title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Academic Paediatrics, Centre of International Child Health, Imperial College London, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Seddon
authors.affiliation: School of Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: James
authors.initials: J
authors.lastname: Paton
authors.affiliation: Department of Paediatrics, Great North Children's Hospital, Newcastle upon Tyne, Tyne and Wear, UK Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Nademi
authors.affiliation: Department of Academic Paediatrics, Centre of International Child Health, Imperial College London, London, UK.
authors.forename: Denis
authors.initials: D
authors.lastname: Keane
authors.affiliation: Department of Paediatrics, London North West Healthcare NHS Trust, Harrow, Middlesex, UK.
authors.forename: Bhanu
authors.initials: B
authors.lastname: Williams
authors.affiliation: Department of Paediatrics, London North West Healthcare NHS Trust, Harrow, Middlesex, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Williams
authors.affiliation: Birmingham Chest Clinic, Heart of England NHS Foundation Trust, Birmingham, West Midlands, UK.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Welch
authors.affiliation: Department of Paediatrics, Newham University Hospital, Barts Health NHS Trust, London, UK.
authors.forename: Sue
authors.initials: S
authors.lastname: Liebeschutz
authors.affiliation: The Children's Hospital at the Royal London Hospital, Barts Health NHS Trust, London, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Riddell
authors.affiliation: Department of Paediatric Infectious Diseases, Bristol Royal Hospital for Children, Bristol, UK.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Bernatoniene
authors.affiliation: Department of Paediatric Infectious Diseases and Immunology, Southampton Children's Hospital, Southampton, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Paediatric Infectious Diseases, Evelina Children's Hospital, London, UK.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martinez-Alier
authors.affiliation: Department of Paediatric Infectious Diseases, North Manchester General Hospital, Manchester, UK.
authors.forename: Paddy
authors.initials: P
authors.lastname: McMaster
authors.affiliation: Department of Academic Paediatrics, Centre of International Child Health, Imperial College London, London, UK Vaccines & Immunity Theme, Medical Research Council Unit, Atlantic Boulevard, Fajara, The Gambia.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
mesh_terms: D000293:Adolescent; D000375:Aging / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D019317:Evidence-Based Medicine / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D059425:Interferon-gamma Release Tests; D008297:Male; D008403:Mass Screening / Q000379:methods; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D014373:Tuberculin / Q000276:immunology; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D014373:Tuberculin
keywords: Paediatric Lung Disaese; Respiratory Infection; Tuberculosis