title: Use of T cell-based diagnosis of tuberculosis infection to optimize interpretation of tuberculin skin testing for child tuberculosis contacts.
abstract: BACKGROUND
  Treatment of recent tuberculosis infection in children aged <2 years is essential, because of high risk of progression to disease, but diagnosis is hindered by the inaccuracy of the tuberculin skin test (TST). More-accurate T cell-based tests of infection could enhance diagnosis by optimizing interpretation of the TST results.
  
  
  METHODS
  A total of 979 child tuberculosis contacts in Istanbul underwent the TST and enzyme-linked immunospot assay. Using enzyme-linked immunospot test results as a reference standard, we assessed the effect of age and bacille Calmette-Guérin (BCG) vaccination on the sensitivity and specificity of the TST, and we computed the optimal TST cutoff points, using receiver operating characteristic curves.
  
  
  RESULTS
  With a TST cutoff point of >or=10 mm, the sensitivity of the TST was 66% for children aged <2 years, which was lower than that for older children (P= .006). Specificity was 75% for BCG-vaccinated children, compared with 92% for unvaccinated children (P= .001). Optimal cutoff points improved TST specificity for children with 1 BCG scar, with little loss of sensitivity. Despite the use of optimal cutoff points, TST sensitivity remained <70% for children aged <2 years, specificity remained <87% for BCG-vaccinated children aged >or=2 years, and overall accuracy was low for children with >1 BCG scar.
  
  
  CONCLUSIONS
  Negative results of the TST cannot exclude tuberculosis infection for child tuberculosis contacts aged <2 years, which supports the use of preventive therapy regardless of the TST results for this age group. In children aged >or=2 years, the accuracy of the TST can be improved by adjustment of cutoff points for BCG-vaccinated children but remains poor for children with >1 BCG scar. This methodology can define optimal TST cutoff points for diagnosis of tuberculosis infection tailored to target populations.
authors.affiliation: Department of Paediatrics, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Bakir
authors.forename: Davinder P S
authors.initials: DP
authors.lastname: Dosanjh
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Deeks
authors.forename: Ahmet
authors.initials: A
authors.lastname: Soysal
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Millington
authors.forename: Serpil
authors.initials: S
authors.lastname: Efe
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Aslan
authors.forename: Dilek
authors.initials: D
authors.lastname: Polat
authors.forename: Nihat
authors.initials: N
authors.lastname: Kodalli
authors.forename: Aysegul
authors.initials: A
authors.lastname: Yagci
authors.forename: Isil
authors.initials: I
authors.lastname: Barlan
authors.forename: Nerin
authors.initials: N
authors.lastname: Bahceciler
authors.forename: Emel E
authors.initials: EE
authors.lastname: Demiralp
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000293:Adolescent; D001500:BCG Vaccine / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis*; D014421:Turkey
chemical_list: D001500:BCG Vaccine