恶性疟原虫的耐药性损害了抗疟治疗的有效性。这项研究旨在评估从加纳返回的国际旅行者获得的寄生虫的耐药性程度,以指导疟疾病例的管理。从2016-2018年从加纳返回的患者中获得了82种临床寄生虫分离株,其中29种适用于连续体外培养。它们对一组11种抗疟药物的几何平均IC50值,使用标准SYBRGreen-I药物敏感性试验进行评估,蒿甲醚为2.1、3.8、1.0、2.7、17.2、4.6、8.3、8.3、19.6、55.1和11,555nM,青蒿琥酯,双氢青蒿素,lumefantrine,甲氟喹,哌喹,萘酚喹,吡喃萘啶,氯喹,奎宁,和乙胺嘧啶,分别。除了氯喹和乙胺嘧啶,其他受试药物的IC50值低于耐药阈值.平均环阶段生存测定值为0.8%,有4个分离株超过1%。平均哌喹存活测定值为2.1%,低于10%。与氯喹抗性相关的突变(pfcrtK76T和pfmdr1N86Y)很少,与十年前停用氯喹一致.相反,pfmdr186N-184F-1246D单倍型占主导地位,建议通过广泛使用蒿甲醚-lumefantrine进行选择。在pfk13螺旋桨结构域中未检测到突变。与磺胺多辛-乙胺嘧啶抗性相关的pfdhfr/pfdhps四重突变体IRNGK的患病率达到82%。此外,五个分离株有pfgch1基因扩增,但是,有趣的是,增加对乙胺嘧啶的敏感性。这项研究表明,源自加纳的寄生虫对青蒿素和基于青蒿素的联合疗法的伙伴药物敏感。基因分型药物抗性基因鉴定了蒿甲醚-氟美醇的选择特征。寄生虫对抗叶酸药物表现出相当大的抗性。持续的耐药性监测对于指导药物政策的及时变化是必要的。
Drug resistance in Plasmodium falciparum compromises the effectiveness of antimalarial therapy. This study aimed to evaluate the extent of drug resistance in parasites obtained from international travelers returning from Ghana to guide the management of malaria cases. Eighty-two clinical parasite isolates were obtained from patients returning from Ghana in 2016-2018, of which 29 were adapted to continuous in vitro culture. Their geometric mean IC50 values to a panel of 11 antimalarial drugs, assessed using the standard SYBR Green-I drug sensitivity assay, were 2.1, 3.8, 1.0, 2.7, 17.2, 4.6, 8.3, 8.3, 19.6, 55.1, and 11,555 nM for artemether, artesunate, dihydroartemisinin, lumefantrine, mefloquine, piperaquine, naphthoquine, pyronaridine, chloroquine, quinine, and pyrimethamine, respectively. Except for chloroquine and pyrimethamine, the IC50 values for other tested drugs were below the resistance threshold. The mean ring-stage survival assay value was 0.8%, with four isolates exceeding 1%. The mean piperaquine survival assay value was 2.1%, all below 10%. Mutations associated with chloroquine resistance (pfcrt K76T and pfmdr1 N86Y) were scarce, consistent with the discontinuation of chloroquine a decade ago. Instead, the pfmdr1 86N-184F-1246D haplotype was predominant, suggesting selection by the extensive use of artemether-lumefantrine. No mutations in the pfk13 propeller domain were detected. The pfdhfr/pfdhps quadruple mutant IRNGK associated with resistance to sulfadoxine-pyrimethamine reached an 82% prevalence. In addition, five isolates had pfgch1 gene amplification but, intriguingly, increased susceptibilities to pyrimethamine. This study showed that parasites originating from Ghana were susceptible to artemisinins and the partner drugs of artemisinin-based combination therapies. Genotyping drug resistance genes identified the signature of selection by artemether-lumefantrine. Parasites showed substantial levels of resistance to the antifolate drugs. Continuous resistance surveillance is necessary to guide timely changes in drug policy.