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Giving people antimalarials during and after visiting the forest reduced their risk of contracting malaria 6-fold, and could be the missing piece towards eliminating malaria in Asia-Pacific and South America, say Mahidol and Oxford University researchers in a study published in The Lancet Infectious Diseases.

An improvised village in Cambodia for forest workers, who sustain themselves with food gathered from the surrounding jungle. © MORU 2022. Photography: Rupam Tripura and James Callery.
An improvised village in Cambodia for forest workers, who sustain themselves with food gathered from the surrounding jungle.

Leading malaria experts say this could be a game-changer in the fight to eliminate malaria in Asia-Pacific and South America.

“This is a novel use of prophylaxis for people living in endemic areas. Previously prophylaxis had been thought of mainly as something for travellers from rich countries and not an elimination tool for communities with malaria. And it is a strong result,” said Prof Richard Maude, of the University of Oxford and the Mahidol Oxford Tropical Medicine Research Unit (MORU), Bangkok.

Malaria in the eastern Greater Mekong subregion has declined to historic lows. Countries in the Greater Mekong subregion are accelerating malaria elimination in the context of increasing antimalarial drug resistance. Infections are now increasingly concentrated in remote, forested foci. No intervention has yet shown satisfactory efficacy against forest-acquired malaria – until now.

Conducting an open-label, individually randomised controlled trial in Cambodia, the researchers gave randomly allocated recruited participants aged 16–65 years staying overnight in forests either a placebo of multivitamins or antimalarial chemoprophylaxis, a 3-day course of twice-daily artemether–lumefantrine, followed by the same daily dosing once a week while travelling in the forest and for a further 4 weeks after leaving the forest.

Percentage of participants with malaria infection over time

Participants receiving the antimalarial were found to be 6 times less likely to have malaria parasites or clinical malaria

Malaria infection was defined as PCR parasite positivity on days 0 (baseline), 28–35 (month 1), 56–63 (month 2), or 84–91 (month 3), or a case of confirmed clinical malaria during month 1, month 2, or month 3.Malaria infection was defined as PCR parasite positivity on days 0 (baseline), 28–35 (month 1), 56–63 (month 2), or 84–91 (month 3), or a case of confirmed clinical malaria during month 1, month 2, or month 3.

Funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria and Wellcome Trust, the study found that antimalarial chemoprophylaxis with artemether–lumefantrine was well tolerated and substantially reduced the risk of malaria.

This study adds to existing evidence for the efficacy and tolerability of antimalarial chemoprophylaxis in groups at high risk of malaria in low-endemic settings. It demonstrates that chemoprophylaxis is effective to prevent malaria in forest goers and can be safely managed with relatively low-intensity monthly follow-up through close engagement with, and involvement of, the local community. Malaria chemoprophylaxis among high-risk groups such as forest goers could be a valuable additional tool for malaria elimination in the Greater Mekong subregion.

Funders

The Global Fund to Fight AIDS, Tuberculosis and Malaria; Wellcome Trust.

References

Antimalarial chemoprophylaxis for forest goers in southeast Asia: an open-label, individually randomised controlled trial. Tripura R, von Seidlein L, Sovannarath 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, Chaotthanawathit P, Soviet U, Pell C, Juanguppama J, Hekl H, Tarning J, Imwong M, Mukaka M, White NJ, Dondorp AM, Maude RJ. THE LANCET ID. Published: September 26, 2022.
DOI: https://doi.org/10.1016/S1473-3099(22)00492-3

Podcast

In conversation with…Richard Maude. Richard Maude discusses a new article in The Lancet Infectious Diseases that assesses the efficacy of malaria chemoprophylaxis among forest goers in Cambodia.

Commentary

Study protocol: an open-label individually randomised controlled trial to assess the efficacy of artemether-lumefantrine prophylaxis for malaria among forest goers in Cambodia

Acceptability and feasibility of malaria prophylaxis for forest goers: findings from a qualitative study in Cambodia

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Lao PDR

Forest malaria and prospects for anti-malarial chemoprophylaxis among forest goers: findings from a qualitative study in Thailand

Background

Novel Approaches to Control Malaria in Forested Areas of Southeast Asia