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Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

Uwimana, A. et al. (2020) Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nature Medicine, 26(10), pp. 1602-1608. (doi: 10.1038/s41591-020-1005-2) (PMID:32747827) (PMCID:PMC7541349)

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Abstract

Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1,2,3,4. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance5,6, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda7. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stokes, Ms Barbara
Authors: Uwimana, A., Legrand, E., Stokes, B. H., Ndikumana, J.-L. M., Warsame, M., Umulisa, N., Ngamije, D., Munyaneza, T., Mazarati, J.-B., Munguti, K., Campagne, P., Criscuolo, A., Ariey, F., Murindahabi, M., Ringwald, P., Fidock, D. A., Mbituyumuremyi, A., and Menard, D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Nature Medicine
Publisher:Nature Research
ISSN:1078-8956
ISSN (Online):1546-170X
Published Online:03 August 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Nature Medicine 26(10): 1602-1608
Publisher Policy:Reproduced under a Creative Commons License
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