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Rabies

Last updated: May 26, 2021

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Rabies is a neurotropic virus contracted from the bite of an infected animal. The virus enters the patient's skin from the saliva of the animal and migrates along the peripheral nerves to the central nervous system (CNS). An incubation period of 4–12 weeks typically precedes the clinical appearance of the disease, which manifests with a prodrome of nonspecific flu-like symptoms, followed by acute rabies encephalitis. Clinical findings include fever, hydrophobia, hypersalivation, and stupor alternating with mania. Coma and eventually death due to respiratory and circulatory collapse ensue. A minority of rabies cases are paralytic rather than encephalitic, presenting with ascending paralysis similar to that of Guillain-Barré syndrome and culminating in cardiac and respiratory arrest. With adequate post-exposure prophylaxis (PEP) (i.e., with rabies immunoglobulin plus rabies vaccine) and wound care following a rabid animal bite, rabies infection is preventable. No curative treatment is available once the signs and symptoms of rabies have appeared, and the disease is almost always fatal. Preexposure prophylaxis with the rabies vaccine is recommended for individuals traveling to areas where the virus is widespread, as well as for those with jobs that predispose them to infection (e.g., veterinarians).

  • Found in animal reservoirs in most countries throughout the world
  • Considerable divide between developed and developing countries in terms of human death due to rabies
    • Incidence worldwide: Up to 70,000 people die of rabies each year. [1]
    • Incidence in the US: Three people on average die of rabies each year.

Epidemiological data refers to the US, unless otherwise specified.

  • Pathogen
    • Rabies is caused by several different members of the Rhabdoviridae family.
    • Rhabdoviruses are rod or bullet shaped
    • Genus: Lyssavirus
    • ssRNA
  • Transmission
    • Most common animal reservoir worldwide: dogs
    • Most common animal reservoirs in the US: bats, raccoons, skunks, and foxes
    • Spread through saliva of rabid animal after bite injury
    • Via aerosols (e.g., bat caves); rare

References:[2]

References:[3]

General

Encephalitic rabies (most common type)

Paralytic rabies (< 20% of cases)

The pathognomonic feature of rabies is hydrophobia due to pharyngeal muscle spasm. This may present along with agitation, strange behavior, mental status changes, and possibly foaming at the mouth.
References:[5][6][7][8]

In the case of a bite injury from a suspicious animal, see PEP algorithm in “Treatment” below.

Antemortem diagnosis

Several tests using multiple specimens must be performed to diagnose rabies because individual tests have limited sensitivity. Evidence of the virus can only be obtained after disease onset.

Postmortem diagnosis

Rabies risk assessment

  • Administer PEP
    • Bite by a known wild reservoir for rabies (e.g., bats, raccoons, skunks, foxes), if the animal is not available for testing or if the test comes back positive
    • Bite by a domestic carnivore (e.g., dog) not available for observation or displaying symptoms of rabies
  • Observe/test animal and possibly administer PEP
    • Attack by an unvaccinated domestic carnivore without symptoms of rabies (e.g., dog) → observe animal for a 10-day period
      • Animal remains normal: PEP is not necessary
      • Animal starts to display symptoms of rabies
        • Euthanize and study brain samples of the animal
        • Administer PEP to patient
        • PEP is stopped if test results of the animal are negative
  • PEP is not required
    • Bite by a vaccinated domestic carnivore
    • Bite by an indoor domestic herbivore

Rabies post-exposure prophylaxis [10][11]

Treatment with PEP in suspected cases of a bite by a rabid animal should take place urgently, as the disease is fatal once it becomes symptomatic. Suspicion of rabies is sufficient indication for PEP!

Symptomatic encephalitic or paralytic rabies

  • Mortality: Symptomatic rabies is almost always fatal.
  • Rabies is preventable following exposure to a rabid animal with adequate PEP (see “Treatment” section above)

Rabies is almost always fatal once the symptoms have appeared.

References:[13]

Vaccination (preexposure prophylaxis)

  • Vaccine: inactivated (killed) vaccine
  • Indications
    • People with frequent occupational contact with potentially rabid animals
    • Travelers to regions in which rabies is widespread (especially if PEP may not be readily available)

Obligation to report

  1. Koury R, Warrington SJ. Rabies. StatPearls. 2021 .
  2. Rabies: Wild Animals. https://www.cdc.gov/rabies/location/usa/surveillance/wild_animals.html. Updated: April 29, 2016. Accessed: February 28, 2017.
  3. Poisson N, Gaudin Y, Jacob Y, et al. Molecular basis for the interaction between rabies virus phosphoprotein P and the dynein light chain LC8: dissociation of dynein-binding properties and transcriptional functionality of P. J Gen Virol. 2001; 82 (11): p.2691-2696. doi: 10.1099/0022-1317-82-11-2691 . | Open in Read by QxMD
  4. Mader EC, Maury JS, Santana-gould L, et al. Human Rabies with Initial Manifestations that Mimic Acute Brachial Neuritis and Guillain-Barré Syndrome. Clin Med Insights Case Rep. 2012; 5 : p.49-55. doi: 10.4137/CCRep.S9318 . | Open in Read by QxMD
  5. Consales CA, Bolzan VL. Rabies review: immunopathology, clinical aspects and treatment. J. Venom. Anim. Toxins incl. Trop. Dis [online]. 2007; 13 (1): p.5-38. doi: 10.1590/S1678-91992007000100002 . | Open in Read by QxMD
  6. Li H. Radiology of Infectious Diseases. Springer ; 2015
  7. Brent A, Davidson R, Seale A. Oxford Handbook of Tropical Medicine. Oxford University Press ; 2014
  8. Rabies. http://www.merckmanuals.com/professional/neurologic-disorders/brain-infections/rabies. Updated: February 28, 2017. Accessed: February 28, 2017.
  9. Rabies: Ante Mortem Testing. https://www.cdc.gov/rabies/specific_groups/doctors/ante_mortem.html. Updated: April 15, 2016. Accessed: February 14, 2017.
  10. Human Rabies Immune Globulin. https://www.cdc.gov/rabies/medical_care/hrig.html. Updated: April 22, 2011. Accessed: March 20, 2017.
  11. Immunity Types. https://www.cdc.gov/vaccines/vac-gen/immunity-types.htm. Updated: May 19, 2014. Accessed: March 20, 2017.
  12. Rabies: What care will I receive?. https://www.cdc.gov/rabies/medical_care/. Updated: March 23, 2016. Accessed: February 14, 2017.
  13. Rabies. http://www.who.int/mediacentre/factsheets/fs099/en/. Updated: March 1, 2016. Accessed: February 28, 2017.
  14. Herold G. Internal Medicine. Herold G ; 2014