National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, WHO Collaborating Center for Tropical Diseases, National Centre for International Research on Tropical Diseases, NHC Key Laboratory of Parasite and Vector Biology (National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention), Shanghai, 200025, China.
Yunnan Institute of Parasitic Diseases, Puer, 665000, China.
Front Med. 2022 Feb;16(1):83-92. doi: 10.1007/s11684-021-0894-x. Epub 2022 Mar 7.
The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.
恶性疟原虫二氢叶酸还原酶（dhfr）和二氢蝶酸合成酶（dhps）基因作为抗叶酸耐药相关基因，用于耐药性监测。本研究收集了 2009 年至 2019 年中国不同地理来源的 375 株恶性疟原虫分离株，用于检测 Pvdhfr 和 Pvdhps。大多数分离株携带 Pvdhfr（94.5%）和 Pvdhps（68.2%）的突变型等位基因。最常见的点突变是 Pvdhfr 的 S117T/N（77.7%）和 Pvdhps 的 A383G（66.8%）。在 Pvdhfr 中鉴定出 9 个残基的氨基酸变化。在 16 种不同的 Pvdhfr 单倍型中，57、58、61 和 117 位的四重突变单倍型最为常见（57.4%）。在 Pvdhps 中检测到 6 个密码子的突变，双突变 A383G/A553G 最为常见（39.3%）。在中国，Pvdhfr 的突变发生率和多样性均高于 Pvdhps。来自云南的大多数分离株携带多种突变单倍型，而来自温带地区和海南岛的大多数样本携带野生型或单一突变型。本研究表明，中国不同地区恶性疟原虫寄生虫的抗叶酸耐药水平不同，分子标记物可用于快速监测耐药性。研究结果为更新国家药物政策和治疗指南提供了依据。
