Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana; Ecole Doctorale n°587, Diversités, Santé, et Développement en Amazonie, Université de Guyane, Cayenne, French Guiana
Horace Cox
Ministry of Public Health, Georgetown, Guyana
Angela M Early
Broad Institute of MIT and Harvard, Cambridge, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United States
Yassamine Lazrek
Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United States
Maria-Paz Ade
Department of Communicable Diseases and Environmental Determinants of Health, Pan American Health Organization/World Health Organization, Washington, United States
Naomi W Lucchi
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, United States
Quacy Grant
Ministry of Public Health, Georgetown, Guyana
Venkatachalam Udhayakumar
Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, United States
Jean SF Alexandre
Pan American Health Organization, Georgetown, Guyana
Magalie Demar
Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Andrée Rosemon, Cayenne, French Guiana; Ecosystèmes Amazoniens et Pathologie Tropicale (EPAT), EA3593, Université de Guyane, Cayenne, French Guiana
Pascal Ringwald
Global Malaria Program, World Health Organization, Geneva, Switzerland
Broad Institute of MIT and Harvard, Cambridge, United States; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, United States
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, United States; Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, United States
Laboratoire de parasitologie, Centre Nationale de Référence du Paludisme, World Health Organization Collaborating Center for surveillance of antimalarial drug resistance, Institut Pasteur de la Guyane, Cayenne, French Guiana
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.
