Interferon-gamma release assay positivity in populations at high risk of TB infection.
A F Dagnew, L L Han, A Cinar, D Gaikwad, A L Garcia-Basteiro, M T Gler, S R Hadinegoro, W A Hanekom, et al. (23 authors)
IJTLD open · 2026-04
Abstract
BACKGROUND: Phase 3 TB vaccine trials are challenging in low-incidence settings due to the need for large sample sizes and extended follow-up. This global, observational study evaluated population-based interferon-gamma release assay (IGRA) status - a measure of TB infection (TBI), as a proxy for TB incidence to identify trial sites in high-incidence areas.
METHODS: Participants (15-34 years) were recruited from 45 sites in 14 countries. IGRA status at Day 1 and Month 12, association of IGRA status with age, and IGRA conversion (TBI) were assessed.
RESULTS: Among 7,164 enrolled participants, Day 1 IGRA positivity varied across sites and within countries, with the highest prevalence observed in South Africa (58.7%, site 1006; 53.1%, site 1010; 51.9%, site 1007) and the Democratic Republic of Congo (50.0%, site 2303). IGRA positivity was generally higher among older participants. At Month 12, sites with highest IGRA conversion were observed in the Philippines (32.3%, site 1507) and Zambia (30.6%, site 1303).
CONCLUSION: In TB vaccine efficacy trials with clinical endpoints, selecting sites with the highest TB incidence is critical to optimise sample size and follow-up duration. Site-level IGRA status could inform site selection by identifying communities at increased risk ofinfection.