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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Evolution of multidrug resistance in plasmodium falciparum: A longitudinal study of genetic resistance markers in the greater mekong subregion
Antimicrobial Agents and Chemotherapy, Volume 65, No. 12, Article e01121-21, Year 2021
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Description
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. © 2021 American Society for Microbiology. All rights reserved.
Authors & Co-Authors
Imwong, Mallika
Thailand, Nakhon Pathom
Mahidol University
Suwannasin, Kanokon
Thailand, Nakhon Pathom
Mahidol University
Srisutham, Suttipat
Thailand, Bangkok
Chulalongkorn University
Vongpromek, Ranitha
United Kingdom, Oxford
Worldwide Antimalarial Resistance Network
Promnarate, Cholrawee
United Kingdom, Oxford
Worldwide Antimalarial Resistance Network
Proux, Stéphane
Thailand, Nakhon Pathom
Mahidol University
Pongvongsa, Tiengkham
Laos, Savannakhet
Savannakhet Provincial Health Department
Nguon, Chea
Cambodia, Phnom Penh
Entomology
Miotto, Olivo
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Hinxton
Wellcome Sanger Institute
United Kingdom, Oxford
University of Oxford
Tripura, Rupam
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Hinxton
Wellcome Sanger Institute
Lek, Dysoley
Cambodia, Phnom Penh
Entomology
Peto, Thomas Julian
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Callery, James John
Thailand, Nakhon Pathom
Mahidol University
van der Pluijm, Rob W.
Thailand, Nakhon Pathom
Mahidol University
Amaratunga, Chanaki
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Mukaka, Mavuto F.J.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Von-Seidlein, Lorenz
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Mayxay, Mayfong
United Kingdom, Oxford
University of Oxford
Laos, Vientiane
Ministry of Health Laos
Thailand
Mahosot Hospital, Lao
Thuy-Nhien, Nguyen Thanh
United Kingdom, London
University College London Hospitals Nhs Foundation Trust
Newton, Paul N.
United Kingdom, Oxford
University of Oxford
Day, Nichloas P.J.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Ashley, Elizabeth A.
United Kingdom, Oxford
University of Oxford
Thailand
Mahosot Hospital, Lao
Nosten, François Henry
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Smithuis, Frank M.
Myanmar, Yangon
Myanmar Oxford Clinical Research Unit
United Kingdom, Oxford
University of Oxford
Dhorda, M. J.
Thailand, Nakhon Pathom
Mahidol University
Thailand, Bangkok
Chulalongkorn University
United Kingdom, Oxford
University of Oxford
White, Nicholas John
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Dondorp, A. M.
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 15
Authors: 27
Affiliations: 12
Identifiers
Doi:
10.1128/AAC.01121-21
ISSN:
00664804
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative