We estimate substantial impacts on TB morbidity and mortality due to reductions in international donor funding. Expanded support from domestic and international donors is essential to address immediate gaps in prevention, diagnosis, and treatment.

Impact details available upon request.

Impact details available upon request.

Impact details available upon request.

Impact details available upon request.

Tuberculosis (TB) remains a leading cause of infectious disease death. Modelling predicts new TB vaccines may reduce global burden but rely on assumptions about vaccine efficacy by TB disease stage and TB natural history, which may be incorrect. We explored the sensitivity of estimates of the impact of new TB vaccines to uncertainties in efficacy by disease stage and natural history.Methods: We developed a dynamic compartmental TB model for India, including early TB disease stages. Scenarios assumed 50% vaccine efficacy for 10 years and prevented progression to a) only infectious symptomatic disease, or b) any infectious disease, or c) any disease. We estimated impact on averting disease episodes over 2030–2050, compared to no-new-vaccine introduction.Results: Results suggest, over three years, there was little difference in the proportion of cumulative symptomatic disease episodes averted by vaccines preventing only infectious symptomatic disease, any infectious disease, or any disease (1.8%, 2.3%, and 2.4%, respectively). However, over 20 years, compared to vaccines preventing only infectious symptomatic disease, vaccines preventing any infectious disease, or any disease, averted a markedly higher proportion of symptomatic disease episodes (8.2%, 21.0%, and 25.1%, respectively), due to preventing continued transmission from infectious asymptomatic disease.Conclusions: The population impact of new TB vaccines may depend on efficacy against infectious asymptomatic disease. TB vaccine trials should measure impact on infectious asymptomatic disease to enable better estimates of the potential value of new TB vaccines. Further data collection is required to better understand the transmissibility, morbidity, and dynamics of asymptomatic disease.

New tuberculosis (TB) vaccines may be available soon. However, efficacy results will only be available for IGRA-positive individuals aged ~15+. In reality, countries may decide to introduce the vaccine routinely to adolescents younger than aged 15 with higher school attendance, e.g., alongside HPV vaccination. Most adolescents younger than aged 15 are IGRA-negative and have low TB incidence. We estimated the health impact of introducing new TB vaccines to 9–14 year olds in India and South Africa.Methods: We used previously developed and calibrated TB infection transmission models to estimate the impact of introducing a vaccine with 50% efficacy to prevent disease in India and South Africa over 2030–50. We delivered the vaccine routinely to those aged 9 years and as one mass campaign for ages 10–14 years. The vaccine was assumed to be effective in either IGRA-positives only or irrespective of IGRA status.Results: Modelling suggested that the health impact of vaccines effective only in IGRA-positive individuals was considerably smaller than for vaccines effective irrespective of IGRA status (India: 1.9 vs 6.1, South Africa: 0.2 vs 0.6, millions of averted TB episodes, respectively). The cost per disability adjusted life year (DALY) averted for vaccines effective only in IGRA-positives was larger than for vaccines effective irrespective of IGRA status (India: 412 vs 116, South Africa: 290 vs 75, USD per DALY averted).Conclusions: If new TB vaccines only work in IGRA-positive individuals, and initial delivery is only to adolescents aged 9–14, impact is likely to be low, with much vaccine wastage. Further, given the low TB incidence in this population, the lack of efficacy in IGRA-negative individuals would take many years to detect. We need to include younger adolescents in the development of new TB vaccines and plan to measure efficacy in this key group.