Rabies

ByRobyn S. Klein, MD, PhD, University of Western Ontario
Reviewed/Revised Jul 2024
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Rabies is a viral encephalitis transmitted by the saliva of infected bats and certain other infected mammals. Symptoms include depression and fever, followed by agitation, excessive salivation, and laryngeal spasms with hydrophobia. Diagnosis is by skin biopsy with fluorescent antibody or polymerase chain reaction testing. Vaccination is indicated for people at high risk of exposure. Postexposure prophylaxis involves wound care and passive and active immunoprophylaxis and, if promptly and meticulously executed, almost always prevents human rabies. Otherwise, the disorder is almost universally fatal. Treatment is supportive.

(See also Introduction to Brain Infections.)

Rabies causes > 59,000 human deaths worldwide annually, mostly in Africa and Asia, where canine rabies is endemic (1). In the United States, vaccination of domestic animals has reduced rabies cases in people to < 3 a year (2), mostly transmitted by infected bats. Infected raccoons, skunks, and foxes can transmit rabies. Transmission of rabies to humans from small rodents (such as squirrels, chipmunks, rats, mice, hamsters, guinea pigs, gerbils) and lagomorphs (including rabbits and hares) has not been reported.

Rabid animals transmit the infection through their saliva, usually by biting. Rarely, the virus can enter through a skin abrasion or across mucous membranes of the eyes, nose, or mouth. The virus travels from the site of entry via peripheral nerves to the spinal cord (or to the brain stem when the face is bitten), then to the brain. It then spreads from the central nervous system (CNS) via peripheral nerves to other parts of the body. Involvement of the salivary glands and oral mucosa is responsible for transmissibility.

General references

  1. 1. World Health Organization: Rabies. Accessed July 3, 2024.

  2. 2. Centers for Disease Control and Prevention: About Rabies. Accessed Jul 3, 2024.

Symptoms and Signs of Rabies

Pain or paresthesias may develop at the site of the bite. Rapidity of progression depends on the viral inoculum and proximity of the wound to the brain. The incubation period averages 1 to 2 months but may be > 1 year.

Initial symptoms of rabies are nonspecific: fever, headache, and malaise. Within days, encephalitis (furious rabies; in 80%) or paralysis (dumb rabies; in 20%) develops. Encephalitis causes restlessness, confusion, agitation, bizarre behavior, hallucinations, and insomnia. Salivation is excessive, and attempts to drink cause painful spasms of the laryngeal and pharyngeal muscles (hydrophobia). In the paralytic form, ascending paralysis and quadriplegia develop without delirium and hydrophobia.

Diagnosis of Rabies

  • Skin biopsy with fluorescent antibody testing

  • Sometimes polymerase chain reaction (PCR) testing of fluid or tissue samples

Rabies is suspected in patients with encephalitis or ascending paralysis and a history of an animal bite or exposure to bats; bat bites may be superficial and overlooked.

Direct fluorescent antibody testing of a biopsy specimen of skin from the nape of the neck is the diagnostic test of choice. Diagnosis can also be made by PCR of cerebrospinal fluid (CSF), saliva, or tissue. Specimens tested for rabies antibodies include serum and CSF.

CT, MRI, and EEG are normal or show nonspecific changes.

Treatment of Rabies

  • Supportive care

after clinical rabies develops may cause more rapid deterioration.

Prevention of Rabies

Rabid animals can often be recognized by their strange behavior; they may be agitated and vicious, weak, or paralyzed and may show no fear of people. Nocturnal animals (eg, bats, skunks, raccoons) may be out during the day. Bats may make unusual noises and have difficulty flying. An animal suspected of having rabies should not be approached. Local health authorities should be contacted to remove the animal.

Because bats are an important reservoir for rabies virus in the United States and because bat bites may be hard to detect, contact with a bat is an absolute indication for postexposure prophylaxis.

Recommendations for preexposure and postexposure prophylaxis are available (1).

Preexposure rabies prophylaxis

A total of two 1-mL doses are given IM, one each on days 0 and 7. Vaccination provides lifetime protection to some degree. However, protection decreases with time; if exposure is likely to continue, serologic testing every 6 months (for continuous exposure) or every 2 years (for frequent exposure) is recommended, and a booster dose of vaccine is given if the antibody titer is below a certain level (2, 3).

Postexposure rabies prophylaxis

Rabies Postexposure Prophylaxis), and the animal’s brain is tested for virus. Local or state health departments or the Centers for Disease Control and Prevention (CDC) usually conduct testing and can advise on other treatment issues.

Pearls & Pitfalls

  • Consider raccoons, skunks, or foxes that have bitten a person to have rabies.

Table
Table

4

Prevention references

  1. 1. Manning SE, Rupprecht CE, Fishbein D, et al: Human Rabies Prevention — United States, 2008 Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep 57 (RR03):1–26,28, 2008.

  2. 2. Rao AK, Briggs D, Moore SM, et al: Use of a modified preexposure prophylaxis vaccination schedule to prevent human rabies: Recommendations of the Advisory Committee on Immunization Practices—United States, 2022. MMWR Morb Mortal Wkly Rep 17(18):619-627.

  3. 3. Centers for Disease Control and Prevention: Rabies Pre-Exposure Vaccination. Accessed May 31, 2024.

  4. 4. Rupprecht CE, Briggs D, Brown CM, et al: Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: Recommendations of the advisory committee on immunization practices. MMWR Recomm Rep 59 (RR-2):1–9, 2010.

Key Points

  • Worldwide, rabies still causes tens of thousands of deaths yearly, mostly in Africa and Asia, where canine rabies is endemic.

  • In the United States, rabies kills only a few people yearly; it is usually transmitted by bats, but possibly by racoons, skunks, or foxes.

  • Pain and/or paresthesias at the bite site are followed by encephalitis (causing restlessness and agitation) or by ascending paralysis.

  • Biopsy neck skin for fluorescent antibody testing or do PCR of saliva, CSF, or tissue if patients have unexplained encephalitis or ascending paralysis.

  • Treat patients supportively.

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