Based on real-world data: Risk factors and prediction model for mental disorders induced by rabies vaccination

Abstract

BACKGROUND

Rabies is a zoonotic viral disease affecting the central nervous system, caused by the rabies virus, with a case-fatality rate of 100% once symptoms appear.

AIM

To analyze high-risk factors associated with mental disorders induced by rabies vaccination and to construct a risk prediction model to inform strategies for improving patients’ mental health.

METHODS

Patients who received rabies vaccinations at the Department of Infusion Yiwu Central Hospital between August 2024 and July 2025 were included, totaling 384 cases. Data were collected from medical records and included demographic characteristics (age, gender, occupation), lifestyle habits, and details regarding vaccine type, dosage, and injection site. The incidence of psychiatric disorders following vaccination was assessed using standardized anxiety and depression rating scales. Patients were categorized into two groups based on the presence or absence of anxiety and depression symptoms: The psychiatric disorder group and the non-psychiatric disorder group. Differences between the two groups were compared, and high-risk factors were identified using multivariate logistic regression analysis. A predictive model was then developed based on these factors to evaluate its predictive performance.

RESULTS

Among the 384 patients who received rabies vaccinations, 36 cases (9.38%) were diagnosed with anxiety, 52 cases (13.54%) with depression, and 88 cases (22.92%) with either condition. Logistic regression analysis identified the following significant risk factors for psychiatric disorders: Education level of primary school or below, exposure site at the head and neck, exposure classified as grade III, family status of divorced/widowed/unmarried/living alone, number of wounds greater than one, and low awareness of rabies prevention and control (P < 0.05). The risk prediction model demonstrated good performance, with an area under the receiver operating characteristic curve of 0.859, a specificity of 74.42%, and a sensitivity of 93.02%.

CONCLUSION

In real-world settings, psychiatric disorders following rabies vaccination are relatively common and are associated with factors such as lower education level, higher exposure severity, vulnerable family status, and limited awareness of rabies prevention and control. The developed risk prediction model may aid in early identification of high-risk individuals and support timely clinical intervention.

Key Words: Rabies; Vaccination; Mental disorders; High risk factors; Risk prediction model

Core Tip: Identifying risk factors for mental disorders induced by vaccination and constructing predictive models is essential for safeguarding the mental health of patients especially those receiving rabies vaccination. This study is based on real-world data and provides the first comprehensive and systematic analysis of the risk factors for mental disorders caused by rabies vaccination, and constructs a predictive model.

INTRODUCTION

Rabies is a zoonotic viral disease of the central nervous system caused by the rabies virus, characterized by a case-fatality rate of 100% once clinical symptoms appear[1,2]. Patients typically present with severe agitation, hydrophobia, impaired consciousness, paralysis, and coma, ultimately succumbing to cardiac arrest, circulatory failure, or respiratory insufficiency[3]. Given the absence of specific therapeutic options, immediate wound care and rabies vaccination are essential for preventing disease onset[4]. With the increasing number of household pets and personal pet ownership in China, the risk and incidence of rabies exposure have risen significantly, resulting in higher vaccination rates[5]. However, many patients experience psychological distress such as anxiety, panic, and depression following rabies vaccination, often due to misconceptions about the disease or concerns regarding the vaccine’s efficacy[6]. These mental health issues can adversely affect patients’ daily functioning and work productivity. Although several studies have investigated the psychological condition of patients post-vaccination, most have been clinical trials or retrospective analyses that do not fully reflect the diversity and complexity of real-world settings. Real-world studies, conducted in routine clinical and everyday environments, offer more accurate insights into disease characteristics, treatment outcomes, and adverse reactions. Such studies yield comprehensive, authentic, and broadly applicable data. Accordingly, this project utilized real-world data to identify high-risk factors for psychiatric disorders following rabies vaccination and to develop a risk prediction model to support vaccine safety. The findings are presented below.

