Abstract

BackgroundThe World Health Organization has yet to endorse deployment of topical repellents for malaria prevention as part of public health campaigns. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination.Methods and findingsBetween April 2015 and June 2016, a 15-month stepped-wedge cluster randomised trial was conducted in 116 villages in Myanmar (stepped monthly in blocks) to test the effectiveness of 12% N,N-diethylbenzamide w/w cream distributed by VHVs, on Plasmodium spp. infection. The median age of participants was 18 years, approximately half were female, and the majority were either village residents (46%) or forest dwellers (40%). No adverse events were reported during the study. Generalised linear mixed modelling estimated the effect of repellent on infection detected by rapid diagnostic test (RDT) (primary outcome) and polymerase chain reaction (PCR) (secondary outcome). Overall Plasmodium infection detected by RDT was low (0.16%; 50/32,194), but infection detected by PCR was higher (3%; 419/13,157). There was no significant protection against RDT-detectable infection (adjusted odds ratio [AOR] = 0.25, 95% CI 0.004–15.2, p = 0.512). In Plasmodium-species-specific analyses, repellent protected against PCR-detectable P. falciparum (adjusted relative risk ratio [ARRR] = 0.67, 95% CI 0.47–0.95, p = 0.026), but not P. vivax infection (ARRR = 1.41, 95% CI 0.80–2.47, p = 0.233). Repellent effects were similar when delayed effects were modelled, across risk groups, and regardless of village-level and temporal heterogeneity in malaria prevalence. The incremental cost-effectiveness ratio was US$256 per PCR-detectable infection averted. Study limitations were a lower than expected Plasmodium spp. infection rate and potential geographic dilution of the intervention.ConclusionsIn this study, we observed apparent protection against new infections associated with the large-scale distribution of repellent by VHVs. Incorporation of repellent into national strategies, particularly in areas where bed nets are less effective, may contribute to the interruption of malaria transmission. Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform WHO public health policy on the deployment of topical repellents for malaria prevention.Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12616001434482).

Highlights

  • While there have been major gains in reducing the global burden of malaria since the turn of the millennium, the progress in reducing malaria has recently stalled [1]

  • Further studies are warranted across different transmission settings and populations, from the Greater Mekong Subregion (GMS) and beyond, to inform World Health Organization (WHO) public health policy on the deployment of topical repellents for malaria prevention

  • Further studies are warranted across different transmission settings and populations, from the GMS and beyond, to inform World Health Organization public health policy on the deployment of topical repellents for malaria prevention

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Summary

Introduction

While there have been major gains in reducing the global burden of malaria since the turn of the millennium, the progress in reducing malaria has recently stalled [1]. Namely insecticide-treated bed nets (ITNs) and indoor residual spraying (IRS) have contributed significantly to the reductions in malaria globally [1]. Evidence for additional tools that target residual transmission not covered by ITNs and IRS is needed in order to achieve malaria control and elimination goals. There is strong evidence for topical repellents’ efficacy against mosquito biting [4], and some evidence of repellent effectiveness against malaria in clinical trials [5], the World Health Organization (WHO) has yet to endorse deployment of topical repellents for malaria prevention as an intervention with public health value [6]; importantly, no trial to our knowledge has investigated the effectiveness of the distribution of repellents in the context of largescale disease prevention programmes in order to establish real-world effectiveness. We aimed to quantify the effectiveness of repellent distributed by the village health volunteer (VHV) network in the Greater Mekong Subregion (GMS) in reducing malaria in order to advance regional malaria elimination

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