title: Interferon-gamma release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis.
abstract: BACKGROUND
  Diagnosis of childhood tuberculosis (TB) is challenging. The widely used tuberculin skin test (TST) may produce -positive results because of cross-reactivity with nontuberculous mycobacteria or bacille Calmette-Guerin vaccination, resulting in unnecessary treatment. Two recently developed interferon- gamma release assays (IGRAs) show good diagnostic accuracy for active TB in adults; pediatric data are limited, particularly in areas with a low incidence of TB. We assessed the diagnostic accuracy of IGRAs for TB in children in an area with a low incidence of TB.
  
  
  METHODS
  In a hospital-based study, the diagnostic accuracy of the TST and 2 IGRAs (T SPOT-TB [T-SPOT; Oxford Immunotec] and QuantiFERON-TB Gold In-Tube [QFT-IT; Cellestis]) were assessed in a cohort of 73 children (median age, 39 months); 28 children with bacteriologically confirmed TB were compared with children without TB (23 with bacteriologically confirmed nontuberculous mycobacterial lymphadenitis and 22 with other nonmycobacterial respiratory tract infections).
  
  
  RESULTS
  The specificity for TB of QFT-IT was 100% (95% confidence interval [CI], 91%-100%), and the specificity of T-SPOT was 98% (95% CI, 87%-100%), both of which were considerably higher than the specificity of TST (58%; 95% CI, 42%-73%). The specificity of the TST was 10.5% (95% CI, 1%-33%) in children with nontuberculous mycobacterial lymphadenitis and was 100% (95% CI, 83%-100%) in children with other nonmycobacterial respiratory tract infections. The sensitivity of both QFT-IT and T-SPOT was 93% (95% CI, 77%-99%), and the sensitivity of the TST was 100% (95% CI, 88%-100%). Agreement between the IGRAs was 95.6% ( kappa =0.91); 6.8% of the IGRAs showed indeterminate results.
  
  
  CONCLUSIONS
  Both IGRAs showed high diagnostic value in bacteriologically confirmed childhood TB. Their advantage in this study, when performed in addition to the TST, was the ability to distinguish -positive TST results caused by nontuberculous mycobacterial disease, thereby reducing overdiagnosis of TB and guiding clinical management.
authors.affiliation: Department of Pediatric Pneumology and Immunology, Charite University Medical Center, Berlin, Germany. anne.detjen@charite.de
authors.forename: A K
authors.initials: AK
authors.lastname: Detjen
authors.forename: T
authors.initials: T
authors.lastname: Keil
authors.forename: S
authors.initials: S
authors.lastname: Roll
authors.forename: B
authors.initials: B
authors.lastname: Hauer
authors.forename: H
authors.initials: H
authors.lastname: Mauch
authors.forename: U
authors.initials: U
authors.lastname: Wahn
authors.forename: K
authors.initials: K
authors.lastname: Magdorf
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D007223:Infant; D007371:Interferon-gamma / Q000097:blood* / Q000378:metabolism*; D009164:Mycobacterium Infections / Q000175:diagnosis*; D018579:Patient Selection; D012680:Sensitivity and Specificity; D014374:Tuberculin Test; D014376:Tuberculosis / Q000175:diagnosis* / Q000453:epidemiology
chemical_list: D007371:Interferon-gamma