Selective Sweeps and Genetic Lineages of Plasmodium falciparum Drug -Resistant Alleles in Ghana
Selective Sweeps and Genetic Lineages of Plasmodium falciparum Drug -Resistant Alleles in Ghana
复制标题
DOI：
10.1093/infdis/jiq038
复制
发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Koram, Kwadwo A.
中科院分区：
文献类型：
--
作者：
Alam, Md Tauqeer;de Souza, Dziedzom K.;Koram, Kwadwo A.
背景2005年，加纳采用青蒿素类复方疗法作为恶性疟疾的初级治疗。对耐药相关突变及其遗传谱系的全面研究将有助于更好地了解该地区抗疟药耐药性的演变。对恶性疟原虫加纳分离株中与氯喹（CQ）和磺胺嘧啶-乙胺嘧啶（SP）抗性相关的pfcrt、pfmdr 1、dhps和dhfr突变以及这些基因侧翼的微卫星位点进行基因分型。在加纳，与CQ和SP耐药相关的突变发生率很高。然而，我们观察到加纳北方的pfcrt K76 T突变的患病率在药物政策从CQ改为ACT后下降。对这4个基因侧翼微卫星位点的遗传多样性和分化分析表明，由于CQ和SP的使用，它们一直处于强选择下。加纳的pfcrt和dhfr三突变等位基因来自东南亚，而dhfr、dhps和pfmdr 1双突变等位基因来自非洲。由于pfmdr 1在阿莫地喹和甲氟喹耐药性中可能发挥的作用，证明对pfmdr 1的选择并确定非洲人群中耐药等位基因的谱系具有重要意义。
Background. In 2005, Ghana adopted artemisinin-based combination therapy (ACT) for primary treatment of falciparum malaria. A comprehensive study of the drug-resistance-associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region.Methods. The pfcrt, pfmdr1, dhps, and dhfr mutations associated with chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) resistance and the microsatellite loci flanking these genes were genotyped in Plasmodium falciparum isolates from Ghana.Results. The prevalence of mutations associated with both CQ and SP resistance was high in Ghana. However, we observed a decrease in prevalence of the pfcrt K76T mutation in northern Ghana after the change in drug policy from CQ to ACT. Analysis of genetic diversity and differentiation at microsatellite loci flanking all 4 genes indicated that they have been under strong selection, because of CQ and SP use. The triple-mutant pfcrt and dhfr alleles in Ghana were derived from Southeast Asia, whereas the double-mutant dhfr, dhps, and pfmdr1 alleles were of African lineage.Conclusion. Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance.