The Pre-brief
The Pre-brief:
- Rabies is a preventable zoonotic disease that is most often transmitted through the bite of a rabid animal
- 1 – 3 cases of human rabies are reported annually in the United States (US)
- In the past decade (2009 – 2018) 25 cases of human rabies were reported in the US with seven of these infections being acquired outside of the US and its territories
- The principal reservoir hosts for rabies in the US include bats, raccoons, skunks, and foxes
- Annually, hundreds of thousands of animals are placed under observation or have to be tested for rabies, and between 30,000 – 60,000 people need to receive rabies post-exposure prophylaxis (PEP)
Pathophysiology:
Rabies is a viral zoonosis caused by any of the 15 recognized RNA viruses in the family Rhabdoviridae of the genus Lyssavirus and the order Mononegavirale. It is characterized by a bullet-shaped structure. Most commonly transmitted via a bite from a rabid animal, rabies may also be transmitted when fresh saliva from an infected animal comes into contact with wounds or mucous membranes of another mammal. In the US, contact with infected bats is the leading cause of human rabies death. People may not recognize a bat scratch or bite, as they may be smaller than a pencil eraser; however, this is still considered an exposure and can still spread rabies. If a patient awakens to find a bat in the same room they were sleeping in and is unaware if a bite or direct contact has occurred, this may qualify as an exposure. Once entry is gained and the virus is in the central nervous system, it can cause an acute, progressive encephalomyelitis that is almost always fatal. In humans, the incubation period is usually several weeks to months, but may range from days to years. Bites to the head, face, neck, and hands with bleeding present the greatest risk and are associated with shorter incubation periods. Rabies affects only mammals. Small rodents (squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (rabbits and hares), are almost never found to be infected with rabies and have not been known to transmit rabies to humans. Non-bite exposures include inhalation of aerosolized virus and cornea/organ transplants.

Management:
Bite wounds should be thoroughly washed with soap and water. If available, a virucidal (e.g. povidone-iodine solution) should be used to irrigate the wound. This should be completed for patients who are previously vaccinated and those not previously vaccinated. Rabies vaccine administration +/- rabies immune globulin (RIG) is an essential part of wound management and is highly effective in preventing human rabies following exposure.
The rabies vaccine is essential in PEP management. For patients who are not previously vaccinated and are immunocompetent, a four-shot series is indicated and is administered IM on days 0, 3, 7, and 14. For patients who are immunocompromised, a fifth dose is needed on day 28. In patients who are previously vaccinated, two doses are needed on days 0 and 3. The vaccine should be administered IM in the deltoid muscle. Administration in the gluteal area should be avoided as it may result in a diminished immunological response. RIG and the rabies vaccine should not be mixed in the same syringe and should be administered at different anatomical sites.
For patients not previously vaccinated, RIG should be administered at a dose of 20 international units/kg of body weight with the first dose of the vaccine (day 0). If not administered when the vaccination was begun, it may be administered up to and including day 7 of the PEP series. If anatomically feasible, the entire dose should be infiltrated around and into the wound. The remaining amount should be administered IM at a site distant from vaccine administration (in the deltoid muscle of the arm or lateral thigh muscle). The gluteal area should be avoided to reduce the risk of sciatic nerve damage or unpredictable absorbance unless the gluteal region has been affected. Patients that have been previously vaccinated do not require administration of RIG. RIG provides passive immunity while the vaccine-induced humoral immune response is initiated.
Guidelines exist for the CDC as well as the World Health Organization for PEP and are summarized below:

The Debrief:
- Human rabies is extremely rare in the US and occurs in approximately 1 – 3 patients annually
- Carnivorous mammals, hematophagous bats, and insectivorous bats are the main reservoir for the virus
- In the US, the main reservoir species include bats, raccoons, skunks, foxes, and mongooses
- PEP is essential in the management of these patients and comprises irrigation of the wound with soap and water (and a virucidal agent if possible), and rabies vaccine administration +/- RIG
- Public health officials should be consulted if there are any questions regarding animal exposure and rabies management
References
- Human Rabies. Centers for Disease Control and Prevention. April 2020. https://www.cdc.gov/rabies/location/usa/surveillance/human_rabies.html. Accessed May 23, 2021.
- Ma X, Monroe B, Cleaton J, et. al. Rabies surveillance in the United States during 2018. J Am Vet Med Assoc. 2020; 256: 195 – 208.
- What is Rabies? Centers for Disease Control and Prevention. November 2020. https://www.cdc.gov/rabies/about.html. Accessed May 23, 2021.
- Rabies. World Health Organization. May 2021. https://www.who.int/en/news-room/fact-sheets/detail/rabies. Accessed May 23, 2021.
- Manning S, Rupprecht C, Fishbein D, et. al. Human rabies prevention – United States, 2008 recommendations of the advisory committee on immunization practices. MMWR Recomm Rep. 2008; 57(RR-3): 1-28.
- Singh R, Singh K, Cherian S, et. al. Rabies – epidemiology, pathogenesis, public health concerns and advances in diagnosis and control: a comprehensive review. Vet Q. 2017; 37(1): 212 – 251.
- Rupprecht C, Briggs D, Brown C, et. al. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies. MMWR Recomm Rep. 2010; 59(RR-2): 1 – 9.
- Baevsky R, Bartfield J. Human rabies – a review. Am J Emerg Med. 1993; 11: 279 – 286.
- Neglected Tropical Diseases. World Health Organization – WHO Announcies new rabies recommendations. January 2018. https://www.who.int/neglected_diseases/news/Rabies_WHO_has_published_new_recommendations_for_immunization/en/. Accessed May 26, 2021.
Great article!