Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
Antimicrob Agents Chemother. 2010 Sep;54(9):3714-6. doi: 10.1128/AAC.00358-10. Epub 2010 Jun 14.
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.
疟原虫 falciparum 基因 pfcrt 和 pfmdr1 的突变可被在非洲的羟氯喹治疗所选择。为了研究这些突变在接受羟氯喹治疗的亚洲寄生虫中的重要性,我们对来自阿富汗的临床试验中的羟氯喹治疗失败病例进行了治疗前后的基因型检测。在所有检测的样本中,pfcrt 密码子 72 至 76 的 SVMNT 单倍型在治疗前后均存在。羟氯喹并没有明显选择任何 pfmdr1 基因型,但在四个样本中检测到了一种新的突变 pfmdr1 N86F。我们提供了体内数据来支持体外 pfcrt SVMNT 与增加对羟氯喹代谢物的耐药性之间的相关性。