Effect of interventions to reduce malaria incidence among military personnel on active duty: study protocol for a cluster randomised controlled trial of the impact of etofenprox-treated uniforms, permethrin-treated uniforms and DEET insect repellent

Daniel Msellemu, Amanda Ross, Lucky Temu, Irene Moshi, Lorenz Hofer, Charles Mwanziva, Yadon M Kohi, Sarah J Moore, Daniel Msellemu, Amanda Ross, Lucky Temu, Irene Moshi, Lorenz Hofer, Charles Mwanziva, Yadon M Kohi, Sarah J Moore

Abstract

Background: While there is strong evidence that bite protection methods such as permethrin-treated clothing and topical insect repellents are protective against insect bites, there are few studies assessing the impact on malaria infection. This study will estimate the protective efficacy of treated uniforms and DEET insect repellent on the incidence of malaria infection among military personnel in an operational setting. Permethrin-treated uniforms used with DEET lotion will be compared to etofenprox-treated uniforms with DEET lotion. The effect of DEET lotion will be estimated by comparing permethrin-treated uniforms with DEET or placebo lotion.

Method: A cluster randomised double-blind placebo-controlled trial is planned to evaluate the effectiveness of the interventions on preventing malaria infections in soldiers on active duty at Mgambo National Service Camp in Tanga, Tanzania. The arms are (1) permethrin-treated uniform with 30% DEET liposome formula; (2) permethrin-treated uniform with placebo lotion; (3) candidate insect repellent system, i.e. etofenprox-treated uniform with 30% DEET liposome formula; and (4) placebo, i.e. untreated uniforms with placebo lotion. The primary outcome is the incidence of Plasmodium falciparum malaria infection detected by polymerase chain reaction (PCR) by active case detection using surveys every 2 weeks for 12 months. Rapid diagnostic tests will be used for the diagnosis of participants with symptoms. The unit of randomisation will be combania: companies formed by recruits aged 18 to 25 years; combania do activities together and sleep in the same dormitory. Unequal randomisation will be used to optimise statistical power for the primary comparison between permethrin-treated uniforms with DEET and etofenprox-treated uniforms with DEET.

Discussion: This trial will provide the estimate of the effects of permethrin with DEET compared to those of the new fabric treatment etofenprox with DEET and any additional effect of using DEET. The results will inform strategies to protect military personnel and civilians who have more outdoor or occupational malaria exposure than the general public.

Trial registration: ClinicalTrials.gov NCT02938975 .

Keywords: CRT; Cluster randomised trial; DEET; Etofenprox; Insecticide-treated clothing; Malaria; Military uniforms; Permethrin; Repellent.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Schedule of events for the trial

