中国云南省西部与抗药性相关的疟原虫分离株分子标志物的流行率。
Prevalence of molecular markers associated with drug resistance of Plasmodium vivax isolates in Western Yunnan Province, China.
机构信息
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Key Laboratory of Parasite and Vector Biology, MOH, and WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai, People's Republic of China.
Zhejiang Provincial Center for Disease Control and Prevention, Zhejiang, People's Republic of China.
出版信息
BMC Infect Dis. 2020 Apr 25;20(1):307. doi: 10.1186/s12879-020-05032-4.
BACKGROUND
Plasmodium vivax is the most widely distributed malaria parasite, and its drug resistance poses unique challenges to malaria elimination. The Greater Mekong Subregion (GMS) is known as the global epicenter of multidrug resistance. Surveillance of molecular markers associated with drug resistance in this area will help to inform drug policy.
METHODS
Dry blood spots from 58 patients out of 109 with P. vivax infection between 2017, December and 2019, March were obtained from Yingjiang County, Yunnan Province, along the China-Myanmar border. Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were amplified and sequenced to assess gene mutations. The polymorphism and prevalence of these molecular markers were analyzed.
RESULTS
Mutations in Pvdhfr at codons 57, 58, 61, 99 and 117 were detected in 27.59, 48.28, 27.59, 32.76 and 48.28% of the isolates, respectively. Single mutant haplotype (IFSTSSI) was the most frequent (29.31%, 17/58), followed by double mutant haplotype (20.69%, 12/58). Of three types of tandem repeat variations of Pvdhfr, deletion type was the most common. Pvdhps showed a lower prevalence among mutation genotypes. Single mutant was dominant and accounted for 34.48% (20/58). Prevalence of Pvmdr1 mutations at codons 958 and 1076 were 100.00% and 84.48%, respectively. The proportion of double and single mutant types was 84.48% (49/58) and 15.52% (9/58), respectively. Eleven samples (18.97%, 11/58) showed K10 "AAG" insertion in chloroquine resistance transporter gene Pvcrt-o.
CONCLUSIONS
There was moderate diversity of molecular patterns of resistance markers of Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o in imported P. vivax cases to Yingjiang county in Western Yunnan, along the China-Myanmar border. Prevalence and molecular pattern of candidate drug resistance markers Pvdhfr, Pvdhps, Pvmdr1 and Pvcrt-o were demonstrated in this current study, which would help to update drug policy.
背景
间日疟原虫是分布最广泛的疟原虫，其耐药性对消除疟疾构成了独特的挑战。大湄公河次区域（GMS）被认为是全球多药耐药的中心。该地区耐药相关分子标志物的监测将有助于制定药物政策。
方法
2017 年 12 月至 2019 年 3 月，从中缅边境云南省盈江县采集了 109 例间日疟原虫感染患者中的 58 例患者的干血斑。扩增和测序 Pvdhfr、Pvdhps、Pvmdr1 和 Pvcrt-o 以评估基因突变。分析这些分子标记物的多态性和流行率。
结果
在 58 例分离株中，分别检测到 Pvdhfr 密码子 57、58、61、99 和 117 处突变 27.59%、48.28%、27.59%、32.76%和 48.28%。单一突变单倍型（IFSTSSI）最为常见（29.31%，17/58），其次是双突变单倍型（20.69%，12/58）。Pvdhfr 的三种串联重复变异中，缺失型最为常见。Pvdhps 的突变基因型发生率较低。单突变占主导地位，占 34.48%（17/58）。Pvmdr1 密码子 958 和 1076 突变的发生率分别为 100.00%和 84.48%。双突变和单突变的比例分别为 84.48%（49/58）和 15.52%（9/58）。11 例（18.97%，11/58）显示氯喹耐药转运蛋白基因 Pvcrt-o 中的 K10“AAG”插入。
结论
中缅边境云南省盈江县输入性间日疟原虫病例中，Pvdhfr、Pvdhps、Pvmdr1 和 Pvcrt-o 的耐药相关分子标记物的分子模式具有中等多样性。本研究表明了候选耐药标记物 Pvdhfr、Pvdhps、Pvmdr1 和 Pvcrt-o 的流行率和分子模式，有助于更新药物政策。
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