About Rabies

Even though rabies has been around for more than 4000 years, it still remains one of the deadliest diseases in the world.1 After the onset of symptoms, there is no effective treatment, and only a handful of people worldwide have ever recovered from it. Human infections usually occur as a result of being bitten by an infected animal.2

The rabies virus, from the saliva of an infected animal deposited in the wound site, enters muscle cells, replicates, then rapidly travels within axons to the central nervous system, resulting in fatal encephalitis. A remarkable aspect of the rabies virus that adds to its lethality is its ability to evade host immune mechanisms1,3

Rabies can occur from different types of exposures, including2,4,5:

Handling an infected animal*

*In some cases, handling bats has resulted in human rabies. Patients were physically holding the animal and were not bitten or scratched.4

A bite or scratch

Contact of broken skin or mucous membranes with infected saliva

Contact with infected neural tissue

Inhalation of aerosolized infectious material

Animals at high risk for rabies in the US6:

*Events where >10 persons are exposed to a potentially rabid bat.

Bats are the most common source of human rabies exposures in the United States7

Bat exposures can be difficult to identify since they are smaller than other exposures, which may lead to delayed reporting and treatment. Bat exposures are responsible for the most human rabies-related deaths in the US.7-9
~175 mass bat exposures are reported every year by the US public health system.7*

Rabies is essentially10,11:

†Three patients in the US have recovered from rabies without postexposure prophylaxis. Patients received a controversial intensive care strategy involving antiviral therapy and induced therapeutic coma. Numerous patients have subsequently failed this experimental protocol.12

Postexposure Prophylaxis for Rabies

In the United States, approximately 55,000 people report coming in contact with potentially rabid animals and receive rabies postexposure prophylaxis (PEP) each year.7

If PEP has been initiated and appropriate laboratory diagnostic testing (eg, the direct fluorescent antibody test) indicates that the animal that caused the exposure was not rabid, PEP may be discontinued.2

Be sure to follow the CDC PEP schedule13:

CDC, Centers for Disease Control and Prevention; HDCV, human diploid cell vaccine; PCECV, purified chick embryo cell vaccine.
* Infiltrate full dose around and into the wound (if possible). For remaining volume (or if there is no wound), inject HRIG in the deltoid area or lateral thigh muscle opposite of the vaccine injection.14
† Infiltrate full dose in the deltoid area opposite of the HRIG injection or wound13

If patients are exposed to an animal bite, they are also at risk for tetanus—check tetanus vaccination history when treating for rabies.15

Find out more information about tetanus immune globulin
Find out more information about tetanus vaccination

For more information, recommendations, and guidelines

CDC Advisory Committee on Immunization Practices (ACIP)

Rabies vaccines can take weeks to build immunity—HRIGs such as HyperRAB provide immediate protection16,17

  • The most commonly encountered causes of PEP management failures are when HRIG is not used at all, it is injected only IM and not into wound(s), or not all bite wound(s) are injected.18
  • The virus may continue to spread and replicate without HRIG.19,20

Provide immediate protection after exposure to rabies13,16-20:

Day 0

Administer HRIG and the FIRST rabies vaccine dose (1 mL IM). Antibodies start working Immediately at the site of infection
Day 3

Administer rabies vaccine (1 mL IM)

Day 7

Administer rabies vaccine (1 mL IM). Antibody production begins

Day 14

Administer rabies vaccine (1 mL IM)

Day 0 Day 3 Day 7 Day 14

Administer HRIG and the FIRST rabies vaccine dose (1 mL IM). Antibodies start working Immediately at the site of infection

Administer rabies vaccine (1 mL IM)

Administer rabies vaccine (1 mL IM). Antibody production begins

Administer rabies vaccine (1 mL IM)
  • HRIG can be given up to 7 days after the first dose of rabies vaccine.13
  • Patients who are immunocompromised should be given a fifth dose of the rabies vaccine on day 28.13

Looking for additional insights regarding rabies?

RabiesWatch, your comprehensive source for information on rabies and rabies exposure in the US.

