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Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study

Walker, Timothy M; Choisy, Marc; Dedicoat, Martin; Drennan, Philip G; Wyllie, David; Yang-Turner, Fan; Crook, Derrick; ... Peto, Timothy EA; + view all (2022) Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study. Lancet Regional Health Europe , 17 , Article 100361. 10.1016/j.lanepe.2022.100361. Green open access

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Abstract

Background: Over 10-years of whole-genome sequencing (WGS) of Mycobacterium tuberculosis in Birmingham presents an opportunity to explore epidemiological trends and risk factors for transmission in new detail. Methods: Between 1st January 2009 and 15th June 2019, we obtained the first WGS isolate from every patient resident in a postcode district covered by Birmingham's centralised tuberculosis service. Data on patients’ sex, country of birth, social risk-factors, anatomical locus of disease, and strain lineage were collected. Poisson harmonic regression was used to assess seasonal variation in case load and a mixed-effects multivariable Cox proportionate hazards model was used to assess risk factors for a future case arising in clusters defined by a 5 single nucleotide polymorphism (SNP) threshold, and by 12 SNPs in a sensitivity analysis. Findings: 511/1653 (31%) patients were genomically clustered with another. A seasonal variation in diagnoses was observed, peaking in spring, but only among clustered cases. Risk-factors for a future clustered case included UK-birth (aHR=2·03 (95%CI 1·35–3·04), p < 0·001), infectious (pulmonary/laryngeal/miliary) tuberculosis (aHR=3·08 (95%CI 1·98-4·78), p < 0·001), and M. tuberculosis lineage 3 (aHR=1·91 (95%CI 1·03–3·56), p = 0·041) and 4 (aHR=2·27 (95%CI 1·21–4·26), p = 0·011), vs. lineage 1. Similar results pertained to 12 SNP clusters, for which social risk-factors were also significant (aHR 1·72 (95%CI 1·02–2·93), p = 0·044). There was marked heterogeneity in transmission patterns between postcode districts. Interpretation: There is seasonal variation in the diagnosis of genomically clustered, but not non-clustered, cases. Risk factors for clustering include UK-birth, infectious forms of tuberculosis, and infection with lineage 3 or 4. Funding: Wellcome Trust, MRC, UKHSA

Type: Article
Title: Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.lanepe.2022.100361
Publisher version: https://doi.org/10.1016/j.lanepe.2022.100361
Language: English
Additional information: © 2022 Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/)
Keywords: Mycobacterium tuberculosis, Epidemiology, Whole genome sequencing, Seasonality, Transmission
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10144788
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