Evaluation of the effectiveness of topical repellent distributed by village health volunteer networks against Plasmodium spp. infection in Myanmar: A stepped-wedge cluster randomised trial

Autoři: Paul A. Agius aff001;  Julia C. Cutts aff001;  Win Han Oo aff001;  Aung Thi aff003;  Katherine O’Flaherty aff001;  Kyaw Zayar Aung aff001;  Htin Kyaw Thu aff001;  Poe Poe Aung aff001;  Myat Mon Thein aff001;  Nyi Nyi Zaw aff001;  Wai Yan Min Htay aff001;  Aung Paing Soe aff001;  Zahra Razook aff005;  Alyssa E. Barry aff001;  Win Htike aff001;  Angela Devine aff004;  Julie A. Simpson aff004;  Brendan S. Crabb aff001;  James G. Beeson aff001;  Naanki Pasricha aff001;  Freya J. I. Fowkes aff001
Působiště autorů: Burnet Institute, Victoria, Australia, and Yangon, Myanmar aff001;  Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia aff002;  Department of Public Health, Myanmar Ministry of Health and Sports, Nay Pyi Taw, Myanmar aff003;  Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Victoria, Australia aff004;  Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia aff005;  Global Health Division, Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia aff006;  Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia aff007;  Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia aff008;  Central Clinical School, Monash University, Melbourne, Victoria, Australia aff009
Vyšlo v časopise: Evaluation of the effectiveness of topical repellent distributed by village health volunteer networks against Plasmodium spp. infection in Myanmar: A stepped-wedge cluster randomised trial. PLoS Med 17(8): e32767. doi:10.1371/journal.pmed.1003177
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003177



The 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 findings

Between 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.


In 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 registration

Australian and New Zealand Clinical Trials Registry (ACTRN12616001434482).

Klíčová slova:

Diagnostic medicine – Malaria – Medical risk factors – Plasmodium – Plasmodium falciparum – Polymerase chain reaction – Public and occupational health – Statistical distributions


1. World Health Organization. World malaria report 2019. Geneva: World Health Organization; 2019.

2. World Health Organization. Global report on insecticide resistance in malaria vectors: 2010–2016. Geneva: World Health Organization; 2018.

3. Sokhna C, Ndiath MO, Rogier C. The changes in mosquito vector behaviour and the emerging resistance to insecticides will challenge the decline of malaria. Clin Microbiol Infect. 2013;19(10):902–7. doi: 10.1111/1469-0691.12314 23910459

4. Lupi E, Hatz C, Schlagenhauf P. The efficacy of repellents against Aedes, Anopheles, Culex and Ixodes spp.—a literature review. Travel Med Infect Dis. 2013;11(6):374–411. doi: 10.1016/j.tmaid.2013.10.005 24201040

5. Wilson 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;13:446. doi: 10.1186/1475-2875-13-446 25413142

6. World Health Organization. Guidelines for malaria vector control. Geneva: World Health Organization; 2019.

7. World Health Organization. Strategy for malaria elimination in the Greater Mekong Subregion: 2015–2030. Manila: World Health Organization Regional Office for the Western Pacific; 2015.

8. Trung HD, Bortel WV, Sochantha T, Keokenchanh K, Briet OJ, Coosemans M. Behavioural heterogeneity of Anopheles species in ecologically different localities in Southeast Asia: a challenge for vector control. Trop Med Int Health. 2005;10(3):251–62. doi: 10.1111/j.1365-3156.2004.01378.x 15730510

9. Oo WH, Cutts JC, Agius PA, Aung KZ, Poe Poe A, Aung T, et al. Effectiveness of repellent delivered through village health volunteers on malaria incidence in villages in South-East Myanmar: a stepped-wedge cluster-randomised controlled trial protocol. BMC Infect Dis. 2018;18(1):663. doi: 10.1186/s12879-018-3566-y 30547749

10. R Core Team. R: a language and environment for statistical computing. Version 3.6.1. Vienna: R Foundation for Statistical Computing; 2019.

11. Mittal PK, Sreehari U, Razdan RK, Dash AP, Ansari MA. Efficacy of Advanced Odomos repellent cream (N, N-diethyl-benzamide) against mosquito vectors. Indian J Med Res. 2011;133:426–30. 21537097

12. World Health Organization. Guidelines for efficacy testing of mosquito repellents for human skin. Geneva: World Health Organization; 2009.

