Safety and Compliance to Purified Vero Cell Intradermal Rabies Vaccine Given as Pre Exposure Prophylaxis among Veterinary College Staff and Students in Bangalore: A Descriptive Study

Introduction

Rabies is a zoonotic disease, with the predominant vector being exposure to rabid animals. India reports the highest number of rabies cases in the world and the incidence of animal exposure ranges from 0.9-1.7%.^1-3 The National Action Plan for Dog Mediated Rabies Elimination from India by 2030 (NAPRE) was launched by the Government of India in 2023.⁴ The mainstay of treatment for animal exposure continues to focus on post-exposure prophylaxis (PrEP).

Rabies pre-exposure prophylaxis (PrEP) is another measure that provides an additional layer of protection, reducing the chances of fatality in case of animal exposure. PrEP consists of the administration of three doses of rabies vaccine by intramuscular/intradermal route on days- 0, 7 and 21/28. WHO-prequalified cell culture vaccines are recommended for PrEP, and the use of cell culture vaccines is recommended in National guidelines.⁵ PrEP is recommended for high-risk populations who may come in contact with animals, such as animal handlers, courier persons, veterinarians, laboratory staff, etc.⁶ The intra-dermal rabies (IDRV) vaccine is cost-effective, safe, and immunogenic with minimum adverse events.⁷

The awareness and acceptance of rabies PrEP in the general population is low. The introduction of rabies pre-exposure immunization in India's National immunization schedule is necessary to prevent rabies. Due to their occupational risk, veterinary students and professionals are frequently exposed to animals, making them a high-risk group for rabies exposure. The objective of the study was to assess the safety of rabies (PrEP) administered via the intradermal route among students and faculty at a veterinary college in Bangalore and to evaluate the compliance with the intradermal rabies vaccine among the study subjects.

Materials and Methods

A descriptive study was conducted during the last quarter of 2024 among veterinary college students and staff at the Veterinary College situated in Bangalore. All individuals at the veterinary college who volunteered for the PrEP vaccination were included as study subjects. Subjects with no previous exposure to anti-rabies vaccine and willing to give informed consent were included. The subjects who were not present on the day of vaccination, the seriously ill population and those with known contraindications to vaccines were excluded.

Ethical clearance was taken from the KIMS IEC (A234/M/2024). The veterinary college was visited on specified dates (Day 0, 7 & 21) after obtaining the required permissions. Informed consent was obtained from all the subjects and confidentiality of data was maintained at all times. Information in terms of age, gender, and religion of the study population was collected using a pre-tested, semi-structured proforma. Information regarding primary vaccination for individuals receiving a booster dose was obtained using the recall method. All the study subjects were administered three doses of rabies vaccine via the intradermal route as per PrEP schedule i.e., on Days 0, 7 & 21 on the left arm. The purified Vero cell rabies vaccine was administered and manufactured by Human Biologicals. Vaccine safety was assessed by reported adverse reactions to the vaccine, such as local or systemic side effects, and further classifying them as mild, moderate, and severe. All the subjects were followed up for 35 days to monitor their adverse effects. Compliance was assessed based on adherence to the three-dose schedule (Days 0, 7 & 21) by each subject as per the schedule of the vaccination, and the reasons for non-compliance or delays in the PrEP schedule were also recorded. Animal handlers working in the veterinary hospital consisted of students and staff involved in the medical care of animals. Data analysis was done using descriptive statistics (percentages, means, standard deviations) and MS Excel was used to analyze the data.

Results

A total of 101 subjects received rabies PrEP via the intradermal route. Among the subjects who received rabies PrEP, 14 were faculty and 87 were students. The median age of the study subjects was 24 years with IQR 9.7 and the age range of the subjects was 19-56 yrs as described in Table 1. There were 53 (52.4%) males and 48 (47.5%) females among the study subjects. Hindus were the majority, comprising 99 subjects (98.0%), followed by 1 (1.0%) Muslim and Jain. Out of the study population, 45 (44.5%) subjects were involved in animal caregiving for one year, while 34 (33.7%) subjects were involved for 1-3 years.

