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对骨结核的基因组研究强调了亚临床肺结核在传播中的作用。

Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission.

机构信息

Beijing Chest Hospital, Capital Medical University, Beijing, China; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Beijing Chest Hospital, Capital Medical University, Beijing, China; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

出版信息

Tuberculosis (Edinb). 2024 Sep;148:102534. doi: 10.1016/j.tube.2024.102534. Epub 2024 Jun 13.

DOI:10.1016/j.tube.2024.102534
PMID:38909563
Abstract

BACKGROUND

Extrapulmonary tuberculosis (EPTB) without symptomatic pulmonary involvement has been thought to be non-transmissible, but EPTB with asymptomatic pulmonary tuberculosis (PTB) could transmit tuberculosis (TB). Genomic investigation of Mycobacterium tuberculosis (Mtb) isolates from EPTB may provide insight into its epidemiological role in TB transmission.

METHODS

Between January 2017 and May 2020, 107 Mtb isolates were obtained from surgical drainage of bone TB patients at the Beijing Chest Hospital, and 218 Mtb strains were isolated from PTB cases. These 325 Mtb isolates were whole-genome sequenced to reconstruct a phylogenetic tree, identify transmission clusters, and infer transmission links using a Bayesian approach. Possible subclinical PTB in the bone TB patients was investigated with chest imaging by two independent experts.

RESULTS

Among 107 bone TB patients, 10 were in genomic clusters (≤12 SNPs). Phylogenetic analysis suggested that three bone TB patients transmitted the infection to secondary cases, supported by epidemiological investigations. Pulmonary imaging of 44 bone TB patients revealed that 79.5 % (35/44) had radiological abnormalities suggestive of subclinical PTB.

CONCLUSIONS

This study provides genomic evidence that bone TB patients without clinically diagnosed PTB can be sources of TB transmission, underscoring the importance of screening for subclinical, transmissible PTB among EPTB cases.

摘要

背景

无肺部症状的肺外结核(EPTB)被认为不具有传染性,但无症状肺结核(PTB)合并 EPTB 可能具有传染性。对 EPTB 分枝杆菌(Mtb)分离株进行基因组研究可能有助于了解其在结核病传播中的流行病学作用。

方法

2017 年 1 月至 2020 年 5 月,从首都医科大学附属北京胸科医院骨结核患者的外科引流中获得了 107 株 Mtb 分离株,从肺结核患者中分离出了 218 株 Mtb 菌株。对这 325 株 Mtb 分离株进行全基因组测序,构建系统发育树,采用贝叶斯方法鉴定传播簇,并推断传播关系。由两位独立专家对骨结核患者进行胸部影像学检查,以确定可能存在的亚临床肺结核。

结果

107 例骨结核患者中,有 10 例存在基因组聚类(≤12 SNPs)。系统发育分析表明,3 例骨结核患者通过流行病学调查将感染传播给了二级病例。对 44 例骨结核患者的肺部影像学检查显示,79.5%(35/44)的患者存在放射学异常,提示存在亚临床肺结核。

结论

本研究提供了基因组证据,表明无临床诊断的肺结核的骨结核患者可能是结核病传播的源头,这凸显了对肺外结核病例进行亚临床、可传播肺结核筛查的重要性。

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