Characteristics of Plasmodium falciparum dhfr haplotypes that confer pyrimethamine resistance, Kilifi, Kenya, 1987-2006
Characteristics of Plasmodium falciparum dhfr haplotypes that confer pyrimethamine resistance, Kilifi, Kenya, 1987-2006
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DOI：
10.1086/588198
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发表时间：
2008-06-15
影响因子：
6.4
通讯作者：
Sibley, Carol Hopkins
中科院分区：
文献类型：
--
作者：
Certain, Laura K.;Briceno, Marnie;Sibley, Carol Hopkins
20世纪60年代，抗疟疾药物磺胺多辛(SP)在亚洲恶性疟原虫中出现抗药性，随后蔓延到非洲。目前尚不清楚赋予SP抗性的等位基因是否也独立出现在非洲。我们确定了1987-2006年在肯尼亚基里菲收集的恶性疟原虫DHFR等位基因的编码区和微卫星单倍型。携带双突变或三突变DHFR等位基因的分离株被检测到的频率很低，即使在1987-1988年间也是如此。两个双突变体均携带一种独特的单倍型，且均与同一群体的野生型单倍型相关。携带三个突变的DHFR等位基因的菌株数量在SP导入后迅速增加，并与来自亚洲的三个突变的单倍型相同。我们没有观察到单倍型与非洲野生型和双突变等位基因相关的三重突变等位基因。
Resistance to the antimalarial drug sulfadoxine-pyrimethamine (SP) emerged in Plasmodium falciparum from Asia in the 1960s and subsequently spread to Africa. It is not known whether alleles that confer SP resistance also arose independently in Africa. We defined the coding region and microsatellite haplotypes of dhfr alleles in P. falciparum collected in Kilifi, Kenya, during 1987-2006, which spans the period when SP was first introduced. Isolates that carried a double-mutant or triple-mutant dhfr allele were detected at a low frequency, even during 1987-1988. Each of 2 double mutants carried a unique haplotype, and both were related to wild-type haplotypes from the same population. The number of isolates that carried a triple-mutant dhfr allele increased rapidly after introduction of SP and shared the haplotype of the triple mutant derived form Asia. We observed no triple-mutant alleles with haplotypes related to those of the Africa-derived wild-type and double-mutant alleles.