Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Antimicrob Agents Chemother. 2011 Jan;55(1):155-64. doi: 10.1128/AAC.00691-10. Epub 2010 Oct 18.
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.
疟原虫对青蒿素类药物耐药性的出现和传播是全球疟疾控制的主要障碍。早期的研究表明，与氯喹（CQ）耐药性相似，恶性疟原虫对嘧啶耐药性水平在全球范围内独立出现了 4 到 5 次，包括在泰国-柬埔寨边境的一次起源。在这项研究中，我们描述了泰国磺胺多辛抗性二氢叶酸合成酶（dhps）等位基因的起源和传播。对从沿缅甸、柬埔寨和马来西亚边境的 11 个泰国省份采集的恶性疟原虫分离株进行了 dhps 突变和侧翼微卫星位点的基因分型。结果表明，耐药 dhps 等位基因在泰国已固定，主要是 SGEGA、AGEAA 和 SGNGA 三重突变体和 AGKAA 双突变体（突变密码子加下划线）。这些等位基因具有不同的地理分布。SGEGA 等位基因主要在缅甸边境发现，而 SGNGA 等位基因主要在柬埔寨边境和附近省份发生。微卫星数据表明，泰国存在两种主要的三重突变体遗传谱系，一种常见于 SGEGA/SGNGA 等位基因，另一种独立于 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。亚拉省（马来西亚边境）的所有寄生虫都具有 AGKAA 等位基因，其侧翼微卫星单倍型几乎相同。它们在染色体 2 和 3 上的假定中性位点也是相同的，这表明亚拉省寄生虫群体具有克隆性质。总之，这项研究表明泰国存在多种独立起源的耐药 dhps 等位基因。
