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Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic

Abstract

The global adoption of artemisinin-based combination therapies (ACTs) in the early 2000s heralded a new era in effectively treating drug-resistant Plasmodium falciparum malaria. However, several Southeast Asian countries have now reported the emergence of parasites that have decreased susceptibility to artemisinin (ART) derivatives and ACT partner drugs, resulting in increasing rates of treatment failures. Here we review recent advances in understanding how antimalarials act and how resistance develops, and discuss new strategies for effectively combatting resistance, optimizing treatment and advancing the global campaign to eliminate malaria.

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Figure 1: Plasmodium's life cycle and its relationship to drug resistance.
Figure 2: Molecular targets of and mechanisms of resistance to major antimalarial drugs.
Figure 3: History of the introduction of the principal antimalarials and of the first emergence of resistance in the field.
Figure 4: Emergence and spread of P. falciparum resistance to CQ, pyrimethamine and ART derivatives.

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Acknowledgements

D.A.F. was supported by US National Institutes of Health (NIH) R01 grants AI50234, AI109023 and AI124678.

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Supplementary information

Supplementary Table 1

Antimalarial drugs and associated clinical and molecular markers of resistance in Plasmodium falciparum asexual blood stage parasites. (XLSX 22 kb)

Supplementary Table 2

In vitro resistance to experimental antimalarials in Plasmodium falciparum asexual blood stage parasites. (XLSX 14 kb)

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Blasco, B., Leroy, D. & Fidock, D. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat Med 23, 917–928 (2017). https://doi.org/10.1038/nm.4381

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