Public Health England.

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.

IntroductionNICE 2016 Tuberculosis guidance recommends significant changes in contact screening. Tuberculin Skin Test (TST) is advocated for diagnosis of latent tuberculosis infection (LTBI), with a positive TST redefined as 5mm regardless of BCG status, IGRA only to be used in diagnostic uncertainty, upper age for LTBI treatment raised from 35 to 65, and contact tracing no longer recommended for extra-pulmonary TB.We use a 2 step test, with IGRA for those with TST > 10 mm in context of BCG, and treat LTBI on basis of IGRA result. We aimed to assess the implications for our service of adopting the new guidance.MethodsWe reviewed written and electronic records for all contacts screened in Leeds in 2015. NICE 2016 guidance was applied retrospectively to analyse the impact of each recommendation and the guidance as a whole.Results216 contacts were screened. Full records were available for 193. 14 were treated for LTBI, 2 for active TB, and 6 contacts over 35 had X-ray follow up. 34 had TST > 10 mm, an additional 13 had TST 5–9 mm. Of 34 with TST > 10 mm, 14 (41%) had positive IGRA. 97/193 (50%) were contacts of extrapulmonary tuberculosis. 4 of these were treated for LTBI, but 21 had TST > 5 mm.Using TST > 5 mm cut off would increase the number of IGRA tests from 34 to 46. Treating on basis of TST alone would increase the number given chemoprophylaxis from 14 to 46. Stopping screening for contacts of extrapulmonary cases would reduce the number screened by 50% and the number treated from 46 to 29. However, this would be at the cost of missing at least 4/14 LTBI with positive IGRA.ConclusionAdopting the new NICE guidance in full would reduce the number screened but significantly increase the numbers treated for LTBI. Using the 2 step test with a TST cut off of 5mm would modestly increase the number of IGRA tests but would be unlikely to have a large impact on the number treated. Stopping screening for contacts of extrapulmonary TB would reduce the screening workload by 50% but reduce the number of LTBI cases diagnosed by 29%.