Abstract
BACKGROUND: Rabies is a fatal yet preventable viral infection of the central nervous system zoonotic disease, with an almost 100% case fatality rate once symptoms appear. Despite the availability of effective vaccines and post-exposure prophylaxis, rabies continues to cause substantial mortality, particularly in parts of Asia and across the African continent where access to post-exposure prophylaxis (PEP), timely diagnosis, and dog vaccination programs remain limited. OBJECTIVES: Rabies is a nearly invariably fatal zoonotic encephalitis caused by lyssaviruses, with an estimated 59 000 human deaths annually, predominantly in Asia and cross the African continent where access to PEP and dog vaccination is limited. Due to historical underreporting and fragmented surveillance, the true burden remains unclear. Using Global Burden of Diseases (GBD) 2021 data, we systematically assess the global, regional, and national burden of rabies from 1990 to 2021 to identify key drivers of change and persistent disparities. METHODS: We extracted rabies incidence and disability-adjusted life-year (DALY) data from the GBD 2021 via the Global Health Data Exchange. Countries were stratified into five sociodemographic index (SDI) categories. Age-standardized rates per 100 000 population were computed using the GBD world standard. We applied Bayesian age-period-cohort (APC) modeling to characterize temporal trends and project future age-standardized incidence rate (ASIR) and age-standardized DALY rates (ASDR), decomposition analysis to partition burden changes into epidemiological, population growth, and aging components, and frontier benchmarking to assess each country's performance relative to its SDI. RESULTS: From 1990 to 2021, global rabies ASIR fell by 69.4% (0.42 to 0.13/100 000) and annual cases by 54% (22 035-10 181). Over the same period, DALYs declined 58.4% (1 368 780-569 550) and ASDR dropped from 24.48 to 7.51/100 000. In 2021, the highest ASIRs were in Nepal (1.71), Ethiopia (1.05) and Malawi (0.77/100 000). Age-period-cohort analysis showed net drifts of -3.96%/year for incidence and -3.90%/year for DALYs. Decomposition attributed ~170% of incidence decline to epidemiological gains, offset by ~60% from population growth and ~52% from aging. CONCLUSIONS: Scale up mass dog vaccination, ensure affordable PEP and strategic Pre-exposure prophylaxis, focus on high-risk age cohorts, bolster surveillance and data-driven governance, and sustain multisectoral investment through the phased "Zero by 30" framework. By aligning programmatic efforts with the demonstrated successes in high-performing countries and addressing the implementation deficits in lagging regions, the global community can accelerate progress toward the World Health Organization (WHO) goal of zero dog-mediated human rabies deaths by 2030.