A new perspective on the application of mosquito repellents
Authors: Sarah Jane Moore
Journal: The Lancet Infectious Diseases (2016)

Great effort is expended in understanding the effect of malaria control interventions on the plasmodium parasite and its anopheles mosquito vector. However, no intervention will work unless it is properly used, and human behaviour is not always carefully considered during controlled trials of vector control interventions. A study in The Lancet Infectious Diseases by Vincent Sluydts and colleagues1Sluydts V Durnez L Heng S et al.Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial.Lancet Infect Dis. 2016; (published online June 29.)http://dx.doi.org/10.1016/S1473-3099(16)30148-7PubMed Google Scholar showed that community-scale distribution of free topical mosquito repellents in Cambodia did not reduce malaria transmission because of human behaviour. In the study area, a high proportion of malaria vectors bite outdoors in the evenings when people are active;2Gryseels C Durnez L Gerrets R et al.Re-imagining malaria: heterogeneity of human and mosquito behaviour in relation to residual malaria transmission in Cambodia.Malar J. 2015; 14: 165Crossref PubMed Scopus (62) Google Scholar therefore, theoretically a mosquito repellent could prevent malaria in this setting. However, even though the repellent was freely available and highly effective,3Van Roey K Sokny M Denis L et al.Field evaluation of picaridin repellents reveals differences in repellent sensitivity between southeast Asian vectors of malaria and arboviruses.PLoS Negl Trop Dis. 2014; 8: e3326Crossref PubMed Scopus (24) Google Scholar the authors also did a mixed-methods study and discovered that only 8% of participants regularly used it,4Gryseels C Uk S Sluydts V et al.Factors influencing the use of topical repellents: implications for the effectiveness of malaria elimination strategies.Sci Rep. 2015; 5: 16847Crossref PubMed Scopus (40) Google Scholar despite 70% reporting daily use. User compliance is difficult to measure in trials and the study team used parallel observational studies4Gryseels C Uk S Sluydts V et al.Factors influencing the use of topical repellents: implications for the effectiveness of malaria elimination strategies.Sci Rep. 2015; 5: 16847Crossref PubMed Scopus (40) Google Scholar to show disparity between reported and actual compliance with the intervention. Low compliance resulted in a non-significant association between repellent allocation and malaria risk. This study is the largest and most comprehensive controlled study done to measure the effect of mosquito repellents for additional malaria control when used in conjunction with long-lasting insecticidal nets. This cluster randomised trial1Sluydts V Durnez L Heng S et al.Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trial.Lancet Infect Dis. 2016; (published online June 29.)http://dx.doi.org/10.1016/S1473-3099(16)30148-7PubMed Google Scholar included roughly 25 000 participants in each study group (picaradin mosquito repellent vs identical placebo), and regularly screened around 2500 participants per group for malaria with sensitive molecular diagnostics. This robust design gives strong evidence that distribution of effective personal protection tools do not necessarily translate into protective efficacy against clinical malaria at an individual or community level. If compliance with repellents is suboptimum and requires substantial behavioural change by users, repellents are unlikely to be selected by donors for inclusion in programmatic malaria control. Topical insect repellents are excellent tools for personal mosquito bite prevention with a long history of use and excellent safety profiles.5Strickman D Topical repellent active ingredients in common use.in: Debboun M Frances SP Strickman D Insect Repellents Handbook. 2nd edn. CRC Press, Taylor & Francis Group, Boca Raton, FL2014Crossref Google Scholar Although several controlled trials have shown that repellents do prevent malaria, a systematic review and meta-analysis showed no overall trend in protective efficacy.6Wilson AL Chen-Hussey V Logan JG Lindsay SW Are topical insect repellents effective against malaria in endemic populations? A systematic review and meta-analysis.Malar J. 2014; 13: 446Crossref PubMed Scopus (54) Google Scholar Topical repellents are an imperfect vector control tool simply because they must be used frequently, inevitably resulting in inconsistent compliance and incorrect application.7Thrower Y Goodyer L Application of insect repellents by travelers to malaria endemic areas.J Travel Med. 2006; 13: 198-202Crossref PubMed Scopus (10) Google Scholar Even soldiers who are well educated about repellents did not apply them daily if they did not perceive a biting nuisance or risk of disease.8Frances SP Auliff AM Edstein MD Cooper RD Survey of personal protection measures against mosquitoes among Australian defense force personnel deployed to East Timor.Mil Med. 2003; 168: 227-230PubMed Google Scholar Massive scaling up of malaria vector control has averted an estimated 663 million clinical cases of malaria in Africa through widespread free or subsidised distribution of long-lasting insecticidal nets that kill mosquitoes attempting to feed on people sleeping under them and spraying of dwellings with residual insecticides that kill mosquitoes resting inside houses (68% and 11% of cases averted, respectively).9Bhatt S Weiss DJ Cameron E et al.The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.Nature. 