Tracking Origins and Spread of Sulfadoxine-Resistant Plasmodium falciparum dhps Alleles in Thailand
Tracking Origins and Spread of Sulfadoxine-Resistant Plasmodium falciparum dhps Alleles in Thailand
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DOI：
10.1128/aac.00691-10
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Udhayakumar, Venkatachalam
中科院分区：
文献类型：
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作者：
Alam, Md Tauqeer;Vinayak, Sumiti;Udhayakumar, Venkatachalam
抗药性恶性疟原虫的出现和传播一直是全世界控制疟疾的主要障碍。早期的研究表明，与氯喹（CQ）耐药性相似，恶性疟原虫对乙胺嘧啶的高水平耐药性在全球范围内独立起源4至5次，其中一次起源于泰国-柬埔寨边境。在这项研究中，我们描述的起源和传播硫代嘌呤抗性赋予二氢蝶酸合酶（dhps）等位基因在泰国。对从沿着缅甸、柬埔寨和马来西亚边境的11个泰国省收集的恶性疟原虫分离株的dhps突变和侧翼微卫星位点进行基因分型。结果表明，抗性dhps等位基因在泰国是固定的，主要是SGEGA、AGEAA和SGNGA三重突变体和AGKAA双突变体（突变的密码子加下划线）。这些等位基因具有不同的地理分布。SGEGA等位基因主要分布在缅甸边境，SGNGA等位基因主要分布在柬埔寨边境及邻近省份。微卫星数据表明，有两个主要的遗传谱系的三重突变体在泰国，一个共同的SGEGA/SGNGA等位基因和另一个独立的AGEAA。重要的是，新报道的SGNGA等位基因可能起源于泰国-柬埔寨边境。也拉省（马来西亚边境）的所有寄生虫都有AGKAA等位基因，侧翼微卫星单倍型几乎相同。他们也是相同的pupelium中性位点上的染色体2和3，这表明在亚拉的寄生虫种群的克隆性质。总之，这项研究表明，在泰国的耐药dhps等位基因的多个和独立的起源。
The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.