Abstract
Malaria, which is caused by infection of red blood cells with Plasmodium parasites, can be fatal in non-immune individuals if left untreated. The recent approval of the pre-erythrocytic vaccines RTS, S/AS01 and R21/Matrix-M has ushered in hope of substantial reductions in mortality rates, especially when combined with other existing interventions. However, the efficacy of these vaccines is partial, and chemotherapy remains central to malaria treatment and control. For many antimalarial drugs, clinical efficacy has been compromised by the emergence of drug-resistant Plasmodium falciparum strains. Therefore, there is an urgent need for new antimalarial medicines to complement the existing first-line artemisinin-based combination therapies. In this Review, we discuss various opportunities to expand the present malaria treatment space, appraise the current antimalarial drug development pipeline and highlight examples of promising targets. We also discuss other approaches to circumvent antimalarial resistance and how potency against drug-resistant parasites could be retained.
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Acknowledgements
Work in the authors’ laboratory was supported by the National Institutes of Health (R01 AI109023, R37 AI050234, R01 AI124678, R01 AI185559), the Department of Defense (E01 W81XWH2210520) and the Bill & Melinda Gates Foundation (INV-033538). The authors thank the MalDA Consortium (PI: Elizabeth Winzeler) and the Medicines for Malaria Venture for their support.
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Okombo, J., Fidock, D.A. Towards next-generation treatment options to combat Plasmodium falciparum malaria. Nat Rev Microbiol 23, 178–191 (2025). https://doi.org/10.1038/s41579-024-01099-x
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DOI: https://doi.org/10.1038/s41579-024-01099-x
