We used whole-genome sequencing to delineate transmission networks and investigate the benefits of whole-genome sequencing during cluster investigation.

We included clustered cases of M/XDR-TB linked by MIRU-VNTR, or epidemiological information in the national cluster B1006, notified between 2007-2013 in the UK. We excluded cases whose isolates differed by >12 SNPs from further investigation. Data relating to patients’ social networks were collected.

Twenty-seven cases were investigated, 22 had whole-genome sequencing; 8 (36%) of which were excluded as their isolates differed by >12 SNPs to other cases. Eighteen cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in 39% (7/18) of cases in the transmission network following whole-genome sequencing and epidemiological investigation.

This investigation of a drug resistant TB cluster illustrates the opportunities and limitations of whole-genome sequencing in understanding transmission in a setting with a high proportion of migrant cases. The use of WGS should be combined with classical epidemiological methods. However not every cluster will be solvable, regardless of the quality of genomic data.