MATERIALS AND METHODS

Study subjects

This observational study was conducted using real-world data. A total of 384 patients who received rabies vaccinations at the Department of Infusion our hospital between August 2024 and July 2025 were included. The inclusion criteria were as follows: (1) Confirmed dog bite verified through clinical examination; (2) Age 18 years or older; (3) Presentation to the hospital within 24 hours of the bite; (4) Absence of infection at the wound site; (5) Eligibility for rabies vaccination; and (6) Provision of written informed consent after explanation of the study’s purpose and procedures. The exclusion criteria were: (1) Pre-existing psychiatric symptoms prior to the dog bite; (2) Presence of severe organ disease, hematological disorders, or immunodeficiency; (3) Impaired consciousness or cognitive dysfunction; (4) Contraindications to rabies vaccination or a history of related allergic reactions; (5) Critical condition preventing completion of the psychological assessment prior to vaccination; and (6) Pregnancy or breastfeeding. For data collection, snowball sampling was used to distribute electronic questionnaires. Initially, a small number of eligible patients were identified and invited to participate. These participants were provided with a quick response code to complete the survey and asked to recommend other individuals who met the inclusion criteria. Each new participant received the same quick response code and completed the questionnaire electronically. This recruitment process continued until 400 questionnaires were distributed, resulting in 384 valid responses and a response rate of 96.0%. This approach enabled a gradual expansion of the sample to reach the target population size.

Methods

Risk factor investigation: A self-designed questionnaire developed by the research team was used to collect detailed information based on patients’ medical records. Personal information included age, gender, occupation, lifestyle habits, and vaccine-related details such as type, dosage, and injection site.

Psychological assessment

Anxiety assessment: The generalized anxiety disorder scale[7] was used to assess recent anxiety symptoms. The scale consists of seven items, each scored from 0 to 3, with a maximum score of 21. A score of ≥ 5 indicates anxiety, with 5-9 classified as mild, 10-14 as moderate, and 15-21 as severe anxiety.

Depression assessment: The patient health questionnaire-9[8] was used to assess recent depressive symptoms. The scale comprises nine items, each scored from 0 to 3, with a total score of 27. A score of ≥ 5 indicates depression, with 5-9 representing mild, 10-14 moderate, 15-19 moderately severe, and 20-27 severe depression.

Rabies vaccine knowledge survey

A self-developed survey on rabies prevention and control knowledge was used. The survey covered basic knowledge of rabies, wound management, and post-vaccination precautions. It included 14 items, each scored from 0 to 1, for a total score of 14. A score greater than 8 was considered indicative of sufficient awareness.

Data collection

Snowball sampling was used to distribute electronic questionnaires. Participants accessed the survey by scanning a quick response code, and data were collected through an online platform. Before completing the survey, participants were informed of the study’s purpose and significance. Any questions were addressed via voice or video calls. A total of 400 questionnaires were distributed, of which 384 were valid, yielding a response rate of 96.0%.

Risk model construction

All participants completed the mental health assessment and were categorized into two groups based on the presence or absence of anxiety and depression symptoms: The psychiatric disorder group and the non-psychiatric disorder group. These groups served as the modeling cohort for developing a risk prediction model for psychiatric disorders following rabies vaccination, based on identified risk factors. The model’s predictive accuracy was subsequently validated.

Statistical analysis

All data were analyzed using SPSS version 26.0. For normally distributed continuous variables, results were reported as mean ± SD and analyzed using independent sample t-tests. For non-normally distributed data, results were described using medians and interquartile ranges. Categorical variables were presented as percentages (%) and analyzed using χ² tests. Risk factors were identified using multivariate logistic regression analysis. The predictive performance of the risk prediction model was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). A P value of < 0.05 was considered statistically significant.

RESULTS

Detection of psychiatric disorders

Among the 384 patients who received rabies vaccinations, 36 cases (9.38%) were diagnosed with anxiety, 52 cases (13.54%) with depression, and 88 cases (22.92%) with either condition. The remaining 296 patients (77.08%) constituted the non-psychiatric disorder group.

