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Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa

Nature Reviews Microbiology volume 22, pages 373–384 (2024)Cite this article

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An Author Correction to this article was published on 27 February 2024

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Abstract

Malaria, mostly due to Plasmodium falciparum infection in Africa, remains one of the most important infectious diseases in the world. Standard treatment for uncomplicated P. falciparum malaria is artemisinin-based combination therapy (ACT), which includes a rapid-acting artemisinin derivative plus a longer-acting partner drug, and standard therapy for severe P. falciparum malaria is intravenous artesunate. The efficacy of artemisinins and ACT has been threatened by the emergence of artemisinin partial resistance in Southeast Asia, mediated principally by mutations in the P. falciparum Kelch 13 (K13) protein. High ACT treatment failure rates have occurred when resistance to partner drugs is also seen. Recently, artemisinin partial resistance has emerged in Rwanda, Uganda and the Horn of Africa, with independent emergences of different K13 mutants in each region. In this Review, we summarize our current knowledge of artemisinin partial resistance and focus on the emergence of resistance in Africa, including its epidemiology, transmission dynamics and mechanisms. At present, the clinical impact of emerging resistance in Africa is unclear and most available evidence suggests that the efficacies of leading ACTs remain excellent, but there is an urgent need to better appreciate the extent of the problem and its consequences for the treatment and control of malaria.

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Fig. 1: Structures of artemisinin and three clinically important derivatives.
Fig. 2: Mechanisms of artemisinin action and partial resistance.
Fig. 3: Prevalence of mutations associated with artemisinin partial resistance in eastern Africa.
Fig. 4: K13 mutations that have emerged in eastern Africa.

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Acknowledgements

Work by the authors is supported by the National Institutes of Health (R01AI075045, R01AI117001, R01AI139179, U01AI141308, U19AI089674 to P.J.R.; R01AI173557 to M.D.C.); The Bill and Melinda Gates Foundation (INV-035751); and the Medicines for Malaria Venture. V.A. is the recipient of a PAMAfrica PhD fellowship, supported by the European & Developing Countries Clinical Trials Partnership. The authors thank David Fidock, Columbia University, for a critical review of this manuscript, and Faiza Siddiqui and Liwang Cui, University of South Florida, for generously providing Fig. 4.

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  1. University of California, San Francisco, CA, USA

    Philip J. Rosenthal & Melissa D. Conrad

  2. Infectious Diseases Research Collaboration, Kampala, Uganda

    Victor Asua

  3. University of Tübingen, Tübingen, Germany

    Victor Asua

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Malaria: Artemisinin partial resistance: https://www.who.int/news-room/questions-and-answers/item/artemisinin-resistance

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Rosenthal, P.J., Asua, V. & Conrad, M.D. Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa. Nat Rev Microbiol 22, 373–384 (2024). https://doi.org/10.1038/s41579-024-01008-2

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