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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
  1. James A Seddon1,
  2. James Paton2,
  3. Zohreh Nademi3,4,
  4. Denis Keane1,
  5. Bhanu Williams5,
  6. Amanda Williams5,
  7. Steven B Welch6,
  8. Sue Liebeschutz7,
  9. Anna Riddell8,
  10. Jolanta Bernatoniene9,
  11. Sanjay Patel10,
  12. Nuria Martinez-Alier11,
  13. Paddy McMaster12,
  14. Beate Kampmann1,13
  1. 1Department of Academic Paediatrics, Centre of International Child Health, Imperial College London, London, UK
  2. 2School of Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK
  3. 3Department of Paediatrics, Great North Children's Hospital, Newcastle upon Tyne, Tyne and Wear, UK
  4. 4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK
  5. 5Department of Paediatrics, London North West Healthcare NHS Trust, Harrow, Middlesex, UK
  6. 6Birmingham Chest Clinic, Heart of England NHS Foundation Trust, Birmingham, West Midlands, UK
  7. 7Department of Paediatrics, Newham University Hospital, Barts Health NHS Trust, London, UK
  8. 8The Children's Hospital at the Royal London Hospital, Barts Health NHS Trust, London, UK
  9. 9Department of Paediatric Infectious Diseases, Bristol Royal Hospital for Children, Bristol, UK
  10. 10Department of Paediatric Infectious Diseases and Immunology, Southampton Children's Hospital, Southampton, UK
  11. 11Department of Paediatric Infectious Diseases, Evelina Children's Hospital, London, UK
  12. 12Department of Paediatric Infectious Diseases, North Manchester General Hospital, Manchester, UK
  13. 13Vaccines & Immunity Theme, Medical Research Council Unit, Atlantic Boulevard, Fajara, The Gambia
  1. Correspondence to Professor Beate Kampmann, Department of Paediatrics, Centre of International Child Health, Imperial College London, Norfolk Place, London W2 1PG, UK; b.kampmann{at}imperial.ac.uk

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.

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