Preventing antimalarial drug resistance with triple artemisinin-based combination therapies

Tran Dang Nguyen, Bo Gao, Chanaki Amaratunga, Mehul Dhorda, Thu Nguyen-Anh Tran, Nicholas J. White, Arjen M. Dondorp, Maciej F. Boni () and Ricardo Aguas ()
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Tran Dang Nguyen: Pennsylvania State University
Bo Gao: University of Oxford
Chanaki Amaratunga: University of Oxford
Mehul Dhorda: University of Oxford
Thu Nguyen-Anh Tran: Pennsylvania State University
Nicholas J. White: University of Oxford
Arjen M. Dondorp: University of Oxford
Maciej F. Boni: Pennsylvania State University
Ricardo Aguas: University of Oxford

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: Abstract Increasing levels of artemisinin and partner drug resistance threaten malaria control and elimination globally. Triple artemisinin-based combination therapies (TACTs) which combine artemisinin derivatives with two partner drugs are efficacious and well tolerated in clinical trials, including in areas of multidrug-resistant malaria. Whether early TACT adoption could delay the emergence and spread of antimalarial drug resistance is a question of vital importance. Using two independent individual-based models of Plasmodium falciparum epidemiology and evolution, we evaluated whether introduction of either artesunate-mefloquine-piperaquine or artemether-lumefantrine-amodiaquine resulted in lower long-term artemisinin-resistance levels and treatment failure rates compared with continued ACT use. We show that introduction of TACTs could significantly delay the emergence and spread of artemisinin resistance and treatment failure, extending the useful therapeutic life of current antimalarial drugs, and improving the chances of malaria elimination. We conclude that immediate introduction of TACTs should be considered by policy makers in areas of emerging artemisinin resistance.

Date: 2023
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DOI: 10.1038/s41467-023-39914-3

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