PFMDR1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border
PFMDR1 and in vivo resistance to artesunate-mefloquine in falciparum malaria on the Cambodian-Thai border
复制标题
DOI：
10.4269/ajtmh.2007.76.641
复制
发表时间：
2007-04-01
影响因子：
3.3
通讯作者：
Meshnick, Steven R.
中科院分区：
文献类型：
--
作者：
Alker, Alisa P.;Lim, Pharath;Meshnick, Steven R.
在大多数疟疾流行国家，青蒿素联合疗法最近已被作为治疗恶性疟原虫感染的一线疗法。在这项研究中，我们估计了青蒿琥酯-甲氟喹治疗失败与假定转运体pfmdr1的遗传变化之间的关系。2004年在柬埔寨拜林进行的一项体内疗效研究中，研究人员从80名患者中采集了血液样本，并对pfmdr1拷贝数和单倍型进行了基因分型。有3个或更多拷贝1的寄生体的治疗前fmdr1与复发密切相关（风险比[HR] = 8.30; 95% Cl: 2.60-26.43）。在控制初始寄生虫密度和红细胞压积时，这种关系保持不变（HR = 7.91; 95% Cl: 2.38 ~ 26.29）。选择青蒿琥酯-甲氟喹治疗是为了增加pfmdr1拷贝数，因为来自复发发作的分离株的拷贝数高于配对入组样本（Wilcoxon秩检验，P = 0.040）。应进一步评价pfmdr1拷贝数作为柬埔寨青蒿琥酯-甲氟喹耐药性监测工具。
Artemisinin combination therapies (ACTs) have recently been adopted as first-line therapy for Plasmodium falcipartim infections in most malaria-endemic countries. In this study, we estimated the association between artesunate-mefloquine therapy failure and genetic changes in the putative transporter, pfmdr1. Blood samples were acquired from 80 patients enrolled in an 2004 in vivo efficacy study in Pailin, Cambodia, and genotyped for pfmdr1 copy number and haplotype. Having parasites with three or more copies of 1. fmdr1 before treatment was strongly associated with recrudescence (hazard ratio [HR] = 8.30; 95% Cl: 2.60-26.43). This relationship was maintained when controlling for initial parasite density and hematocrit (HR = 7.91; 95% Cl: 2.38-26.29). Artesunate-mefloquine treatment selected for increased pfmdr1 copy number, because isolates from recurrent episodes had higher copy numbers than the paired enrollment samples (Wilcoxon rank test, P = 0.040). pfmdr1 copy number should be evaluated further as a surveillance tool for artesunate-mefloquine resistance in Cambodia.