Population impact of new TB vaccines may depend on efficacy against infectious asymptomatic TB: a modelling study

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. 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 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. 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.