Rabies is a zoonotic disease that is decreasing in incidence in the United States. Rabies causes can acute, progressive encephalitis, and has the highest case fatality of any infectious disease if prompt post-exposure prophylaxis (PEP) is not initiated. 



  • The virus that causes rabies belongs to the Rhabdoviridae family in the genus Lyssavirus. It is a bullet-shaped virus that consists of a single-standed RNA core and a lipoprotein envelope. 
  • At least seven serotypes of the Lyssavirus genus infect humans and animals, but the most common cause of human rabies is Lyssavirus serotype-1, aka "the rabies virus." 



  • Humans acquire rabies through exposure to an infected animal. Human-to-human transmission is rare, but has occured after corneal and other organ transplants. 
  • Some parts of the world are considered rabies-free: Antarctica, Hawaii, many Pacific islands, and some areas of the Carribean. 
  • Dogs were the major source of human rabies in the United States until the mid-20th century. Vaccination campaigns controlled canine rabies in the U.S.; wild animals are now the major reservoir. 
  • Wildlife have accounted for >80% of reported rabid animals in the U.S. since 1975. Reservoir species include: raccoons, bats, skunks, foxes, and mongooses (Puerto Rico). While chipmunks, rabbits, squirrels and hamsters are susceptible to rabies, they rarely transmit the virus to humans; the virus tends to kill small rodents before they are able to pass it on. 
  • Vaccination of wildlife and pets, education campaigns, and PEP have dramatically reduced the burden of human rabies in the U.S. 
  • Over the past two decades, human rabies in the U.S. has been primarily associated with exposure to bats. Studies show that patients are often unable to recall a bite event, and confirmed cases of human rabies have occurred after minimal bat exposure. As a result, PEP recommendations require a low threshold of suspicion for all people with a possible bat exposure, especially if the patient is unable to reliably report whether a bite or scratch occurred (i.e. a sleeping or intoxicated adult, person with mental disabilites, or small child who has been in the presence of a bat). 
  • In 2010, 48 states and Peurto Rico reported 6,154 rabid animals and two human rabies cases to the CDC. 92% of reported rabid animals were wildlife (raccoons, skunks, bats, foxes, feral cats, cattle, and dogs, which are listed in order of decreasing frequency). Both cases of human rabies, which occured in Louisiana and Wisconsin, were related to exposure to a bat. 
  • Rabies in domestic animals accounted for 8% of all rabid animals reported in 2010.  The majority of these animals were cats. 
  • While the number of human rabies cases is very low, the CDC estimates that nearly 40,000 people in the U.S. receive PEP annually. 
  • Cases of human and animal rabies are nationally notifiable conditions in the U.S. The CDC collects this data and uses it to inform their recommendations about PEP and rabies risk in a given geographic area. 
  • In 2010, Illinois' only reported cases of rabies occurred in bats. No rabid skunks have been reported in IL since 2006. 



  • The rabies virus is transmitted when saliva inoculates a bite or cut on the skin. 
  • The virus replicates in muscle tissue around the site of inoculation during the incubation period (which may last from days to years). 
  • After the incubation period, the virus proceeds to the peripheral nerves via the neuromuscular connections. Once inside a peripheral nerve, the virus may travel 12-24 mm/day. 
  • The virus travels from the peripheral nerves to the CNS via the sensory neurons and dorsal root ganglia. 
  • Once in the CNS, the virus replicates further and infects virtually every neuron. 
  • From the CNS, the virus spreads to the rest of the body via the peripheral nerves. The virus actively replicates within the salivary glands.
  • The pathologic changes of rabies are proportionally minimal, especially in the context of its devasting clinical presentation. Eosinophilic intracytoplasmic viral inclusions called Negri bodies may be seen in the hippocampus, cortical neurons, and cerebellum, as well as in the skin, cornea, and other infected tissues. 


