Local Emergence in Amazonia of C580Y Mutants Associated with Artemisinin Resistance

Overview

Journal Elife

Specialty Biology

Date 2020 May 13

PMID 32394893

Citations 80

Authors

Luana C Mathieu

Horace Cox

Angela M Early

Sachel Mok

Yassamine Lazrek

Jeanne-Celeste Paquet

Maria-Paz Ade

Naomi W Lucchi

Quacy Grant

Venkatachalam Udhayakumar

Jean Sf Alexandre

Magalie Demar

Pascal Ringwald

Daniel E Neafsey

David A Fidock

Lise Musset

Affiliations

Soon will be listed here.

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.

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