Targeted tuberculosis vaccination strategies in the United States: A modeling study.

BACKGROUND: Tuberculosis (TB) incidence in the United States has remained elevated above pre-pandemic levels since 2021, with over 85% of cases resulting from reactivation of Mycobacterium tuberculosis (Mtb) infection. New vaccines that would prevent TB in adults are under development, but the potential health impact of a program prioritizing non-U.S.-born persons and persons with medical comorbidities, including persons living with HIV (PLWH), has not been evaluated. METHODS: We developed a deterministic compartmental transmission model that simulates Mtb infection, transmission, and progression to TB in the U.S., stratified into four risk groups. We calibrated the model to 2024 U.S. TB surveillance data and estimated annual cases prevented, percent reduction in TB cases, and number needed to vaccinate (NNV) for targeted vaccination strategies under optimistic and conservative scenarios, varying vaccine efficacy, duration of protection, and vaccination coverage. RESULTS: Under an optimistic scenario, vaccinating all high-risk groups (PLWH, non-U.S.-born persons, and persons with medical comorbidities) prevented 5385 cases per year (51.8% reduction, 95% UI: 35.2-66.8, NNV = 366). Under a conservative scenario, the same strategy prevented 1348 cases per year (13.0% reduction, 95% UI: 6.4-19.8, NNV = 510). Strategy rankings were preserved across all sensitivity and uncertainty analyses. CONCLUSIONS: Targeted vaccination of adults at high risk of progression from Mtb infection to TB disease can reduce U.S. TB incidence substantially. Strategies that include non-U.S.-born persons and PLWH are most efficient and impactful.