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Rabies
Alan M. Ehrlich, MD
image BASICS
DESCRIPTION
  • A rapidly progressive CNS infection caused by a ribonucleic acid (RNA) rhabdovirus affecting mammals, including humans
  • Generally considered to be 100% fatal once symptoms develop
  • System(s) affected: nervous
  • Synonym(s): hydrophobia (inability to swallow water)
EPIDEMIOLOGY
Incidence
  • Most cases are in developing countries.
  • Estimated 55,000 deaths worldwide per year
  • Typically only 1 to 3 cases per year in the United States, with 1/3 of those being due to exposure outside of the United States
  • Predominant age: any
  • Predominant sex: male = female
ETIOLOGY AND PATHOPHYSIOLOGY
Lyssavirus, an RNA virus in the family Rhabdoviridae
  • Rabies virus is a neurotropic virus present in saliva of infected animals.
  • Transmission occurs via bites from infected animals or when saliva from an infected animal comes in contact with an open wound or mucous membranes.
  • Bats are most common reservoir in the United States.
RISK FACTORS
  • Professions or activities with exposure to potentially infected (wild or domestic) animals (e.g., animal handlers, lab workers, veterinarians, cave explorers)
  • Most U.S. cases are associated with bat exposure.
  • Internationally, rabies is widespread in both domestic and feral dogs.
  • Human-to-human transmission has occurred through transplantation of cornea, solid organs, and other tissues.
  • Travel to countries where canine rabies is endemic.
GENERAL PREVENTION
  • Preexposure vaccination for high-risk groups (veterinarians, animal handlers, and certain laboratory workers)
  • Consider preexposure vaccination for travelers to areas (such as North Africa) that have increased risk of rabies from domestic animals.
  • Immunization of dogs and cats
  • Contact animal control and avoid approaching or handling wild (or domestic) animals exhibiting strange behaviors.
  • Avoid wild and unknown domestic animals.
  • Seek treatment promptly if bitten, scratched, or in contact with saliva from potentially infected animal.
  • Prevent infection by prompt postexposure treatment.
  • Consider postexposure prophylaxis for individuals in direct contact with bats, unless it is known that an exposure did not occur.
  • Hospital contacts of patients infected with rabies do not require postexposure prophylaxis unless there has been exposure through mucous membranes or an open wound (including a bite) to saliva, CSF, or brain tissue from the infect patient.
image DIAGNOSIS
PHYSICAL EXAM
Findings range from normal exam to severe neurologic findings, including paralysis and coma, depending on the stage of rabies at the time of presentation.
DIFFERENTIAL DIAGNOSIS
  • Any rapidly progressive encephalitis; important to exclude treatable causes of encephalitis, especially herpes
  • Transverse myelitis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Lumbar puncture. WBC count is normal or shows moderate pleocytosis; protein normal or moderately elevated
  • Skin biopsy to detect rabies antigen in hair follicles
    • Available through state and federal reference labs
  • Rabies antibody titer of serum and CSF
  • Skin biopsy from nape of neck for direct fluorescent antibody examination
  • Viral isolation from saliva or CSF
  • Corneal smear stains are positive by immunofluorescence in 50% of patients.
  • Hyponatremia is common.
  • Head CT scan: normal or nonspecific findings consistent with encephalitis
  • MRI can help rule out other forms of encephalitis.
Follow-Up Tests & Special Considerations
Submit brain of the biting animal for testing if possible.
Test Interpretation
Encephalitis may be found on brain biopsy. Other abnormal findings (e.g., brainstem, midbrain, cerebellum) often found only postmortem.
image TREATMENT
Thorough wound cleansing with soap and water is first line of treatment. Irrigate wound with virucidal agent, such as povidone-iodine, if available.
GENERAL MEASURES
  • Evaluate risk based on exposure and consult public health officials about the need for rabies prophylaxis.
  • In the United States, raccoons, skunks, bats, foxes, and coyotes are the animals most likely to be infected. Any carnivore can carry the disease.
  • Before initiating antirabies treatment, consider:
    • Type of exposure (bite or nonbite)
    • Epidemiology of rabies in species involved
    • Circumstances surrounding exposure (provoked vs. unprovoked bite)
    • Vaccination status of offending animal
MEDICATION
Pregnancy Considerations
  • Pregnancy is not a contraindication to postexposure prophylaxis.
  • Rabies vaccination is not associated with a higher incidence of spontaneous abortion, premature births, or fetal abnormalities.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Clinical rabies
  • Comfort care and sedation for all patients.
  • Milwaukee protocol: experimental treatment using ketamine, midazolam, and amantadine (originally included ribavirin but no longer recommended) (1,4)[C]. One patient who did not receive pre- or postexposure prophylaxis recovered from clinical rabies in 2004 after being treated with medically induced coma and amantadine l (1)[C].
  • Control cerebral artery vasospasm (with an agent such as nimodipine) (4,5)[C].
  • Fludrocortisone and hypertonic saline if needed to maintain normal sodium level (5)[C]
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
After primary vaccination, serologic testing is necessary only if the patient has a disease or takes immunosuppresive medication.
PATIENT EDUCATION
Use screens over ventilation areas in the roof to secure from bats. Avoid exposure to wild mammalian species known to carry rabies and report potential exposures immediately.
PROGNOSIS
  • No postexposure failures in the United States since the 1970s.
  • If untreated, rabies has the highest case fatality rate of any infectious disease; generally considered to be 100% fatal once symptoms develop.
  • There have only been a small number of cases of successful recovery from rabies. Almost all received some form of pre- or postexposure immunization.
REFERENCES
1. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352(24):2508-2514.
2. Rupprecht CE, Briggs D, Brown CM, et al. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2010;59(RR-2):1-9.
3. 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(RR-3):1-28.
4. Aramburo A, Willoughby RE, Bollen AW, et al. Failure of the Milwaukee protocol in a child with rabies. Clin Infect Dis. 2011;53(6):572-574.
5. Hu WT, Willoughby RE Jr, Dhonau H, et al. Long-term follow-up after treatment of rabies by induction of coma. N Engl J Med. 2007;357(9):945-946.
Additional Reading
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  • Centers for Disease Control and Prevention. http://www.cdc.gov/rabies/
  • Centers for Disease Control and Prevention. Recovery of a patient from clinical rabies—California, 2011. MMWR Morb Mortal Wkly Rep. 2012;61(4):61-65.
  • Crowcroft NS, Thampi N. The prevention and management of rabies. BMJ. 2015;350:g7827.
  • De Serres G, Skowronski DM, Mimault P, et al. Bats in the bedroom, bats in the belfry: reanalysis of the rationale for rabies postexposure prophylaxis. Clin Infect Dis. 2009;48(11):1493-1499.
  • Eckerle I, Rosenberger KD, Zwahlen M, et al. Serologic vaccination response after solid organ transplantation: a systematic review. PLoS One. 2013;8(2):e56974.
  • Hemachudha T, Ugolini G, Wacharapluesadee S, et al. Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol. 2013;12(5): 498-513.
  • Vora NM, Basavaraju SV, Feldman KA, et al. Raccoon rabies virus variant transmission through solid organ transplantation. JAMA. 2013;310(4):398-407.
See Also
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Bites, Animal and Human
Codes
&NA;
ICD10
  • A82.9 Rabies, unspecified
  • Z20.3 Contact with and (suspected) exposure to rabies
Clinical Pearls
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  • Rabies is rare in the United States but more common in other areas of the world.
  • Seek immediate treatment if exposed to scratch, bite, or saliva of potentially infected animal (e.g., feral dog, bat, fox, raccoon, or other wild mammals).
  • Postexposure prophylaxis consists of three steps: local wound cleansing, passive immunization with rabies immunoglobulin, and active immunization with HDCV.
  • Consider postexposure prophylaxis for those reporting direct contact with bats, unless it can be verified that an exposure did not occur.