Clinical Presentation

  • Three possible outcomes follow a definite rabies exposure: no infection, asymptomatic infection, or symptomatic rabies.
  • In animals, the first sign of rabies is usually a change in behavior. Domesticated animals may seem restless and fearful, while wild animals may exhibit an atypical lack of fear of humans. Over the course of a few days, animals develop the classic symptoms of drooling, teeth-snapping and restless behavior. Most canines die within 10 days of symptom onset, while smaller animals expire more quickly. 
  • In humans, a rabies infection follows five clinical phases:
  1. Incubation: Asymptomatic. Varies in length, and may last from a few days to several years. For most patients, the incubation period is 30-90 days. The length of incubation is related to the location of the inoculation (i.e. proximity to the CNS), depth and number of bites, innervation of the bite site, quantity of virus inoculated, and the age and immune status of the host. 
  2. Prodrome: Typically lasts 2-10 days, and correlates with the invasion of the virus into the CNS. Patients may have mild, nonspecific, GI or respiratory symptoms at first, but will develop changes in personality, photophobia and insomnia with time. Many patients report paresthesias at the bite site during this period.
  3. Acute Neurologic Phase: Correlates with widespread invasion of the CNS. Obvious signs of neurologic dysfunction develop: fever, nuchal rigidity, fasciculations, convulsions, hyperventilation, and hypersalivation. Patients develop either furious rabies or paralytic rabies (less common) during this stage:

    -Furious rabies: 80% of cases. Patients have anxiety, agitation, hallucinations, and a variety of other odd behaviors. Hydrophobia and aerophobia (fear of breeze) may develop, associated with painful spasms of the pharynx. Patients are hyper-reflexive and demonstrate many signs of a hyper-cholinergic state: pyrexia, hypersalivation, lacrimation, and mydriasis. Paralysis and coma follow unless the patient dies abruptly during this stage. 

    -Paralytic rabies: Seen in 20% of cases. A variety of patterns exist, but the most common is paresthesias and weakness that rapidly progress from the site of the bite to a quadriplegic state. 
  4. Coma: When patients transition from the acute neurologic phase to coma, they may have periods of irregular, jerky breathing followed by generalized paralysis and then coma. Patients will die of respiratory failure if they are not ventilated. 
  5. Death or Recovery: Most patients die of rabies. Patients may die because of complications of prolonged ventilatory support, or because of severe neurotransmitter imbalances. A few survivors have, however, been documented in the literature. 



  • Rabies is frequently misdiagnosed, especially in countries where infections are rare. 
  • Twenty percent of cases have no documented history of an animal exposure. 
  • The CDC considers administration of PEP to be a medical urgency, not an emergency. That said, they do not recommend delaying decisions about PEP. 
  • No tests are able to diagnose the infection during the incubation period. 
  • The patient's history is of great importance. Key points include place of residence, recent travel, and animal exposures. The specific timeline of events is also relevant. 
  • Specific tests for rabies are not available in many hospitals, but can be requested from the state department of health:
    -A direct fluorescent antibody staining test that detects rabies specific antigen is reliable and rapid. Saliva, brain tissue, and other neural tissues can be used. A common method utilizes a full-thickness biopsy of the skin at the nape of the neck (the nerve plexus around the hair follicle turns positive early in the illness).
    -Virus can be isolated in culture from CSF, urine, saliva, and respiratory secretions. These cultures grow best after symptoms have been present for 2-3 weeks.  
    -Nowadays, the most commonly used diagnostic test is a reverse transcriptase PCR, which is both sensitive and specific. Saliva and brain tissue can be used as specimens. The rabies RT-PCR test can be used on decomposing tissue, and can identify the geographic origin and species of the source animal. 



