Publication:
Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study

2

Issued Date

2019-09-01

Resource Type

Article

ISSN

14744457
14733099

DOI

10.1016/S1473-3099(19)30392-5

Other identifier(s)

2-s2.0-85069647774

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Infectious Diseases. Vol.19, No.9 (2019), 943-951

Suggested Citation

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 Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study. The Lancet Infectious Diseases. Vol.19, No.9 (2019), 943-951. doi:10.1016/S1473-3099(19)30392-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/51453

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Title

Evolution and expansion of multidrug-resistant malaria in southeast Asia: a genomic epidemiology study

Author(s)

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

Other Contributor(s)

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

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.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/51453

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Scopus 2019