We used whole-genome sequencing (WGS) to delineate transmission networks and investigate the benefits of WGS during cluster investigation.
We included clustered cases of multidrug-resistant (MDR) tuberculosis (TB)/extensively drug-resistant (XDR) TB linked by mycobacterial interspersed repetitive unit variable tandem repeat (MIRU-VNTR) strain typing or epidemiological information in the national cluster B1006, notified between 2007 and 2013 in the UK. We excluded from further investigation cases whose isolates differed by greater than 12 single nucleotide polymorphisms (SNPs). Data relating to patients' social networks were collected.
27 cases were investigated and 22 had WGS, eight of which (36%) were excluded as their isolates differed by more than 12 SNPs to other cases. 18 cases were ruled into the transmission network based on genomic and epidemiological information. Evidence of transmission was inconclusive in seven out of 18 cases (39%) in the transmission network following WGS and epidemiological investigation.
This investigation of a drug-resistant TB cluster illustrates the opportunities and limitations of WGS 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.
Author contributions: M.K. Lalor, H.L. Thomas and I. Abubakar conceived and designed the study. M.K. Lalor, L.F. Anderson, J.A. Davidson, N. Ratna, C. Mullarkey, M. Gent, K. Foster and F. Drobniewski collected data for the study. T.M. Walker and N. Casali conducted sequencing and sequencing analysis for the study. M.K. Lalor carried out the analysis and wrote the manuscript. T. Brown, J. Magee, A. Barrett and F. Drobniewski provided isolates for the study. All authors were involved in the incident, contributed to the design of the analysis and commented on manuscript versions. All authors have read and approved the final version of this manuscript. Ethics approval and consent to participate: Public Health England has authority under the Health and Social Care Act 2012 to hold and analyse national surveillance data for public health and research purposes.
Conflict of interest: None declared.
Support statement: This study was supported by Public Health England, no external funding was received. F. Drobniewski and N. Casali were supported by the Imperial Biomedical Research Centre.
Received November 9, 2017.
Accepted April 26, 2018.
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