Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University; Department of Parasitology; Provincial Key Laboratory of Modern Pathogen Biology, Guizhou Medical University, Guiyang, 550025, China.
Guizhou Provincial Center for Disease Control and Prevention, Guiyang, 550004, China.
BMC Infect Dis. 2020 Jul 16;20(1):513. doi: 10.1186/s12879-020-05228-8.
Imported falciparum malaria from Africa has become a key public health challenge in Guizhou Province since 2012. Understanding the polymorphisms of molecular markers of drug resistance can guide selection of antimalarial drugs for the treatment of malaria. This study was aimed to analyze the polymorphisms of pfcrt, pfmdr1, and K13-propeller among imported falciparum malaria cases in Guizhou Province, China.
Fifty-five imported falciparum malaria cases in Guizhou Province during 2012-2016 were included in this study. Their demographic information and filter paper blood samples were collected. Genomic DNA of Plasmodium falciparum was extracted from the blood samples, and polymorphisms of pfcrt, pfmdr1, and K13-propeller were analyzed with nested PCR amplification followed by sequencing. Data were analyzed with the SPSS17.0 software.
The prevalence of pfcrt K76T, pfmdr1 N86Y, and pfmdr1 Y184F mutation was 56.6, 22.2, and 72.2%, respectively, in imported falciparum malaria cases in Guizhou Province. We detected two mutant haplotypes of pfcrt, IET and MNT, with IET being more commonly found (54.7%), and five mutant haplotypes of pfmdr1, of which NFD was the most frequent (53.7%). There were totally 10 combined haplotypes of pfcrt and pfmdr1, of which the haplotype IETNFD possessed a predominance of 28.8%. In addition, three nonsynonymous mutations (S459T, C469F, and V692L) and two synonymous mutations (R471R and V589V) were detected in K13-propeller, all having prevalence less than 6.0%. In particular, a candidate K13 resistance mutation, C469F, was identified for the first time from Democratic Republic of the Congo with the prevalence of 2.0%.
The high prevalence of IET haplotype of pfcrt and NFD haplotype of pfmdr1 suggests the presence of chloroquine, artemether/lumefantrine, and dihydroartemisinin/piperaquine resistance in these cases. Therefore cautions should be made to artemisinin therapy for P. falciparum in Africa. Continuous monitoring of anti-malarial drug efficacy in imported malaria cases is helpful for optimizing antimalarial drug therapy in Guizhou Province, China.
自 2012 年以来，来自非洲的输入性恶性疟已成为贵州省的一个主要公共卫生挑战。了解耐药性分子标记物的多态性可以指导抗疟药物的选择，用于治疗疟疾。本研究旨在分析贵州省输入性恶性疟病例中 pfcr t、pfmdr1 和 K13-推进器的多态性。
纳入贵州省 2012-2016 年 55 例输入性恶性疟病例，收集其人口统计学信息和滤纸血样。从血样中提取恶性疟原虫基因组 DNA，采用巢式 PCR 扩增后测序分析 pfcrt、pfmdr1 和 K13-推进器的多态性。采用 SPSS17.0 软件进行数据分析。
贵州省输入性恶性疟病例中 pfcrt K76T、pfmdr1 N86Y 和 pfmdr1 Y184F 突变的流行率分别为 56.6%、22.2%和 72.2%。检测到 pfcrt 的两种突变单倍型 IET 和 MNT，其中 IET 更为常见（54.7%），pfmdr1 的五种突变单倍型，其中 NFD 最为常见（53.7%）。共检测到 10 种 pfcrt 和 pfmdr1 的组合单倍型，其中 IETNFD 单倍型占优势，为 28.8%。此外，在 K13-推进器中检测到 3 个非同义突变（S459T、C469F 和 V692L）和 2 个同义突变（R471R 和 V589V），其流行率均低于 6.0%。特别是，首次从刚果民主共和国发现 K13 耐药突变 C469F，其流行率为 2.0%。
pfcrt 的 IET 单倍型和 pfmdr1 的 NFD 单倍型的高流行率表明这些病例存在氯喹、青蒿素/哌喹和双氢青蒿素/哌喹耐药性。因此，在治疗来自非洲的恶性疟原虫感染时应慎重使用青蒿素类药物。对输入性疟疾病例抗疟药物疗效的持续监测有助于优化贵州省的抗疟药物治疗。
