title: Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis.
abstract: BACKGROUND
  Children infected with Mycobacterium tuberculosis have significant risk of developing tuberculosis(TB) and can therefore benefit from preventive therapy.
  
  
  OBJECTIVE
  To assess the value of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST)in the diagnosis of TB infection and disease in children.
  
  
  METHODS
  Thirty-three studies were included, assessing commercial IGRAs (QuantiFERON®-TB [QFT] andT-SPOT.®TB) and TST. Reference standards for infection were incident TB or TB exposure. Test performance for disease diagnosis was evaluated in studies assessing children with confirmed and/or clinically diagnosed TB,compared to children where TB was excluded.
  
  
  RESULTS
  Two small studies measured incident TB in children tested with QFT and found weak positive predictive value. Association of test response with exposure-categorized dichotomously or as a gradient-was similar for all tests. The sensitivity and specificity of all tests were similar in diagnosing the disease. Stratified analysis suggested lower sensitivity for all tests in young or human immuno deficiency virus infected children.
  
  
  CONCLUSIONS
  Available data suggest that TST and IGRAs have similar accuracy for the detection of TB infection or the diagnosis of disease in children. Heterogeneous methodology limited the comparability of studies and the interpretation of results. A rigorous, standardized approach to evaluate TB diagnostic tests in children is needed.
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio, USA. anna.mandalakas@case.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Mandalakas
authors.forename: A K
authors.initials: AK
authors.lastname: Detjen
authors.forename: A C
authors.initials: AC
authors.lastname: Hesseling
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
authors.forename: D
authors.initials: D
authors.lastname: Menzies
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000592:standards; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology*; D014374:Tuberculin Test / Q000592:standards; D014376:Tuberculosis / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology
chemical_list: D007371:Interferon-gamma