Emerg Infect Dis. 2022 Apr;28(4):812-819. doi: 10.3201/eid2804.210533.
Single-nucleotide polymorphisms at several loci have been correlated with Plasmodium falciparum drug resistance. We examined the prevalence of resistance markers in P. falciparum from imported malaria cases in Canada during 3 time periods, 2008-2009, 2013-2014, and 2017-2018. We evaluated single-nucleotide polymorphisms at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter), cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13). Over time, we observed increasing mutant genotypes for dhfr S108N and dhps A613T and decreasing mutant genotypes for mdr1 N86Y, D1246Y, pfcrt K76T, and pfcrt 74-75; we identified no kelch13 mutations. We observed fewer mutations indicative of chloroquine resistance over time, which may reflect reduced chloroquine pressure in specimens from travelers to Africa. Mutations conferring proguanil resistance increased over time. Minor genotypes confirm the heterogeneous nature of infection and may affect treatment success.
在多个基因座的单核苷酸多态性与恶性疟原虫抗药性有关。我们在三个时间段检查了加拿大输入性疟疾病例中恶性疟原虫的耐药标志物的流行情况,分别为 2008-2009 年、2013-2014 年和 2017-2018 年。我们评估了 atpase6(pfATPase6)、pfcrt(氯喹抗性转运蛋白)、cytb(细胞色素 b)、dhfr(二氢叶酸还原酶)、dhps(二氢喋呤合成酶)、mdr1(多药耐药蛋白)和 mdr1 拷贝数和 kelch13(13 号染色体上的 kelch 蛋白基因)的单核苷酸多态性。随着时间的推移,我们观察到 dhfr S108N 和 dhps A613T 的突变基因型增加,而 mdr1 N86Y、D1246Y、pfcrt K76T 和 pfcrt 74-75 的突变基因型减少;我们没有发现 kelch13 突变。随着时间的推移,我们观察到的指示氯喹耐药的突变减少,这可能反映出来自非洲旅行者的标本中氯喹压力的降低。随着时间的推移,赋予咯萘啶耐药性的突变增加。次要基因型证实了感染的异质性,可能影响治疗效果。