Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Am J Trop Med Hyg. 2011 Dec;85(6):979-83. doi: 10.4269/ajtmh.2011.11-0071.
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.
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。