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老挝北部的恶性疟:恶性疟原虫氯喹抗性转运蛋白(pfcrt)基因单倍型SVMNT的出现及影响

Falciparum malaria in the north of Laos: the occurrence and implications of the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene haplotype SVMNT.

作者信息

Dittrich Sabine, Alifrangis Michael, Stohrer Jörg M, Thongpaseuth Vonthalom, Vanisaveth Viengxay, Phetsouvanh Rattanaxay, Phompida Samlane, Khalil Insaf F, Jelinek Tomas

机构信息

Institute of Tropical Medicine, Berlin, Germany.

出版信息

Trop Med Int Health. 2005 Dec;10(12):1267-70. doi: 10.1111/j.1365-3156.2005.01514.x.

DOI:10.1111/j.1365-3156.2005.01514.x
PMID:16359407
Abstract

OBJECTIVE

The Pfcrt-gene encodes a transmembrane protein located in the Plasmodium falciparum digestive vacuole. Chloroquine resistant (CQR) strains of African and Southeast Asian origin carry the Pfcrt-haplotype (c72-76) CVIET, whereas most South American and Papua New Guinean CQR stains carry the SVMNT haplotype.

METHOD

Eighty-eight samples from an area with reported in vivo Chloroquine and in vitro Amodiaquine-resistance were screened for the K76T mutation and their Pfcrt-haplotype (c72-76) using a new SSOP-ELISA.

RESULTS

Hundred percent of the analysed samples showed the K76T mutation which is highly associated with in vivo drug failure. This very high rate of a CQR-marker is alarming in an area were CQ is still used as first line drug. The distribution of the three main Pfcrt-haplotypes was as follows: 68% CVIET, 31% SVMNT, 0% CVMNT.

CONCLUSIONS

These data show, for the first time, the South American/PNG -haplotype (SVMNT) on mainland Southeast Asia. SVMNT-haplotype and others might be associated with a decreased efficacy of Amodiaquine and could therefore be potential markers for of amodiaquine resistance (AQR). If there is a correlation between AQR and the SVMNT-haplotype as suggested, 31% prevalence of a potential resistance marker is cause for concern.

摘要

目的

Pfcrt基因编码一种位于恶性疟原虫消化液泡中的跨膜蛋白。非洲和东南亚来源的氯喹抗性(CQR)菌株携带Pfcrt单倍型(c72 - 76)CVIET,而大多数南美和巴布亚新几内亚的CQR菌株携带SVMNT单倍型。

方法

使用一种新的SSOP - ELISA方法,对来自一个报告有体内氯喹和体外阿莫地喹抗性地区的88份样本进行K76T突变及其Pfcrt单倍型(c72 - 76)筛查。

结果

100%的分析样本显示出K76T突变,该突变与体内药物治疗失败高度相关。在一个仍将氯喹用作一线药物的地区,这种非常高比例的CQR标记令人担忧。三种主要Pfcrt单倍型的分布如下:68%为CVIET,31%为SVMNT,0%为CVMNT。

结论

这些数据首次在东南亚大陆显示出南美/巴布亚新几内亚单倍型(SVMNT)。SVMNT单倍型及其他单倍型可能与阿莫地喹疗效降低有关,因此可能是阿莫地喹抗性(AQR)的潜在标记。如果如所提示的那样AQR与SVMNT单倍型之间存在相关性,那么一种潜在抗性标记31%的流行率令人担忧。

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