Publication:
Evolution of multidrug resistance in plasmodium falciparum: A longitudinal study of genetic resistance markers in the greater mekong subregion

Issued Date

2021-12-01

Resource Type

Article

ISSN

10986596
00664804

DOI

10.1128/AAC.01121-21

Other identifier(s)

2-s2.0-85119422974

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Antimicrobial Agents and Chemotherapy. Vol.65, No.12 (2021)

Suggested Citation

Mallika Imwong, Kanokon Suwannasin, Suttipat Srisutham, Ranitha Vongpromek, Cholrawee Promnarate, Aungkana Saejeng, Aung Pyae Phyo, Stephane Proux, Tiengkham Pongvongsa, Nguon Chea, Olivo Miotto, Rupam Tripura, Chau Nguyen Hoang, Lek Dysoley, Nghia Ho Dang Trung, Thomas J. Peto, James J. Callery, Rob W. Van der Pluijm, Chanaki Amaratunga, Mavuto Mukaka, Lorenz Von Seidlein, Mayfong Mayxay, Nguyen Thanh Thuy-Nhien, Paul N. Newton, Nicholas P.J. Day, Elizabeth A. Ashley, Francois H. Nosten, Frank M. Smithuis, Mehul Dhorda, Nicholas J. White, Arjen M. Dondorp Evolution of multidrug resistance in plasmodium falciparum: A longitudinal study of genetic resistance markers in the greater mekong subregion. Antimicrobial Agents and Chemotherapy. Vol.65, No.12 (2021). doi:10.1128/AAC.01121-21 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/77477

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Title

Evolution of multidrug resistance in plasmodium falciparum: A longitudinal study of genetic resistance markers in the greater mekong subregion

Author(s)

Mallika Imwong
 Kanokon Suwannasin
 Suttipat Srisutham
 Ranitha Vongpromek
 Cholrawee Promnarate
 Aungkana Saejeng
 Aung Pyae Phyo
 Stephane Proux
 Tiengkham Pongvongsa
 Nguon Chea
 Olivo Miotto
 Rupam Tripura
 Chau Nguyen Hoang
 Lek Dysoley
 Nghia Ho Dang Trung
 Thomas J. Peto
 James J. Callery
 Rob W. Van der Pluijm
 Chanaki Amaratunga
 Mavuto Mukaka
 Lorenz Von Seidlein
 Mayfong Mayxay
 Nguyen Thanh Thuy-Nhien
 Paul N. Newton
 Nicholas P.J. Day
 Elizabeth A. Ashley
 Francois H. Nosten
 Frank M. Smithuis
 Mehul Dhorda
 Nicholas J. White
 Arjen M. Dondorp

Other Contributor(s)

Faculty of Tropical Medicine, Mahidol University
 Ministry of Health Laos
 Chulalongkorn University
 University College London Hospitals NHS Foundation Trust
 Thailand Ministry of Public Health
 Mahosot Hospital, Lao
 Nuffield Department of Medicine
 Wellcome Sanger Institute
 Myanmar Oxford Clinical Research Unit
 Entomology
 Savannakhet Provincial Health Department

Abstract

Increasing resistance in Plasmodium falciparum to artemisinins and their artemisinin combination therapy (ACT) partner drugs jeopardizes effective antimalarial treatment. Resistance is worst in the Greater Mekong subregion. Monitoring genetic markers of resistance can help to guide antimalarial therapy. Markers of resistance to artemisinins (PfKelch mutations), mefloquine (amplification of P. falciparum multidrug resistance-1 [PfMDR1]), and piperaquine (PfPlasmepsin2/3 amplification and specific P. falciparum chloroquine resistance transporter [PfCRT] mutations) were assessed in 6,722 P. falciparum samples from Vietnam, Lao People's Democratic Republic (PDR), Cambodia, Thailand, and Myanmar between 2007 and 2019. Against a high background prevalence of PfKelch mutations, PfMDR1 and PfPlasmepsin2/3 amplification closely followed regional drug pressures over time. PfPlasmepsin2/3 amplification preceded piperaquine resistance- associated PfCRT mutations in Cambodia and reached a peak prevalence of 23/28 (82%) in 2015. This declined to 57/156 (38%) after first-line treatment was changed from dihydroartemisinin-piperaquine to artesunate-mefloquine (ASMQ) between 2014 and 2017. The frequency of PfMDR1 amplification increased from 0/293 (0%) between 2012 and 2017 to 12/156 (8%) in 2019. Amplification of PfMDR1 and PfPlasmepsin2/3 in the same parasites was extremely rare (4/6,722 [0.06%]) and was dispersed over time. The mechanisms conferring mefloquine and piperaquine resistance may be counterbalancing. This supports the development of ASMQ plus piperaquine as a triple artemisinin combination therapy.

Keyword(s)

Medicine
 Pharmacology, Toxicology and Pharmaceutics

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URI

https://repository.li.mahidol.ac.th/handle/123456789/77477

Collections

Scopus 2021