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Rabies is a zoonosis generally transmitted to humans by the bite of a rabid animal and caused by rabies virus—a nonsegmented, negative sense, single-stranded RNA virus in the family Rhabdoviridae. Each animal reservoir harbors distinct rabies virus variants.


Worldwide, canine rabies causes ~55,000 human deaths each year, most of them affecting rural populations and children in Asia and Africa.

  • Endemic canine rabies has been eliminated in the United States and most other resource-rich countries but persists in bats, raccoons, skunks, and foxes. In 2012, there were 6162 confirmed animal cases of rabies in the United States.

  • Bats (especially silver-haired and tricolored bats) cause most human cases in North America, although there may be no known history of a bat bite or other bat exposure.


The incubation period can range from a few days to >1 year but is usually 20–90 days. During most of this period, rabies virus is present at or close to the site of the bite.

  • The virus binds to postsynaptic nicotinic acetylcholine receptors and spreads centripetally along peripheral nerves toward the CNS at a rate of up to ~250 mm/d. Establishment of CNS infection is followed by centrifugal spread along peripheral nerves to other tissues, including salivary glands—hence the excretion of virus in the saliva of rabid animals.

  • The most characteristic pathologic CNS finding is the Negri body—an eosinophilic cytoplasmic inclusion that is composed of rabies virus proteins and viral RNA and is found primarily within Purkinje cells of the cerebellum and in pyramidal neurons of the hippocampus.

Clinical Manifestations

Rabies usually presents as atypical encephalitis with preservation of consciousness; the disease may be difficult to recognize after the onset of coma. This disease, which usually leads to death despite aggressive therapy, has three phases.

  • Prodrome: Pts have fever, headache, malaise, nausea, vomiting, and anxiety or agitation lasting 2–10 days. Paresthesias, pain, or pruritus near the site of exposure (which has usually healed at this point) is found in 50–80% of cases and strongly suggests rabies.

  • Acute neurologic phase: Pts present with the encephalitic (furious) form of rabies in 80% of cases and with the paralytic form in 20%.

    • Encephalitic form: Pts develop signs and symptoms common to other viral encephalitides (e.g., fever, confusion, hallucinations, combativeness, and seizures) that last 2–10 days. Autonomic dysfunction is common and includes hypersalivation, gooseflesh, cardiac arrhythmia, and/or priapism.

      • A distinguishing feature of rabies is prominent early brainstem dysfunction resulting in hydrophobia and aerophobia (involuntary, painful contraction of the diaphragm and the accessory respiratory, laryngeal, and pharyngeal muscles in response to swallowing liquid or exposure to a draft of air).

      • Hypersalivation and pharyngeal dysfunction produce characteristic foaming at the mouth.

      • Death usually occurs within days of brainstem involvement. With ...

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