Rabies

Aka: Rabies, Rabies Encephalitis, St Hubert's Disease, Lyssa Virus Infection, Lyssavirus Infection, Lyssavirus, Hydrophobia, Rhabdoviridae Infection, Rhabdovirus Infection, Rhabdoviridae, Rhabdovirus

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II. Epidemiology

  1. Worldwide: Responsible for 59,000 deaths worldwide per year (95% in Asia and Africa)
    1. Children under age 15 years account for 40% of cases
  2. U.S.
    1. Typically 1-3 Rabies (up to 8-10 in some years) cases in U.S. per year
    2. Most cases of Rabies are from exposure to wild animals in U.S. (90%)
    3. Up to 8000/year in U.S. of documented cases of Rabies in animals
      1. The most common reported domestic Rabies cases are in cats
      2. Although rodents and rabbits can carry Rabies, no human cases have been attributed to these animals

III. Pathophysiology

  1. Rabies is a zoonotic neurotropic virus (virus acquired from animals, targeting neurologic tissue)
    1. Genus: Lyssavirus
    2. Family: Rhabdoviridae (Rhabdovirus)
  2. Rhabdoviridae (Rhabdovirus) are enveloped, helical (but uniquely bullet shaped) single stranded RNA Viruses
    1. Rabies is the only virus in Rhabdoviridae family that infects humans
  3. Rhabdoviridae are Anti-Message Sense RNA Viruses (Negative Stranded, -ssRNA)
    1. Anti-Message sense RNA (-ssRNA) need to first be transcribed into +ssRNA
    2. RNA dependent RNA Polymerase (RNA replicase, RdRp)
      1. RdRp is an enzyme carried by the -ssRNA virus within its capsid
      2. RdRp transcribes -ssRNA into +ssRNA within the host cell
    3. Translation follows +ssRNA transcription from -ssRNA (by RdRp)
      1. As with mRNA, +ssRNA translated by host ribosomes into Protein
  4. Transmitted by bite or scratch from infected mammals
    1. Saliva, brain and other nerve tissue are infectious
    2. Blood, urine, and stool are not infectious
    3. Mucosal contact with bats may also transmit Rabies (unique to bats)
  5. Course
    1. Incubation Period is 4-12 weeks
    2. Virus replicates at wound site and then slowly migrates up nerve axons to the CNS
    3. Ultimately causes a uniformly fatal Encephalitis (in those not undergoing prophylaxis as below)
  6. Highest risk animals
    1. Bats
      1. See Bat Bite
      2. Responsible for most U.S. cases of Rabies (87% of cases 1980-2015)
      3. Even indirect exposure (no bite) may indicate prophylaxis
    2. Dogs
      1. See Dog Bite
      2. Worldwide, these are main vector for infection
      3. However, in U.S. Rabies is less common in dogs (70 cases/year in U.S.)
        1. Responsible for 11 of 31 U.S. human Rabies cases 2003-2016
    3. Cats
      1. See Cat Bite
      2. Most common domesticated animal with Rabies in U.S. (257 cases of cats with Rabies in 2012)
    4. Raccoons
      1. Most common vector in the U.S. East Coast
    5. Skunks
      1. Most common vector in the U.S. midwest and West Coast
    6. Foxes
      1. Gray fox is the most common vector in the U.S. southwest
    7. Coyotes
    8. Bobcats
    9. Woodchucks
    10. Ferrets

IV. Risk Factors

  1. Travel to endemic regions (africa, Asia, Eastern Europe), esp. rural or wilderness areas
  2. Extremes of age (young children, elderly)
  3. Bites or scratches from infected animals (esp. bats, raccoons, skunks, foxes, dogs)
    1. Unprovoked bites (aggressive animals)
    2. Bite proximity to the brain increases risk
  4. Occupational exposure risks
    1. Veterinary field, animal handlers or wildlife biologists
    2. Related laboratory workers)

V. Symptoms

  1. Incubation Period: Days to months
  2. Early (Prodromal)
    1. Local radiating Paresthesia from bite site
      1. Local muscle Fasciculations may occur
    2. Malaise
    3. Nausea
    4. Pharyngitis
    5. Fever
    6. Headache
  3. Late (Neurologic)
    1. Restlessness
    2. Significant Agitation
    3. Hallucinations
    4. Bizarre behavior or personality change
    5. Seizures
    6. Aerophobia and Hydrophobia are pathognomonic

VI. Signs

  1. Early
    1. Wound Inflammation
    2. Hyperesthesia at wound site
  2. Late (Encephalitis)
    1. Dysarthria
    2. Hoarseness
    3. Aphonia
    4. Severe Dysphagia on Swallowing fluids (Hydrophobia)
    5. Shallow or irregular breathing
    6. Seizure
    7. Delirium
    8. Opisthotonos stimulated by lights or noises
    9. Hyperactive Deep Tendon Reflexes
    10. Nuchal Rigidity
    11. Abnormal Babinski Reflex (Up-going toes)
  3. Terminal signs
    1. Flaccid Paralysis
    2. Hospitalization <1 week after symptom onset
    3. Coma within one week of encephalopathy signs
    4. Death

VII. Labs

  1. Live Observation of suspected infected mammal
  2. Rabies Virus Antigen Testing
    1. Saliva contains virus
    2. Brain and spinal cord of suspected infected animal (necropsy)
  3. Necropsy of affected animal
    1. Negri bodies (collections of Rhabdovirus virions in the cytoplasm) are pathognomonic

VIII. Management

  1. See Rabies Postexposure Prophylaxis
  2. See Dog Bite
  3. General wound care (in addition to Rabies Prophylaxis)
    1. Clean wounds with copious irrigation including antiseptics (e.g. Chlorhexidine)

IX. Prognosis

  1. Prevention of Rabies Encephalitis is highly effective
    1. Early Rabies Postexposure Prophylaxis after Animal Bite is critical
  2. Rabies Encephalitis
    1. Supportive care and induced coma (e.g. Ketamine, Midazolam)
    2. Antivirals (e.g. Ribavirin, Amantadine) have been used
    3. Central apnea with Respiratory Failure
      1. Typical cause of death
    4. Rabies Encephalitis is uniformly fatal once patient is symptomatic
      1. Although very rare cases of survival with severe Disability have occurred

X. Prevention

  1. Rabies Vaccine
    1. For Rabies Postexposure Prophylaxis and preexposure prophylaxis
  2. Rabies Immunoglobulin
    1. Rabies Postexposure Prophylaxis
  3. Avoid bat exposure
    1. Remove bat roosts from home
    2. Bats trapped within a home living space are more likely to be sick (disabled navigation)
  4. Pets should be vaccinated against Rabies
    1. In U.S., of pets causing a bite evaluated in ER, only 45% of dogs and 8% of cats were vaccinated against Rabies
  5. Test for Rabies in pets who succumb to illness quickly

XI. References

  1. Nordt and Shah (2025) Rabies, EM:Rap, 2/17/2025
  2. Swaminathan and Hope in Herbert (2018) EM:Rap 18(12): 11-2
  3. Messenger (2002) Clin Infect Dis 35:738-47 [PubMed]
  4. Wilde (2003) Clin Infect Dis 37:96-100 [PubMed]

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