TY - JOUR TI - Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance AU - Mathieu, Luana C AU - Cox, Horace AU - Early, Angela M AU - Mok, Sachel AU - Lazrek, Yassamine AU - Paquet, Jeanne-Celeste AU - Ade, Maria-Paz AU - Lucchi, Naomi W AU - Grant, Quacy AU - Udhayakumar, Venkatachalam AU - Alexandre, Jean SF AU - Demar, Magalie AU - Ringwald, Pascal AU - Neafsey, Daniel E AU - Fidock, David A AU - Musset, Lise A2 - Soldati-Favre, Dominique A2 - Cui, Liwang VL - 9 PY - 2020 DA - 2020/05/12 SP - e51015 C1 - eLife 2020;9:e51015 DO - 10.7554/eLife.51015 UR - https://doi.org/10.7554/eLife.51015 AB - Antimalarial drug resistance has historically arisen through convergent de novo mutations in Plasmodium falciparum 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 pfk13 mutations, primarily C580Y. We report that mutant pfk13 has emerged independently in Guyana, with genome analysis indicating an evolutionary origin distinct from Southeast Asia. Pfk13 C580Y parasites were observed in 1.6% (14/854) of samples collected in Guyana in 2016–2017. Introducing pfk13 C580Y or R539T mutations by gene editing into local parasites conferred high levels of in vitro artemisinin resistance. In vitro growth competition assays revealed a fitness cost associated with these pfk13 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. KW - Guyana KW - artemisinin resistance KW - evolution KW - kelch 13 KW - South America KW - malaria JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -