DESCRIPTION 
CNS infectious disease of mammals caused by the rabies virus:
- Highest case fatality rate of any known infectious disease
ETIOLOGY
- Epidemiology:
- 30,000–70,000 people die/yr worldwide
- Especially common in Southeast Asia, Philippines, Africa, South America, and Indian subcontinent
- US has 2–3 human cases per year.
- Most clinical cases in US from foreign travel and bat exposures
- Raccoons, skunks, foxes, bats, dogs, woodchucks, groundhogs are reservoirs.
- In US bats are the most common reservoir while abroad dogs are more common.
- Squirrels, rats, mice, hamsters, guinea pigs, gerbils, chipmunks, and rabbits can also be infected but there has never been a reported case of human transmission.
- Pathophysiology:
- Negative-stranded RNA genome, family Rhabdoviridae, genus Lyssavirus
- Mode of transmission:
- Contact with infected saliva of host
- Bite: Most common
- Nonbite: Saliva or bat aerosol exposure to an open wound or mucous membrane
- Transplant procedures are the only well-documented person-to-person transmission
- Not considered a transmission risk: Petting rabid animal or contact with the blood, urine, or feces of a rabid animal
- Progression after infection:
- Virus multiplies in local tissue and is taken up into muscle through n-acetylcholine receptors.
- Virus enters peripheral nerves and is transported to CNS via retrograde axoplasmic flow at ~1–4 inches per day
- Once in CNS, rapid replication and dissemination cause encephalitis.
- Centrifugal spread of virus to peripheral nerves, including salivary glands
[Outline]
SIGNS AND SYMPTOMS
- Once a patient exhibits clinical signs course is almost universally fatal.
- 5 stages: Incubation, prodrome, encephalitis, coma, death (or recovery):
- Incubation: 1–3 mo (range 10 days to 1 yr):
- Virus amplifies in peripheral tissues
- Time depends on amount inoculated and proximity to CNS, thus shorter incubation for head or neck bites
- Prodrome: 1–7 days:
- Nonspecific symptoms: Fever, headache, malaise, myalgias, anorexia, sore throat, nausea, and vomiting
- Paresthesias or fasciculations around bite site give clue to diagnosis.
- Encephalitis (classic form): 2–7 days:
- Anxiety, agitation, hallucinations, confusion or delirium, muscle spasms, opisthotonos, and seizure
- Aerophobia (pathognomonic): Pharyngeal spasm from draft of air
- Hydrophobia (pathognomonic): Violent involuntary muscle contraction of diaphragm, pharyngeal, laryngeal, and accessory respiratory muscles when attempting to swallow (seen in up to half of cases)
- Dysrhythmias, myocarditis, autonomic instability, and fevers
- Brainstem involvement: Diplopia, facial paralysis
- Coma:
- Death (or recovery):
- Almost universally fatal if no pre- or postexposure prophylaxis (PEP) given
- Rare case reports of survival without prophylaxis
- Known survivors have some residual neurologic deficits
- 3 manifestations of disease:
- Classic or encephalitic rabies accounts for ~80% of cases. See above.
- Paralytic rabies (~20%): Ascending paralysis mimicking Guillain–Barré syndrome
- Atypical rabies (< 1%): Seen with bat-associated rabies. Characterized by neuropathic pain, sensory or motor deficits, choreiform movements, myoclonus, and seizures
History
- Bite wound or other known exposure
- Bat found in room with person unable to give history (e.g., child or intoxicated): Assume exposure
- Travel to endemic areas with associated dog exposure
- Rabid animals more likely to attack unprovoked. Any handling of the animal prior to bite is considered a provoked attack.
Physical Exam
- Fever
- A bat bite wound often not visible on exam
- Altered mental status, seizures, encephalopathy
- Percussion myoedema: Muscle mounds at percussion site
- Autonomic manifestations: Dilated pupils, perspiration, hypersalivation, orthostatic hypotension
ESSENTIAL WORKUP
- Saliva:
- Rabies RNA by reverse transcription polymerase chain reaction (RT-PCR)
- Virus isolation in cell culture
- Serum:
- Rabies antibodies are diagnostic only if not vaccinated.
