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 W ; Robinson, Esther R ; Walker, A Sarah ; Smith, E Grace ... show 1 more
Walker, Timothy M
Choisy, Marc
Drennan, Philip G
Wyllie, David
Yang-Turner, Fan
Crook, Derrick W
Robinson, Esther R
Walker, A Sarah
Smith, E Grace
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2022-03-24
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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.
Citation
Walker TM, Choisy M, Dedicoat M, Drennan PG, Wyllie D, Yang-Turner F, Crook DW, Robinson ER, Walker AS, Smith EG, Peto TEA. Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: An observational study. Lancet Reg Health Eur. 2022 Mar 24;17:100361. doi: 10.1016/j.lanepe.2022.100361
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Article