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

Aline Uwimana | Eric Legrand | Barbara H Stokes | Jean-Louis Mangala Ndikumana | Marian Warsame | Noella Umulisa | Daniel Ngamije | Tharcisse Munyaneza | Jean-Baptiste Mazarati | Kaendi Munguti | Pascal Campagne | Alexis Criscuolo | Frédéric Ariey | Monique Murindahabi | Pascal Ringwald | David A Fidock | Aimable Mbituyumuremyi | Didier Menard
Nature medicine | 2020

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.

Pubmed ID: 32747827

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Associated grants

  • Agency: World Health Organization, International
    Id: 001
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI109023
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI106711

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