Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance

Antimalarial drug resistance has historically arisen through convergent mutations in parasite populations in Southeast Asia and South America. For the past decade in Southeast Asia, artemisinins, the core component of first-line antimalarial therapies, have experienced delayed parasite clearance associated with several mutations, primarily C580Y. We report that mutant has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016-2017. Introducing C580Y or R539T mutations by gene editing into local parasites conferred high levels of artemisinin resistance. growth competition assays revealed a fitness cost associated with these variants, potentially explaining why these resistance alleles have not increased in frequency more quickly in South America. These data place local malaria control efforts at risk in the Guiana Shield.