Estimating total human deaths from rabies: A statistical framework leveraging reports of rabies transmission from deceased organ and tissue donors.

Estimating the global burden of human rabies is notoriously challenging because the infection is often misdiagnosed or not reported. Although rare, instances of donor-derived human-to-human rabies transmission have been identified after organ or tissue transplantation. Here, we present a statistical framework leveraging these instances to estimate both the probability that a death from rabies is diagnosed for an infected individual and the number of total deaths from rabies. Of the 33 canine-rabies-endemic and 13 canine-rabies-free countries assessed, rabies was identified among deceased donors after transplantation in China (n = 4) between 2015 and 2024 and the United States of America (US) (n = 3) between 2000 and 2024. Assuming the same proportion of deaths from rabies among deceased donors and decedents in the general population, we estimated that China and the US diagnosed rabies in only 28.7% (95%CI: 14.8-56.5%) and 6.1% (95%CI: 2.4-21.1%) of rabies decedents, respectively, during the study years. In 2024, these corresponded to 581 (95%CI: 308-1,056) and 75 (95%CI: 19-242) estimated total deaths from rabies compared to 167 and 4 reported deaths from rabies, respectively. Although parameters were imprecisely estimated for the remaining countries, for countries with a relatively large number of deceased donors, our framework provided informative upper confidence bounds on total deaths from rabies, which can inform the design of surveillance and control measures. For example, in 2023, this upper bound was estimated to be 2,227 deaths from rabies for India. Parameter estimates were sensitive to the assumed relative risk of rabies between deceased donors and decedents in the general population, highlighting the need for future research to estimate this quantity and improve inference within our framework. Our findings show substantial underreporting of human deaths from rabies in both canine-rabies-endemic and canine-rabies-free countries, underscoring the need to strengthen surveillance and diagnostic capacity and raise risk awareness.