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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51453
Title: Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study
Authors: William L. Hamilton
Roberto Amato
Rob W. van der Pluijm
Christopher G. Jacob
Huynh Hong Quang
Nguyen Thanh Thuy-Nhien
Tran Tinh Hien
Bouasy Hongvanthong
Keobouphaphone Chindavongsa
Mayfong Mayxay
Rekol Huy
Rithea Leang
Cheah Huch
Lek Dysoley
Chanaki Amaratunga
Seila Suon
Rick M. Fairhurst
Rupam Tripura
Thomas J. Peto
Yok Sovann
Podjanee Jittamala
Borimas Hanboonkunupakarn
Sasithon Pukrittayakamee
Nguyen Hoang Chau
Mallika Imwong
Mehul Dhorda
Ranitha Vongpromek
Xin Hui S. Chan
Richard J. Maude
Richard D. Pearson
T. Nguyen
Kirk Rockett
Eleanor Drury
Sónia Gonçalves
Nicholas J. White
Nicholas P. Day
Dominic P. Kwiatkowski
Arjen M. Dondorp
Olivo Miotto
Wellcome Trust Centre for Human Genetics
Harvard T.H. Chan School of Public Health
University of Oxford
National Institute of Allergy and Infectious Diseases
Cambridge University Hospitals NHS Foundation Trust
Mahidol University
Nuffield Department of Clinical Medicine
Wellcome Sanger Institute
Asia Regional Centre
Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU)
Royal Society of Thailand
University of Health Sciences
Provincial Health Department
Institute of Malariology, Parasitology and Entomology
Centre of Malariology
Oxford University Clinical Research Unit
National Center for Parasitology, Entomology and Malaria Control
Keywords: Medicine
Issue Date: 1-Sep-2019
Citation: The Lancet Infectious Diseases. Vol.19, No.9 (2019), 943-951
Abstract: © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: A multidrug-resistant co-lineage of Plasmodium falciparum malaria, named KEL1/PLA1, spread across Cambodia in 2008–13, causing high rates of treatment failure with the frontline combination therapy dihydroartemisinin-piperaquine. Here, we report on the evolution and spread of KEL1/PLA1 in subsequent years. Methods: For this genomic epidemiology study, we analysed whole genome sequencing data from P falciparum clinical samples collected from patients with malaria between 2007 and 2018 from Cambodia, Laos, northeastern Thailand, and Vietnam, through the MalariaGEN P falciparum Community Project. Previously unpublished samples were provided by two large-scale multisite projects: the Tracking Artemisinin Resistance Collaboration II (TRAC2) and the Genetic Reconnaissance in the Greater Mekong Subregion (GenRe-Mekong) project. By investigating genome-wide relatedness between parasites, we inferred patterns of shared ancestry in the KEL1/PLA1 population. Findings: We analysed 1673 whole genome sequences that passed quality filters, and determined KEL1/PLA1 status in 1615. Before 2009, KEL1/PLA1 was only found in western Cambodia; by 2016–17 its prevalence had risen to higher than 50% in all of the surveyed countries except for Laos. In northeastern Thailand and Vietnam, KEL1/PLA1 exceeded 80% of the most recent P falciparum parasites. KEL1/PLA1 parasites maintained high genetic relatedness and low diversity, reflecting a recent common origin. Several subgroups of highly related parasites have recently emerged within this co-lineage, with diverse geographical distributions. The three largest of these subgroups (n=84, n=79, and n=47) mostly emerged since 2016 and were all present in Cambodia, Laos, and Vietnam. These expanding subgroups carried new mutations in the crt gene, which arose on a specific genetic background comprising multiple genomic regions. Four newly emerging crt mutations were rare in the early period and became more prevalent by 2016–17 (Thr93Ser, rising to 19·8%; His97Tyr to 11·2%; Phe145Ile to 5·5%; and Ile218Phe to 11·1%). Interpretation: After emerging and circulating for several years within Cambodia, the P falciparum KEL1/PLA1 co-lineage diversified into multiple subgroups and acquired new genetic features, including novel crt mutations. These subgroups have rapidly spread into neighbouring countries, suggesting enhanced fitness. These findings highlight the urgent need for elimination of this increasingly drug-resistant parasite co-lineage, and the importance of genetic surveillance in accelerating malaria elimination efforts. Funding: Wellcome Trust, Bill & Melinda Gates Foundation, UK Medical Research Council, and UK Department for International Development.
URI: http://repository.li.mahidol.ac.th/dspace/handle/123456789/51453
metadata.dc.identifier.url: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85069647774&origin=inward
ISSN: 14744457
14733099
Appears in Collections:Scopus 2019

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