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Elife DOI:10.7554/eLife.51015

Local emergence in Amazonia of C580Y mutants associated with artemisinin resistance.

Publication TypeJournal Article
Year of Publication2020
AuthorsMathieu, LC, Cox, H, Early, AM, Mok, S, Lazrek, Y, Paquet, J-C, Ade, M-P, Lucchi, NW, Grant, Q, Udhayakumar, V, Alexandre, JSf, Demar, M, Ringwald, P, Neafsey, DE, Fidock, DA, Musset, L
JournalElife
Volume9
Date Published2020 May 12
ISSN2050-084X
Abstract

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.

DOI10.7554/eLife.51015
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/32394893?dopt=Abstract

Alternate JournalElife
PubMed ID32394893
PubMed Central IDPMC7217694
Grant ListR37 AI50234 / NH / NIH HHS / United States
U19AI110818 / / National Institute of Allergy and Infectious Diseases /
Global Malaria Program / WHO_ / World Health Organization / International
OPP1201387 / / Bill and Melinda Gates Foundation /
Long-Term Fellowship / / Human Frontier Science Program /
R37 AI050234 / AI / NIAID NIH HHS / United States
R01 124678 / NH / NIH HHS / United States
ANR-10-LABX-25-01 / / Agence Nationale de la Recherche /
R01 AI124678 / AI / NIAID NIH HHS / United States
R01 AI109023 / AI / NIAID NIH HHS / United States
NRC for malaria / / Sante Publique France /
R01 AI109023 / NH / NIH HHS / United States
W81XWH1910086 / / U.S. Department of Defense /
Synergie GY0012082 / / European Commission /