Background: Recommended vector control tools against malaria, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), mainly target mosquitoes that rest and feed on human hosts indoors. However, in some malaria-endemic areas, such as Southeast Asia and South America, malaria vectors primarily bite outdoors meaning that LLINs and IRS may be less effective. In these situations the use of topical insect repellents may reduce outdoor biting and morbidity from malaria. A systematic review and meta-Analysis was conducted to assess the efficacy of topical insect repellents against malaria. Methods: Studies were identified using database searches (MEDLINE, EMBASE, Web of Science and clinical trials registers), as well as reference list searches and contact with researchers. Randomized and non-randomized controlled trials were included that assessed the effect of topical repellents (all active ingredients and concentrations) on Plasmodium falciparum or Plasmodium vivax malaria or infection in malaria-endemic populations. Meta-Analysis of clinical data was conducted in order to generate summary risk ratios. Results: Ten trials met the inclusion criteria. Studies varied in terms of repellent active ingredient and formulation, co-interventions, study population, compliance, and follow-up period. Topical repellents showed an 18% protective efficacy against P. falciparum malaria, although this was not significant (95% CI:-8%, 38%). Similarly, the average protective efficacy of topical repellents against P. vivax malaria did not reach significance (protective efficacy: 20%, 95% CI:-37%, 53%). Exclusion of non-randomized trials from the meta-Analysis did not alter the findings. Conclusions: Although topical repellents can provide individual protection against mosquitoes, the results of this meta-Analysis indicate that topical repellents are unlikely to provide effective protection against malaria. However, there was substantial heterogeneity between studies included and the relatively small number of studies meant that this heterogeneity could not be fully explored in the analysis. Further well-designed trials of topical repellents at appropriate doses and alternative modes of repellent delivery, such as spatial repellents and long-lasting insecticide-Treated clothing, are required.
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