Mosquito repellents for malaria prevention

Marta F Maia, Merav Kliner, Marty Richardson, Christian Lengeler, Sarah J Moore, Marta F Maia, Merav Kliner, Marty Richardson, Christian Lengeler, Sarah J Moore

Abstract

Background: Malaria is an important cause of illness and death across endemic regions. Considerable success against malaria has been achieved within the past decade mainly through long-lasting insecticide-treated nets (LLINs). However, elimination of the disease is proving difficult as current control methods do not protect against mosquitoes biting outdoors and when people are active. Repellents may provide a personal protection solution during these times.

Objectives: To assess the impact of topical repellents, insecticide-treated clothing, and spatial repellents on malaria transmission.

Search methods: We searched the following databases up to 26 June 2017: the Cochrane Infectious Diseases Group Specialized Register; the Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; US AFPMB; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials.

Selection criteria: We included randomized controlled trials (RCTs) and cluster-randomized controlled trials of topical repellents proven to repel mosquitoes; permethrin-treated clothing; and spatial repellents such as mosquito coils. We included trials that investigated the use of repellents with or without LLINs, referred to as insecticide-treated nets.

Data collection and analysis: Two review authors independently reviewed trials for inclusion, extracted the data, and assessed the risk of bias. A third review author resolved any discrepancies. We analysed data by conducting meta-analysis and stratified by whether the trials had included LLINs. We combined results from cRCTs with individually RCTs by adjusting for clustering and presented results using forest plots. We used GRADE to assess the certainty of the evidence.

Main results: Eight cRCTs and two RCTs met the inclusion criteria. Six trials investigated topical repellents, two trials investigated insecticide-treated clothing, and two trials investigated spatial repellents.Topical repellentsSix RCTS, five of them cluster-randomized, investigated topical repellents involving residents of malaria-endemic regions. Four trials used topical repellents in combination with nets, but two trials undertaken in displaced populations used topical repellents alone. It is unclear if topical repellents can prevent clinical malaria (RR 0.65, 95% CI 0.4 to 1.07, very low certainty evidence) or malaria infection (RR 0.84, 95% CI 0.64 to 1.12, low-certainty evidence) caused by P. falciparum. It is also unclear if there is any protection against clinical cases of P. vivax (RR 1.32, 95% CI 0.99 to 1.76, low-certainty evidence) or incidence of infections (RR 1.07, 95% CI 0.80 to 1.41, low-certainty evidence). Subgroup analysis of trials including insecticide-treated nets did not show a protective effect of topical repellents against malaria. Only two studies did not include insecticide-treated nets, and they measured different outcomes; one reported a protective effect against clinical cases of P. falciparum (RR 0.40, 95% CI 0.23 to 0.71); but the other study measured no protective effect against malaria infection incidence caused by either P. falciparum or P. vivax.Insecticide-treated clothingInsecticide-treated clothing were investigated in trials conducted in refugee camps in Pakistan and amongst military based in the Colombian Amazon. Neither study provided participants with insecticide-treated nets. In the absence of nets, treated clothing may reduce the incidence of clinical malaria caused by P. falciparum by approximately 50% (RR 0.49, 95% CI 0.29 to 0.83, low-certainty evidence) and P. vivax (RR 0.64, 95% CI 0.40 to 1.01, low-certainty evidence).Spatial repellentsTwo cluster-randomized RCTs investigated mosquito coils for malaria prevention. We do not know the effect of spatial repellents on malaria prevention (RR 0.24, 95% CI 0.03 to 1.72, very low certainty evidence). There was large heterogeneity between studies and one study had high risk of bias.

Authors' conclusions: There is insufficient evidence to conclude topical or spatial repellents can prevent malaria. There is a need for better designed trials to generate higher certainty of evidence before well-informed recommendations can be made. Adherence to daily compliance remains a major limitation. Insecticide-treated clothing may reduce risk of malaria infection in the absence of insecticide-treated nets; further studies on insecticide-treated clothing in the general population should be done to broaden the applicability of the results.

Conflict of interest statement

MM, MK, MR, and CL have no conflicts of interest in any way related to the content of the review. They have no financial interests in relation to repellents for mosquito avoidance, either in the form of participations or incomes from commercial activities, patents, or from any form of sponsorship.

SJM has received salary coverage from BMGF research grant and PSI for two studies included in this review. However she did not have any role in deciding inclusion, assessment of risk of bias, data extraction, or interpretation of the results of those trials. In addition, SJM currently holds a research grant funded by the Deployed War Fighters Protection Fund evaluating permethrin‐treated clothing, which has been included in the review as an on‐going study. SJM declares no further known conflicts of interest.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
3
3
Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.1 Clinical malaria caused by P. falciparum.
4
4
Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.2 P. falciparum parasitaemia.
5
5
Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.3 Clinical malaria caused by P. vivax.
6
6
Forest plot of comparison: 1 Topical repellent compared to placebo or no treatment, outcome: 1.4 P. vivax parasitaemia.
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7
Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.1 Clinical malaria caused by P. falciparum.
8
8
Forest plot of comparison: 2 ITC compared to placebo or no treatment, outcome: 2.2 Clinical malaria caused by P. vivax.
9
9
Forest plot of comparison: 3 Spatial repellents compared to placebo or no treatment, outcome: 3.1 Plasmodium spp. parasitaemia.
1.1. Analysis
1.1. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.
1.2. Analysis
1.2. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 2 Plasmodium falciparum parasitaemia.
1.3. Analysis
1.3. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 3 Clinical malaria caused by Plasmodium vivax.
1.4. Analysis
1.4. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 4 Plasmodium vivax parasitaemia.
1.5. Analysis
1.5. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 5 Anaemia.
1.6. Analysis
1.6. Analysis
Comparison 1 Topical repellent compared to placebo or no treatment, Outcome 6 All‐cause fever.
2.1. Analysis
2.1. Analysis
Comparison 2 ITC compared to placebo or no treatment, Outcome 1 Clinical malaria caused by Plasmodium falciparum.
2.2. Analysis
2.2. Analysis
Comparison 2 ITC compared to placebo or no treatment, Outcome 2 Clinical malaria caused by Plasmodium vivax.
3.1. Analysis
3.1. Analysis
Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 1 Plasmodium spp. parasitaemia.
3.3. Analysis
3.3. Analysis
Comparison 3 Spatial repellents compared to placebo or no treatment, Outcome 3 Reduction in mosquito bites.

References

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Source: PubMed

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