An observational study of M. tuberculosis transmission in Oxfordshire using whole pathogen genome sequences

Tuberculosis incidence has risen by over 20% since 2000 with additional cases largely accounted for by patients born overseas. To understand the relative contributions of reactivated and newly acquired disease to overall incidence, we use whole genome sequencing (WGS) to investigate the epidemiology of tuberculosis in Oxfordshire. We identified all Oxfordshire tuberculosis patients between 2007-2012 and sequenced positive cultures at the Wellcome Trust Centre for Human Genetics in Oxford using Illumina technology. Epidemiological data was derived from past contact investigations and from the PHE Extended Tuberculosis Surveillance database. In total 385 patients with tuberculosis were identified and 253/269 of those with culture confirmed diseases sequenced. 11% of cases were genomically linked to another case, but epidemiological investigations had previously identified only up to 50% of these transmission events. 254 patients were born in a country with an incidence >50/100000, but it was those born in countries with an incidence less than 50/100000 who were more likely to have pulmonary disease (p=0.02), and who were more likely be part of a WGS defined cluster (p<0.001). Interrogating an archive of previously sequenced cases, Oxfordshire patients could be genomically linked to patients in the Midlands on two occasions. These results demonstrate how WGS can help clarify local tuberculosis epidemiology, direct contact investigations and inform the design of control measures, and identify potential transmission events across geographical boundaries.