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Title: Origins of the current outbreak of multidrug-resistant malaria in southeast Asia: a retrospective genetic study
Authors: Roberto Amato
Richard D. Pearson
Jacob Almagro-Garcia
Chanaki Amaratunga
Pharath Lim
Seila Suon
Sokunthea Sreng
Eleanor Drury
Jim Stalker
Olivo Miotto
Rick M. Fairhurst
Dominic P. Kwiatkowski
University of Oxford
National Institute of Allergy and Infectious Diseases
Mahidol University
Wellcome Sanger Institute
National Center for Parasitology, Entomology and Malaria Control
Keywords: Medicine
Issue Date: 1-Mar-2018
Citation: The Lancet Infectious Diseases. Vol.18, No.3 (2018), 337-345
Abstract: © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Antimalarial resistance is rapidly spreading across parts of southeast Asia where dihydroartemisinin–piperaquine is used as first-line treatment for Plasmodium falciparum malaria. The first published reports about resistance to antimalarial drugs came from western Cambodia in 2013. Here, we analyse genetic changes in the P falciparum population of western Cambodia in the 6 years before those reports. Methods: We analysed genome sequence data on 1492 P falciparum samples from 11 locations across southeast Asia, including 464 samples collected in western Cambodia between 2007 and 2013. Different epidemiological origins of resistance were identified by haplotypic analysis of the kelch13 artemisinin resistance locus and the plasmepsin 2–3 piperaquine resistance locus. Findings: We identified more than 30 independent origins of artemisinin resistance, of which the KEL1 lineage accounted for 140 (91%) of 154 parasites resistant to dihydroartemisinin–piperaquine. In 2008, KEL1 combined with PLA1, the major lineage associated with piperaquine resistance. By 2013, the KEL1/PLA1 co-lineage had reached a frequency of 63% (24/38) in western Cambodia and had spread to northern Cambodia. Interpretation: The KEL1/PLA1 co-lineage emerged in the same year that dihydroartemisinin–piperaquine became the first-line antimalarial drug in western Cambodia and spread rapidly thereafter, displacing other artemisinin-resistant parasite lineages. These findings have important implications for management of the global health risk associated with the current outbreak of multidrug-resistant malaria in southeast Asia. Funding: Wellcome Trust, Bill & Melinda Gates Foundation, Medical Research Council, UK Department for International Development, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases.
ISSN: 14744457
Appears in Collections:Scopus 2018

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