title: The utility of an interferon gamma release assay for diagnosis of latent tuberculosis infection and disease in children: a systematic review and meta-analysis.
abstract: BACKGROUND
  The utility of interferon gamma release assays (IGRAs) has been assessed in adults, but remains unclear in children. We reviewed the literature on the use of a commercial IGRA in immunocompetent children for the diagnosis of both latent tuberculosis infection (LTBI) and TB disease.
  
  
  METHODS
  We searched PubMed for studies published before January 2010 on the diagnosis of TB in children using an IGRA. We compared the specificity and sensitivity of the tuberculin skin test (TST) and the IGRA for LTBI and conducted a random effects meta-analysis on sensitivity of the IGRA for TB disease.
  
  
  RESULTS
  Of 68 studies identified, 20 were included in this review. There was increased specificity of the IGRA for LTBI in children compared with TST, but varying sensitivities. Sensitivity of the IGRA in detecting TB disease in children also varied when compared with TST (mean κ score, 0.57). For all TB cases, the pooled sensitivity was 66% (95% confidence interval [CI], 53%-78%) with heterogeneity (I² = 74.8%). Stratification by background TB incidence highlighted a significantly reduced IGRA sensitivity of 55% (95% CI, 37%-73%) in high incidence settings when compared with low incidence settings, 70% (95% CI, 53%-84%).
  
  
  CONCLUSIONS
  There was no clear evidence that IGRAs should replace TST for detecting LTBI in children. Sensitivity of the IGRA for TB disease was no different from TST, and a significantly reduced IGRA sensitivity was found in high-burden TB settings compared with low-burden TB settings. Further studies are needed to determine the value of IGRAs in LTBI and TB disease diagnosis in children.
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Shingai
authors.initials: S
authors.lastname: Machingaidze
authors.forename: Charles Shey
authors.initials: CS
authors.lastname: Wiysonge
authors.forename: Yulieth
authors.initials: Y
authors.lastname: Gonzalez-Angulo
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.forename: Sizulu
authors.initials: S
authors.lastname: Moyo
authors.forename: Willem
authors.initials: W
authors.lastname: Hanekom
authors.forename: Hassan
authors.initials: H
authors.lastname: Mahomed
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019411:Clinical Laboratory Techniques / Q000379:methods*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D055985:Latent Tuberculosis / Q000175:diagnosis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012680:Sensitivity and Specificity; D014374:Tuberculin Test
chemical_list: D007371:Interferon-gamma