Rabies is a fatal zoonotic illness caused by a number of species of neurotropic viruses in the Rhabdoviridae family and transmitted to human beings by the bite of an infected animal.

• Hydrophobia

• Incubation period is usually 1 to 3 mo in humans but can range from several days to 8 yr
• Shorter incubation period with bites on the face. Longer if extremities involved
• In domestic animals, a quarantine of 10 days is usually mandated
• Prodrome:
  1. Fever
  2. Headache
  3. Malaise
  4. Pain or anesthesia at exposure site
  5. Sore throat
  6. GI symptoms
  7. Psychiatric symptoms
• Acute neurologic period, with objective evidence of central nervous system involvement
• Two types of presentation
• "Furious" (encephalopathic) rabies (80% of cases):
  1. Extreme hyperactivity and bizarre behavior alternating with periods of relative calm
  2. Hallucinations, disorientation
  3. Seizures
  4. Paralysis
  5. Fear, pain, and spasm of the pharynx and larynx caused by drinking
  6. Coma, death
• "Dumb" (paralytic) rabies (20% of cases):
  1. Ascending flaccid paralysis
  2. Often prominent in the bitten limb
  3. Deep tendon and plantar reflexes lost
  4. Fasciculations

• Rabies virus: Bullet-shaped viruses that belong to Rhabdoviridae family, genus Lyssavirus
• Cases in the U.S. are associated with:
  1. Bats
  2. Raccoons
  3. Foxes
  4. Skunks
• Small rodents (squirrels, mice, rats, chipmunks) and lagomorphs such as rabbits almost never have rabies and have never been a source of transmission of rabies to humans in the U.S.
• In 13/25 cases of rabies occurring in the U.S. from 2009 to 2018, exposure to bats was thought to be the source, although many did not have a clinically evident bite or scratch
• Imported cases are usually associated with dogs
• Unusual acquisition:
  1. By organ transplantation: Kidney, liver, arterial segment
  2. By aerosol transmission in laboratory workers and spelunkers

• Delirium tremens
• Tetanus
• Hysteria
• Psychiatric disorders
• Other viral encephalitides (Box E1)
• Guillain-Barré syndrome
• Poliomyelitis
• Rigidity/Paralysis from other causes (Box E2)

• Antemortem diagnosis requires multiple specimens (saliva, skin that requires a full-thickness biopsy from posterior neck at the hairline, cerebrospinal fluid, serum) and multiple testing modalities: Polymerase chain reaction (PCR), antibodies, immunofluorescence of viral antigens, viral culture. Laboratory criteria used to confirm rabies is summarized in Box E3.
• Animals submitted for rabies testing should be euthanized in a way that maintains the integrity of the brain.
• Negri bodies are eosinophilic cytoplasmic inclusions found in neurons. They are the best-known histologic feature of rabies usually found at postmortem examination.
• The national case definition for animal rabies requires laboratory confirmation by either:
  1. A positive DFA test (preferably performed on central nervous system [CNS] tissue) or
  2. Isolation of rabies virus (in cell culture or in a laboratory animal)
• Fig. E1 describes an approach to assessing rabies exposure and initiating postexposure prophylaxis (PEP) in the U.S.

Figure E1 Decision tree for potential rabies exposures.

(From Walls RM et al: Rosen’s emergency medicine, concepts and clinical practice, ed 10, Philadelphia, 2023, Elsevier.)

• Isolation of the patient to prevent transmission to others
• Supportive therapy

• No known beneficial therapy. A case report from 2005 describes a 15-yr-old girl who survived rabies and had been treated with a combination of ketamine, midazolam, ribavirin, and amantadine. It is known as the Milwaukee protocol. The protocol has been unsuccessful in over 60 subsequent reports and is considered ineffective.
• Other nonproven agents include interferon, corticosteroids, therapeutic coma, minocycline, and prevention of cerebral vasospasm. Research is ongoing in vitro and in mice with favipiravir, a viral RNA polymerase inhibitor.
• Emphasis is placed on prophylaxis of potentially exposed individuals after an exposure (Table E1):
  1. Thorough wound cleansing and irrigation of the wound with soap and water as soon as possible. If available, a viricidal agent (e.g., povidone-iodine solution) should be used to irrigate the wounds.
  2. Active and passive immunization is most effective when used within 72 h of exposure.
• Vaccinations: The Centers for Disease Control and Prevention has recently recommended reducing the number of vaccine doses for postexposure prophylaxis. Current recommendations for rabies postexposure prophylaxis are as follows:
  1. Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1 ml intramuscularly (IM) (deltoid area) 1 each on days 0, 3, 7, and 14 in patients not previously vaccinated. In patients previously vaccinated, administer HDCV or PCECV 1 ml IM (deltoid area) 1 each on days 0 and 3. Human rabies hyperimmune globulin (RIG) 20 IU/kg body weight should be administered to persons not previously vaccinated. If anatomically feasible, the full dose should be infiltrated into the wound; any remaining volume should be given IM at a site separate from vaccine administration.
• Preexposure prophylaxis with HDCV or RVA (1 ml in on days 0, 7, and 21 or 28) in individuals at high risk for acquisition:
  1. Veterinarians
  2. Laboratory workers working with rabies virus
  3. Spelunkers
  4. Visitors to endemic areas

Virtually always fatal once clinical syndrome develops. Rabies has one of the highest case/fatality ratios of any infectious disease.

• To infectious disease consultant
• To local health authorities

• Most cases in the U.S. are caused by:
  1. Bat bites, often after minimal contact and inapparent exposure to infected bat saliva.
  2. Dog bites occurring outside the U.S.
  3. In the U.S., successful vaccine campaigns to vaccinate dogs against rabies has eliminated dogs as a source of rabies.
  4. In 2019 there were 4690 lab confirmed cases of rabies in animals in the U.S.
• Rare cases can be transmitted by mucous membrane contact with aerosolized virus (caves, laboratory-acquired cases).
• Rabies is preventable if exposed persons receive postexposure prophylaxis. Public understanding of rabies exposure risk from bat contact needs to be improved.
• The World Health Organization (WHO) has a goal of eliminating cases of rabies transmitted by dogs by 2030.

• Rabies (Patient Information)