Molecular Surveillance and in vitro Drug Sensitivity Study of Plasmodium falciparum Isolates from the China-Myanmar Border

The emergence and spread of resistance in to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of from the China-Myanmar border in 2014-2016, adapted these parasites to continuous cultur...

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Bibliographic Details
Published in:The American journal of tropical medicine and hygiene 2020-09, Vol.103 (3), p.1100-1106
Main Authors: Wang, Siqi, Xu, Shiling, Geng, Jinting, Si, Yu, Zhao, Hui, Li, Xinxin, Yang, Qi, Zeng, Weilin, Xiang, Zheng, Chen, Xi, Zhang, Yanmei, Li, Cuiying, Kyaw, Myat Phone, Cui, Liwang, Yang, Zhaoqing
Format: Article
Language:English
Subjects:
Antimalarials - pharmacology
Artemisinins - pharmacology
China - epidemiology
Chloroquine - pharmacology
Dihydrofolate reductase
Drug Resistance - genetics
Epidemiological Monitoring
Erythrocytes
Humans
Lumefantrine - pharmacology
Malaria, Falciparum - drug therapy
Malaria, Falciparum - epidemiology
Malaria, Falciparum - parasitology
Mefloquine - pharmacology
Membrane Transport Proteins - genetics
Mutation
Myanmar - epidemiology
Parasites
Parasitic Sensitivity Tests
Plasmodium falciparum - drug effects
Plasmodium falciparum - genetics
Pyrimethamine - pharmacology
Quinine - pharmacology
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Summary:The emergence and spread of resistance in to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of from the China-Myanmar border in 2014-2016, adapted these parasites to continuous culture, and performed in vitro drug assays on seven antimalarial drugs. Data for 23 parasites collected in 2010 and 2012 from the same area reported in an early study were used to assess longitudinal changes in drug sensitivity. Parasites remained highly resistant to chloroquine (CQ) and pyrimethamine, whereas they were generally sensitive to mefloquine (MFQ), lumefantrine (LMF), naphthoquine (NQ), and pyronaridine (PND). Parasites showed a similar temporal trend in sensitivity to CQ, NQ, and PND, with gradual reduction in the half-maximal inhibitory concentrations (IC s) after 2012. The IC s to the aminoalcohol drugs MFQ, LMF, and quinine (QN) all significantly declined in 2014, followed by various degrees of increase in 2016. Pyrimethamine displayed a continuous increase in IC over the years. The Dd2-like mutations were fixed or nearly fixed in the parasite population. The F1226Y mutation was detected in 80% parasites in 2016 and associated with reduced sensitivity to LMF and QN ( < 0.05). The N51I in and K540E/N and A581G in that are associated with antifolate resistance were either fixed or were approaching fixation in recent years. This study provides an updated picture and temporal trend of antimalarial drug resistance in the China-Myanmar border region, which will serve as a reference for antimalarial treatment.
ISSN:0002-9637
1476-1645
DOI:10.4269/ajtmh.20-0235