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

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

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

Results: 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.

Conclusions and relevance: 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.

Figure 1.. Analysis Workflow for Rabies Risk Assessment Tools

PEP indicates postexposure prophylaxis; Pr(death|exposure), the probability that an animal would test positive for rabies virus given that a person was exposed; RABV, rabies virus.

Figure 2.. Quantitative Risk Assessment Survey Results for Whether Rabies Postexposure Prophylaxis (PEP) Would Be Recommended Given 24 Scenarios Describing Possible Rabies Virus Exposures

The survey was administered to state and local public health officials in the US with experience making professional recommendations regarding rabies PEP. Spearman rank correlation was −0.49 (P < .001). Median and 95% credible intervals (error bars) corresponding to each scenario are shown. Colors indicate the main rabies virus reservoir for each jurisdiction. Some scenarios in the “strongly disagree” category were outliers (eTable 5 in Supplement 1).

Figure 3.. Logistic Regression Predicting Whether Rabies Postexposure Prophylaxis (PEP) Would Be Recommended

The vertical dotted line indicates the risk threshold (0.0004). Although the outcome is exclusively binary (PEP is not recommended = 0, or PEP is recommended = 1), we jittered the points and added transparency to avoid overlap and improve readability. Pr(death|exposure) indicates the probability that a person would die from rabies given that they were exposed to a suspect rabid animal and did not receive PEP.

Figure 4.. Number Needed to Treat (NNT) to Prevent 1 Rabies Death and Postexposure Prophylaxis (PEP) Cost per Death Averted by the Probability of Death Given Human Exposure to a Suspect Rabid Animal, Pr(death|exposure)

Examples of low- and high-risk exposures are shown by the dashed lines. The low-risk exposure corresponds to a single bite to the arm from a vaccinated cat in Michigan that was ill and provoked, while the high-risk exposure corresponds to multiple bites to the head by a skunk in Georgia that was unprovoked and ill or acting strangely.