- Earliest positive, day 6
- CSF:
- Mildly elevated WBC and protein, normal glucose
- Virus isolation
- Rabies antibodies in CSF are diagnostic, even if immunized.
DIAGNOSIS TESTS & INTERPRETATION
Lab
- CBC: May have leukocytosis
- Electrolytes, BUN, creatinine, glucose
- Blood cultures/urinalysis:
- Search for other infection/illness
- Neck biopsy: RT-PCR, immunofluorescent staining for viral antigen
Imaging
- CT head: Usually normal but may show cerebral edema, evaluate for other causes of symptoms
- Chest radiograph: Other infectious etiologies
Diagnostic Procedures/Surgery
Lumbar puncture
DIFFERENTIAL DIAGNOSIS
[Outline]
PRE-HOSPITAL
- Thoroughly wash wound with soap and water.
- If safely able, capture wild animal for sacrifice and testing.
INITIAL STABILIZATION/THERAPY
- Airway, breathing, and circulation
- Intubation as needed
- Treatment of seizures
ED TREATMENT/PROCEDURES
- Wound cleansing and irrigation
- Tetanus immunization
- Determine if exposure requires prophylaxis:
- Consult local health department
- Domestic animal bite:
- Home monitoring of animal for 10 days
- If animal displays no signs of illness, patient does not need PEP.
- Wild animal bite:
- Rabies testing of sacrificed animal head-Negri bodies are diagnostic
- Start PEP and stop if test is negative
- Treat if animal not captured.
- Unprovoked attacks should be assumed high risk for exposure.
- PEP:
- Passive immunization with human rabies immune globulin (HRIG)
- HRIG: 20 IU/kg:
- Majority infiltrated in and around wound
- Remainder given IM (gluteus)
- Active immunization with rabies vaccine
- Rabies vaccine: 1 mL (2.5 IU) IM days 0, 3, 7, 14, add day 28 if immunocompromised
- 3 vaccines approved in US:
- Imovax–human diploid cell culture
- RabAvert–chick embryo cell culture
- Rabies vaccine adsorbed–inactivated virus, for US military
- Administration location:
- Deltoid in adults or anterior thigh in small children or infants
- For those with pre-exposure prophylaxis and rabies exposure:
- Do not require HRIG
- Need vaccine booster on days 0 and 3
- If care delayed after rabies exposure:
- HRIG not indicated > 7 days after exposure
- Vaccine should be administered as usual
- Pre-exposure prophylaxis:
- Rabies vaccine on days 0, 7, 21, 28
- Target groups: Veterinarians, animal handlers, virus lab workers, foreign travelers in endemic regions
Pediatric Considerations
Treat as in adults.
Pregnancy Considerations
Treatment considered safe during pregnancy.
[Outline]
DISPOSITION
Ensure adequate access for subsequent vaccine administration post rabies exposure.
Admission Criteria
Patient with clinical signs of rabies
Discharge Criteria
- Stable patient
- No evidence of reaction to vaccine
Issues for Referral
Public health and CDC for suspicious cases
FOLLOW-UP RECOMMENDATIONS
- Ensure access to subsequent vaccine doses
- Patient should follow up with animal control if source animal has been sacrificed or is being observed.
[Outline]
- American Academy of Pediatrics. Report of the Committee on Infectious Report. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
- Centers for Disease Control and Prevention. Rabies. Available at http://www.cdc.gov/rabies./ Updated December 13, 2012.
- Centers for Disease Control and Prevention (CDC). Recovery of a patient from clinical rabies–California, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(4):61–65.
- Franka R, Rupprecht CE. Treatment of rabies in the 21st century: Curing the incurable. Future Microbiol. 2011;6:1135–1140.
- Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention—United States, 2008: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57:1–28.
- Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352:2508–2514.
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