Risk of Rabies and Implications for Postexposure Prophylaxis Administration in the US

In the US, rabies postexposure prophylaxis (PEP) is often administered without a comprehensive and regionally appropriate rabies risk assessment. For low-risk exposures, this can result in patients incurring out-of-pocket expenses or experiencing adverse effects of PEP unnecessarily.

To use a model to estimate (1) the probability that an animal would test positive for rabies virus (RABV) given that a person was exposed, and (2) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP, and to propose a risk threshold for recommending PEP according to model estimates and a survey.

In this decision analytical modeling study, positivity rates were calculated using more than 900 000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from a subset of the surveillance data and the literature. Probabilities were estimated using Bayes' rule. A survey was administered among a convenience sample of state public health officials in all US states (excluding Hawaii) plus Washington, DC and Puerto Rico to determine a risk threshold for PEP recommendation. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

A quantitative and regionally appropriate approach for helping health care practitioners and public health professionals determine whether to recommend and/or administer rabies PEP.

A total of 1728 unique observations were obtained from the model for the probability that an animal would test positive for RABV given that a person was exposed, and 41 472 for ) the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP. The median probability that an animal would test positive for RABV given that a person was exposed ranged from 3 × 10-7 to 0.97, while the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP ranged from 1 × 10-10 to 0.55. Fifty public health officials out of a target sample size of 102 responded to the survey. Using logistic regression, a risk threshold was estimated for PEP recommendation of 0.0004; PEP may not be recommended for exposures with probabilities below this threshold.

In this modeling study of rabies in the US, the risk of death|exposure was quantified and a risk threshold was estimated. These results could be used to inform the decision-making process as to the appropriateness of recommending rabies PEP.