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The use of whole-genome sequencing in cluster investigation of a multidrug-resistant tuberculosis outbreak

Lookup NU author(s): Dr Kirsty Foster, Professor John Magee


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Copyright ©ERS 2018. 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.

Publication metadata

Author(s): Lalor MK, Casali N, Walker TM, Anderson LF, Davidson JA, Ratna N, Mullarkey C, Gent M, Foster K, Brown T, Magee J, Barrett A, Crook DW, Drobniewski F, Thomas HL, Abubakar I

Publication type: Article

Publication status: Published

Journal: European Respiratory Journal

Year: 2018

Volume: 51

Issue: 6

Print publication date: 01/06/2018

Online publication date: 21/06/2018

Acceptance date: 26/04/2018

ISSN (print): 0903-1936

ISSN (electronic): 1399-3003

Publisher: European Respiratory Society


DOI: 10.1183/13993003.02313-2017

PubMed id: 29748309


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