Taylor Steve M, Antonia Alejandro L, Harrington Whitney E, Goheen Morgan M, Mwapasa Victor, Chaluluka Ebbie, Fried Michal, Kabyemela Edward, Madanitsa Mwayi, Khairallah Carole, Kalilani-Phiri Linda, Tshefu Antoinette K, Rogerson Stephen J, Ter Kuile Feiko O, Duffy Patrick E, Meshnick Steven R
Emerg Infect Dis. 2014 Jul;20(7):1140-8. doi: 10.3201/eid2007.131720.
Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
对磺胺多辛耐药的恶性疟原虫破坏了磺胺多辛/乙胺嘧啶对疟疾的预防作用。携带高度耐药性突变二氢蝶酸合酶(dhps)单倍型的寄生虫最近在东非出现;它们抵消了磺胺多辛/乙胺嘧啶的预防益处,并且可能会加剧胎盘疟疾。我们通过对dhps基因座侧翼的遗传微卫星进行分析,探索了马拉维、刚果民主共和国和坦桑尼亚dhps突变单倍型的新兴谱系。在马拉维,2010年出现了一种三突变dhps SGEG(突变氨基酸加下划线)单倍型,它与先前存在的双突变SGEA单倍型密切相关,这表明它是在马拉维本地起源的。当我们通过多项独立分析将突变菌株与来自刚果民主共和国和坦桑尼亚的寄生虫进行比较时,我们发现SGEG寄生虫按国家被划分到不同的谱系中。这些发现支持了SGEG dhps单倍型本地起源而非地理扩散的模型,并对寄生虫耐药性的出现和影响的研究具有启示意义。