Rabies Post-Exposure Prophylaxis

Key Points

• Rabies is a viral disease often transmitted through animal bites that can affect the central nervous system (CNS). Death and other neurological sequelae can be prevented with proper wound care and timely post-exposure prophylaxis (PEP) (i.e., rabies vaccine and human rabies immune globin, if indicated).^1,2,5,6
• For patients unvaccinated against rabies, a four-dose vaccine series administered over a 14-day period starting with the day of the rabies exposure and then on days 3, 7, and 14 post-vaccination. If previously vaccinated against rabies, a 2-dose vaccine series should be given on the first day of exposure and day 7 post-vaccination.^1-3,5-8
• Human rabies immune globulin (HRIG) is indicated for unvaccinated individuals to provide immediate passive immunity while waiting for active immunity to set in following vaccination.^1,2,4-6
• Consult with the Utah Department of Health and Human Services, your local health department, or the Utah Poison Control Center at 800-222-1222.
• Patient assistance programs exist to provide care to uninsured and underinsured patients who need either HRIG or the vaccine series.^1,2

Background

Rabies is a CNS disease caused by the rabies virus, Rabies lyssavirus. Symptoms usually occur after an incubation period of weeks to months, and up to years in rare cases. Symptoms typically include confusion, abnormal behavior, delirium, hallucinations, hydrophobia, and insomnia. Most cases of rabies result in death once clinical signs are present. However, the disease is preventable with the use of PEP following exposure to an animal bite or scratch exposed to an infected animal’s saliva. Human rabies is rare in the United States, with approximately 1 to 2 cases occurring each year. Most of these cases come from exposure to infected bats, but can also come from skunks, foxes, raccoons, and other wild animals.^1,2

For information regarding risk of exposure, see Rabies Risk from Animal Bites and Exposures article.

Indications for Rabies Post-exposure Prophylaxis (PEP)

When deciding whether to provide PEP, consultation with local public health officials can help to determine the risk of transmission. In general, bites or exposure of wounds to saliva are considered high risk in specific animal species and populations. The risk of rabies increases with multiple bites and when bites are in close proximity to the CNS. PEP is often provided empirically due to the difficulty of confirming a true rabies exposure.^1,2,5,6

Factors that should be considered to decide if a patient needs PEP:

• Epidemiology of animal rabies in the region
• Animal species
• Type of contact made with the animal
• Additional factors that could indicate an animal is likely to be rabid includes the animal having no history of rabies vaccination, an unprovoked attack, recent animal behavioral changes, recent bites or wounds on the animal
• Animal observation/testing

Medical Management

Although no treatment exists for rabies, the disease remains almost completely preventable with rabies post-exposure prophylaxis (PEP) regimens. The rabies virus typically has an incubation period of weeks to months in human hosts, making rabies PEP an effective way to provide immediate immunity for most patients. Without administration of PEP, patients infected with rabies will develop CNS symptoms with disease progression, with a high likelihood of death. ^1,2,5,6

Rabies PEP comprises a vaccine series with or without rabies immune globulin (RIG).^1,2 For unvaccinated individuals, the vaccine series consist of 4 doses of the vaccine over a 14-day treatment period. The first dose is provided on the day of the rabies exposure and then again on days 3, 7, and 14 post-vaccination. RIG is also indicated for unvaccinated individuals. For previously vaccinated individuals or those with a documented rabies virus-neutralizing antibody titer, the vaccine series consists of 2 doses, and the patient does not need RIG. It is essential to follow the rabies vaccine and RIG schedule as data are limited on the efficacy of alternative dosing schedules, and under dosing may lead to irreversible neurological effects or death.^1,2,5,6

There are currently two rabies vaccines in the United States (US): human diploid cell vaccine (HDCV) (Imovax) and purified chick embryo cell vaccine (PCECV) (RabAvert). Each vial contains ≥2.5 IU rabies antigen to be reconstituted with 1 ml diluent prior to administration. Vaccines should be administered intramuscularly into the deltoid muscle, preferably. The anterolateral aspect of the thigh may be an alternative in pediatric patients. Gluteal administration should be avoided due to the possibility of lower blood titers.¹ Previously, the Advisory Committee on Immunization Practices (ACIP) recommended a 5-dose rabies vaccination series. However, this was reduced to a 4-dose series based on research that showed no additional favorable outcomes existed with the 5-dose series.³

RIG contains pooled plasma samples derived from humans (human RIG; HRIG) or horses (equine RIG; ERIG). Only HRIG is currently available in the US. HRIG products with a potency of 150 IU/mL include Imogam®Rabies-HT, KEDRAB, and HyperRab^TMS/D. These formulations do not usually require dilution, but the volumes needed may be painful for patients. HyperRab® is more concentrated with a potency 300 IU/mL but may require dilution with dextrose 5% in water (D5W) to have enough volume for wound infiltration. HRIG should ideally be administered on the first day of exposure, along with the first vaccine dose. It is recommended to administer HRIG around the wound itself with any remaining volume administered intramuscularly at a distal site from where the vaccine was administered. HRIG may be administered through the seventh day after administering the first dose of the vaccine but is not recommended afterward because an antibody response should already provide some immunity.^1,2,4-6

Both the vaccine and the RIG are usually well-tolerated. After receiving the vaccine, patients may experience mild local injection site reactions (redness, swelling, itching) and/or injection site pain. Patients may rarely experience headaches, nausea, dizziness, abdominal pain, or muscle aches. After administration of HRIG, patients may experience local injection site pain and/or a low-grade fever.^3-6  

Available HRIG products in the US:

^¥Avoid IM administration of immunoglobulin in the same site as the IM vaccine administration

 References

1. Rabies [internet]. Atlanta (GA): Centers for Disease Control and Prevention (CDC); 2022 Dec 8 [cited 2023 Feb 17]. Available from: https://www.cdc.gov/rabies/index.html
2. Rabies [internet]. Salt Lake City (UT): Utah Department of Health Bureau of Epidemiology; 2019 [cited 2023 Feb 17]. Available from: https://epi.health.utah.gov/rabies/
3. Rao AK, Briggs D, Moore SM, et al. Use of a Modified Preexposure Prophylaxis Vaccination Schedule to Prevent Human Rabies: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022. MMWR 2022;71:619–627. DOI: http://dx.doi.org/10.15585/mmwr.mm7118a2external icon
4. Bookstaver PB, Akpunonu P, Nguyen HB, Swan JT, Howington GT. Administration of rabies immunoglobulin: Improving evidence-based guidance for wound infiltration. Pharmacotherapy. 2021 Aug;41(8):644-648.
5. Moran GJ, Talan DA, Mower W, et al. Appropriateness of rabies postexposure prophylaxis treatment for animal exposures. Emergency ID Net Study Group. JAMA 2000; 284:1001.
6. Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med 2004; 351:2626.
7. Rupprecht CE, Briggs D, Brown CM, et al. Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals. Vaccine. 2009;27(51):7141-7148.
8. Rabies Vaccine: Vaccine Information Statements. Atlanta, (GA): Centers for Disease Control and Prevention, 2022 [cited 2023 Feb 17]. Available from: https://www.cdc.gov/vaccines/hcp/vis/vis-statements/rabies.pdf

Author: Brittany Harnicher, PharmD, Emergency Medicine Pharmacist, Intermountain Utah Valley Hospital