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

By A. Uwimana, E. Legrand, Barbara H. Stokes, Jean-Louis Mangala Ndikumana, M. Warsame, Noella Umulisa, D. Ngamije, Tharcisse Munyaneza, J. Mazarati, Kaendi J. Munguti and 8 more. Nature Medicine, 2020

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Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1–4. 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. Identification in Rwanda of mutations in Plasmodium falciparum capable of conferring in vitro resistance to artemisinin, an essential medicine for the treatment of malaria, underscore the crucial need for surveillance in Africa to safeguard efficacy of life-saving therapies.

Subfields: Computational Theory and Mathematics, Epidemiology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/e6971c45334fb6f4de767580ee0b1b7d242f74fc

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Citations in the corpus

Plasmodium 6-Cysteine Proteins: Functional Diversity, Transmission-Blocking Antibodies and Structural Scaffolds (2022, background): “In addition, resistance to anti-malarial drugs is a growing issue, with recent reports of resistance to first-line drugs in Africa (Uwimana et al., 2020; Balikagala et al., 2021; Uwimana et al., 2021), the region that accounts for approximately 95% of cases and 96% of deaths (WHO, 2021).”