The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection

Seddon, J. A. et al. (2016) The impact of BCG vaccination on tuberculin skin test responses in children is age dependent: evidence to be considered when screening children for tuberculosis infection. Thorax, 71(10), pp. 932-939. (doi: 10.1136/thoraxjnl-2015-207687) (PMID:27335104) (PMCID:PMC5036222)

Abstract

Background: Following exposure to TB, contacts are screened to target preventive treatment at those at high risk of developing TB. The UK has recently revised its recommendations for screening and now advises a 5 mm tuberculin skin test (TST) cut-off irrespective of age or BCG status. We sought to evaluate the impact of BCG on TST responses in UK children exposed to TB and the performance of different TST cut-offs to predict interferon γ release assay (IGRA) positivity. Methods: Children <15 years old were recruited from 11 sites in the UK between January 2011 and December 2014 if exposed in their home to a source case with sputum smear or culture positive TB. Demographic details were collected and TST and IGRA undertaken. The impact of BCG vaccination on TST positivity was evaluated in IGRA-negative children, as was the performance of different TST cut-offs to predict IGRA positivity. Results: Of 422 children recruited (median age 69 months; IQR: 32–113 months), 300 (71%) had been vaccinated with BCG. BCG vaccination affected the TST response in IGRA-negative children less than 5 years old but not in older children. A 5 mm TST cut-off demonstrated good sensitivity and specificity in BCG-unvaccinated children, and an excellent negative predictive value but was associated with low specificity (62.7%; 95% CI 56.1% to 69.0%) in BCG-vaccinated children. For BCG-vaccinated children, a 10 mm cut-off provided a high negative predictive value (97.7%; 95% CI 94.2% to 99.4%) with the positive predictive value increasing with increasing age of the child. Discussion: BCG vaccination had little impact on TST size in children over 5 years of age. The revised TST cut-off recommended in the recent revision to the UK TB guidelines demonstrates good sensitivity but is associated with impaired specificity in BCG-vaccinated children.

• Item Type: Articles
• Additional Information: This work was funded by a NIHR Senior Research Fellowship to BK (NIHR/ SRF-2009-02-07). JAS was supported by an NIHR Academic Clinical Lectureship and also through grants from the Academy of Medical Sciences and the BRC. The research and DK were supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Paton, Dr James
• Authors: Seddon, J. A., Paton, J., Nademi, Z., Keane, D., Williams, B., Williams, A., Welch, S. B., Liebeschutz, S., Riddell, A., Bernatoniene, J., Patel, S., Martinez-Alier, N., McMaster, P., and Kampmann, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Thorax
• Publisher: BMJ Publishing Group
• ISSN: 0040-6376
• ISSN (Online): 1468-3296
• Published Online: 22 June 2016
• Copyright Holders: Copyright © 2016 The Authors
• First Published: First published in Thorax 71(10): 932-939
• Publisher Policy: Reproduced under a Creative Commons License