• Topical repellents may slightly reduce the incidence and prevalence of malaria caused by Plasmodium falciparum.
• These changes seem to be particularly important in high-risk populations, specifically in refugees living in camps where there are fewer other options.
• Topical repellents may make little or no difference in malaria prevalence and incidence in settings where insecticide-treated nets, and other options to control the transmission of malaria are readily available.
What is malaria?
Malaria is a disease caused by at least five species of parasites from the genus Plasmodium, and spread by the bite of Anopheles mosquitoes. The disease regularly affects people in tropical areas of Central and South America, South and Southeast Asia, and particularly, Africa. Over 247 million malaria cases and 619,000 deaths occurred in 2021, mostly in Africa. The disease affects the function of red blood cells, which transport oxygen through the body. This generally causes fever, malaise (a feeling of 'just not feeling well'), and other mild symptoms. However, some people can develop complicated disease, which is associated with a severe reduction in the number of circulating red blood cells, and problems in the liver, brain, and other organs.
Malaria can be treated with different medicines, which are generally effective. Certain tools that prevent mosquito bites, like nets treated with insecticides, can protect people from getting it, and have helped to significantly reduce the number of cases around the world. Nonetheless, most of these approaches target mosquitoes that feed indoors and on humans. They are less effective against species that can feed outdoors, so do not really eliminate the disease.
What did we want to find out?
The aim of this Cochrane Review was to find out if topical insect repellents (substances applied to the skin to prevent mosquito bites) can prevent malaria in people living in regions where this disease occurs regularly. We were particularly interested in their effect on people who might not be adequately protected by other measures, which are more commonly used to prevent malaria.
We wanted to find out if topical repellents were better than a placebo, or no intervention at all, to reduce two indicators of malaria transmission:
• Malaria incidence (the number of new cases in a period of time);
• Malaria prevalence (the number of all cases at a certain moment).
We also wanted to know if topical repellents caused any adverse side effects to people who used them.
What did we do?
We searched the existing literature for studies that compared the effect of topical repellents (alone or in combination with other tools to prevent mosquito bites) with a placebo or no intervention. We compared and summarized the results of the included studies, and rated our confidence in the evidence they provided, based on the methods used in each one.
What did we find?
We included a total of eight studies, which included over 60,000 people. The studies took place in areas with low malaria transmission, mostly in Southeast Asia and South America.
The topical repellents evaluated included lotions, soaps, and cosmetics. We found evidence suggesting that topical repellents may slightly reduce the incidence and prevalence of malaria cases caused by P falciparum in settings where other tools to prevent mosquito bites are not available. Despite this, our findings suggest that repellents probably make little or no difference in places where these tools are already widely used. Topical repellents are considered safe, and the prevalence of adverse side effects was very low.
What are the limitations of the evidence?
The benefits of topical repellents were particularly clear among refugees. However, shortfalls in the design of the included studies did not allow us to generalize these observations to other contexts. We only included cases of malaria caused by the parasite P falciparum. We also recognize that studies measured and reported adherence differently, and often did not know if the participants actually used the repellent as advised.
How up to date is this review?
The evidence is up to date to 11 January 2023.
There is insufficient evidence to conclude that topical repellents can prevent malaria in settings where other vector control interventions are in place. We found the certainty of evidence for all outcomes to be low, primarily due to the risk of bias. A protective effect was suggested among high-risk populations, specially refugees, who might not have access to other standard vector control measures.
More adequately powered clinical trials carried out in refugee camps could provide further information on the potential benefit of topical repellents in this setting. Individually randomized studies are also likely necessary to understand whether topical repellents have an effect on personal protection, and the degree to which diversion to non-protected participants affects overall transmission dynamics.
Despite this, the potential additional benefits of topical repellents are most likely limited in contexts where other interventions are available.
Insecticide-based interventions, such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS), remain the backbone of malaria vector control. These interventions target mosquitoes that prefer to feed and rest indoors, but have limited capacity to prevent transmission that occurs outdoors or outside regular sleeping hours. In low-endemicity areas, malaria elimination will require that these control gaps are addressed, and complementary tools are found. The use of topical repellents may be particularly useful for populations who may not benefit from programmatic malaria control measures, such as refugees, the military, or forest goers. This Cochrane Review aims to measure the effectiveness of topical repellents to prevent malaria infection among high- and non-high-risk populations living in malaria-endemic regions.
To assess the effect of topical repellents alone or in combination with other background interventions (long-lasting insecticide-treated nets, or indoor residual spraying, or both) for reducing the incidence of malaria in high- and non-high-risk populations living in endemic areas.
We searched the following databases up to 11 January 2023: the Cochrane Infectious Diseases Group Specialised Register; CENTRAL (in the Cochrane Library); MEDLINE; Embase; CAB Abstracts; and LILACS. We also searched trial registration platforms and conference proceedings; and contacted organizations and companies for ongoing and unpublished trials.
We included randomized controlled trials (RCTs) and cluster-randomized controlled trials (cRCTs) of topical repellents proven to repel mosquitoes. We also included non-randomized studies that complied with pre-specified inclusion criteria: controlled before-after studies (CBA), controlled interrupted time series (ITS), and controlled cross-over trials.
Four review authors independently assessed trials for inclusion, and extracted the data. Two authors independently assessed the risk of bias (RoB) using the Cochrane RoB 2 tool. A fifth review author resolved any disagreements. We analysed data by conducting a meta-analysis, stratified by whether studies included populations considered to be at high-risk of developing malaria infection (for example, refugees, forest goers, or deployed military troops). We combined results from cRCTs with RCTs by adjusting for clustering and presented results using forest plots. We used the GRADE framework to assess the certainty of the evidence. We only included data on Plasmodium falciparum infections in the meta-analysis.
Thirteen articles relating to eight trials met the inclusion criteria and were qualitatively described. We included six trials in the meta-analysis (five cRCTs and one RCT).
Effect on malaria incidence
Topical repellents may slightly reduce P falciparum infection and clinical incidence when both outcomes are considered together (incidence rate ratio (IRR) 0.74, 95% confidence interval (CI) 0.56 to 0.98; 3 cRCTs and 1 RCT, 61,651 participants; low-certainty evidence); but not when these two outcomes were considered independently. Two cRCTs and one RCT (12,813 participants) evaluated the effect of topical repellents on infection incidence (IRR 0.76, 95% CI 0.56 to 1.02; low-certainty evidence). One cRCT (48,838 participants) evaluated their effect on clinical case incidence (IRR 0.66, 95% CI 0.32 to 1.36; low-certainty evidence). Three studies (2 cRCTs and 1 RCT) included participants belonging to groups considered at high-risk of being infected, while only one cRCT did not include participants at high risk.
Topical repellents are considered safe. The prevalence of adverse events among participants who used topical repellents was very low (0.6%, 283/47,515) and limited to mild skin reactions.
Effect on malaria prevalence
Topical repellents may slightly reduce P falciparum prevalence (odds ratio (OR) 0.81, 95% CI 0.67 to 0.97; 3 cRCTs and 1 RCT; 55,366 participants; low-certainty evidence). Two of these studies (1 cRCT and 1 RCT) were carried out in refugee camps, and included exclusively high-risk populations that were not receiving any other background vector control intervention.