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在引入基于青蒿素的联合疗法前后,坦桑尼亚科罗戈韦地区疟原虫多药耐药基因(Pfmdr-1)的单核苷酸多态性的流行情况。

Prevalence of single nucleotide polymorphisms in the Plasmodium falciparum multidrug resistance gene (Pfmdr-1) in Korogwe District in Tanzania before and after introduction of artemisinin-based combination therapy.

机构信息

Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

出版信息

Am J Trop Med Hyg. 2011 Dec;85(6):979-83. doi: 10.4269/ajtmh.2011.11-0071.

Abstract

Tanzania implemented artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in November of 2006 because of resistance to sulfadoxine-pyrimethamine. AL remains highly efficacious, but widespread use may soon facilitate emergence of artemisinin tolerance/resistance, which initially may be detected at the molecular level as temporal changes in the frequency of single nucleotide polymorphisms (SNPs) in the Pfmdr-1 gene associated with AL resistance. In Tanzania, 830 Plasmodium falciparum-positive samples collected between 2003 and 2010 were examined for SNPs of Pfmdr-1 at codons 86, 184, and 1246. Both the N86 and 184F increased from 2006 to 2010 (logistic regression; N86: odds ratio [95% confidence interval] = 1.35 [1.07-1.71], P = 0.01; 184F: odds ratio = 1.42 [1.07-1.88], P = 0.02), and no change was found for D1246 (odds ratio = 1.01 [0.80-1.28], P = 0.9). The observed changes may be because of introduction of AL, and if so, this finding gives cause for concern and argues for continued surveillance of these molecular markers.

摘要

坦桑尼亚于 2006 年 11 月因对磺胺多辛-乙胺嘧啶的耐药性而将青蒿琥酯-咯萘啶(AL)作为治疗无并发症疟疾的一线药物。AL 仍然具有很高的疗效,但广泛使用可能很快会促进青蒿素耐药性的出现,这种耐药性最初可能在分子水平上被检测到,表现为 Pfmdr-1 基因与 AL 耐药性相关的单核苷酸多态性(SNP)的频率发生暂时变化。在坦桑尼亚,对 2003 年至 2010 年间采集的 830 个疟原虫阳性样本进行了 Pfmdr-1 基因 86、184 和 1246 密码子的 SNP 检测。N86 和 184F 从 2006 年到 2010 年都有所增加(逻辑回归;N86:比值比[95%置信区间] = 1.35 [1.07-1.71],P = 0.01;184F:比值比 = 1.42 [1.07-1.88],P = 0.02),而 1246D 没有变化(比值比 = 1.01 [0.80-1.28],P = 0.9)。观察到的变化可能是由于 AL 的引入,如果是这样,这一发现令人担忧,并呼吁继续监测这些分子标记物。

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