References

    1. Monroe A, Moore S, Koenker H, Lynch M, Ricotta E. Measuring and characterizing night time human behaviour as it relates to residual malaria transmission in sub-Saharan Africa: a review of the published literature. Malaria Journal. 2019;18(1):6. doi: 10.1186/s12936-019-2638-9.
    1. Kitchen LW, Lawrence KL, Coleman RE. The role of the United States military in the development of vector control products, including insect repellents, insecticides, and bed nets. J Vector Ecol. 2009;34(1):50–61. doi: 10.1111/j.1948-7134.2009.00007.x.
    1. Pages F, Faulde M, Orlandi-Pradines E, Parola P. The past and present threat of vector-borne diseases in deployed troops. Clin Microbiol Infect. 2010;16(3):209–224. doi: 10.1111/j.1469-0691.2009.03132.x.
    1. Recht J, Siqueira AM, Monteiro WM, Herrera SM, Herrera S, Lacerda MVG. Malaria in Brazil, Colombia, Peru and Venezuela: current challenges in malaria control and elimination. Malar J. 2017;16(1):273. doi: 10.1186/s12936-017-1925-6.
    1. von Seidlein L, Peto TJ, Tripura R, Pell C, Yeung S, Kindermans JM, Dondorp A, Maude R. Novel approaches to control malaria in forested areas of Southeast Asia. Trends Parasitol. 2019;35(6):388–398. doi: 10.1016/j.pt.2019.03.011.
    1. Kounnavong S, Gopinath D, Hongvanthong B, Khamkong C, Sichanthongthip O. Malaria elimination in Lao PDR: the challenges associated with population mobility. Infect Dis Poverty. 2017;6(1):81. doi: 10.1186/s40249-017-0283-5.
    1. da Silva-Nunes M, Codeço CT, Malafronte RS, da Silva NS, Juncansen C, Muniz PT, Ferreira MU. Malaria on the Amazonian frontier: transmission dynamics, risk factors, spatial distribution, and prospects for control. Am J Trop Med Hyg. 2008;79(4):624–635. doi: 10.4269/ajtmh.2008.79.624.
    1. Abdul-Ghani R, Mahdy MAK, Al-Eryani SMA, Fouque F, Lenhart AE, Alkwri A, Al-Mikhlafi AM, Wilke ABB, Thabet AAQ, Beier JC. Impact of population displacement and forced movements on the transmission and outbreaks of Aedes-borne viral diseases: dengue as a model. Acta Tropica. 2019;197:105066. doi: 10.1016/j.actatropica.2019.105066.
    1. WHO . Mass drug administration for falciparum malaria: a practical field manual. Geneva: World Health Organization; 2017.
    1. Wen S, Harvard KE, Gueye CS, Canavati SE, Chancellor A, Ahmed BN, Leaburi J, Lek D, Namgay R, Surya A, Thakur GD, Whittaker MA, Gosling RD. Targeting populations at higher risk for malaria: a survey of national malaria elimination programmes in the Asia Pacific. Malar J. 2016;15(1):271. doi: 10.1186/s12936-016-1319-1.
    1. Norris EJ, Coats JR. Current and future repellent technologies: the potential of spatial repellents and their place in mosquito-borne disease control. Int J Environ Res Public Health. 2017;14(2). 10.3390/ijerph14020124.
    1. Banks 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(Suppl 1):14–25. doi: 10.1111/mve.12068.
    1. Bernier U: New developments in skin repellents and repellent-treated uniforms for the United States military. In 61st Meeting of the Entomological Society of America. Austin, Texas, USA 2013.
    1. Agramonte NM, Bloomquist JR, Bernier UR. Pyrethroid resistance alters the blood-feeding behavior in Puerto Rican Aedes aegypti mosquitoes exposed to treated fabric. PLoS Negl Trop Dis. 2017;11(9):e0005954. doi: 10.1371/journal.pntd.0005954.
    1. DeGennaro M. The mysterious multi-modal repellency of DEET. Fly (Austin) 2015;9(1):45–51. doi: 10.1080/19336934.2015.1079360.
    1. Leal WS. The enigmatic reception of DEET - the gold standard of insect repellents. Curr Opin Insect Sci. 2014;6:93–98. doi: 10.1016/j.cois.2014.10.007.
    1. Moore SJ, Mordue Luntz AJ, Logan JG. Insect bite prevention. Infect Dis Clin North Am. 2012;26(3):655–673. doi: 10.1016/j.idc.2012.07.002.
    1. Maia MF, Kliner M, Richardson M, Lengeler C, Moore SJ. Mosquito repellents for malaria prevention. Cochrane Database Syst Rev. 2018;2(2):CD011595.
    1. World Health Organisation: Guidelines for malaria vector control Geneva 2019.