Univariate analysis

Compared to the non-psychiatric disorder group, patients in the psychiatric disorder group had higher rates of urban residence, education level of primary school or below, occupations as farmers or workers, and monthly per capita family income < 5000 Chinese yuan. They also had higher frequencies of exposure to the head and neck, grade III exposure, and more than one wound (P < 0.05). Additionally, they demonstrated lower rates of family completeness and lower awareness of rabies prevention and control knowledge (P < 0.05). No statistically significant differences were observed in other general characteristics between the two groups (P > 0.05). Detailed results are presented in Table 1.

Table 1 Comparison of general characteristics between the psychiatric disorder group and the non-psychiatric disorder group, n (%).

Variable	Psychiatric disorder group (n = 88)	Non-psychiatric disorder group (n = 296)	χ² value	P value
Gender			0.006	0.937
Male	42 (48.84)	146 (49.32)
Female	44 (51.16)	150 (50.68)
Age (years)			0.470	0.791
18-35	31 (35.23)	98 (33.11)
36-60	42 (47.73)	138 (46.62)
> 60	15 (17.05)	60 (20.27)
Residence			12.522	0.001
Urban	52 (59.09)	112 (37.84)
Rural	36 (40.91)	184 (62.16)
Education level			15.643	< 0.001
Primary school or below	44 (50.00)	86 (29.05)
Middle/high school	28 (31.82)	104 (35.14)
College or above	16 (18.18)	106 (35.81)
Occupation			4.665	0.046
Healthcare worker	4 (4.55)	34 (11.49)
Public institution	24 (27.27)	112 (37.84)
Corporate employee	25 (28.41)	108 (36.49)
Self-employed	18 (20.45)	27 (9.12)
Farmer/worker	12 (13.64)	13 (4.05)
Other	5 (5.68)	2 (0.68)
Monthly family income (Chinese yuan)			11.553	0.003
< 5000	28 (31.82)	46 (15.54)
5001-10000	42 (47.73)	175 (59.12)
> 10000	18 (20.45)	75 (25.34)
Family status			6.638	0.024
Complete	25 (28.41)	128 (43.24)
Living alone	22 (25.00)	65 (21.96)
Unmarried	18 (20.45)	48 (16.22)
Divorced/widowed	23 (26.14)	55 (18.58)
Exposure method			0.026	0.987
Bite	35 (39.77)	115 (38.85)
Scratch	42 (47.73)	143 (48.31)
Other	11 (12.50)	38 (12.84)
Exposure site			20.303	< 0.001
Head/neck	30 (34.09)	45 (15.20)
Trunk	35 (39.77)	108 (36.49)
Limbs	23 (26.14)	143 (48.31)
Exposure degree			22.646	< 0.001
Grade II	62 (70.45)	268 (90.54)
Grade III	26 (29.55)	28 (9.46)
Number of wounds			8.416	0.004
1 wound	65 (73.86)	257 (86.82)
> 1 wound	23 (26.14)	39 (13.18)
Wound management			0.317	0.853
Self-managed	31 (35.23)	95 (32.09)
Unmanaged	14 (15.91)	51 (17.23)
Clinic managed	43 (48.86)	150 (50.68)
Time from injury to visit			1.970	0.374
< 6 hours	25 (28.41)	92 (31.08)
6-12 hours	36 (40.91)	135 (45.61)
> 12 hours	27 (30.68)	69 (23.31)
Rabies immune globulin			0.438	0.508
Yes	73 (82.95)	254 (85.81)
No	15 (17.05)	42 (14.19)
Full vaccine course			0.412	0.521
Yes	82 (93.18)	283 (95.61)
No	6 (6.82)	13 (4.39)
Awareness of rabies prevention			15.930	< 0.001
Aware	45 (51.14)	218 (73.65)
Unaware	43 (48.86)	78 (26.35)

Multivariate analysis

Variables with statistically significant differences in the univariate analysis were further analyzed using logistic regression, with psychiatric disorder status as the dependent variable (n = 1 indicating the presence of a disorder, n = 0 indicating absence). As shown in Table 2, the following were identified as independent risk factors for psychiatric disorders: Education level of primary school or below, exposure site on the head and neck, grade III exposure, family status of divorced/widowed/unmarried/Living alone, having more than one wound, and low awareness of rabies prevention and control (P < 0.05). These results are summarized in Table 3 and visualized in Figure 1.

