• 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.
    • Rhabdoviruses are rod or bullet shaped
    • Genus: Lyssavirus
    • ssRNA
  • Transmission
    • Spread through saliva of rabid animal after bite injury
      • Occasionally by other means of contact such as scratches, mucous membrane contact with infected bodily fluids
    • Most common animal reservoir worldwide: dogs
    • Most common animal reservoirs in the US: bats, raccoons, skunks, and foxes
      • Most common overall: bats
      • Eastern US: especially raccoons
      • Central US and California: especially skunks
      • Texas, Arizona, and Alaska: especially foxes
      • Puerto Rico: especially mongoose
    • Occurs in very rare cases after organ transplantation from infected donors




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
    • Anxiety, agitation and combativeness alternating with calm periods
    • Confusion and hallucinations
    • Fasciculations
    • Seizures
    • ↑ Muscle tone and reflexes with nuchal rigidity
    • Extensor plantar responses
  • 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
    • Cornea: Epithelial scrapings for reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence staining
    • 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
      • Including potential exposure to a bat without evidence of scratch or bite wounds
    • 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
  • Other scenarios (e.g., bite by livestock, domestic herbivore): contact local health department

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 as much as possible, with any remaining given IM
    • PLUS rabies vaccine given IM on days 0, 3, 7, and 14 (+ 28 in immunosuppressed patients)
  • Prior immunization
    • Even patients who have been vaccinated against rabies should be treated after exposure!
    • Rabies vaccine IM on days 0 and 3.
    • No immunoglobulin
    • Check antibody titers on day 14.

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)
  • There are a few examples of rabies survival in the literature


Vaccination (preexposure prophylaxis)

  • Inactivated (killed) vaccine
  • Given three times IM on days 0, 7, and 21–28
  • 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)
  • Booster doses
    • May be necessary to maintain immunity
    • People with occupations involving prolonged risk of rabies → periodic testing of immunity and booster shots as required.

Obligation to report

Rabies is a nationally notifiable disease according to the CDC.