In vitro susceptibility of Plasmodium falciparum isolates from the China-Myanmar border area to artemisinins and correlation with K13 mutations

作者：Jie Zhang, Na Li, Faiza Amber Siddiqui, Shiling Xu, Jinting Geng, Jiaqi Zhang, Xi He, Luyi Zhao, Liang Pi, Yanmei Zhang, Cuiying Li, Xi Chen, Yanrui Wu, Jun Miao, Yaming Cao, Liwang Cui, Zhaoqing Yang · 发表于：International Journal for Parasitology Drugs and Drug Resistance · 年份：2019 · DOI：10.1016/j.ijpddr.2019.04.002 · 被引用次数：46 · 研究领域：Malaria Research and Control、Mosquito-borne diseases and control、Toxoplasma gondii Research Studies

Mutations in the Kelch domain of the K13 gene (PF3D7_1343700) were previously associated with artemisinin resistance in Plasmodium falciparum . This study followed the dynamics of the K13 polymorphisms in P. falciparum parasites from the China-Myanmar border area obtained in 2007–2016, and their in vitro sensitivities to artesunate (AS) and dihydroartemisinin (DHA). The 50% effective concentration (EC 50 72h ) values of 133 culture-adapted field isolates to AS and DHA, measured by the conventional 72 h SYBR Green I-based assay, varied significantly among the parasites from different years; all were significantly higher than that of the reference strain 3D7. Compared with parasites from 2007 to 2008, ring survival rates almost doubled in parasites obtained in later years. Sequencing the full-length K13 genes identified 11 point mutations present in 85 (63.9%) parasite isolates. F446I was the predominant (55/133) variant, and its frequency was increased from 17.6% (3/17) in 2007 to 55.9% (19/34) in 2014–2016. No wild-type (WT) Kelch domain sequences were found in the 34 samples obtained from 2014 to 2016. In the 2014–2016 samples, a new mutation (G533S) appeared and reached 44.1% (15/34). Collectively, parasites with the Kelch domain mutations (after amino acid 440) had significantly higher ring survival rates than the WT parasites. Individually, F446I, G533S and A676D showed significantly higher ring survival rates than the WT. Although the drug sensitivity phenotypes measured...