    1. Lalani T, Yun H, Tribble D, Ganesan A, Kunz A, Fairchok M, Schnaubelt E, Fraser J, Mitra I, Kronmann KC, Burgess T, Deiss RG, Riddle MS, Johnson MD. A comparison of compliance rates with anti-vectorial protective measures during travel to regions with dengue or chikungunya activity, and regions endemic for Plasmodium falciparum malaria. J Travel Med. 2016;23(5):taw043. doi: 10.1093/jtm/taw043.
    1. Kalinga A, Kavishe RA, Ishengoma DS, Kagaruki G, Clement Mweya SM, Mahikwano L, Kamau E, Hickman M, Waters N, Temu L, et al. Prevalence of asymptomatic malaria infections in selected military camps in Tanzania. Tanzania Journal of Health Research. 2019;21(1):1–11. doi: 10.4314/thrb.v21i1.4.
    1. Richards SL, Agada N, Balanay JAG, White AV. Permethrin treated clothing to protect outdoor workers: evaluation of different methods for mosquito exposure against populations with differing resistance status. Pathog Glob Health. 2018;112(1):13–21. doi: 10.1080/20477724.2018.1437692.
    1. Faulde M, Uedelhoven W. A new clothing impregnation method for personal protection against ticks and biting insects. Int J Med Microbiol. 2006;296(Suppl 40):225–229. doi: 10.1016/j.ijmm.2006.01.008.
    1. Vaughn MF, Meshnick SR. Pilot study assessing the effectiveness of long-lasting permethrin-impregnated clothing for the prevention of tick bites. Vector Borne Zoonotic Dis. 2011;11(7):869–875. doi: 10.1089/vbz.2010.0158.
    1. EPA: Clothing factory-treated with permethrin . Washington: Environmental Protection Agency; 2012.
    1. Frances SP, Sferopoulos R, Lee B. Protection from mosquito biting provided by permethrin-treated military fabrics. J Med Entomol. 2014;51(6):1220–1226. doi: 10.1603/ME14084.
    1. Bernier U, Perry M, Agramonte N, Knue G: Development of etofenprox-treated U.S. military combat uniforms Mosquito and Fly Research: Gainesville, FL: Agricultural Research Service U.S. Department of Agriculture; 2016.
    1. USEPA: “U.S. Environmental Protection Agency. Office of Pesticides and Toxic Substances. Special Pesticide Review Division. N,N-diethyl-m-toluamide (DEET) Pesticide Registration Standard (EPA-540/RS-81-004). Washington, DC: U.S. Environmental Protection Agency; 1980. (PB81-207722) ". 1980.
    1. Osimitz T, Grothaus RH. The present safety assessment of deet. Journal of the American Mosquito Control Association. 1995;11(2 Pt 2):274–278.
    1. Veltri JC, Osimitz TG, Bradford DC, Page BC. Retrospective analysis of calls to poison control centers resulting from exposure to the insect repellent N, N-diethyl-m-toluamide (DEET) from 1985-1989. Clinical Toxicology. 1994;32(1):1–16. doi: 10.3109/15563659409000426.
    1. Barnard DR, Xue RD. Laboratory evaluation of mosquito repellents against Aedes albopictus, Culex nigripalpus, and Ochlerotatus triseriatus (Diptera: Culicidae) Journal of medical entomology. 2004;41(4):726–730. doi: 10.1603/0022-2585-41.4.726.
    1. Goodyer L, Behrens RH. Short report: The safety and toxicity of insect repellents. The American Journal of Tropical Medicine and Hygiene. 1998;59(2):323–324. doi: 10.4269/ajtmh.1998.59.323.
    1. Goodyer LI, Croft AM, Frances SP, Hill N, Moore SJ, Onyango SP, Debboun M. Expert review of the evidence base for arthropod bite avoidance. Journal of travel medicine. 2010;17(3):182–192. doi: 10.1111/j.1708-8305.2010.00402.x.
    1. Fradin MS. Mosquitoes and mosquito repellents. Ann of Internal Med. 1998;128(11):931–940. doi: 10.7326/0003-4819-128-11-199806010-00013.
    1. Fradin MS, Day JF. Comparative efficacy of insect repellents against mosquito bites. N Engl J Med. 2002;347(1):13–18. doi: 10.1056/NEJMoa011699.
    1. Schindler T, Robaina T, Sax J, Bieri JR, Mpina M, Gondwe L, Acuche L, Garcia G, Cortes C, Maas C, Daubenberger C. Molecular monitoring of the diversity of human pathogenic malaria species in blood donations on Bioko Island, Equatorial Guinea. Malar J. 2019;18(1):9. doi: 10.1186/s12936-019-2639-8.
    1. Kamau E, Alemayehu S, Feghali KC, Saunders D, Ockenhouse CF. Multiplex qPCR for detection and absolute quantification of malaria. PLoS One. 2013;8(8):e71539. doi: 10.1371/journal.pone.0071539.
