# Risk factors for adverse events following rabies vaccination: a multivariate analysis of real-world data

## TL;DR

This study identifies risk factors for adverse reactions after rabies vaccination and creates a predictive model to help clinicians manage patient risk.

## Contribution

The study is the first to identify bilateral deltoid vaccination as an independent risk factor for adverse reactions to rabies vaccine.

## Key findings

- High-risk exposure grade, bilateral deltoid vaccination, allergy history, and delayed wound management are significant risk factors for adverse reactions.
- A 4-dose immunization schedule and greater injection-site skinfold thickness are protective factors against adverse reactions.
- The predictive nomogram model achieved high accuracy (AUC 0.826) and showed clinical net benefit for risk stratification.

## Abstract

To investigate independent risk and protective factors associated with adverse reactions following rabies vaccination in a Chinese population; to develop and validate a predictive nomogram for clinical utility; to support risk stratification management in clinical practice.

A retrospective analysis was conducted on data from 806 patients who visited the Animal Bite Outpatient Clinic of Ningbo Ninth Hospital between September 2023 and August 2025. Variables were screened using LASSO regression, and a multivariate logistic regression-based nomogram model was constructed. The model’s performance was evaluated using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis, and ten-fold cross-validation.

This study identified high-risk exposure grade (OR = 1.37), bilateral deltoid vaccination (OR = 4.93), history of allergy (OR = 5.07), and delayed wound management (OR = 2.13) as significant risk factors (p < 0.05). In contrast, a 4-dose immunization schedule (OR < 0.01) and greater injection-site skinfold thickness (OR < 0.01) were key protective factors. The constructed nomogram demonstrated excellent discriminative ability, with AUC values of 0.826 in the training set and 0.817 in the test set. Ten-fold cross-validation yielded an accuracy of 80.0%. Decision curve analysis indicated a clinical net benefit threshold ranging from 4 to 97%. Subgroup analysis newly revealed that hypertensive patients experienced a 4.4-fold increase in risk (OR = 4.43) following high-risk exposure. Additionally, vaccination during summer and autumn was associated with significantly elevated risks (OR range: 2.11–3.74).

This study is the first to identify bilateral deltoid vaccination as an independent risk factor for adverse reactions to rabies vaccine. The constructed nomogram model demonstrates high accuracy in identifying high-risk individuals. Clinically, it is recommended that high-risk exposure patients receive single-site vaccination combined with a 4-dose regimen, with wound management completed within 24 h. Enhanced monitoring is advised for hypertensive patients to mitigate potential risks.