BackgroundPhase 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.MethodsParticipants (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.ResultsAmong 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).ConclusionIn 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 of Mycobacterium tuberculosis infection.