Local emergence in Amazonia of Plasmodium falciparum k13 C580Y mutants associated with in vitro artemisinin resistance
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 12, 2020
- Source ID
- 10.7554/elife.51015
Entities
People
- Angela M Early
- Daniel Neafsey
- David A. Fidock
- Horace Cox
- Jean Sf Alexandre
- Jeanne-Celeste Paquet
- Lise Musset
- Luana C Mathieu
- Magalie Demar
- Maria-paz Ade
- Naomi W Lucchi
- Pascal Ringwald
- Quacy Grant
- Sachel Mok
- Venkatachalam Udhayakumar
- Yassamine Lazrek
Organizations
- Agence Nationale de la Recherche
- Broad Institute
- Centers for Disease Control and Prevention
- Columbia University
- European Commission
- Gates Foundation
- Harvard University
- Human Frontier Science Program
- Ministry of Public Health
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Pan American Health Organization
- United States Department of Defense
- World Health Organization