New tuberculosis vaccines in India: Modelling the potential health and economic impacts of adolescent/adult vaccination with M72/AS01 E and BCG-revaccination

Abstract

Background India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed Phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. Methods We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected baseline epidemiology to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025-2050 exploring uncertainty in product characteristics (vaccine efficacy, mechanism of effect, infection status required for vaccine efficacy, duration of protection) and implementation (achieved vaccine coverage and ages targeted). We estimated reductions in tuberculosis cases and deaths by each scenario compared to no-new-vaccine introduction, as well as costs and cost-effectiveness from health-system and societal perspectives. Results M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. Conclusions M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially given unknowns surrounding mechanism of effect and infection status required for vaccine efficacy. Greater investment in vaccine development and delivery is needed to resolve these unknowns in vaccine product characteristics.

Figure 1

Cumulative cases and deaths averted (in 1,000s) by 2050 from M72/AS01_E and BCG-revaccination scenarios. The top of the bar is the median estimate of the number averted for each scenario compared to the estimated number predicted by 2050 with the no-newvaccine baseline with 95% uncertainty range. The horizontal line is the median value of the Basecase for each vaccine. The cases and deaths averted by each scenario are compared to 72.2 (63.3–79.7) million incident tuberculosis cases and 13.8 (12.9–15.2) million tuberculosis deaths predicted by the Status Quo baseline between 2025–2050.

Figure 2

Efficiency frontiers (discounted total costs [US$ billions] per disability-adjusted life year (DALY) averted) for Policy Scenarios for each vaccine product

Figure 3

Comparison of ICERs for Vaccine Characteristic and Coverage Scenarios compared to the no-new-vaccine baseline for each vaccine product. The Basecase M72/AS01_E scenario assumes a 50% efficacy POD vaccine efficacious with any infection status at the time of vaccination, with 10 years duration of protection reaching 80% coverage for 15-year-olds and 70% coverage for those aged 16–34. Each M72/AS01_E scenario is delivered routinely to those aged 15 and as a campaign for those aged 16–34. The Basecase BCG-revaccination scenario assumes a 45% efficacy POI vaccine efficacious with no current infection at the time of vaccination, with 10 years duration of protection and reaching 80% coverage. Each BCG-revaccination scenario is delivered routinely to those aged 10 and as a campaign for those aged 11–18. The scenarios on the figure are labelled with the difference in product characteristics for that scenario compared to the Basecase. The 20 years protection and 60% efficacy scenarios for M72/AS01_E overlap and appear as one point on the figure.

Figure 4

Incremental costs by year until 2050 for the Basecase M72/AS01_E and BCG-revaccination scenarios compared to the no-new-vaccine baseline. Abbreviations: USD$ = United States dollars.