Whole genome sequencing for tuberculosis in Victoria, Australia: A genomic implementation study from 2017 to 2020

Background Whole genome sequencing (WGS) is increasingly used by tuberculosis (TB) programs to monitor Mycobacterium tuberculosis (Mtb) transmission. We aimed to characterise the molecular epidemiology of TB and Mtb transmission in the low-incidence setting of Victoria, Australia, and assess the utility of WGS. Methods WGS was performed on all first Mtb isolates from TB cases from 2017 to 2020. Potential clusters (& LE;12 single nucleotide polymorphisms [SNPs]) were investigated for epidemiological links. Transmission events in highly -related (<= 5 SNPs) clusters were classified as likely or possible, based on the presence or absence of an epidemiological link, respectively. Case characteristics and transmission settings (as defined by case relationship) were summarised. Poisson regression was used to examine associations with secondary case number. Findings Of 1844 TB cases, 1276 (69.2%) had sequenced isolates, with 182 (14.2%) in 54 highly-related clusters, 2-40 cases in size. Following investigation, 140 cases (11.0% of sequenced) were classified as resulting from likely/ possible local-transmission, including 82 (6.4%) for which transmission was likely. Common identified transmission settings were social/religious (26.4%), household (22.9%) and family living in different households (7.1%), but many were uncertain (41.4%). While household transmission featured in many clusters (n = 24), clusters were geerally smaller (median = 3 cases) than the fewer that included transmission in social/religious settings (n = 12, median = 7.5 cases). Sputum-smear-positivity was associated with higher secondary case numbers. Interpretation WGS results suggest Mtb transmission commonly occurs outside the household in our low -incidence setting. Further work is required to optimise the use of WGS in public health management of TB. Copyright (c) 2022 The Authors. Published by Elsevier Ltd.

Automated summary

This study used whole genome sequencing to characterize the molecular epidemiology of tuberculosis and Mycobacterium tuberculosis transmission in a low-incidence setting in Victoria, Australia. The results suggest that Mtb transmission commonly occurs outside the household, particularly in social/religious settings. Further research is needed to optimize the use of whole genome sequencing in the public health management of tuberculosis.