Hit Me With Your Best Shot: Rabies Pre-exposure Vaccination

Rabies is an acute, fatal, progressive viral disease that claims nearly 60,000 lives a year.¹

Most deaths occur in Africa and Asia, with approximately 80% in rural areas. Human rabies is rare in the United States because of animal control programs and veterinary vaccination.² Any mammal can be infected by the rabies virus and may become a carrier, but the most common wild reservoirs include bats, foxes, raccoons, and skunks. The most common domestic reservoirs include cats, cattle, and dogs.³ Contact with infected bats is the leading cause of human rabies in the United States. Worldwide, contact with infected dogs is the leading cause of human rabies death.⁴

The rabies virus is transmitted via direct contact with infectious tissue or fluids of infected mammals. This includes nervous tissue, saliva, respiratory tract fluids, and tears. Direct contact implies broken skin or mucous membranes of the eyes, mouth, or nose.⁵ The incubation period is between 20 and 60 days but can span several years before the virus enters the central nervous system. The disease manifests as furious rabies, causing hyperactivity, hydrophobia, and sometimes aerophobia, or as paralytic rabies, causing paralysis starting at the site of transmission. Once clinical symptoms appear, survival is rare and associated with permanent disability and severe brain damage.^4,6,7 Fortunately, vaccinations have nearly eliminated death from rabies.⁷

Recommendations for Prophylaxis and Vaccinations

Per CDC guidelines, the United States population at large does not need vaccinations. Travelers to other countries, particularly Africa and Asia, should visit the CDC Poxvirus and Rabies Branch website (https://www.cdc.gov/rabies/resources/countries-risk.html) to evaluate their risk of rabies exposure and assess their need for postexposure prophylaxis (PEP).⁴ PEP consists of 1 dose of rabies immune globin and 4 doses of rabies vaccines on days 0,3, 7, and 14.⁸

Travelers should consider preexposure prophylaxis (PrEP) vaccination if planned activities include encounters with domestic or wild animals, if staying longer than a month in an area where dog rabies is common, or if visiting remote areas where medical care may be delayed.⁴ The CDC categorizes risk into 3 categories: continuous, frequent, and infrequent. The degree of risk is determined by the extent of contact with the rabies virus, such as working in a research lab or in vaccine production (continuous risk), working with animals in endemic rabies areas (frequent risk), traveling to an endemic area, or working with animals in areas where rabies is not endemic (infrequent risk).⁹

In addition to these categories, people who are more likely to encounter rabid animals include adventure travelers, campers, cave explorers, and visitors to rural areas. Consider immunizing children because they may not report bites or may receive more severe bites.⁴

PrEP vaccination was recently updated for immunocompetent individuals 18 years and older to 2 doses on days 0 and 7 rather than 3 doses on days 0, 7, and 21 or 28. The Advisory Committee on Immunization Practices further recommended an intramuscular booster dose of rabies vaccines in lieu of a titer check for immunocompetent individuals 18 years and older with elevated and sustained risk of rabies exposures. This booster dose should be administered no sooner than day 21 and no later than 3 years after the 2-dose PrEP vaccinations.¹⁰

Vaccine Specifics

Those considering PrEP vaccination do not need to delay for minor illness, such as colds.

Consider delaying vaccination for those with AIDS/HIV, allergic reactions to the rabies vaccine in the past, cancer, or severe allergies, or individuals who are breastfeeding, pregnant, or taking immunocompromising medication. After rabies exposure, all patients should be vaccinated, regardless of any of the above conditions.⁷ Adverse effects of the vaccine are usually mild and may include dizziness, headache, muscle aches, pain, redness and swelling at the injection site, stomach pain, and upset stomach. Symptoms are self-limiting and resolve in a few days.⁸

The same vaccine is used before and after exposure. The 2 rabies vaccines available in the United States are the human diploid cell vaccine (Imovax Rabies; Sanofi Pasteur SA) and the purified chick embryo cell vaccine (RabAvert; GlaxoSmithKline).^7,11 Both are administered intramuscularly and contain inactivated rabies virus.⁵ In the event of a shortage or if one vaccine becomes unavailable, the vaccines are interchangeable. If a patient started a series with one vaccine, the other may be used to complete both a pre- and postexposure series.

Conclusion

PrEP is something to consider if traveling to areas with a high probability of encountering domestic or wild animals or if working in a high-risk field. PrEP vaccination does not eliminate the need for treatment after exposure, but it will simplify treatment and provide protection to those unable to seek higher-level care quickly.

Kathryn Lincoln, PharmD, BCIDP, is a clinical pharmacist of infectious diseases at Olathe Health in Kansas City, Missouri.

Jerline Hsin, PharmD, BCOP, BCPS, is chief of hematology oncology pharmacy at Tripler Army Medical Center in Honolulu, Hawaii.

REFERENCES

1. Wallace RM, Petersen BW, Shlim DR. Travel-related infectious diseases - rabies. In: CDC Yellow Book 2020. Oxford University Press; 2019:169-392. Accessed August 13, 2021. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/rabies

2. Rabies and your pet. American Veterinary Medical Association. Accessed August 14, 2021. https://www.avma.org/resources/public-health/rabies-and-your-pet

3. What kind of animal did you come in contact with? CDC. June 11, 2019. Accessed August 13, 2021. https://www.cdc.gov/rabies/exposure/animals/index.html

4. Rabies. CDC. Updated September 25, 2020. Accessed August 13, 2021. https://www.cdc.gov/rabies/index.html

5. Manning SE, Rupprecht CE, Fishbein D, et al; Advisory Committee on Immunization Practices Centers for Disease Control and Prevention (CDC). Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57(RR-3):1-28.

6. Rabies. World Health Organization. May 17, 2021. Accessed August 14, 2021. https://www.who.int/news-room/fact-sheets/detail/rabies

7. RabAvert. Prescribing information. GlaxoSmithKline; 2018. Accessed August 14, 2021. https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert---RabAvert.pdf

8. Vaccines by disease. US Department of Health & Human Services. Updated April 29, 2021. Accessed August 14, 2021. https://www.vaccines.gov/diseases/rabies

9. Preexposure vaccinations. CDC. Updated April 22, 2011. Accessed August 14, 2021. https://www.cdc.gov/rabies/specific_groups/travelers/pre-exposure_vaccinations.html

10. ACIP recommendations. CDC. Updated July 13, 2021. Accessed August 14, 2021. https://www.cdc.gov/vaccines/acip/recommendations.html

11. Imovax Rabies. Prescribing information. Sanofi Pasteur SA; 2019. Accessed August 14, 2021. https://www.fda.gov/media/75709/download

The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied healthcare professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit sidp.org.