Pre-exposure prophylaxis as a complementary vaccination strategy to reduce rabies in Kerala, India: a cost-effectiveness modelling study

Background Post-exposure prophylaxis (PEP) and dog vaccination continue to be the widely adopted vaccination strategy for rabies control in high-burden countries like India. To determine the public health and economic impacts of childhood pre-exposure prophylaxis (PrEP) relative to existing strategies, we carried out a modelling analysis in the state of Kerala, India. Methods We adapted a probabilistic decision-tree model over a 10-year time horizon (2026–2035). This timeframe is sufficient for dog vaccination to interrupt rabies transmission and for protection to accrue from PrEP delivered through routine childhood immunisation. The model simulates interactions between dog vaccination, PrEP, and PEP to estimate health provider costs, quality-adjusted life years (QALYs) gained, and net health benefit across a range of willingness-to-pay thresholds. Findings Assuming current practice of four-dose intradermal PEP and sub-optimal dog vaccination, we projected 431 rabies deaths (95% Prediction interval [PI] 353–523) and a cost of US$50.3 million over ten years, with dog vaccination responsible for almost 70% of deaths averted by this strategy. Routine childhood PrEP increased costs by US$10.5–36.5 million (INR 1.0–3.4 billion), depending on the regimen used, and cumulatively prevented only ten additional deaths beyond those averted by current practice. Incorporating PrEP was not optimal (probability ≤12%) across India's willingness-to-pay threshold. The intensified owned-dog vaccination strategy achieved the highest benefit at India's mean willingness-to-pay (739,420 QALYs; 28% probability of optimality), while adopting WHO's recommended abridged PEP regimen was the only cost-saving strategy (US$6.3 million saved; equivalent mortality to status quo). Comprehensive dog vaccination coverage of 70% combined with abridged PEP regimens became optimal at India's upper willingness-to-pay threshold, reducing deaths by 83% compared to current practice. Interpretation In high-PEP-access settings, PrEP is not cost-effective and provides negligible benefit. To maximise lives saved, PrEP should only be considered once gains from strengthening dog vaccination and PEP delivery have been exhausted. Funding Wellcome Trust; Indian Council of Medical Research - Department of Health Research (ICMR-DHR) International Fellowship for Senior Biomedical Scientists.