<i>Mycobacterium tuberculosis</i> transmission in Birmingham, UK, 2009-19: An observational study.

Abstract

Over 10-years of whole-genome sequencing (WGS) of <i>Mycobacterium tuberculosis</i> in Birmingham presents an opportunity to explore epidemiological trends and risk factors for transmission in new detail. 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. 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), <i>p</i> < 0·001), infectious (pulmonary/laryngeal/miliary) tuberculosis (aHR=3·08 (95%CI 1·98-4·78), <i>p</i> < 0·001), and <i>M. tuberculosis</i> lineage 3 (aHR=1·91 (95%CI 1·03-3·56), <i>p</i> = 0·041) and 4 (aHR=2·27 (95%CI 1·21-4·26), <i>p</i> = 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), <i>p</i> = 0·044). There was marked heterogeneity in transmission patterns between postcode districts. 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. Wellcome Trust, MRC, UKHSA.