Relating Tuberculosis (TB) Contact Characteristics to QuantiFERON-TB-Gold and Tuberculin Skin Test Results in the Toronto Pediatric TB Clinic

Background. Few data relate interferon-gamma-release-assay results in children to source case sputum status, the best predictor of infectiousness of tuberculosis (TB) patients. We evaluated the QuantiFERON-Gold-in-tube assay (QFT) and tuberculin skin test (TST) in children with different types of TB exposure. Methods. The TST and QFT were performed in referred TB-exposed children and adolescents who had not undergone prior TST screening (tested in parallel), and the QFT was performed in referred TST-positive individuals. Source case characteristics were obtained from referring public health units. We excluded children with known immunocompromising conditions and those known to have TB disease at the time of evaluation. Results. For 103 patients tested in parallel, overall test agreement was very good in the Bacillus Calmette-Guerein (BCG) unimmunized contacts (kappa = 0.83) and contacts of household smear-positive (HS+) cases (kappa = 0.67), but test agreement was poor in those with lower-risk contact (kappa = 0.34). Only 3 of 59 HS+ patients were QFT-positive and TST-negative. On multivariate analysis, a positive QFT was strongly associated with HS + exposure (odds ratio [OR], 6.6; 95% confidence interval [CI], 2.2-20]) but not BCG; and a positive TST was associated with BCG alone. For 92 referred TST-positive individuals, the QFT was negative in 21% of HS+ contacts, 65% of lower-risk contacts (OR, 6.8; 95% CI, 1.9-25), and 82% of the patients with unknown contact history (OR, 15.5; 95% CI, 5-54). Application of the Canadian 2010 guidelines would exclude from treatment 43 (72%) of the 73 TST+, QFT- patients. Conclusions. For close contacts of HS+ individuals, the QFT added little sensitivity to the TST for detection of TB infection. The QFT correlated much better with exposure than the TST, especially in BCG-immunized children, and it has the greatest potential benefit for evaluation of those at lower risk of latent TB infection.