Study to Assess Efficacy of Artemether-lumefantrine Prophylaxis Against Forest Malaria in Cambodia (PAL_Cambodia)

Summary

In the Greater Mekong Subregion (GMS) adults are at highest risk for malaria. The most relevant disease vectors bite during daytime and outdoors which makes forest work a high-risk activity for malaria. The absence of effective vector control strategies and limited periods of exposure during forest visits suggest that chemoprophylaxis could be an appropriate strategy to protect forest workers against malaria. The investigators propose the use of Artemether-lumefantrine (AL), a drug whose efficacy remains high in the GMS, unlike, for example DHA/piperaquine \[20\]. The proposed study will help to assess the efficacy and feasibility of prophylaxis to prevent malaria in forest workers, help to identify the optimal regimen, and predict its efficacy in reducing overall transmission. The proposed study is a critical step for future use of chemoprophylaxis to protect forest workers in the GMS against malaria. Funder: Wellcome Trust of Great Britain grant number 106698/Z/14/Z and 220211.

Timeline

Start

2020-03-11

Primary completion

2021-03-17

Completion

2021-03-17

Publications

• Background Guerra CA, Snow RW, Hay SI. A global assessment of closed forests, deforestation and malaria risk. Ann Trop Med Parasitol. 2006 Apr;100(3):189-204. doi: 10.1179/136485906X91512.
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• Background Sanh NH, Van Dung N, Thanh NX, Trung TN, Van Co T, Cooper RD. Forest malaria in central Vietnam. Am J Trop Med Hyg. 2008 Nov;79(5):652-4.
• Background Thang ND, Erhart A, Speybroeck N, Hung le X, Thuan le K, Hung CT, Ky PV, Coosemans M, D'Alessandro U. Malaria in central Vietnam: analysis of risk factors by multivariate analysis and classification tree models. Malar J. 2008 Jan 30;7:28. doi: 10.1186/1475-2875-7-28.
• Background Erhart A, Thang ND, Hung NQ, Toi le V, Hung le X, Tuy TQ, Cong le D, Speybroeck N, Coosemans M, D'Alessandro U. Forest malaria in Vietnam: a challenge for control. Am J Trop Med Hyg. 2004 Feb;70(2):110-8.
• Background Dysoley L, Kaneko A, Eto H, Mita T, Socheat D, Borkman A, Kobayakawa T. Changing patterns of forest malaria among the mobile adult male population in Chumkiri District, Cambodia. Acta Trop. 2008 Jun;106(3):207-12. doi: 10.1016/j.actatropica.2007.01.007. Epub 2008 Apr 7.
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• Background Lengeler C. Insecticide-treated bednets and curtains for preventing malaria. Cochrane Database Syst Rev. 2000;(2):CD000363. doi: 10.1002/14651858.CD000363.
• Background Thang ND, Erhart A, Speybroeck N, Xa NX, Thanh NN, Ky PV, Hung le X, Thuan le K, Coosemans M, D'Alessandro U. Long-Lasting Insecticidal Hammocks for controlling forest malaria: a community-based trial in a rural area of central Vietnam. PLoS One. 2009 Oct 7;4(10):e7369. doi: 10.1371/journal.pone.0007369.
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• Background York A. Seasonal malaria chemoprevention in the Sahel. Lancet Infect Dis. 2017 Jun;17(6):588. doi: 10.1016/S1473-3099(17)30255-4. No abstract available.
• Background Snow RW. Seasonal Malaria Chemoprevention: An Evolving Research Paradigm. PLoS Med. 2016 Nov 22;13(11):e1002176. doi: 10.1371/journal.pmed.1002176. eCollection 2016 Nov.
