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
Epidemiological data refers to the US, unless otherwise specified.
- 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
- Rabies virus binds the ACh receptor of peripheral nerves in the bite wound → migrates retrogradely along the axonal microtubules (using motor protein dynein) → enters the CNS → infects the brain
- Incubation period: 4–12 weeks average
- Prodromal symptoms
Encephalitic rabies (most common type)
- Hydrophobia: Rabies patients experience involuntary, painful pharyngeal muscle spasms when trying to drink; later on in the disease, the sight of water alone may provoke nausea or vomiting.
- CNS symptoms
- Autonomic symptoms (e.g., hypersalivation, hyperhidrosis)
- 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.
In the case of a bite injury from a suspicious animal, see PEP algorithm in “Treatment” below.
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.
- Four specimens are required for testing: serum, saliva, CSF, and skin 
- RT-PCR to detect rabies RNA
- Cell culture to isolate the virus
- Fluorescent antibody testing (FAT) to detect viral antigen in a smear or frozen section of a biopsy
Antibody testing ( )
- Serum antibodies detected in individuals who are not immunized and did not receive postexposure prophylactic immunoglobulins indicate the diagnosis
- Rising serum antibody levels over several days in immunized patients are suggestive of rabies infection
- Antibodies in the CSF regardless of the immunization history are indicative of rabies infection
- Additional tests
- Postmortem brain tissue autopsy
Australian bat lyssavirus infection 
- Definition: rabies-like condition endemic to Australia that is transmitted via infected bats
- Extremely rare
- Individuals who have contact with bats (e.g., due to occupation) are at higher risk.
- Etiology: Australian bat lyssavirus
- Clinical features
- Diagnostics: clinical diagnosis
- Prognosis: Untreated ABLV infection is fatal.
- Prevention: rabies vaccination, avoiding contact with bats
The differential diagnoses listed here are not exhaustive.
Rabies risk assessment
- 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
- Attack by an unvaccinated domestic carnivore without symptoms of rabies (e.g., dog) → observe animal for a 10-day period
- PEP is not required
- Bite by a vaccinated domestic carnivore
- Bite by an indoor domestic herbivore
Rabies post-exposure prophylaxis 
- Cleaning and debridement, as with all
- Tetanus shot and antibiotic prophylaxis may be indicated
- Nonimmunized patient: postexposure prophylaxis (passive-active immunization)
- Prior immunization 
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.
Vaccination (preexposure prophylaxis)
- Vaccine: inactivated (killed) vaccine
- 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)