title: Incremental value of T-SPOT.TB for diagnosis of active pulmonary tuberculosis in children in a high-burden setting: a multivariable analysis.
abstract: BACKGROUND
  Interferon γ release assays (IGRAs) are increasingly used for tuberculosis (TB) infection, but their incremental value beyond patient demographics, clinical signs and conventional tests for active disease has not been evaluated in children.
  
  
  METHODS
  The incremental value of T-SPOT.TB was assessed in 491 smear-negative children from two hospitals in Cape Town, South Africa. Bayesian model averaging was used to select the optimal set of patient demographics and clinical signs for predicting culture-confirmed TB. The added value of T-SPOT.TB over and above patient characteristics and conventional tests was measured using statistics such as the difference in the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).
  
  
  RESULTS
  Cough longer than 2 weeks, fever longer than 2 weeks, night sweats, malaise, history of household contact and HIV status were the most important predictors of culture-confirmed TB. Binary T-SPOT.TB results did not have incremental value when added to the baseline model with clinical predictors, chest radiography and the tuberculin skin test. The AUC difference was 3% (95% CI 0% to 7%). Using risk cut-offs of <10%, 10-30% and >30%, the NRI was 7% (95% CI -8% to 31%) but the CI included the null value. The IDI was 3% (95% CI 0% to 11%), meaning that the average predicted probability across all possible cut-offs improved marginally by 3%.
  
  
  CONCLUSIONS
  In a high-burden setting, the T-SPOT.TB did not have added value beyond clinical data and conventional tests for diagnosis of TB disease in smear-negative children.
authors.affiliation: Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec, Canada.
authors.forename: Daphne I
authors.initials: DI
authors.lastname: Ling
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nicol
authors.forename: Madhukar
authors.initials: M
authors.lastname: Pai
authors.forename: Sandra
authors.initials: S
authors.lastname: Pienaar
authors.forename: Nandini
authors.initials: N
authors.lastname: Dendukuri
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
mesh_terms: D019540:Area Under Curve; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D059425:Interferon-gamma Release Tests; D008297:Male; D015999:Multivariate Analysis; D012372:ROC Curve; D011859:Radiography; D013019:South Africa; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000000981:diagnostic imaging
keywords: Clinical Epidemiology; Tuberculosis