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  • Christine Ahn MD
    Carl Allen DDS, MSD
    Brandon Ayres MD
    Howard P. Baden MD
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  • Am. Journal of Trop. Med & Hygiene
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ContentsSynopsisCodesLook ForDiagnostic PearlsDifferential Diagnosis & PitfallsBest TestsManagement PearlsTherapyReferencesView all Images (3)
Emergency: requires immediate attention
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Contributors: Rizwan Ul Hassan MBBS, William Bonnez MD, James H. Willig MD, MSPH
Other Resources UpToDate PubMed


Rabies is a zoonotic disease caused by a virus belonging to genus Lyssavirus and family Rhabdoviridae. It principally affects the central nervous system (CNS). It is transmitted to humans by close contact with infected saliva as a result of a bite or scratch. Rabies is a disease with almost 100% mortality.

Rabies occurs worldwide. Dogs are the source of 99% of human rabies deaths, and 95% of human deaths due to rabies occur in Asia and Africa. The epidemiology of human rabies reflects that of local animal rabies; thus in areas where dogs are immunized, most human cases follow exposure to rabid wild animals. High-risk occupations include veterinarians, scientists working with live virus, and those handling animals or animal meat from an unprotected reservoir. Residence in a rabies-affected region also confers high risk. Children are particularly at high risk if living in a rabies-affected area. Travelers with extensive outdoor exposure in rural high-risk areas where immediate access to appropriate medical care may be limited should be considered at high risk regardless of the duration of their stay.

Only in the Americas is the rabies virus found in bats. In the United States, rabies remains rare in dogs, cats, and other domestic animals because of animal control and vaccination programs. Therefore, over 90% of animal rabies cases in the United States occur in wildlife. At present there are 4 terrestrial reservoir species in the United States: raccoons, skunks, foxes, and coyotes. Rabid bats are found in every state except Hawaii. Rodent bites are also common, and so rodents are often tested for rabies in the United States.

After inoculation, the virus replicates locally in skeletal muscle cells. The viral glycoprotein (G protein) attaches to the postsynaptic nicotinic acetylcholine receptor of the skeletal muscle. After an incubation period, the virus then enters the nervous system via unmyelinated sensory and motor terminals and is transported to the spinal ganglia and travels up to the gray matter of the brain, where it predominantly affects neurons of the limbic system, midbrain, and hypothalamus (centripetal spread via peripheral nerves to the CNS). From the brain the virus travels down to the acinar glands of the submaxillary glands and concentrates in the saliva, thus allowing further transmission. The virus can also spread to other organs such as the heart and in particular to the autonomic and sensory neurons surrounding hair follicles. This is the basis for the viral diagnosis on a skin biopsy taken from the nape of the neck, above the hairline, an area closest to the brain.

Once the virus attaches to the nerve, it is sequestered from the immune system; vaccination can no longer be effective, and rabies may be inevitable.

The mortality from the bite of a proven rabid dog varies from 35% to 60% depending on the severity of the bite and the amount of virus in the saliva.

Although the infection causes inflammatory changes in the brain, it is more neuronal dysfunction than death that accounts for the disease manifestations. The involvement of the region around the nucleus ambiguus, in the brainstem, is thought to be the basis of hydrophobia, or fear of water, a manifestation unique to rabies. On pathology, the presence of eosinophilic cytoplasmic viral inclusions called Negri bodies is a classic finding.

  • The rabies virus multiplies in many organs, but the salivary glands are important for disease transmission. Dogs may have virus in saliva for many days before symptoms occur, but transmission of rabies to humans has not been reported from dogs that appeared normal for 10 days after a biting incident.
  • People are infected through the skin following a bite or a scratch by an infected animal. Claws are dangerous, as rabid animals often lick their claws. Dogs are the main source for almost all deaths from rabies in Asia and Africa.
  • Transmission can also occur if the infected saliva comes in contact with human mucosa or open skin wounds.
  • Human-to-human transmission of rabies is theoretically possible but has never been recorded. Cases of rabies have been documented after corneal and solid organ transplantations.


A82.9 – Rabies, unspecified

14168008 – Rabies

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Differential Diagnosis & Pitfalls

  • Paralytic rabies may be confused with Guillain-Barré syndrome, poliomyelitis, or posterior reversible vaccine encephalopathy syndrome. Careful neurological examination and cerebrospinal fluid (CSF) examination will often help rule out these conditions. 
  • Tetanus can be differentiated, as trismus is not seen in rabies, and hydrophobia is not seen in tetanus. 
  • Botulism causes paralysis, but the absence of sensory changes should exclude rabies. 
  • Hysteria is the most difficult differential diagnosis, ie, when a person thinks they have rabies. This pseudo-rabies can be ruled out by normal blood gases and the absence of variation in the bizarre behavior. 
  • Epilepsy 

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Last Updated: 03/28/2017
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Rabies (Prodromal Symptoms) : Chills, Fever, Headache, Nausea/vomiting, Wild animal exposure, Anorexia, Myalgia
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