2015; 526: 207-211Crossref PubMed Scopus (1563) Google Scholar However, in many malaria endemic regions including South America10Sinka ME Rubio-Palis Y Manguin S et al.The dominant anopheles vectors of human malaria in the Americas: occurrence data, distribution maps and bionomic precis.Parasit Vectors. 2010; 3: 72Crossref PubMed Scopus (135) Google Scholar and southeast Asia,11Sinka ME Bangs MJ Manguin S et al.The dominant anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic precis.Parasit Vectors. 2011; 4: 89Crossref PubMed Scopus (331) Google Scholar malaria vectors have a high preference for outdoor and early evening feeding which means that they do not often come into contact with either long-lasting insecticidal nets or residual insecticides used indoors. Worryingly, in some areas of Africa, the proportion of control achievable through residual insecticides and long-lasting insecticidal nets might decline as vectors evolve resistance to insecticides12Hemingway J Ranson H Magill A et al.Averting a malaria disaster: will insecticide resistance derail malaria control?.Lancet. 2016; 387: 1785-1788Summary Full Text Full Text PDF PubMed Scopus (255) Google Scholar or adapt to bite during the evenings or mornings when people are not under their long-lasting insecticidal nets because this is the only time they can find their preferred blood host unprotected.13Gatton ML Chitnis N Churcher TS et al.The importance of mosquito behavioural adaptations to malaria control in Africa.Evolution. 2013; 67: 1218-1230Crossref PubMed Scopus (191) Google Scholar Therefore, a method to prevent malaria transmission outside of sleeping hours is urgently needed for malaria elimination: ideally one that will kill mosquitoes. However, there remains an absence of existing tools with this capacity. Fortunately, several tools are in development with good potential for future implementation, including toxic sugar baits14Marshall JM White MT Ghani AC Schlein Y Muller GC Beier JC Quantifying the mosquito's sweet tooth: modelling the effectiveness of attractive toxic sugar baits (ATSB) for malaria vector control.Malar J. 2013; 12: 291Crossref PubMed Scopus (26) Google Scholar and killing stations baited with synthetic human odours.15Matowo NS Koekemoer LL Moore SJ et al.Combining synthetic human odours and low-cost electrocuting grids to attract and kill outdoor-biting mosquitoes: field and semi-field evaluation of an improved mosquito landing box.PLoS One. 2016; (published online Jan 20.)https://doi.org/10.1371/journal.pone.0145653Crossref PubMed Scopus (16) Google Scholar There is also renewed interest in the use of larval source management to kill immature mosquitoes. Although the large-scale distribution of topical repellents might not fill the requirement for community malaria protection outside of sleeping hours, repellents are still useful. Providing repellents to specific risk groups that potentially contribute disproportionately to malaria transmission16Parker BS Paredes Olortegui M Penataro Yori P et al.Hyperendemic malaria transmission in areas of occupation-related travel in the Peruvian Amazon.Malar J. 2013; 12: 178Crossref PubMed Scopus (47) Google Scholar and development of longer-lasting personal protection measures needing minimum compliance (eg, insecticidal clothing that protects for 3–6 months17Banks SD Murray N Wilder-Smith A Logan JG Insecticide-treated clothes for the control of vector-borne diseases: a review on effectiveness and safety.Med Vet Entomol. 2014; 28: 14-25Crossref PubMed Scopus (82) Google Scholar) should be pursued. Additionally, travellers to malaria endemic areas are strongly advised to use repellents because they are highly effective bite prevention tools when used correctly and consistently. I have received funds in the past from SC Johnson to evaluate their products. Efficacy of topical mosquito repellent (picaridin) plus long-lasting insecticidal nets versus long-lasting insecticidal nets alone for control of malaria: a cluster randomised controlled trialMass distribution of highly effective topical repellents in resource-sufficient conditions did not contribute to a further decline in malaria endemicity in a pre-elimination setting in the Greater Mekong subregion. Daily compliance and appropriate use of the repellents remains the main obstacle. Full-Text PDF Open Access