Abstract
Background: Tuberculosis is a serious health issue causing substantial morbidity and mortality worldwide. An estimated 10.6 million people developed tuberculosis disease in 2021, and 1.6 million people died. Collectively, India and South Africa accounted for 31% of cases and 36% of deaths globally. Novel vaccines or vaccination strategies will likely be key to eliminate the burden of tuberculosis. M72/AS01E and BCG-revaccination of adolescents/adults have both recently completed Phase IIb trials, and vaccine developers and implementers require estimates of their likely health and economic impact. We estimated the potential cost and cost-effectiveness of vaccination with BCG-revaccination and M72/AS01E vaccines in India and South Africa and investigated the impact of variation in delivery strategies and vaccine profile.
Methods: We developed separate age-stratified compartmental tuberculosis models for India and South Africa and calibrated to country-specific epidemiologic data to simulate current trends to 2050 assuming no-new-vaccine introduction. We simulated vaccines with characteristics informed by clinical trial data; a Basecase M72/AS01E vaccine with 50% prevention of disease efficacy with 10-years average protection, efficacious with any infection status at vaccination introduced in 2030 routinely to age 15 (80% coverage) and as a campaign for ages 16-34 (70% coverage, repeat campaign in 2040) with two doses at $2.5 USD per dose, and a Basecase BCG-revaccination vaccine with 45% prevention of infection efficacy with 10-years average protection, and efficacious with no current infection at time of vaccination introduced in 2025 routinely to age 10 (80% coverage) and as a campaign for ages 11-18 (80% coverage) with repeat campaigns in 2035 and 2045 with one dose at $0.17 per dose. We varied product and implementation characteristics univariately to explore uncertainty in vaccine profile and decisions regarding delivery.
We calculated incremental costs for each vaccine scenario compared to the no-new-vaccine baseline from the health system perspective. We calculated disability-adjusted life years (DALYs) as well as budget impact and cost-effectiveness outcomes such as incremental cost per DALY averted.
Results: In both India and South Africa, M72/AS01E vaccines were predicted to avert more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Both M72/AS01E and BCG-revaccination scenarios are likely to be highly cost-effective in both countries. Due to the higher assumed cost-per-dose ($2.5 vs $0.17) and requiring two doses per course, M72/AS01E vaccines were estimated to be around four times more expensive and have cost-effectiveness ratios around three to seven times greater than BCG-revaccination in both countries, but nearly all scenarios were cost-effective at the lowest threshold. Both vaccines are likely to have lower cost-effectiveness ratios in South Africa compared to India due to the higher tuberculosis burden, and vaccine roll out was likely 20 times more expensive per year in India due to population size.
Implications: Novel tuberculosis vaccines with characteristics similar to BCG-revaccination and M72/AS01E are likely to be highly cost-effective in both India and South Africa and have the potential to have a substantial positive impact on the tuberculosis burden in both countries.