title: A three-way comparison of tuberculin skin testing, QuantiFERON-TB gold and T-SPOT.TB in children.
abstract: BACKGROUND
  There are limited data comparing the performance of the two commercially available interferon gamma (IFN-gamma) release assays (IGRAs) for the diagnosis of tuberculosis (TB) in children. We compared QuantiFERON-TB gold In Tube (QFT-IT), T-SPOT.TB and the tuberculin skin test (TST) in children at risk for latent TB infection or TB disease.
  
  
  RESULTS
  The results of both IGRAs were compared with diagnosis assigned by TST-based criteria and assessed in relation to TB contact history. Results from the TST and at least one assay were available for 96 of 100 children. Agreement between QFT-IT and T-SPOT.TB was high (93% agreement, kappa = 0.83). QFT-IT and T-SPOT.TB tests were positive in 8 (89%) and 9 (100%) children with suspected active TB disease. There was moderate agreement between TST and either QFT-IT (75%, kappa = 0.50) or T-SPOT.TB (75%, kappa = 0.51). Among 38 children with TST-defined latent TB infection, QFT-IT gold and T-SPOT.TB assays were positive in 47% and 39% respectively. Three TST-negative children were positive by at least one IGRA. Children with a TB contact were more likely than children without a TB contact to have a positive IGRA (QFT-IT LR 3.9; T-SPOT.TB LR 3.9) and a positive TST (LR 1.4). Multivariate linear regression analysis showed that the magnitude of both TST induration and IGRA IFN-gamma responses was significantly influenced by TB contact history, but only the TST was influenced by age.
  
  
  CONCLUSIONS
  Although a high level of agreement between the IGRAs was observed, they are commonly discordant with the TST. The correct interpretation of a negative assay in a child with a positive skin test in clinical practice remains challenging and highlights the need for longitudinal studies to determine the negative predictive value of IGRAs.
authors.affiliation: Department of Paediatrics, University of Melbourne, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia.
authors.forename: Tom G
authors.initials: TG
authors.lastname: Connell
authors.forename: Nicole
authors.initials: N
authors.lastname: Ritz
authors.forename: Georgia A
authors.initials: GA
authors.lastname: Paxton
authors.forename: Jim P
authors.initials: JP
authors.lastname: Buttery
authors.forename: Nigel
authors.initials: N
authors.lastname: Curtis
authors.forename: Sarath C
authors.initials: SC
authors.lastname: Ranganathan
mesh_terms: D000293:Adolescent; D002648:Child; D003627:Data Interpretation, Statistical; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000379:methods*; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D007371:Interferon-gamma