Among the 101 subjects, on taking the first dose (Day-0) of PrEP, 6 (6.0 %) subjects reported experiencing local adverse events, i.e., 3 (50.0%) subjects complained of redness, 2 (40.0%) complained of pain, and 1 (20.0%) reported a mild swelling 5 (5.0%) subjects reported experiencing local adverse events after the second dose of PrEP, with 2 (40.0%) subjects reporting redness, 2 (40.0%) reporting pain, and 1 (20.0%) had mild swelling. Upon receiving the 3rd dose of PrEP, 4 (4.0%) subjects reported local adverse events, 2 (50.0%) reported redness, and 1 (25.0%) each reported swelling and pain at the site of injection. Table 2 describes the adverse events (local and systemic) experienced following vaccination on Day 0, Day 7 and Day 21. Overall, 13 (12.9%) subjects reported one or more local adverse events, while 5 (4.9%) subjects experienced systemic adverse reactions during the course of PrEP (three doses).

On Day 0, 3 (3.0%) subjects reported fever and headache. On Day 7, 2 (2.0%) subjects reported fever, and on Day 21, 1 (1.0%) subject each reported headache and malaise. All the events were managed symptomatically with paracetamol tablet. No moderate or severe adverse reactions were reported among the study subjects. All participants who experienced adverse effects had similar reactions.

Regarding the booster dose, 32 (31.6%) subjects were administered booster dose. Twenty-six (24.0%) subjects had taken two booster doses; 19 (73.0%) among them received one dose each year, while 7 (27.0%) subjects received it once in two years. Six (6.0%) subjects received one booster dose. No adverse effects were observed with the booster dose.

Among the study population, 98 (97.0%) subjects completed the vaccination on time, while 3 (3.0%) subjects attributed the delay to not being available on the day of vaccination. Table 2 represents the compliance to vaccination on Day 7 and Day 21.

No subject experienced an animal bite during the course of PrEP.

Discussion

Rabies pre-exposure prophylaxis (PrEP) was safe and easy to administer, with few minor adverse events reported, which were mostly resolved without any medication. Paracetamol was the most commonly used drug for all the adverse effects and was effective in relieving pain and fever. Most of the subjects adhered to the vaccination schedule. The compliance to pre-exposure prophylaxis was good and the common reason for delay in vaccination was being absent on the day of vaccination. PrEP was well accepted across all groups in the veterinary college, with no barriers related to gender or religion. A PrEP booster dose was administered to 26 subjects, some of whom had received it multiple times.

In the study conducted by Kessels et al., pre-exposure rabies prophylaxis was reported to be safe and immunogenic in children & adults, and observed that the booster intervals could be extended up to 10 years.⁸ Local reactions at the injection site following primary vaccination were noted to be mild and transient in a study conducted by Soentjens et al. in 2019.⁹ A 2017 study assessing the safety of Purified Chick Embryo Cell Vaccine (PCECV) among veterinary students found it to be safe and well-tolerated.¹⁰

PrEP should be considered in populations living in rabies-endemic areas, where the dog bite incidence is >5% per year or vampire bat rabies is known to be present.^11,12 The WHO recommends the following PrEP schedule: a 2-site intradermal rabies vaccine administered on days 0 and 7.¹³

In a similar study conducted to evaluate the safety of PCECV among children, 38 adverse reactions were reported including, pain at the injection site 7 (2.1%), redness 13 (3.8%), itching at the site of injection 11 (3.2%), induration 6 (1.8%) and headache 1 (0.3%). All reactions subsided without any complications.¹⁴ In a study conducted by Furuya-Kanamori et al., three PrEP regimens were examined: 1ID x 3, 2ID x 2, 4ID x 1; seropositivity was found most with 4ID and was safe in all travelers.¹⁵

The present study revealed that the PrEP vaccine was safe, and compliance with ARV was good among the veterinary college population. This can be attributed to greater awareness of rabies-related health risks among veterinarians and their staff. Also, since the vaccination was conducted at their centre, it was easier for the beneficiaries not to miss any dose. Public health workers have a crucial role to play in the prevention of rabies. Vaccination outreach programs among high-risk populations like veterinarians, animal care workers, and field workers are needed from time to time to ensure good compliance and coverage.

Conclusion

Upon completion of the study, it was found that the intradermally administered PrEP vaccine was safe, with most individuals demonstrating compliance. The subjects who missed their vaccination completed the schedule within a week. PrEP could be recommended as a routine vaccination for high-risk individuals.

Conflict of Interest

Nil