboratory capacity diseases that could result from project activities • Improve animal husbandry practice for livestock (including waterborne, water-based, water- and aquaculture related, and vector-borne diseases and both • Improve infrastructure to provide access to water communicable and noncommunicable diseases), and sanitation in HCF, schools, and other facilities taking into consideration differentiated exposure • Monitor antimicrobial use and antibiotic-resistant and higher sensitivity of vulnerable groups to bacteria in water and sanitation systems identify interventions. • Improve waste management practices in agriculture and aquaculture production/processing • Improve human and animal nutrition • Use closed water systems in aquaculture • Expand vaccine coverage Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 288 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION TO ADDRESS AMR MATERIAL MEASURE AND ACTION • Improve hand-hygiene in health care settings • Improve antibiotic prescribing guidelines for health care workers • Conduct public awareness campaigns • Improve the quality of veterinary medical products and their use under supervision by veterinarians • Improve animal husbandry practice for livestock and aquaculture • Strengthen surveillance of AMR in human populations • Promote behavior change campaigns and the provision of alternatives in animal production • Improve safe disposal of unused antimicrobials • Improve waste management practices in agriculture and aquaculture production/processing • Improve infection prevention and control • Expand vaccination coverage • Improve human and animal nutrition • Improve animal husbandry practice for livestock • Implement and maintain adequate disinfection and and aquaculture sterilization procedures and facilities. ESS6: Biodiversity Conservation and Sustainable Management of Living Natural Resources • Improve the quality of veterinary medical products • Develop an action plan for how livestock and and their use under supervision by veterinarians fish farmers can transition away from reliance • Improve animal husbandry practice for livestock on antimicrobials through good animal health and aquaculture practices and biosecurity measures. • Improve human and animal nutrition • Improve the quality of veterinary medical products • Carry out a study to identify production systems and their use under supervision by veterinarians that are heavily reliant on drugs and critical points • Improve animal husbandry practice for livestock in animal life cycles where the use of antimicrobials and aquaculture is highest. • Promote behavior change campaigns and the provision of alternatives in animal production • Improve safe disposal of unused antimicrobials. • Use closed water systems in aquaculture • Improve human and animal nutrition • Expand vaccine coverage • Improve infrastructure to provide access to water • Establish water systems to reduce and sanitation in HCF, schools, and other facilities wastewater pollution. • Improve wastewater management practices in aquaculture production and processing • Monitor antimicrobial use and antibiotic-resistant bacteria in water and sanitation systems • Use closed water systems in aquaculture Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 289 Introduction Chapter 1 Chapter 2 Chapter 3 Chapter 4 Chapter 5 Chapter 6 Appendices INTERVENTION TO ADDRESS AMR MATERIAL MEASURE AND ACTION ESS10: Stakeholder Engagement and Information Disclosure All interventions but the following in particular: • Identify the disadvantaged or vulnerable. • Describe in the Stakeholder Engagement Plan • Conduct public awareness campaigns what measures will be used to remove obstacles • Improve animal husbandry practice for livestock to participation, and how the views of differently and aquaculture affected groups will be captured. Where applicable, • Promote behavior change campaigns and the include differentiated measures in the plan to allow provision of alternatives in animal production the effective participation of the disadvantaged or vulnerable. • Provide stakeholders with access to information on potential risks and impacts that might disproportionately affect the vulnerable and disadvantaged, and describe the differentiated measures taken to avoid and minimize these. • Disclose information in relevant local languages and in a manner that is accessible and culturally appropriate, taking into account any specific needs of groups that may be differentially or disproportionately affected by the project or groups of the population with specific information needs (e.g., related to disability, literacy, gender, mobility, differences in language, or accessibility). Source: World Bank. Note: AMU = antimicrobial use; ESS = Environmental and Social Standard; HCF = health care facilities. Bibliography ReAct. 2020. “Scoping the Significance of Gender for Antimicrobial Resistance.” https://www. reactgroup.org/wp-content/uploads/2020/09/Scoping-the-Significance-of-Gender-for- Antibiotic-Resistance-IDS-ReAct-Report-October-2020.pdf. Review on Antimicrobial Resistance. 2016. “Tackling Drug-Resistant Infections Globally: Final Report and Recommendations.” https://amr-review.org/sites/default/files/160518_Final%20paper_ with%20cover.pdf. UNEP (United Nations Environment Programme). 2017. Frontiers 2017: Emerging Issues of Environmental Concern. Nairobi: United Nations Environment Programme. Wellcome Trust 2018. “Initiatives for Addressing Antimicrobial Resistance in the Environment: Current Situation and Challenges.” https://wellcome.org/sites/default/files/antimicrobial- resistance-environment-report.pdf. World Bank. 2017. The World Bank Environmental and Social Framework. Washington, DC: World Bank. https://thedocs.worldbank.org/en/doc/837721522762050108-0290022018/original/ ESFFramework.pdf. Stopping The Grand Pandemic | A Framework for Action Previous STEP-BAC 290