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

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 Africa 1–4 . Here we genotyped the P. falciparum K13 ( Pfkelch13 ) propeller domain, mutations in which can mediate artemisinin resistance 5,6 , in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda 7 . 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…

• UD
  U.S. Department of Defense

  Awards: W81XWH, W81XWH-19-1-0086, R01 AI109023
• BA
  Bill and Melinda Gates Foundation

  Awards: W81XWH-19-1-0086, OPP1140599, R01 AI109023
• WB
  World Bank Group
• WH
  World Health Organization
• RB
  Rwanda Biomedical Centre
• NI
  National Institutes of Health

  Awards: W81XWH-19-1-0086, AI109023, R01 AI109023, W81XWH