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泰国恶性疟原虫对磺胺多辛/乙胺嘧啶和氯喹耐药的分子标志物。

Molecular Markers for Sulfadoxine/Pyrimethamine and Chloroquine Resistance in Plasmodium falciparum in Thailand.

机构信息

Faculty of Allied Health Sciences, Thammasat University, Pathumthani, 12120, Thailand.

出版信息

Korean J Parasitol. 2022 Apr;60(2):109-116. doi: 10.3347/kjp.2022.60.2.109. Epub 2022 Apr 20.

Abstract

Drug resistance is an important problem hindering malaria elimination in tropical areas. Point mutations in Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes confer resistance to antifolate drug, sulfadoxine-pyrimethamine (SP) while P. falciparum chloroquine-resistant transporter (Pfcrt) genes caused resistance to chloroquine (CQ). Decline in Pfdhfr/Pfdhps and Pfcrt mutations after withdrawal of SP and CQ has been reported. The aim of present study was to investigate the prevalence of Pfdhfr, Pfdhps, and Pfcrt mutation from 2 endemic areas of Thailand. All of 200 blood samples collected from western area (Thai-Myanmar) and southern area (Thai-Malaysian) contained multiple mutations in Pfdhfr and Pfdhps genes. The most prevalent haplotypes for Pfdhfr and Pfdhps were quadruple and double mutations, respectively. The quadruple and triple mutations of Pfdhfr and Pfdhps were common in western samples, whereas low frequency of triple and double mutations was found in southern samples, respectively. The Pfcrt 76T mutation was present in all samples examined. Malaria isolated from 2 different endemic regions of Thailand had high mutation rates in the Pfdhfr, Pfdhps, and Pfcrt genes. These findings highlighted the fixation of mutant alleles causing resistance of SP and CQ in this area. It is necessary to monitor the re-emergence of SP and CQ sensitive parasites in this area.

摘要

耐药性是阻碍热带地区消除疟疾的一个重要问题。恶性疟原虫二氢叶酸还原酶(Pfdhfr)和二氢蝶酸合成酶(Pfdhps)基因的点突变使抗叶酸药物磺胺多辛-乙胺嘧啶(SP)产生耐药性,而恶性疟原虫氯喹耐药转运蛋白(Pfcrt)基因导致对氯喹(CQ)的耐药性。据报道,SP 和 CQ 停药后 Pfdhfr/Pfdhps 和 Pfcrt 突变率下降。本研究旨在调查来自泰国 2 个流行地区的 Pfdhfr、Pfdhps 和 Pfcrt 突变的流行情况。从泰国-缅甸西部和泰国-马来西亚南部两个流行地区采集的 200 份血样均存在 Pfdhfr 和 Pfdhps 基因的多重突变。Pfdhfr 和 Pfdhps 最常见的单倍型分别为四重和双重突变。西部样本中常见四重和三重 Pfdhfr 和 Pfdhps 突变,而南部样本中三重和双重突变的频率较低。所有检测的样本均存在 Pfcrt 76T 突变。从泰国 2 个不同流行地区分离的疟疾在 Pfdhfr、Pfdhps 和 Pfcrt 基因中具有较高的突变率。这些发现强调了该地区 SP 和 CQ 耐药突变等位基因的固定。有必要监测该地区 SP 和 CQ 敏感寄生虫的再次出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731a/9058275/9b698908a461/kjp-60-2-109f1.jpg

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