title: Highly discordant T cell responses in individuals with recent exposure to household tuberculosis.
abstract: BACKGROUND
  There are limited data comparing interferon-gamma release assays (IGRAs) for the detection of Mycobacterium tuberculosis infection in highly endemic settings.
  
  
  METHODS
  A cross-sectional household contact study was conducted to measure the agreement of two IGRAs in relation to the tuberculin skin test (TST) to detect M tuberculosis infection and to assess the influence of M tuberculosis exposure and age.
  
  
  RESULTS
  In 82 individuals in household contact, 93% of children and 42% of adults had a high M tuberculosis contact score. The TST was positive in 78% of adults and 54% of children, the T-SPOT.TB was positive in 89% of children and 66% of adults and the QuantiFERON TB Gold (QTF) was positive in a similar proportion of adults and children (38.1% and 39.6%). In children there was poor agreement between the TST and T-SPOT.TB (kappa = -0.15) and the T-SPOT.TB and the QTF (kappa = -0.03), but good agreement between the TST and the QTF (kappa = 0.78) using 10 mm cut-off. In adults there was fair to moderate agreement between the TST and T-SPOT.TB (kappa = 0.38), the TST and QTF (kappa = 0.34) and T-SPOT.TB and QTF (kappa = -0.50). High levels of exposure to M tuberculosis were associated with at least a sevenfold odds of being T-SPOT.TB positive (95% CI 7.67 to 508.69) and a threefold odds of being QTF positive (95% CI 3.02 to 30.54). There was a significant difference in the magnitude of T-SPOT.TB early secretory antigenic target (ESAT)-6 and culture filtrate protein 10 kD (CFP-10) spot counts between adults and children.
  
  
  CONCLUSIONS
  The T-SPOT.TB may be more sensitive than the TST or QTF for detecting recent M tuberculosis infection in children. Differences between assays and the predictive utility of these findings for subsequent disease development should be prospectively assessed.
authors.affiliation: Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, 7505, South Africa. annekeh@sun.ac.za
authors.forename: A C
authors.initials: AC
authors.lastname: Hesseling
authors.forename: A M
authors.initials: AM
authors.lastname: Mandalakas
authors.forename: H L
authors.initials: HL
authors.lastname: Kirchner
authors.forename: N N
authors.initials: NN
authors.lastname: Chegou
authors.forename: B J
authors.initials: BJ
authors.lastname: Marais
authors.forename: K
authors.initials: K
authors.lastname: Stanley
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: G
authors.initials: G
authors.lastname: Black
authors.forename: N
authors.initials: N
authors.lastname: Beyers
authors.forename: G
authors.initials: G
authors.lastname: Walzl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology; D001426:Bacterial Proteins / Q000378:metabolism; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism*; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test / Q000379:methods; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000276:immunology*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma