Saralamba Naowarat, Nakeesathit Supatchara, Mayxay Mayfong, Newton Paul N, Osorio Lyda, Kim Jung-Ryong, White Nicholas J, Day Nicholas P J, Dondorp Arjen M, Imwong Mallika
Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Malar J. 2016 Sep 21;15(1):484. doi: 10.1186/s12936-016-1543-8.
Non-synonymous mutations in dhfr and dhps genes in Plasmodium vivax are associated with sulfadoxine-pyrimethamine (SP) resistance. The present study aimed to assess the prevalence of point mutations in P. vivax dhfr (pvdhfr) and P. vivax dhps (pvdhps) genes in three countries: Lao PDR, India and Colombia.
Samples from 203 microscopically diagnosed vivax malaria were collected from the three countries. Five codons at positions 13, 57, 58, 61, and 117 of pvdhfr and two codons at positions 383 and 553 of pvdhps were examined by polymerase chain reaction-restriction fragment length polymorphism methodology.
The largest number of 58R/117 N double mutations in pvdhfr was observed in Colombia (94.3 %), while the corresponding wild-type amino acids were found at high frequencies in Lao PDR during 2001-2004 (57.8 %). Size polymorphism analysis of the tandem repeats within pvdhfr revealed that 74.3 % of all the isolates carried the type B variant. Eighty-nine per cent of all the isolates examined carried wild-type pvdhps A383 and A553.
Although SP is not generally used to treat P. vivax infections, mutations in dhfr and dhps that confer antifolate resistance in P. vivax are common. The data strongly suggest that, when used primarily to treat falciparum malaria, SP can exert a substantial selective pressure on P. vivax populations, and this can lead to point mutations in dhfr and dhps. Accurate data on the global geographic distribution of dhfr and dhps genotypes should help to inform anti-malarial drug-use policies.
间日疟原虫二氢叶酸还原酶（dhfr）和二氢蝶酸合酶（dhps）基因中的非同义突变与磺胺多辛-乙胺嘧啶（SP）耐药性相关。本研究旨在评估老挝人民民主共和国、印度和哥伦比亚这三个国家间日疟原虫dhfr（pvdhfr）和间日疟原虫dhps（pvdhps）基因点突变的流行情况。
从这三个国家收集了203份经显微镜诊断为间日疟的样本。采用聚合酶链反应-限制性片段长度多态性方法检测pvdhfr第13、57、58、61和117位的五个密码子以及pvdhps第383和553位的两个密码子。
在哥伦比亚观察到pvdhfr中58R/117N双突变的数量最多（94.3%），而在2001 - 2004年期间，老挝人民民主共和国相应的野生型氨基酸频率较高（57.8%）。pvdhfr内串联重复序列的大小多态性分析显示，所有分离株中有74.3%携带B型变体。所有检测的分离株中有89%携带野生型pvdhps A383和A553。
尽管SP一般不用于治疗间日疟感染，但间日疟原虫中赋予抗叶酸耐药性的dhfr和dhps突变很常见。数据有力地表明，当SP主要用于治疗恶性疟时，它可对间日疟原虫群体施加巨大的选择压力，这可能导致dhfr和dhps的点突变。关于dhfr和dhps基因型全球地理分布的准确数据应有助于为抗疟药物使用政策提供信息。
