Predictive Value of Recent QuantiFERON Conversion for Tuberculosis Disease in Adolescents

Rationale: Conversions and reversions occur with IFN-gamma release assay (IGRA) serial testing, as with the tuberculin skin test (TST). Recent TST conversion is associated with an established risk of developing tuberculosis (TB) disease, but the risk associated with recent IGRA conversions is unknown. Objectives: To compare the incidence rate of TB disease after recent QuantiFERON TB Gold In-Tube (QFT) conversion compared with nonconverters. Methods: Adolescents with converted IGRA status (QFT converters [n = 534]) and randomly chosen adolescents whose IGRA status had remained negative over a period of 2 years (QFT nonconverters [n = 629]) were identified in a cohort study of TB infection and disease. Subsequent TB disease incidence was compared between the two groups. Measurements and Main Results: For QFT converters, the TB incidence rate (all cases) was 1.46 cases per 100 person-years (95% confidence interval [CI], 0.82-2.39), and the cumulative incidence was 2.8% (95% CI, 1.58-4.59). A significantly lower TB incidence rate (0.17 cases per 100 person-yr [95% CI, 0.02-0.62]) and cumulative incidence (0.32% [95% CI, 0.03-1.14]) was observed for QFT nonconverters. The incidence rate ratio was 8.54 (95% CI, 2.51-29.13) for all cases of TB and 9.1 (95% CI, 1.65-50.36) for protocol-defined TB. Conclusions: Recent QFT conversion was indicative of an approximately eight fold higher risk of progression to TB disease (compared with nonconverters) within 2 years of conversion in a cohort of adolescents in a high-TB burden population.