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来自几个地理区域的间日疟原虫二氢叶酸还原酶(DHFR)和二氢蝶酸合成酶(DHPS)中的氨基酸突变及对抗叶酸药物的敏感性。

Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs.

作者信息

Auliff Alyson, Wilson Danny W, Russell Bruce, Gao Qi, Chen Nanhua, Anh Le Ngoc, Maguire Jason, Bell David, O'Neil Michael T, Cheng Qin

机构信息

Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, Qld, Australia.

出版信息

Am J Trop Med Hyg. 2006 Oct;75(4):617-21.

PMID:17038682
Abstract

The increasing use of sulfadoxine-pyrimethamine (SP) for the treatment of chloroquine-resistant Plasmodium falciparum has resulted in increased reports of SP resistance of P. falciparum worldwide. Selection of SP-resistant Plasmodium vivax in areas where P. falciparum and P. vivax co-exist is not entirely clear. We examined the prevalence and extent of point mutations in pvdhfr and pvdhps in 70 P. vivax isolates from China, East Timor, Papua New Guinea (PNG), Philippines, Vanuatu, and Vietnam. Mutations in seven codon positions were found in pvdhfr, with the majority of isolates having double mutations (S58R/S117N). The greatest range of mutations was observed in the PNG and Vanuatu isolates, ranging from single to quadruple mutations (F57L/S58R/T61M/S117T). Single mutations in pvdhps were observed only in parasites with mutations in corresponding pvdhfr. Parasites with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and cycloguanil comparable to that previously reported, but were susceptible to WR99210.

摘要

磺胺多辛-乙胺嘧啶(SP)越来越多地用于治疗对氯喹耐药的恶性疟原虫,这导致全球范围内关于恶性疟原虫对SP耐药的报告增多。在恶性疟原虫和间日疟原虫共存的地区,间日疟原虫对SP耐药的选择情况尚不完全清楚。我们检测了来自中国、东帝汶、巴布亚新几内亚(PNG)、菲律宾、瓦努阿图和越南的70株间日疟原虫分离株中pvdhfr和pvdhps的点突变流行情况及程度。在pvdhfr中发现了7个密码子位置的突变,大多数分离株具有双重突变(S58R/S117N)。在PNG和瓦努阿图的分离株中观察到的突变范围最大,从单重突变到四重突变(F57L/S58R/T61M/S117T)。仅在相应pvdhfr有突变的寄生虫中观察到pvdhps的单重突变。具有S58R/S117N dhfr等位基因类型的寄生虫对乙胺嘧啶和环氯胍的MIC水平与先前报道的相当,但对WR99210敏感。

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