A Whole-Genome Sequencing-Based Study to Delineate the Risk and Characteristics of Tuberculosis Transmission in an Insular Population Over 10 Years in Shanghai.

Min Wang,Genming Zhao,Xin Shen,Yuan Jiang,Qichao Pan,Yangyi Zhang,Cheng Huang,Jing Li

doi:10.3389/fmicb.2021.768659

Abstract

BackgroundTuberculosis (TB) has remained a tough problem in China. This study aims to identify the risk of tuberculosis transmission and to assess its characteristics.MethodsWe performed a molecular epidemiological study for patients with culture-positive Mycobacterium tuberculosis (M. tuberculosis) in Shanghai, from 2009 to 2018. Demographic information was obtained from the Tuberculosis Information Management System. Whole-genome sequencing (WGS) was conducted with a threshold of 12 single-nucleotide polymorphisms (SNPs) to distinguish the genomic cluster. To analyze the characteristics of TB transmission, the contact investigation for clustered cases was performed.ResultsIn total, 94 (27.25%) of the 345 enrolled patients were grouped into 42 genomic clusters, indicating local transmission of M. tuberculosis strains. Compared to a health system delay <14 days, patients with a health system delay ≥14 days [adjusted odds ratios (AOR) = 2.57, 95% confidence interval (CI): 1.34–4.95] were more likely to be clustered. Patients under 65 years old (AOR = 3.11, 95% CI: 1.76–5.49), residents (AOR = 2.43, 95% CI: 1.18–4.99), and Beijing genotype strains (AOR = 3.35, 95% CI: 1.32–8.53) were associated with increased risk of clustering. Interestingly, patients with resistance to isoniazid (AOR = 2.36, 95% CI: 1.15–4.88) had a higher risk of transmission. Sixteen confirmed/probable epidemiological links were identified. Local transmission of imported cases and household transmission were prominent.ConclusionHealth system delay is a crucial factor for TB transmission. Patients with resistance to isoniazid should be priority targets for contact investigation to reduce transmission.

Highlights

Tuberculosis (TB) is a chronic communicable disease and remains a serious public threat worldwide
A systematic review reported that treatment of isoniazid-resistant TB with the standardized first-line regimen led to treatment failure in 11% of the cases, compared with 2% among drug-susceptible TB patients (Gegia et al, 2017)
Our study suggested that patients under 65 years old or residents had a higher risk for transmission

Summary

Introduction

Tuberculosis (TB) is a chronic communicable disease and remains a serious public threat worldwide. Standard TB infection control focuses on patients already on treatment, but the spread of TB should not be ignored under frequent social activities. Transmission leads to new infections and cases. Next-generation sequencing technologies have facilitated the development of molecular epidemiology, and we can study the transmission of TB at a high resolution (Gagneux, 2017). Molecular approaches can help differentiate between reactivation or reinfection among TB cases, whole-genome sequencing (WGS) has been proven invaluable to illustrate the network and direction of transmission in recent years (Walker et al, 2014; Comin et al, 2020). Tuberculosis (TB) has remained a tough problem in China. This study aims to identify the risk of tuberculosis transmission and to assess its characteristics

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