Longitudinal surveillance of drug resistance in Plasmodium falciparum isolates from the China-Myanmar border reveals persistent circulation of multidrug resistant parasites

作者：Yao Bai, Jiaqi Zhang, Jinting Geng, Shiling Xu, Shuang Deng, Weilin Zeng, Zenglei Wang, Huguette Gaelle Ngassa Mbenda, Jie Zhang, Na Li, Yanrui Wu, Cuiying Li, Huae Liu, Yonghua Ruan, Yaming Cao, Zhaoqing Yang, Liwang Cui · 发表于：International Journal for Parasitology Drugs and Drug Resistance · 年份：2018 · DOI：10.1016/j.ijpddr.2018.05.003 · 被引用次数：29 · 研究领域：Malaria Research and Control、Mosquito-borne diseases and control、Drug Transport and Resistance Mechanisms

Multidrug-resistant Plasmodium falciparum in the Greater Mekong Subregion of Southeast Asia is a major threat to malaria elimination and requires close surveillance. In this study, we collected 107 longitudinal clinical samples of P. falciparum in 2007–2012 from the malaria hypoendemic region of the China-Myanmar border and measured their in vitro susceptibilities to 10 antimalarial drugs. Overall, parasites had significantly different IC50 values to all the drugs tested as compared to the reference 3D7 strain. Parasites were also genotyped in seven genes that were associated with drug resistance including pfcrt, pfmdr1, pfmrp1, pfdhfr, pfdhps, pfnhe1, and PfK13 genes. Despite withdrawal of chloroquine and antifolates from treating P. falciparum, parasites remained highly resistant to these drugs and mutations in pfcrt, pfdhfr, and pfdhps genes were highly prevalent and almost reached fixation in the study parasite population. Except for pyronaridine, quinine and lumefantrine, all other tested drugs exhibited significant temporal variations at least between some years, but only chloroquine and piperaquine had a clear temporal trend of continuous increase of IC50s. For the pfmrp1 gene, several mutations were associated with altered sensitivity to a number of drugs tested including chloroquine, piperaquine, lumefantrine and dihydroartemisinin. The association of PfK13 mutations with resistance to multiple drugs suggests potential evolution of PfK13 mutations amid multidrug resi...