• Background Tripura R, Peto TJ, Chea N, Chan D, Mukaka M, Sirithiranont P, Dhorda M, Promnarate C, Imwong M, von Seidlein L, Duanguppama J, Patumrat K, Huy R, Grobusch MP, Day NPJ, White NJ, Dondorp AM. A Controlled Trial of Mass Drug Administration to Interrupt Transmission of Multidrug-Resistant Falciparum Malaria in Cambodian Villages. Clin Infect Dis. 2018 Aug 31;67(6):817-826. doi: 10.1093/cid/ciy196.
• Background Imwong M, Hanchana S, Malleret B, Renia L, Day NP, Dondorp A, Nosten F, Snounou G, White NJ. High-throughput ultrasensitive molecular techniques for quantifying low-density malaria parasitemias. J Clin Microbiol. 2014 Sep;52(9):3303-9. doi: 10.1128/JCM.01057-14. Epub 2014 Jul 2.
• Background Imwong M, Nguyen TN, Tripura R, Peto TJ, Lee SJ, Lwin KM, Suangkanarat P, Jeeyapant A, Vihokhern B, Wongsaen K, Van Hue D, Dong le T, Nguyen TU, Lubell Y, von Seidlein L, Dhorda M, Promnarate C, Snounou G, Malleret B, Renia L, Keereecharoen L, Singhasivanon P, Sirithiranont P, Chalk J, Nguon C, Hien TT, Day N, White NJ, Dondorp A, Nosten F. The epidemiology of subclinical malaria infections in South-East Asia: findings from cross-sectional surveys in Thailand-Myanmar border areas, Cambodia, and Vietnam. Malar J. 2015 Sep 30;14:381. doi: 10.1186/s12936-015-0906-x.
• Background Saunders DL, Vanachayangkul P, Lon C; U.S. Army Military Malaria Research Program; National Center for Parasitology, Entomology, and Malaria Control (CNM); Royal Cambodian Armed Forces. Dihydroartemisinin-piperaquine failure in Cambodia. N Engl J Med. 2014 Jul 31;371(5):484-5. doi: 10.1056/NEJMc1403007. No abstract available.
• Background West African Network for Clinical Trials of Antimalarial Drugs (WANECAM). Pyronaridine-artesunate or dihydroartemisinin-piperaquine versus current first-line therapies for repeated treatment of uncomplicated malaria: a randomised, multicentre, open-label, longitudinal, controlled, phase 3b/4 trial. Lancet. 2018 Apr 7;391(10128):1378-1390. doi: 10.1016/S0140-6736(18)30291-5. Epub 2018 Mar 29.
• Background Bukirwa H, Unnikrishnan B, Kramer CV, Sinclair D, Nair S, Tharyan P. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria. Cochrane Database Syst Rev. 2014 Mar 4;(3):CD006404. doi: 10.1002/14651858.CD006404.pub2.
• Background Marks VA, Latham SR, Kishore SP. On Essentiality and the World Health Organization's Model List of Essential Medicines. Ann Glob Health. 2017 May-Aug;83(3-4):637-640. doi: 10.1016/j.aogh.2017.05.005. Epub 2017 Jun 22.
• Background Agency, E.M., European Public Assessment Report for Pyramax. 2016.
• Tripura R, von Seidlein L, Sovannaroth S, Peto TJ, Callery JJ, Sokha M, Ean M, Heng C, Conradis-Jansen F, Madmanee W, Peerawaranun P, Waithira N, Khonputsa P, Jongdeepaisal M, Pongsoipetch K, Chotthanawathit P, Soviet U, Pell C, Duanguppama J, Rekol H, Tarning J, Imwong M, Mukaka M, White NJ, Dondorp AM, Maude RJ. Antimalarial chemoprophylaxis for forest goers in southeast Asia: an open-label, individually randomised controlled trial. Lancet Infect Dis. 2023 Jan;23(1):81-90. doi: 10.1016/S1473-3099(22)00492-3. Epub 2022 Sep 26.
• Maude RJ, Tripura R, Ean M, Sokha M, Peto TJ, Callery JJ, Imwong M, Vongpromek R, Tarning J, Mukaka M, Waithira N, Soviet O, von Seidlein L, Sovannaroth S. Study protocol: an open-label individually randomised controlled trial to assess the efficacy of artemether-lumefantrine prophylaxis for malaria among forest goers in Cambodia. BMJ Open. 2021 Jul 7;11(7):e045900. doi: 10.1136/bmjopen-2020-045900.

Drugs

Indications