13. Hemming K, Lilford R, Girling AJ. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs. Stat Med. 2015;34(2):181–96. doi: 10.1002/sim.6325 25346484

14. Rubin DB. Inference and missing data. Biometrika. 1976;63:581–92.

15. StataCorp. Stata Statistical Software. Release 13. College Station (TX): StataCorp; 2013.

16. Chaumeau V, Kajeechiwa L, Fustec B, Landier J, Naw Nyo S, Nay Hsel S, et al. Contribution of asymptomatic Plasmodium infections to the transmission of malaria in Kayin State, Myanmar. J Infect Dis. 2019;219(9):1499–509. doi: 10.1093/infdis/jiy686 30500927

17. Nguitragool W, Mueller I, Kumpitak C, Saeseu T, Bantuchai S, Yorsaeng R, et al. Very high carriage of gametocytes in asymptomatic low-density Plasmodium falciparum and P. vivax infections in western Thailand. Parasit Vectors. 2017;10(1):512. doi: 10.1186/s13071-017-2407-y 29065910

18. Zhao Y, Zhao Y, Lv Y, Liu F, Wang Q, Li P, et al. Comparison of methods for detecting asymptomatic malaria infections in the China-Myanmar border area. Malar J. 2017;16(1):159. doi: 10.1186/s12936-017-1813-0 28427455

19. Tripura R, Peto TJ, Chalk J, Lee SJ, Sirithiranont P, Nguon C, et al. Persistent Plasmodium falciparum and Plasmodium vivax infections in a western Cambodian population: implications for prevention, treatment and elimination strategies. Malar J. 2016;15:181. doi: 10.1186/s12936-016-1224-7 27013512

20. Nguyen TN, von Seidlein L, Nguyen TV, Truong PN, Hung SD, Pham HT, et al. The persistence and oscillations of submicroscopic Plasmodium falciparum and Plasmodium vivax infections over time in Vietnam: an open cohort study. Lancet Infect Dis. 2018;18(5):565–72. doi: 10.1016/S1473-3099(18)30046-X 29398388

21. Chen-Hussey V, Carneiro I, Keomanila H, Gray R, Bannavong S, Phanalasy S, et al. Can topical insect repellents reduce malaria? A cluster-randomised controlled trial of the insect repellent N,N-diethyl-m-toluamide (DEET) in Lao PDR. PLoS ONE. 2013;8(8):e70664. doi: 10.1371/journal.pone.0070664 23967083

22. Deressa W, Yihdego YY, Kebede Z, Batisso E, Tekalegne A, Dagne GA. Effect of combining mosquito repellent and insecticide treated net on malaria prevalence in Southern Ethiopia: a cluster-randomised trial. Parasit Vectors. 2014;7:132. doi: 10.1186/1756-3305-7-132 24678612

23. Rowland M, Downey G, Rab A, Freeman T, Mohammad N, Rehman H, et al. DEET mosquito repellent provides personal protection against malaria: a household randomized trial in an Afghan refugee camp in Pakistan. Trop Med Int Health. 2004;9(3):335–42. doi: 10.1111/j.1365-3156.2004.01198.x 14996362

24. Hill N, Lenglet A, Arnez AM, Carneiro I. Plant based insect repellent and insecticide treated bed nets to protect against malaria in areas of early evening biting vectors: double blind randomised placebo controlled clinical trial in the Bolivian Amazon. BMJ. 2007;335(7628):1023. doi: 10.1136/bmj.39356.574641.55 17940319

25. McGready R, Simpson JA, Htway M, White NJ, Nosten F, Lindsay SW. A double-blind randomized therapeutic trial of insect repellents for the prevention of malaria in pregnancy. Trans R Soc Trop Med Hyg. 2001;95(2):137–8. doi: 10.1016/s0035-9203(01)90137-3 11355542

26. Sluydts V, Durnez L, Heng S, Gryseels C, Canier L, Kim 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;16(10):1169–77. doi: 10.1016/S1473-3099(16)30148-7 27371977

27. Myanmar Vector Borne Disease Control Programme. Vector Borne Disease Control Programme annual report. Nay Pyi Taw (Myanmar): Department of Public Health, Ministry of Health and Sports, Republic of the Union of Myanmar; 2016.

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PLOS Medicine

2020 Číslo 8

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