Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76
Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76
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DOI：
10.1128/aac.00358-10
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Hallett, Rachel L.
中科院分区：
文献类型：
--
作者：
Beshir, Khalid;Sutherland, Colin J.;Hallett, Rachel L.
在非洲，恶性疟原虫基因pfcrt和pfmdr1的突变是通过阿莫地喹治疗来选择的。为了检验这些突变在阿莫地喹治疗的亚洲寄生虫中的重要性，我们从阿富汗的一项临床试验中确定了阿莫地喹治疗失败的治疗前和治疗后的基因型。Pfcrt密码子72至76单倍型SVMNT在所有被检测的样本中都存在，治疗前后都是如此。阿莫地喹没有明确选择任何pfmdr1基因型，但在四个样本中检测到一种新的突变pfmdr1 N86F。我们提供的体内数据支持pfcrt SVMNT与阿莫地喹代谢物耐药性增加之间的体外相关性。
Mutations in the Plasmodium falciparum genes pfcrt and pfmdr1 are selected by amodiaquine treatment in Africa. To examine the importance of these mutations in amodiaquine-treated Asian parasites, we determined pre- and posttreatment genotypes for amodiaquine treatment failures from a clinical trial in Afghanistan. The pfcrt codon 72 to 76 haplotype SVMNT was present in all samples tested, both before and after treatment. Amodiaquine did not clearly select for any pfmdr1 genotype, but a novel mutation, pfmdr1 N86F, was detected in four samples. We provide in vivo data to support the in vitro correlation between pfcrt SVMNT and increased resistance to the metabolite of amodiaquine.