Merck Manual

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John E. Greenlee

, MD, University of Utah Health

Reviewed/Revised Mar 2022
Topic Resources

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 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.

Rabies causes > 55,000 human deaths worldwide annually, mostly in Latin America, Africa, and Asia, where canine rabies is endemic. In the US, vaccination of domestic animals has reduced rabies cases in people to < 3 a year, mostly transmitted by infected bats. Infected raccoons, skunks, and foxes can also 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.

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

Treatment once rabies has developed is only supportive and includes heavy sedation (eg, with ketamine and midazolam) and comfort measures. Death usually occurs 3 to 10 days after symptoms begin. Few patients have survived; many received immunoprophylaxis before onset of symptoms. There is evidence that giving rabies vaccine and immune globulin 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 US and because bat bites may be hard to detect, contact with a bat is an absolute indication for postexposure prophylaxis.

Preexposure rabies prophylaxis

Human diploid cell rabies vaccine (HDCV) is safe and recommended for preexposure prophylaxis for people at risk, including veterinarians, animal handlers, spelunkers, workers who handle the virus, and travelers to endemic areas.

A total of three 1-mL doses are given IM, one each on days 0, 7, and between day 21 and 28. 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.

Postexposure rabies prophylaxis

Exposure is considered to be a bite that breaks the skin or any contact between mucous membrane or broken skin and animal saliva. If exposure occurs, prompt, meticulously executed prophylaxis almost always prevents human rabies. The wound is cleansed immediately and thoroughly with soap and water or benzalkonium chloride. Deep puncture wounds are flushed with soapy water using moderate pressure. Wounds are usually left open.

Postexposure prophylaxis with rabies vaccine and rabies immune globulin is given depending on the biting animal and circumstances (see table Rabies Postexposure Prophylaxis Rabies Postexposure 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.

  • Because bat bites can be tiny and hard to detect, give the rabies vaccine and rabies immune globulin to anyone who has had contact with a bat.


For postexposure prophylaxis, rabies immune globulin 20 IU/kg is infiltrated around the wound for passive immunization; if injection volume is too much for distal areas (eg, fingers, nose), some rabies immune globulin may be given IM (2 Prevention references 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... read more ). This treatment is accompanied by the rabies vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]) for active immunization. HDCV is given in a series of four 1-mL IM injections (deltoid area is preferred), beginning on the day of exposure (day 0), in a limb other than the one used for rabies immune globulin. Subsequent injections occur on days 3, 7, and 14; immunosuppressed patients receive a 5th dose on day 28. Rarely, a serious systemic or neuroparalytic reaction occurs; then, completion of vaccination is weighed against the patient’s risk of developing rabies. Rabies antibody titer is measured to help assess risk of stopping vaccination.

Postexposure prophylaxis for a person previously vaccinated against rabies includes 1-mL IM injections of rabies vaccine on days 0 and 3 but no rabies immune globulin.

Prevention references

  • 1. ACIP: Human Rabies Prevention --- United States, 2008 Recommendations of the Advisory Committee on Immunization Practices. Morbidity and Mortality Weekly Report 57 (RR03):1–26,28, 2008.

  • 2. ACIP: (Advisory Committee on Immunization Practices) recommendations: Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies. Morbidity and Mortality Weekly Report 59 (RR02):1–9, 2010.

Key Points

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

  • In the US, 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.

  • Before exposure, give the rabies vaccine to people at risk (eg, veterinarians, animal handlers, spelunkers, workers who handle the virus, travelers to endemic areas).

  • After exposure to an animal who has or is suspected of having rabies, thoroughly clean and debride any wounds, then give the rabies vaccine and rabies immune globulin.

  • Raccoons, skunks, or foxes that have bitten a person should be regarded as rabid; because bat bites can be minute and hard to detect, contact with a bat is an absolute indication for rabies immune globulin and the rabies vaccine.

Drugs Mentioned In This Article

Drug Name Select Trade
Nayzilam, Versed, Versed Syrup
Imovax, RabAvert
Bactine, Care Touch, DermacinRx DiaSinc, Ionax, Kid's Antiseptic Cleansing, Neosporin Wound Cleanser, Pronto Plus, RevitaDERM, Zephiran
BayRab, HyperRAB, HyperRAB S/D, Imogam, KEDRAB
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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