    1. Kamau E, Alemayehu S, Feghali KC, Komisar J, Regules J, Cowden J, Ockenhouse CF. Measurement of parasitological data by quantitative real-time PCR from controlled human malaria infection trials at the Walter Reed Army Institute of Research. Malar J. 2014;13(1):288. doi: 10.1186/1475-2875-13-288.
    1. Hofmann N, Mwingira F, Shekalaghe S, Robinson LJ, Mueller I, Felger I. Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets. PLoS Med. 2015;12(3):e1001788. doi: 10.1371/journal.pmed.1001788.
    1. Kalinga A, Mswanya C, Amoo G, Mwanziva C, Temu L, Chiduo S, Anova L, Wurapa E, Schnabel D, Fine I, et al: Developing a passive malaria case detection strategy using FionetTM Technology in Tanzanian military health facilities. In American Society of Tropical Medicine and Hygiene. Philadelphia 2015.
    1. Taylor BJ, Martin KA, Arango E, Agudelo OM, Maestre A, Yanow SK. Real-time PCR detection of Plasmodium directly from whole blood and filter paper samples. Malaria journal. 2011;10(1):244. doi: 10.1186/1475-2875-10-244.
    1. Singh B, Bobogare A, Cox-Singh J, Snounou G, Abdullah MS, Rahman HA. A genus- and species-specific nested polymerase chain reaction malaria detection assay for epidemiologic studies. Am J Trop Med Hyg. 1999;60(4):687–692. doi: 10.4269/ajtmh.1999.60.687.
    1. Van den Broeck J, Argeseanu Cunningham S, Eeckels R, Herbst K. Data cleaning: detecting, diagnosing, and editing data abnormalities. PLOS Medicine. 2005;2(10):e267. doi: 10.1371/journal.pmed.0020267.
    1. Ellenberg SS, Culbertson R, Gillen DL, Goodman S, Schrandt S, Zirkle M. Data monitoring committees for pragmatic clinical trials. Clin Trials. 2015;12(5):530–536. doi: 10.1177/1740774515597697.
    1. Sangoro O, Moore SJ. Evaluation of repellent efficacy in reducing disease incidence. In: Debboun M, Frances SP, Strickman D, editors. In Insect Repellents Handbook. Second. Boca Raton Florida: CRC Press, Taylor & Francis Group; 2014.
    1. Croft A. Malaria prevention in travellers. Clinical Evidence. 2010;7:1–34.
    1. Sharp TW, DeFraites RF, Thornton SA, Burans JP, Wallace MR. Illness in journalists and relief workers involved in International Humanitarian Assistance Efforts in Somalia, 1992-93. J Travel Med. 1995;2(2):70–76. doi: 10.1111/j.1708-8305.1995.tb00630.x.
    1. Kimani EW, Vulule JM, Kuria IW, Mugisha F. Use of insecticide-treated clothes for personal protection against malaria: a community trial. Malar J. 2006;5(1):63. doi: 10.1186/1475-2875-5-63.
    1. Mboera LE, Mweya CN, Rumisha SF, Tungu PK, Stanley G, Makange MR, Misinzo G, De Nardo P, Vairo F, Oriyo NM. The risk of dengue virus transmission in Dar es Salaam, Tanzania during an epidemic period of 2014. PLoS Negl Trop Dis. 2016;10(1):e0004313. doi: 10.1371/journal.pntd.0004313.
    1. World Health Organization: Report of the third WHOPES working group meeting. Review of deltamethrin 1% SC and 25% WT, etofenprox 10% EC and 10% EW. . WHO/HQ Geneva1999.
    1. Gupta SK. Intention-to-treat concept: a review. Perspectives in clinical research. 2011;2(3):109–112. doi: 10.4103/2229-3485.83221.
    1. White IR, Horton NJ, Carpenter J, Rimas S, Pocock SJ. Strategy for intention to treat analysis in randomised trials with missing outcome data. BMJ. 2011;342(feb07 1):d40. doi: 10.1136/bmj.d40.
    1. Hernán MA, Robins JM. Per-protocol analyses of pragmatic trials. N Engl J Med. 2017;377(14):1391–1398. doi: 10.1056/NEJMsm1605385.
    1. Govella N, Ferguson H. Why use of interventions targeting outdoor biting mosquitoes will be necessary to achieve malaria elimination. Frontiers in Physiology. 2012;3. 10.3389/fphys.2012.00199.
    1. Zhu L, Müller GC, Marshall JM, Arheart KL, Qualls WA, Hlaing WM, Schlein Y, Traore SF, Doumbia S, Beier JC. Is outdoor vector control needed for malaria elimination? An individual-based modelling study. Malaria Journal. 2017;16(1):266. doi: 10.1186/s12936-017-1920-y.

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