The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents

Rationale: Interferon-gamma release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described. Objectives: To assess QuantiFERON TB Gold In-Tube test (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting. Methods: Adolescents aged 12-18 years residing near Cape Town were recruited. Tuberculin skin tests (TSTs) and QFTs were performed at baseline and after 2 years of follow up. Half of the participants had TST and QFT performed at additional time points. Participants were Observed for incident tuberculosis disease for up to 5 years. Measurements and Main Results: Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) had positive QFT and TST results, respectively, at baseline. Annualized QFT and TST conversion risks were 14.0 and 13.0%, respectively, and reversion risks were 5.1 and 4.1%, respectively. Concordance was excellent for conversions (kappa = 0.74), but poor for reversions (kappa = 042). Among recent QFT converters, the magnitude of the QFT value was strongly inversely associated with risk of reversion (P < 0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters than in participants with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, P = 0.011). Conclusions: In this tuberculosis-endemic setting, annual risk of infection was extremely high, whereas QFT and TST conversion concordance was higher and QFT reversion rates were lower than reported in low-burden settings.