Mycobacterium Tuberculosis Transmission in Birmingham, UK, 2009-19: A Prospective Observational Study

Background: Tuberculosis incidence has fallen in England over the past decade, reflecting pre-pandemic trends seen in many parts of the world. Methods: Between 1st January 2009 – 15th June 2019, we obtained the first whole-genome sequenced isolate from every patient resident in a postcode district covered by Birmingham's centralised tuberculosis service. Data on patients' sex, country of birth, UK entry year, 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 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 threshold. Findings 511/1,653 (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=0·27 (95%CI 0·18-0·41) and 0·42 (95%CI 0·34-0·53) vs. patients arriving in the UK within 2 years, or longer ago, respectively; p<0·001), the presence of a social risk factor (aHR=1·64 (95%CI 1·25-2·18), p<0·001), infectious (pulmonary/laryngeal/miliary) tuberculosis (aHR=2·45 (95%CI 1·84-3·26), p<0·001), and M. tuberculosis lineage 3 (aHR=2·40 (95%CI 1·45-3·97), p=0·01) and 4 (aHR=3·15 (95%CI 1·91-5·20), p<0·001), vs. lineage 1. There was marked heterogeneity in transmission patterns between postcode districts. Interpretation: 10·5 years of dense sampling and sequencing in England's second largest city reveals seasonal variation in the diagnosis of clustered cases only, and indicates around whom, when, and where to focus contact tracing