Figure 1 Multivariate logistic regression analysis of risk factors for psychiatric disorders following rabies vaccination. OR: Odds ratio; CI: Confidence interval.

Table 2 Variable assignments for logistic regression analysis of risk factors associated with psychiatric disorders following rabies vaccination.

Factor	Coding
Residence	Urban = 1; Rural = 0
Education level	Primary school or below = 1; Middle/high school = 0; College or above = 0
Occupation	Farmer/worker = 1; All other categories = 0
Monthly family income (Chinese yuan)	< 5000 = 1; 5001–10000 = 0; > 10000 = 0
family status	Living alone/unmarried/divorced or widowed = 1; Complete = 0
Exposure site	Head/neck = 1; Trunk = 0; Limbs = 0
Exposure degree	Grade III = 1; Grade II = 0
Number of wounds	> 1 wound = 1; 1 wound = 0
Awareness of rabies prevention	Unaware = 1; Aware = 0

Table 3 Logistic regression analysis of risk factors associated with psychiatric disorders following rabies vaccination.

Factor	β	SE	Wald	P value	OR	95%CI
Urban	-0.139	0.128	1.179	0.468	0.870	0.248-3.052
Primary school or below	1.179	0.248	22.601	0.001	3.251	1.548-6.826
Non-medical occupation	-0.151	0.276	1.873	0.522	0.588	0.140-5.876
Monthly income < 5000 (Chinese yuan)	0.171	0.108	2.507	0.260	1.187	0.342-4.120
Divorced/widowed/unmarried/living alone	1.247	0.360	11.999	0.001	3.480	1.548-7.825
Head/neck exposure site	1.402	0.271	26.764	< 0.001	4.062	1.675-9.852
Grade III exposure	0.910	0.212	18.425	< 0.001	2.483	1.125-5.482
> 1 wound	1.386	0.412	11.317	< 0.001	3.999	1.848-8.652
Low awareness of rabies prevention	1.028	0.364	7.976	0.010	2.795	1.052-7.425

OR: Odds ratio; CI: Confidence interval.

Construction of the risk prediction model

Based on the results of multivariate logistic regression analysis, a risk prediction model for rabies vaccination-induced psychiatric disorders was developed and presented as a nomogram (see Figure 2). The nomogram displays the relative contribution (score) of each risk factor to the total predicted probability. Model performance was evaluated using the ROC curve, yielding an AUC of 0.859, a specificity of 74.42%, and a sensitivity of 93.02%, as shown in Figure 3.

Figure 2  Nomogram of the risk prediction model for psychiatric disorders induced by rabies vaccination.

Figure 3  Receiver operating characteristic curve of the risk prediction model for psychiatric disorders induced by rabies vaccination.

DISCUSSION

Dog bites are a common occurrence in China. Due to the high bacterial load in a dog’s mouth, muscle tissue exposed to the rabies virus can readily lead to infection if not promptly treated-resulting in death and posing significant challenges for disease prevention and control[9]. Rabies vaccination remains the only effective method for preventing and controlling the disease, helping to halt its progression and reduce mortality[10]. However, some patients experience psychiatric disorders following rabies vaccination, characterized by persistent anxiety, depression, and autonomic symptoms, all of which significantly affect quality of life. In our study, among 384 patients who received rabies vaccinations, 36 cases (9.38%) were diagnosed with anxiety, 52 cases (13.54%) with depression, and 88 cases (22.92%) with psychiatric symptoms overall. These findings suggest that a substantial proportion of patients experience psychiatric disorders of varying severity after vaccination. Warmerdam et al[11] reported that travelers often experience significant anxiety and psychological distress after animal-related injuries, which markedly affects their health. Westgarth et al[12] found that the most common psychological consequences of dog bites in children include post-traumatic stress disorder, cynophobia, nightmares, anxiety symptoms, and avoidant behaviors. These findings underscore that psychiatric disorders are common responses to harmful stimuli and warrant greater clinical attention. Nevertheless, systematic reporting on psychiatric disorders specifically induced by rabies vaccination is lacking. Identifying high-risk factors for these outcomes through real-world research provides more reliable and representative data, thereby supporting the design of future intervention strategies.

