• Clinical science



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 1–12 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.
    • 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.
  • Transmission
    • Spread through saliva of rabid animal after bite injury
    • Most common animal reservoir worldwide: dogs
    • Most common animal reservoirs in the US: bats, raccoons, skunks, and foxes



  • Rabies virus migrates from the bite wound in a retrograde manner along the microtubules (using motor protein dynein) of peripheral nerves, eventually entering the CNS and infecting the brain.
    • Causes acute, progressive, and fatal encephalitis → encephalitic rabies
    • In < 20% of cases, causes ascending flaccid paralysis → paralytic rabies (see “Clinical features” below)


Clinical features

Rabies is almost always fatal once the symptoms have appeared!

  • Incubation period: 1–12 weeks average
  • Prodromal symptoms
    • Flu-like symptoms
    • Locally: pain, paresthesia, and pruritis near the bite site

Encephalitic rabies (most common type)

  • Hydrophobia
  • CNS symptoms
  • Autonomic symptoms: e.g., hypersalivation
  • Coma and death within days to weeks of the development of neurological symptoms

Paralytic rabies (< 20% of cases)

  • Flaccid paralysis, gradually ascending and spreading from bite wound
  • Paraplegia and loss of sphincter tone
  • Respiratory failure and death

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!


  • Bite injury from a suspicious animal: For PEP algorithm see “Treatment” section below

Clinical rabies

  • History: exposure to a potentially rabid animal
  • Laboratory diagnosis
    • Serum
      • Non-immunized patient: rabies antibodies
      • Immunized patient: rising serum antibodies over a few days
    • CSF: findings characteristic of encephalitis
    • Skin: biopsy from the back of the neck for RT-PCR and immunofluorescence staining
    • Saliva: RT-PCR for viral RNA, viral culture
  • Postmortem brain tissue autopsy: Negri bodies



Risk evaluation of animal bites

  • Administer PEP
    • Bite by a known wild reservoir for rabies (e.g., bats, raccoons, foxes), if the animal is not available for testing or if the test comes back positive
    • Bite by a domestic carnivore 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

Post-exposure prophylaxis

  • Cleaning and debridement, as with all bite wounds
  • Tetanus shot and antibiotic prophylaxis may be indicated
  • Nonimmunized patient: postexposure prophylaxis
    • Rabies immunoglobulin spread in and around the wound
    • PLUS rabies vaccine given IM
  • Prior immunization
    • Even patients who have been vaccinated against rabies should be treated after exposure!
    • Rabies vaccine IM
    • No immunoglobulin
    • Check antibody titers

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

Symptomatic encephalitic or paralytic rabies

  • Palliative treatment



  • Mortality: Symptomatic rabies is almost always fatal.[12]
  • Rabies is preventable following exposure to a rabid animal with adequate PEP (→ see “Treatment” section above)


Vaccination (preexposure prophylaxis)

  • 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

Rabies is a nationally notifiable disease according to the CDC.