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全基因组测序揭示了罗甸结核分枝杆菌的分子流行病学和耐药性。

Molecular epidemiology and drug-resistance of tuberculosis in Luodian revealed by whole genome sequencing.

机构信息

Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Dongan Road No.131, Shanghai 200032, China.

Key Laboratory of Infectious Disease & Biosafety, Institute of life Sciences, Zunyi Medical University, No.6 West Xuefu Road, Xinpu District, Zunyi, Guizhou Province 563000, China.

出版信息

Infect Genet Evol. 2021 Sep;93:104979. doi: 10.1016/j.meegid.2021.104979. Epub 2021 Jun 24.

DOI:10.1016/j.meegid.2021.104979
PMID:34175481
Abstract

In this study, we aimed to investigate the molecular epidemiology and drug-resistance profiles of tuberculosis (TB) in Luodian, an area with highest TB incidence and limited healthcare resources in Guizhou, China. The passive case finding strategy was used to identify suspected pulmonary TB with symptoms, and individuals with positive Mycobacterium tuberculosis (MTB) culture were enrolled from May 22, 2018 to April 21, 2019. All the 107 cases except three came from nine towns, including 55.1% from Longping and Bianyang. The phylogeny tree showed that 53.3% of strains were Lineage 2 (Beijing genotype), while 46.7% were Lineage 4 (Euro-American genotype). Among Lineage 2 strains, 66.7% were of "modern" Beijing type. Seven clusters with genomic distance within 12 SNPs were identified. The clusters included 14 strains, accounting for a clustering rate of 13.1%. The distance separating the clustered cases was between 2.1 and 71.0 km (Km), with an average paired distance of 21.8 Km (interquartile range, 2.8-38.0 Km). Based on the gene mutations associated with drug-resistance, we predicted that 4.8% of strains were resistant to isoniazid, 3.7% to rifampicin, and 3.7% to streptomycin; only one strain (0.9%) had multidrug resistance (MDR). This study found low drug-resistance rates in Luodian, and the sub-lineage of the "modern" Beijing branch has recent expansion in Luodian. This work may also serve as a genomic baseline to assess the evolution and spread of MTB in Guizhou.

摘要

在这项研究中,我们旨在调查中国贵州罗甸地区的结核病(TB)分子流行病学和耐药情况。罗甸是贵州发病率最高、医疗资源有限的地区。我们采用被动病例发现策略,对有症状的疑似肺结核进行了调查,并于 2018 年 5 月 22 日至 2019 年 4 月 21 日期间,从有阳性结核分枝杆菌(MTB)培养的个体中招募了参与者。除了 3 例,所有 107 例病例都来自 9 个镇,其中 55.1%来自龙坪镇和边阳镇。系统发育树显示,53.3%的菌株属于谱系 2(北京基因型),而 46.7%属于谱系 4(欧美基因型)。在谱系 2 菌株中,66.7%为“现代”北京型。鉴定出 7 个基因组距离在 12 个 SNP 以内的聚类。这些聚类包括 14 株,占聚类率的 13.1%。聚类病例之间的距离在 2.1-71.0km(Km)之间,平均配对距离为 21.8Km(四分位距 2.8-38.0Km)。基于与耐药性相关的基因突变,我们预测 4.8%的菌株对异烟肼耐药,3.7%对利福平耐药,3.7%对链霉素耐药;只有一株(0.9%)为耐多药(MDR)。本研究发现罗甸的耐药率较低,且“现代”北京支系的亚系在罗甸有近期扩张。这项工作也可以作为评估 MTB 在贵州进化和传播的基因组基线。

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