Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study
<strong>Background<br></strong> 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. <br><strong> Methods<br></stron...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Elsevier
2022
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| _version_ | 1826307890481201152 |
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| author | Walker, T Choisy, M Dedicoat, M Drennan, P Wyllie, D Yang-Turner, F Crook, D Robinson, E Walker, A Smith, EG Peto, T |
| author_facet | Walker, T Choisy, M Dedicoat, M Drennan, P Wyllie, D Yang-Turner, F Crook, D Robinson, E Walker, A Smith, EG Peto, T |
| author_sort | Walker, T |
| collection | OXFORD |
| description | <strong>Background<br></strong>
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.
<br><strong>
Methods<br></strong>
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.
<br><strong>
Findings<br></strong>
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.
<br><strong>
Interpretation<br></strong>
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.
<br><strong>
Funding<br></strong>
Wellcome Trust, MRC, UKHSA |
| first_indexed | 2024-03-07T07:09:48Z |
| format | Journal article |
| id | oxford-uuid:cf6fc75d-f987-4c37-acda-6577e43a86f4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:09:48Z |
| publishDate | 2022 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:cf6fc75d-f987-4c37-acda-6577e43a86f42022-06-06T15:58:55ZMycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cf6fc75d-f987-4c37-acda-6577e43a86f4EnglishSymplectic ElementsElsevier2022Walker, TChoisy, MDedicoat, MDrennan, PWyllie, DYang-Turner, FCrook, DRobinson, EWalker, ASmith, EGPeto, T<strong>Background<br></strong> 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. <br><strong> Methods<br></strong> 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. <br><strong> Findings<br></strong> 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. <br><strong> Interpretation<br></strong> 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. <br><strong> Funding<br></strong> Wellcome Trust, MRC, UKHSA |
| spellingShingle | Walker, T Choisy, M Dedicoat, M Drennan, P Wyllie, D Yang-Turner, F Crook, D Robinson, E Walker, A Smith, EG Peto, T Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title | Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title_full | Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title_fullStr | Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title_full_unstemmed | Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title_short | Mycobacterium tuberculosis transmission in Birmingham, UK, 2009-19: an observational study |
| title_sort | mycobacterium tuberculosis transmission in birmingham uk 2009 19 an observational study |
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