This study identified several risk factors for psychiatric disorders following rabies vaccination through logistic regression analysis. These included lower education level (primary school or below), exposure site on the head and neck, grade III exposure, family status of divorced/widowed/unmarried/Living alone, having more than one wound, and low awareness of rabies prevention and control (P < 0.05). These results suggest that patients are vulnerable to multiple psychosocial and clinical factors that may contribute to the development of psychiatric symptoms after rabies vaccination. Notably, neither the type nor the quantity of the vaccine was significantly associated with the occurrence of psychiatric disorders.

Limited knowledge of rabies presents a significant psychological burden. When exposed to rabies, many patients experience heightened anxiety due to fear of disease onset a potent psychological stressor that can trigger anxiety and depression. Patients with lower educational attainment are often less informed about rabies prevention and the effectiveness of vaccination, leading to misunderstanding and mistrust regarding the vaccine’s efficacy. This misinformation may exacerbate anxiety and depressive symptoms[13]. In contrast, individuals with higher education levels are more likely to access credible and timely medical information, understand the preventive value of rabies vaccination, and exhibit greater trust in its effectiveness.

Family status also plays a crucial role in patients’ psychological well-being. A supportive family can offer emotional reassurance and encouragement, helping patients maintain a positive outlook toward rabies vaccination. Conversely, individuals living alone or grieving the loss of a loved one may experience loneliness and lack social support, which can adversely affect their mental health.

In cases of grade III exposure, referrals to higher-level medical facilities may delay timely treatment and aggravate the patient’s condition, increasing psychological stress and skepticism regarding vaccination. Many primary care institutions lack specialized staff for managing rabies exposure, which may reduce patient confidence in treatment outcomes and subsequent vaccination adherence[14]. Moreover, patients with severe injuries and multiple wounds often require rabies immune globulin injections, which are costly and involve complex wound care. The prolonged wound healing process and uncertainties about vaccine efficacy can lead to increased anxiety and depression[15].

Patients bitten on the head or neck may worry about visible scarring and perceive a higher risk of viral transmission due to the critical nature of these anatomical areas. Such concerns can undermine their trust in the vaccine’s effectiveness and heighten psychological distress. Therefore, identifying risk factors for psychiatric disorders induced by rabies vaccination in real-world settings provides essential insights for early clinical intervention and psychological support.

This study developed a risk prediction model based on identified risk factors and validated it using the ROC curve. The AUC was 0.859, with a specificity of 74.42% and a sensitivity of 93.02%. These results demonstrate strong concordance between the model and actual incidence rates, suggesting that the model can effectively identify individuals at high risk of psychiatric disorders following rabies vaccination and may support targeted clinical interventions.

In summary, by analyzing risk factors for psychiatric disorders induced by rabies vaccination in real-world settings and validating the predictive model through ROC analysis, this study provides a foundation for early identification of high-risk populations and offers meaningful insights for early clinical intervention. However, the study has several limitations. First, all data were collected from a single medical institution, which may limit the representativeness of the sample and reduce the generalizability of the findings. Second, the prediction model has not yet undergone external validation, potentially introducing bias into the results. Future studies should consider multi-center, large-scale trials and external validation to enhance the model’s robustness and provide a more reliable basis for clinical application.

CONCLUSION

In real-world settings, psychiatric disorders induced by rabies vaccination are relatively common and are influenced by factors such as educational background, exposure severity, family status, and awareness of rabies prevention and control. The development of a risk prediction model based on these factors can help identify high-risk groups at an early clinical stage and provide a reference for timely clinical intervention. However, due to limitations in the study design, all participants were recruited from a single medical institution, which may restrict the representativeness of the sample and limit the generalizability of the findings to other regions. Additionally, the absence of external validation for the prediction model may introduce bias into the results. Therefore, future research should consider conducting multi-center, large-sample trials and performing external validation of the model to enhance its robustness and ensure its applicability in broader clinical settings.