The effect of age on whole blood interferon-gamma release assay response among children investigated for latent tuberculosis infection

Objective: To evaluate the effect of age upon QuantiFERON-TB Gold-In-Tube (QFT-IT) assay outcome among children examined for latent tuberculosis infection (LTBI). Study design: A cross-sectional study was conducted among 761 children (mean age ± SD: 7.84 ± 4.68 years) evaluated for LTBI. Participants were examined with both tuberculin skin test and QFT-IT (Cellestis, Australia) and categorized into 4 age groups. Multivariate logistic and linear regressions were used to evaluate the association between selected demographic and patient characteristics upon the qualitative and quantitative QFT-IT outcomes. Agreement between the tuberculin skin test and QFT-IT within groups was evaluated with the κ statistic. Results: QFT-IT indeterminate results occurred more frequently among young children (8.1%; P < .0001) and children (2.7%; P = .025) than adolescents (0.7%). Among QFT-IT positive patients, infants had higher mean (±SD) interferon-gamma (IFNγ) concentration than adolescents. QFT-IT positive (vs negative) outcome was associated with origin from a high tuberculosis endemicity setting (AOR = 4.54; 95% CI, 3.22-6.25) and lack of previous Bacille Calmette Guerin immunization (AOR = 2.70; 95% CI, 1.89-3.85), but not patient age (AOR = 0.96; 95% CI, 0.92-0.99). However, among QFT-IT positive patients, the IFNγ concentration was inversely associated with patient age (P = .009) and positively with mitogen response (P = .0002). Agreement between tests was not significantly different between younger and older children in the different risk groups. Conclusions: Qualitative QFT-IT assay results are not affected by patient age. However, indeterminate results occur more frequently among younger children. Among patients with LTBI the quantitative QFT-IT result (ie, IFNγ) is inversely associated with patient age.