Hawkins Vivian N, Suzuki Stephanie M, Rungsihirunrat Kanchana, Hapuarachchi Hapuarachchige C, Maestre Amanda, Na-Bangchang Kesara, Sibley Carol Hopkins
Department of Genome Sciences, University of Washington, Seattle, Washington 98195-5065, USA.
Am J Trop Med Hyg. 2009 Aug;81(2):348-55.
Infection with Plasmodium vivax is usually treated with chloroquine, but parasites are often exposed inadvertently to sulfadoxine-pyrimethamine. To infer patterns of selection and spread of resistant parasites in natural populations, we determined haplotypes of P. vivax dihydropteroate synthase ( dhps ) alleles that could confer resistance to sulfadoxine. We amplified the P. vivax pyrophosphokinase ( pppk )- dhps region and its flanking intergenic regions from 92 contemporary global isolates. Introns and exons of pppk-dhps were highly polymorphic, as were the flanking intergenic regions. Eighteen haplotypes were associated with wild-type alleles, but several different putatively sulfadoxine-resistant alleles have arisen in areas of intensive sulfadoxine-pyrimethamine use. Even when they encoded changes to the same amino acid, these mutant alleles were associated with multiple different haplotypes. Two main conclusions can be drawn from these data. First, dhps alleles resistant to sulfadoxine have arisen multiple times under drug pressure. Second, there has been convergent evolution of a variety of alleles that could confer resistance to sulfa drugs.
间日疟原虫感染通常用氯喹进行治疗，但寄生虫常常会意外接触到磺胺多辛-乙胺嘧啶。为了推断自然种群中耐药寄生虫的选择和传播模式，我们确定了间日疟原虫二氢蝶酸合酶（dhps）等位基因的单倍型，这些等位基因可能对磺胺多辛产生抗性。我们从92株当代全球分离株中扩增了间日疟原虫焦磷酸激酶（pppk）-dhps区域及其侧翼基因间区域。pppk-dhps的内含子和外显子高度多态，其侧翼基因间区域也是如此。18种单倍型与野生型等位基因相关，但在大量使用磺胺多辛-乙胺嘧啶的地区出现了几种不同的推测对磺胺多辛耐药的等位基因。即使它们编码相同氨基酸的变化，这些突变等位基因也与多种不同的单倍型相关。从这些数据可以得出两个主要结论。第一，在药物压力下，对磺胺多辛耐药的dhps等位基因已多次出现。第二，多种可能对磺胺类药物产生抗性的等位基因发生了趋同进化。