Go to Rabies Watch

Important Safety Information for HyperRAB® (rabies immune globulin [human])

Indication and Usage

HyperRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies.

Limitations of Use

Persons who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine.

For unvaccinated persons, the combination of HyperRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis.

Beyond 7 days (after the first vaccine dose), HyperRAB is not indicated since an antibody response to vaccine is presumed to have occurred.

Important Safety Information

For infiltration and intramuscular use only.

Severe hypersensitivity reactions may occur with HyperRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur.

HyperRAB is made from human blood and may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

The most common adverse reactions in >5% of subjects during clinical trials were injection-site pain, headache, injection-site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain.

Do not administer repeated doses of HyperRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine.

Other antibodies in the HyperRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Defer immunization with live vaccines for 4 months after HyperRAB administration.

Please see full Prescribing Information for HyperRAB.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

References

  1. Schnell MJ, McGettigan JP, Wirblich C, Papaneri A. The cell biology of rabies virus: using stealth to reach the brain. Nat Rev Microbiol. 2010;8(1):51-61.
  2. 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.
  3. Ito N, Moseley GW, Sugiyama M. The importance of immune evasion in the pathogenesis of rabies virus. J Vet Med Sci. 2016;78(7):1089-1098.
  4. Centers for Disease Control and Prevention (CDC). Bats. CDC website. https://www.cdc.gov/rabies/exposure/animals/bats.html. Updated April 22, 2011. Accessed December 7, 2023.
  5. World Health Organization (WHO). Rabies. WHO website. https://www.who.int/news-room/fact-sheets/detail/rabies. Updated January 19, 2023. Accessed December 7, 2023.
  6. Birhane MG, Cleaton JM, Monroe BP, et al. Rabies surveillance in the United States during 2015. J Am Vet Med Assoc. 2017;250(10):1117-1130.
  7. Pieracci EG, Pearson CM, Wallace RM, et al. Vital signs: trends in human rabies deaths and exposures—United States, 1938-2018. MMWR Morb Mortal Wkly Rep. 2019;68(23):524-528.
  8. De Serres G, Dallaire F, Côte M, Skowronski DM. Bat rabies in the United States and Canada from 1950 through 2007: human cases with and without bat contact. Clin Infect Dis. 2008;46(9):1329-1337.
  9. Ma X, Bonaparte S, Corbett P, et al. Rabies surveillance in the United States during 2021. J Am Vet Med Assoc. 2023;261(7):1045-1053.
  10. Crowcroft NS, Thampi N. The prevention and management of rabies. BMJ. 2015;350:g7827.
  11. Noah DL, Drenzek CL, Smith JS, et al. Epidemiology of human rabies in the United States, 1980 to 1996. Ann Intern Med. 1998;128(11):922-930.
  12. Centers for Disease Control and Prevention (CDC). Recovery of a patient from clinical rabies—California, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(4):61-65.
  13. Rupprecht CE, Briggs D, Brown CM, et al; Centers for Disease Control and Prevention (CDC). Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies:recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59(RR-2):1-9.
  14. HyperRAB (rabies immune globulin [human]) Prescribing Information. Grifols.
  15. Baddour LM, Harper M. Patient education: animal bites (beyond the basics). UpToDate website. https://www.uptodate.com/contents/animal-and-human-bites-beyond-the-basics. Updated February 24, 2022. Accessed April 20, 2023.
  16. Baxter D. Active and passive immunity, vaccine types, excipients and licensing. Occup Med (Lond). 2007;57(8):552-556.
  17. Siegrist CA. Vaccine immunology. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 6th ed. Philadelphia: Elsevier-Saunders; 2013:17-36.
  18. Wilde H. Failures of post-exposure rabies prophylaxis. Vaccine. 2007;25(44):7605-7609.
  19. World Health Organization (WHO). WHO expert consultation on rabies. Second report. World Health Org Tech Rep Ser. 2013;(982):1-139, back cover.
  20. Nigg AJ, Walker PL. Overview, prevention, and treatment of rabies. Pharmacotherapy. 2009;29(10):1182-1195.