Bareng Alison Paolo, Espino Fe Esperanza, Chaijaroenkul Wanna, Na-Bangchang Kesara
Research Institute for Tropical Medicine-Department of Health, Muntinlupa City, Philippines; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12121, Thailand.
Research Institute for Tropical Medicine-Department of Health, Muntinlupa City, Philippines.
Acta Trop. 2018 Apr;180:81-87. doi: 10.1016/j.actatropica.2018.01.006. Epub 2018 Jan 17.
The emergence of drug-resistant Plasmodium vivax poses problems for malaria control and elimination in some parts of the world, especially in developing countries where individuals are routinely exposed to the infection. The aim of this study was to determine the single nucleotide polymorphisms (SNPs) in dihydropteroate synthase (pvdhps) and dihydrofolate reductase (pvdhfr) genes associated with sulfadoxine-pyrimethamine (SP) drug resistance among P. vivax isolates collected in Palawan, Philippines. Genetic polymorphisms of pvdhps and pvdhfr were analysed by nested PCR. Analysis at specific codons IPFSTSI associated with pyrimethamine resistance in the pvdhfr gene revealed that most of the samples (66/87, 75.9%) carried double mutation at positions IPFRTNI, while only 18.4% (16/87) of the isolates carried the wild-type haplotype (IPFSTSI). For the pvdhps gene, the codons involved in sulfadoxine resistance SAKAV were investigated. Single mutation at position SGKAV was most observed in 68.0% (68/100) of the samples, whereas wild-type haplotype was found in 26.0% (26/100) of samples. The pvdhps and pvdhfr combination SAKAV/IPFSTSI (wild-type), SGKAV/IPFRTNI, and SAKAV-IPFRTNI were the most frequently observed combination haplotypes from the three study sites. The information on molecular markers associated with antifolate drug-resistance could help better understanding ofthe molecular epidemiology and situation of SP resistant P. vivax malaria in the country. Continuous surveillance of these genetic markers is necessary to monitor the evolution of SP resistance in the Philippines.
抗药间日疟原虫的出现给世界上一些地区的疟疾控制和消除带来了问题，尤其是在个人经常接触该感染的发展中国家。本研究的目的是确定在菲律宾巴拉望收集的间日疟原虫分离株中，与磺胺多辛 - 乙胺嘧啶（SP）耐药性相关的二氢蝶酸合酶（pvdhps）和二氢叶酸还原酶（pvdhfr）基因中的单核苷酸多态性（SNP）。通过巢式PCR分析pvdhps和pvdhfr的基因多态性。对pvdhfr基因中与乙胺嘧啶耐药性相关的特定密码子IPFSTSI进行分析，结果显示大多数样本（66/87，75.9%）在IPFRTNI位点携带双突变，而只有18.4%（16/87）的分离株携带野生型单倍型（IPFSTSI）。对于pvdhps基因，研究了与磺胺多辛耐药性相关的SAKAV密码子。在68.0%（68/100）的样本中最常观察到SGKAV位点的单突变，而在26.0%（26/100）的样本中发现了野生型单倍型。pvdhps和pvdhfr组合SAKAV/IPFSTSI（野生型）、SGKAV/IPFRTNI和SAKAV - IPFRTNI是三个研究地点最常观察到的组合单倍型。与抗叶酸药物耐药性相关的分子标记信息有助于更好地了解该国间日疟原虫疟疾的分子流行病学和SP耐药情况。持续监测这些遗传标记对于监测菲律宾SP耐药性的演变是必要的。
