Assessment of Mycobacterium tuberculosis transmission in Oxfordshire, UK, 2007-12, with whole pathogen genome sequences: An observational study

Timothy M. Walker*, Maeve K. Lalor, Agnieszka Broda, Luisa Saldana Ortega, Marcus Morgan, Lynne Parker, Sheila Churchill, Karen Bennett, Tanya Golubchik, Adam P. Giess, Carlos Del Ojo Elias, Katie J. Jeffery, Ian C.J.W. Bowler, Ian F. Laurenson, Anne Barrett, Francis Drobniewski, Noel D. McCarthy, Laura F. Anderson, Ibrahim Abubakar, Helen ThomasPhilip Monk, E. Grace Smith, A. Sarah Walker, Derrick W. Crook, Tim E.A. Peto, Christopher P. Conlon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)

Abstract

Background: Patients born outside the UK have contributed to a 20% rise in the UK's tuberculosis incidence since 2000, but their effect on domestic transmission is not known. Here we use whole-genome sequencing to investigate the epidemiology of tuberculosis transmission in an unselected population over 6 years. Methods: We identified all residents with Oxfordshire postcodes with a Mycobacterium tuberculosis culture or a clinical diagnosis of tuberculosis between Jan 1, 2007, and Dec 31, 2012, using local databases and checking against the national Enhanced Tuberculosis Surveillance database. We used Illumina technology to sequence all available M tuberculosis cultures from identified cases. Sequences were clustered by genetic relatedness and compared retrospectively with contact investigations. The first patient diagnosed in each cluster was defined as the index case, with links to subsequent cases assigned first by use of any epidemiological linkage, then by genetic distance, and then by timing of diagnosis. Findings: Although we identified 384 patients with a diagnosis of tuberculosis, country of birth was known for 380 and we sequenced isolates from 247 of 269 cases with culture-confirmed disease. 39 cases were genomically linked within 13 clusters, implying 26 local transmission events. Only 11 of 26 possible transmissions had been previously identified through contact tracing. Of seven genomically confirmed household clusters, five contained additional genomic links to epidemiologically unidentified non-household members. 255 (67%) patients were born in a country with high tuberculosis incidence, conferring a local incidence of 109 cases per 100000 population per year in Oxfordshire, compared with 3·5 cases per 100000 per year for those born in low-incidence countries. However, patients born in the low-incidence countries, predominantly UK, were more likely to have pulmonary disease (adjusted odds ratio 1·8 [95% CI 1·2-2·9]; p=0·009), social risk factors (4·4 [2·0-9·4]; p<0·0001), and be part of a local transmission cluster (4·8 [1·6-14·8]; p=0·006). Interpretation: Although inward migration has contributed to the overall tuberculosis incidence, our findings suggest that most patients born in high-incidence countries reactivate latent infection acquired abroad and are not involved in local onward transmission. Systematic screening of new entrants could further improve tuberculosis control, but it is important that health care remains accessible to all individuals, especially high-risk groups, if tuberculosis control is not to be jeopardised. Funding: UK Clinical Research Collaboration (Wellcome Trust, Medical Research Council, National Institute for Health Research [NIHR]), and NIHR Oxford Biomedical Research Centre.

Original languageEnglish
Pages (from-to)285-292
Number of pages8
JournalThe Lancet Respiratory Medicine
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 2014

Bibliographical note

Funding Information:
The study was funded by the UK Clinical Research Collaboration, Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Health Innovation Challenge Fund, and Medical Research Council. TMW is an MRC research training fellow, DWC is an NIHR senior investigator, and IA is an NIHR senior research fellow. We thank David van Santen (Thames Valley Public Health England Centre) and Kunju Shaji (tuberculosis section, Public Health England, London, UK) for their assistance in the retrieval of epidemiological data.

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