Potential impact of spatially targeted adult tuberculosis vaccine in Gujarat, India

Some of the most promising vaccines in the pipeline for tuberculosis (TB) target adolescents and adults. Unlike for childhood vaccines, high-coverage population- wide vaccination is significantly more challenging for adult vaccines. Here, we aimed to estimate the impact of vaccine delivery strategies that were targeted to high-incidence geographical 'hotspots' compared with randomly allocated vaccination. We developed a spatially explicit mathematical model of TB transmission that distinguished these hotspots from the general population. We evaluated the impact of targeted and untargeted vaccine delivery strategies in India - a country that bears more than 25% of global TB burden, andmay be a potential earlyadopter of the vaccine.We collected TB notification data and conducted a demonstration study in the state ofGujarat to validate our estimates of heterogeneity in TB incidence.We then projected the impact of randomly vaccinating8%of adults in a singlemass campaign to a spatially targeted vaccination preferentially delivered to 80% of adults in the hotspots, with both strategies augmented by continuous adolescent vaccination. In consultation with vaccine developers,we considered avaccine efficacyof 60%, andevaluated the population-level impact after 10 years of vaccination. Spatial heterogeneity in TB notification (per 100 000/year) was modest in Gujarat: 190 in the hotspots versus 125 in the remaining population. At this level ofheterogeneity, the spatially targeted vaccination was projected to reduce TB incidence by 28% after 10 years, compared with a 24% reduction projected to achieve via untargeted vaccination - a 1.17-fold augmentation in the impact of vaccination by spatially targeting. The degree of the augmentation was robust to reasonable variation in natural history assumptions, but depended strongly on the extent of spatial heterogeneity and mixing between the hotspot and general population. Identifying high-incidence hotspots and quantifying spatial mixing patterns are critical to accurate estimation of the value of targeted intervention strategies.