Publication: A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil
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Date
2011
ISSN
1935-2735 (Electronic)
1935-2727 (Linking)
Published
2011
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Abstract
BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95% CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). CONCLUSION: A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries.
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Publication Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial(2009-02-14)BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).Publication Promoting Handwashing and Sanitation : Evidence from a Large-Scale Randomized Trial in Rural Tanzania(World Bank Group, Washington, DC, 2015-01)The association between hygiene, sanitation, and health is well documented, yet thousands of children die each year from exposure to contaminated fecal matter. At the same time, evidence on the effectiveness of at-scale behavior change interventions to improve sanitation and hygiene practices is limited. This paper presents the results of two large-scale, government-led handwashing and sanitation promotion campaigns in rural Tanzania. For the campaign, 181 wards were randomly assigned to receive sanitation promotion, handwashing promotion, both interventions together, or neither. One year after the end of the program, sanitation wards increased latrine construction rates from 38.6 to 51 percent and reduced regular open defecation from 23.1 to 11.1 percent. Households in handwashing wards show marginal improvements in handwashing behavior related to food preparation, but not at other critical junctures. Limited interaction is observed between handwashing and sanitation on intermediate outcomes: wards that received both handwashing and sanitation promotion are less likely to have feces visible around their latrine and more likely to have a handwashing station close to their latrine facility relative to individual treatment groups. Final health effects on child health measured through diarrhea, anemia, stunting, and wasting are absent in the single-intervention groups. The combined-treatment group produces statistically detectable, but biologically insignificant and inconsistent, health impacts. The results highlight the importance of focusing on intermediate outcomes of take-up and behavior change as a critical first step in large-scale programs before realizing the changes in health that sanitation and hygiene interventions aim to deliver.Publication The Contribution of Traditional Herbal Medicine Practitioners to Kenyan Health Care Delivery : Results from Community Health-seeking Behavior Vignettes and a Traditional Herbal Medicine Practitioner Survey(World Bank, Washington, DC, 2011-09)This study examines the role that Traditional Herbal Medicine Practitioners (THMPs) play in Kenya in the context of its human resources for health crisis. Two surveys were carried out to obtain evidence. The first documented the choices and perceptions of households in 36 communities on seeking medical assistance for eight common illnesses. The second survey asked 258 THMPs in five provinces to identify their knowledge sources, training, common illnesses treated, forms of payment, challenges, and concerns. Community-derived data show that households make reasonable decisions when faced with difficult circumstances: they prefer hospitals when these are affordable and seek care at clinics and health centers when hospitals are too far away. There is significant self-care and use of pharmacies, although THMPs are preferred for worms and lower respiratory problems. In general, THMPs provide an important though diminishing role in the provision of health care; they are not sought out in situations when inadequate care is dangerous, specifically infant diarrhoea and potential TB. Whilst Human Resources for Health (HRH) policies are urgently required to strengthen the conventional health workforce and increase their accessibility for the poor, policies should not ignore the findings from this study: many of the rural poor currently receive services from a traditional health workforce not linked to, or regulated by, the national government. This paper argues that formal recognition of their role by the government and by the conventional medical associations, and a targeted strategy to strengthen and build on the positive qualities evident in many traditional medicine practices may be beneficial to safeguarding the well-being of the poor.Publication Coping with Risk : The Effects of Shocks on Reproductive Health and Transactional Sex in Rural Tanzania(World Bank, Washington, DC, 2014-01)Transactional sex is believed to be an important risk-coping mechanism for women in Sub-Saharan Africa and a leading contributor to the HIV/AIDS epidemic. This paper uses data from a panel of women in rural Tanzania whose primary occupation is agriculture. The analysis finds that following a negative shock (such as food insecurity), unmarried women are about three times more likely to have been paid for sex. Regardless of marital status, after a shock women have more unprotected sex and are 36 percent more likely to have a sexually transmitted infection. These empirical findings support the claims that transactional sex is not confined to commercial sex workers and that frequently experienced shocks, such as food insecurity, may lead women to engage in transactional sex as a risk-coping behavior.Publication Socioeconomic Status and HIV Seroprevalence in Tanzania : A Counterintuitive Relationship(2008)OBJECTIVE: To examine the relationship between multiple dimensions of socioeconomic status (SES) and HIV seroprevalence in Tanzania. METHODS: Using a large nationally representative sample of 7515 sexually active adults drawn from the 2003-04 Tanzania HIV/AIDS Indicator Survey, we analysed the relationship between multiple SES measures and HIV seroprevalence using weighted logistic regression models. RESULTS: In adjusted models, individuals in the highest quintile of standard of living had increased odds ratio (OR) of being HIV-positive (male: OR 2.38, 95% CI 1.17-4.82; female: OR 3.74, 95% CI 2.16-6.49). Occupational status was differentially associated with HIV in men and women; women in professional jobs had higher OR of being HIV-positive (OR 1.54, 95% CI 1.02-2.38), whereas unemployed men had higher risk of being HIV-positive (OR 3.49, 95% CI 1.43-8.58). No marked association was found between increasing education and HIV seroprevalence for men (P = 0.83) and women (P = 0.87). CONCLUSION: Contrary to the prevailing perception that low SES individuals tend to be more vulnerable to HIV-infection, we found a positive association between standard of living and HIV-infection. Strategies aimed at reducing HIV-infection needs to be cognizant of the complex social heterogeneity in the patterns of HIV-infection.
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