Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission - 05/09/24

Doi : 10.1016/j.tube.2024.102534

Jinfeng Yin ^a,^b,^c,^{^{1
Equal contributions.}}, Guangxuan Yan ^a,^b,^{^{1
Equal contributions.}}, Liyi Qin ^a,^b,^{^{1
Equal contributions.}}, Chendi Zhu ^a,^b,^{^{1
Equal contributions.}}, Jun Fan ^a,^b, Yuwei Li ^a,^b, Junnan Jia ^a,^b, Zhaojun Wu ^a,^b, Hui Jiang ^a,^b, Muhammad Tahir Khan ^d, Jiangdong Wu ^e, Naihui Chu ^a,^b, Howard E. Takiff ^f, Qian Gao ^g, Shibing Qin ^a,^b,^⁎ , Qingyun Liu ^h,^i,^⁎ , Weimin Li ^a,^b,^j,^k,^⁎
^a Beijing Chest Hospital, Capital Medical University, Beijing, China
^b Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
^c China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
^d Institute of Molecular Biology and Biotechnology (IMBB), the University of Lahore, Lahore, Pakistan
^e Key Laboratory of Xinjiang Endemic and Ethnic Diseases Cooperated by Education Ministry with Xinjiang Province, Shihezi University, Shihezi, China
^f Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela
^g Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
^h Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
ⁱ Department of Microbiology and Immunology, UNC-Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA
^j Beijing Key Laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing, China
^k Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China

^⁎Corresponding author. Beijing Chest Hospital, Capital Medical University, Beijing, China.Beijing Chest HospitalCapital Medical UniversityBeijingChina^⁎⁎Corresponding author. Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijingChina^⁎⁎⁎Corresponding author. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.Department of GeneticsUniversity of North Carolina at Chapel HillChapel HillNC27599USA

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.

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Keywords : Bone tuberculosis, Transmission, Whole genome sequence, Epidemiology

Plan

Introduction

Methods

Patients and isolates

Whole-genome sequencing

GWAS and dN/dS analysis

Inferring transmission chains of clustered cases

Basic description of bone TB cases

Phylogenetic characteristics associated with bone TB

Genomic clustering of bone TB isolates

Bone TB patients without clinically diagnosed PTB transmitted tuberculosis

Chest imaging of bone TB patients suggested subclinical PTB

Discussion

Funding information

CRediT authorship contribution statement

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Article 102534- septembre 2024 Retour au numéro

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Genomic investigation of bone tuberculosis highlighted the role of subclinical pulmonary tuberculosis in transmission - 05/09/24

Abstract

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Conclusions

Plan

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