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
ISSN
10986596
00664804
00664804
Other identifier(s)
2-s2.0-85119422974
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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
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
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.