Publication:
Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study

Issued Date

2020-01-01

Resource Type

Article

File Type

video/youtube

ISSN

14744457
14733099

DOI

10.1016/S1473-3099(20)30228-0

Other identifier(s)

2-s2.0-85088801479

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

The Lancet Infectious Diseases. (2020)

Suggested Citation

Mallika Imwong, Mehul Dhorda, Kyaw Myo Tun, Aung Myint Thu, Aung Pyae Phyo, Stephane Proux, Kanokon Suwannasin, Chanon Kunasol, Suttipat Srisutham, Jureeporn Duanguppama, Ranitha Vongpromek, Cholrawee Promnarate, Aungkana Saejeng, Nardlada Khantikul, Rungniran Sugaram, Supinya Thanapongpichat, Nongyao Sawangjaroen, Kreepol Sutawong, Kay Thwe Han, Ye Htut, Khin Linn, Aye Aye Win, Tin M. Hlaing, Rob W. van der Pluijm, Mayfong Mayxay, Tiengkham Pongvongsa, Koukeo Phommasone, Rupam Tripura, Thomas J. Peto, Lorenz von Seidlein, Chea Nguon, Dysoley Lek, Xin Hui S. Chan, Huy Rekol, Rithea Leang, Cheah Huch, Dominic P. Kwiatkowski, Olivo Miotto, Elizabeth A. Ashley, Myat Phone Kyaw, Sasithon Pukrittayakamee, Nicholas P.J. Day, Arjen M. Dondorp, Frank M. Smithuis, Francois H. Nosten, Nicholas J. White Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study. The Lancet Infectious Diseases. (2020). doi:10.1016/S1473-3099(20)30228-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/58342

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Title

Molecular epidemiology of resistance to antimalarial drugs in the Greater Mekong subregion: an observational study

Author(s)

Mallika Imwong
 Mehul Dhorda
 Kyaw Myo Tun
 Aung Myint Thu
 Aung Pyae Phyo
 Stephane Proux
 Kanokon Suwannasin
 Chanon Kunasol
 Suttipat Srisutham
 Jureeporn Duanguppama
 Ranitha Vongpromek
 Cholrawee Promnarate
 Aungkana Saejeng
 Nardlada Khantikul
 Rungniran Sugaram
 Supinya Thanapongpichat
 Nongyao Sawangjaroen
 Kreepol Sutawong
 Kay Thwe Han
 Ye Htut
 Khin Linn
 Aye Aye Win
 Tin M. Hlaing
 Rob W. van der Pluijm
 Mayfong Mayxay
 Tiengkham Pongvongsa
 Koukeo Phommasone
 Rupam Tripura
 Thomas J. Peto
 Lorenz von Seidlein
 Chea Nguon
 Dysoley Lek
 Xin Hui S. Chan
 Huy Rekol
 Rithea Leang
 Cheah Huch
 Dominic P. Kwiatkowski
 Olivo Miotto
 Elizabeth A. Ashley
 Myat Phone Kyaw
 Sasithon Pukrittayakamee
 Nicholas P.J. Day
 Arjen M. Dondorp
 Frank M. Smithuis
 Francois H. Nosten
 Nicholas J. White

Other Contributor(s)

Shoklo Malaria Research Unit
 Thailand Ministry of Public Health
 Mahosot Hospital, Lao
 Mahidol University
 Nuffield Department of Medicine
 Prince of Songkla University
 Wellcome Sanger Institute
 University of Oxford Medical Sciences Division
 Myanmar Health Network Organization
 University of Health Sciences
 Myanmar Oxford Clinical Research Unit
 University of Medicine 1
 Ministry of Health and Sports
 Medical Action Myanmar
 Defence Services Medical Academy
 Buntharik Hospital
 Defence Services Medical Research Centre
 Savannakhet Provincial Health Department
 Royal Society of Thailand
 Worldwide Antimalarial Resistance Network
 National Center for Parasitology, Entomology and Malaria Control
 Office of Disease Prevention and Control

Abstract

© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: The Greater Mekong subregion is a recurrent source of antimalarial drug resistance in Plasmodium falciparum malaria. This study aimed to characterise the extent and spread of resistance across this entire region between 2007 and 2018. Methods: P falciparum isolates from Myanmar, Thailand, Laos, and Cambodia were obtained from clinical trials and epidemiological studies done between Jan 1, 2007, and Dec 31, 2018, and were genotyped for molecular markers (pfkelch, pfcrt, pfplasmepsin2, and pfmdr1) of antimalarial drug resistance. Genetic relatedness was assessed using microsatellite and single nucleotide polymorphism typing of flanking sequences around target genes. Findings: 10 632 isolates were genotyped. A single long pfkelch Cys580Tyr haplotype (from −50 kb to +31·5 kb) conferring artemisinin resistance (PfPailin) now dominates across the eastern Greater Mekong subregion. Piperaquine resistance associated with pfplasmepsin2 gene amplification and mutations in pfcrt downstream of the Lys76Thr chloroquine resistance locus has also developed. On the Thailand–Myanmar border a different pfkelch Cys580Tyr lineage rose to high frequencies before it was eliminated. Elsewhere in Myanmar the Cys580Tyr allele remains widespread at low allele frequencies. Meanwhile a single artemisinin-resistant pfkelch Phe446Ile haplotype has spread across Myanmar. Despite intense use of dihydroartemisinin–piperaquine in Kayin state, eastern Myanmar, both in treatment and mass drug administrations, no selection of piperaquine resistance markers was observed. pfmdr1 amplification, a marker of resistance to mefloquine, remains at low prevalence across the entire region. Interpretation: Artemisinin resistance in P falciparum is now prevalent across the Greater Mekong subregion. In the eastern Greater Mekong subregion a multidrug resistant P falciparum lineage (PfPailin) dominates. In Myanmar a long pfkelch Phe446Ile haplotype has spread widely but, by contrast with the eastern Greater Mekong subregion, there is no indication of artemisinin combination therapy (ACT) partner drug resistance from genotyping known markers, and no evidence of spread of ACT resistant P falciparum from the east to the west. There is still a window of opportunity to prevent global spread of ACT resistance. Funding: Thailand Science Research and Innovation, Initiative 5%, Expertise France, Wellcome Trust.

Keyword(s)

Medicine

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/58342

Collections

Scopus 2020