  • No specific treatments exist once patients develop symptomatic rabies. Supportive care often involves anticonvulsants, sedatives, respiratory support, and careful fluid managment. There is no role for rabies-specific immunoglobulin (RIG) or vaccines once a patient has developed symptoms.
  • Since symptomatic rabies is almost always fatal, the focus is on prevention:
  • Wound Care
    -All bites, scratches and areas of broken skin require vigorous cleansing with soap and water and a virucidal soluation (such as providone-iodine). 
    -High-pressure irrigation, mechanical scrubbing and aggressive debridement are recommended.
    -Avoid sutures and occlusive dressings whenever possible.
    -Provide tetanus vaccinations and antibiotics if appropriate.
  • The guidelines for post-exposure prophylaxis vary by geographic area, species of animal, type of exposure, and the likelihood that the animal was rabid. Local departments of public health can provide guidance. A good general rule: when in doubt, treat.
  • General PEP guidelines:
    -In the U.S., if the animal responsible for the bite/scratch is available, the local departments of public health will provide guidance about how to manage the animal. Dogs, cats and ferrets that appear healthy can be observed for 10 days. No PEP is needed for the bite victim unless the animal begins to exhibit symptoms. If the bite is from a raccoon, skunk, fox, or bat, PEP should be initiated immediately because these animals are assumed to carry rabies. The animal should be immediately euthanized and tested. For bites from other animals (such as squirrels, rodents and rabbits) consult the public health department. Bites from these animals rarely warrant PEP. 
  • PEP is warranted after a bite from an animal when the animal is unavailable to monitor, has not been vaccinated previously, has an unknown vaccination status, and the skin or mucus membrane has been broken.
  • PEP is recommended for all adults and children who have been asleep in the presence of a bat, and in cases when it is difficult to exclude direct contact with a bat (i.e., in the event of a small child, drunken or mentally challenged individual who may have had contact with a bat). 
  • Post-exposure Prophylaxis (PEP) for patients who HAVE NOT been previously vaccinated against rabies:
    -Wound care
    -Rabies-specific immune globulin (RIG), 20 IU per kg of body weight: Infiltrate most of the dose into the wound, and then administer any remaining volume IM at a site distant from the site of vaccine administration. 
    -Rabies Vaccine, 1 mL IM (deltoid) on days 0 (day of exposure), 3, 7, and 14.
         -The vaccine cannot be given in the same syringe or anatomic location
         as the RIG. 
         -Recently, PEP recommendations changed from a five-dose
         vaccination regimen to a four-dose regimen. Most healthy people only
         need four doses. Patients who are immunosuppressed should still
         receive five doses (following the schedule above, with a fifth dose on
         day 28).
  • Post-exposure Prophylaxis (PEP) for patients who HAVE been previously vaccinated against rabies:
    -Wound care
    -Do not give RIG.
    -Rabies Vaccine, 1 mL IM (deltoid) on days 0 and 3. 
         -The vaccine cannot be given in the same syringe or anatomic location
         as the RIG.
  • Pre-exposure Prophylaxis: Pre-exposure prophylaxis is recommended for certain populations, but not for the general public. Guidelines vary, but veterinarians, animal-control workers, wildlife workers, rabies laboratory staff, spelunkers, and some travelers should recieve vaccination. Schedules vary by risk of exposure.
  • The CDC provides a list of state and local rabies consultation contacts on their website: http://www.cdc.gov/rabies/resources/contacts.html
  • In Illinois, the CDC recommends contacting the local health department for recommendations about PEP. Information about local contacts can be found here: http://www.idph.state.il.us/local/alpha.htm



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  2. Bocchini JA. ACIP recommends four-dose rabies vaccine series for most persons. AAP News. 2009; 30(9). 
  3. Centers for Disease Control and Prevention. Human rabies prevention-- United States, 2008: recommendations of the advisory committee on immunization practices. MMWR Early Release 2008; 57(May 7, 2008). 
  4. Committee on Infectious Diseases. Rabies-Prevention Policy Update: New Revised-Dose Schedule. Pediatrics. 2011; 127(785). 
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  6. Mani CS and Murray DL. Rabies. Pediatrics in Review. 2006; 27(129). 
  7. Michos A and Zaoutis T. Bats and rabies: what rabies prophylaxis is needed and when? Contemporary Pediatrics. October 2011. 
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  9. Wyatt J. Rabies- update on a global diseasePediatric Infectious Disease Journal. 2007; 26(4). 

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