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中国南方疟原虫抗疟药物耐药性的基因组流行病学研究。

Genomic Epidemiology of Antimalarial Drug Resistance in in Southern China.

机构信息

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Key Laboratory of Parasite and Vector Biology, Ministry of Health, WHO Collaborating Centre for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, China.

Malaria Programme, Wellcome Sanger Institute, Cambridge, United Kingdom.

出版信息

Front Cell Infect Microbiol. 2021 Jan 8;10:610985. doi: 10.3389/fcimb.2020.610985. eCollection 2020.

DOI:10.3389/fcimb.2020.610985
PMID:33489939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7820777/
Abstract

Emerging artemisinin resistance in Southeast Asia poses a significant risk to malaria control and eradication goals, including China's plan to eliminate malaria nationwide by 2020. was endemic in China, especially in Southern China. Parasites from this region have shown decreased susceptibility to artemisinin and delayed parasite clearance after artemisinin treatment. Understanding the genetic basis of artemisinin resistance and identifying specific genetic loci associated with this phenotype is crucial for surveillance and containment of resistance. In this study, parasites were collected from clinical patients from Yunnan province and Hainan island. The parasites were genotyped using a -specific single nucleotide polymorphism (SNP) microarray. The SNP profiles examined included a total of 27 validated and candidate molecular markers of drug resistance. The structure of the parasite population was evaluated by principal component analysis by using the EIGENSOFT program, and ADMIXTURE was used to calculate maximum likelihood estimates for the substructure analysis. Parasites showed a high prevalence of resistance haplotypes of pfdhfr and pfdhps and moderate prevalence of pfcrt. There was no mutation identified on pfmdr1. Candidate SNPs on chromosomes 10, 13, and 14 that were associated with delayed parasite clearance showed a low prevalence of mutants. Parasites from Southern China were clustered and separated from those from Southeast Asia. Parasites from Yunnan province were substructured from parasites from Hainan island. This study provides evidence for a genomic population with drug resistance in Southern China and also illustrates the utility of SNP microarrays for large-scale parasite molecular epidemiology.

摘要

东南亚出现的青蒿素抗药性对疟疾控制和消除目标构成重大威胁,包括中国到 2020 年在全国消除疟疾的计划。青蒿素在中国曾有流行,特别是在中国南方。该地区的寄生虫对青蒿素的敏感性降低,青蒿素治疗后寄生虫清除时间延迟。了解青蒿素抗药性的遗传基础,确定与这种表型相关的特定遗传基因座,对于监测和遏制抗药性至关重要。在这项研究中,从云南省和海南岛的临床患者中采集了寄生虫。使用-特异性单核苷酸多态性 (SNP) 微阵列对寄生虫进行基因分型。检查的 SNP 图谱包括总共 27 个经过验证和候选的耐药分子标记。使用 EIGENSOFT 程序通过主成分分析评估寄生虫种群结构,使用 ADMIXTURE 计算亚结构分析的最大似然估计。寄生虫显示出高流行的 pfdhfr 和 pfdhps 耐药单倍型和中度流行的 pfcrt。pfmdr1 上没有发现突变。与寄生虫清除延迟相关的染色体 10、13 和 14 上的候选 SNPs 显示突变体的低流行率。来自中国南方的寄生虫聚类并与来自东南亚的寄生虫分离。来自云南省的寄生虫与来自海南岛的寄生虫亚结构。这项研究为中国南方具有耐药性的基因组种群提供了证据,也说明了 SNP 微阵列在大规模寄生虫分子流行病学中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/3b50928d4265/fcimb-10-610985-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/63a1b4e7f2c2/fcimb-10-610985-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/4bfbce5a6aad/fcimb-10-610985-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/257444dd7ab9/fcimb-10-610985-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/2ec3bcb9860d/fcimb-10-610985-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/41466e1c0080/fcimb-10-610985-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/8ad1f0dc370a/fcimb-10-610985-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/3b50928d4265/fcimb-10-610985-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/63a1b4e7f2c2/fcimb-10-610985-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/4bfbce5a6aad/fcimb-10-610985-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/257444dd7ab9/fcimb-10-610985-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/2ec3bcb9860d/fcimb-10-610985-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/41466e1c0080/fcimb-10-610985-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/8ad1f0dc370a/fcimb-10-610985-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10f5/7820777/3b50928d4265/fcimb-10-610985-g007.jpg

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