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RABIES. Atilla Kiss M.D. Prepared by Kellie Zaylor D.O. January 4, 2006. Epidemiology. In the Third World: An estimated 40-70,000 people die from the disease each year Rare in U.S. 40 cases/year prior to vaccination of domestic animals that began in 1947 3 cases/year now reported.

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RABIES

Atilla Kiss M.D.

Prepared by Kellie Zaylor D.O.

January 4, 2006


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Epidemiology

  • In the Third World: An estimated 40-70,000 people die from the disease each year

  • Rare in U.S.

    • 40 cases/year prior to vaccination of domestic animals that began in 1947

    • 3 cases/year now reported


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Epidemiology

  • World wide: Dogs most commonly infected and cause more transmission to humans

  • Bats: An important source in North & South America and Mexico.


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Epidemiology: United States

  • In U.S.- >90% of rabies occurs in wild animals: Principal reservoirs are racoons, skunks, foxes and bats



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Skunks & Racoons

  • Eastern Seaboard: Rabies is endemic in racoons

    • Only one human case of rabies from a racoon variant has ever been documented (no history of exposure is known)

  • North Central, South Central and California: Skunks are important carriers, each with its own regional viral strain


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BATS

  • Rabid bats account for 17% of all cases of rabies in U.S. animals

  • Hawaii- is rabies-free. There are no rabid bats or rabid terrestrial animals.


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Human Cases

  • Between 1990-2003: 39 cases diagnosed with 32 likely acquired in U.S.

    • 88% (28 cases) associated with bats

    • 2 cases associated with the dog and coyote populations of Texas

    • 1 with a racoon in VA.

    • 1 with a mongoose in Puerto Rico


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Human vs. Bat

  • In most cases, history of bat contact was obtained after patient’s death.

    • In 3 cases: victim was aware of the bite, but didn’t seek rabies prophylaxis

    • In half of cases: victim had bat contact, but no bite history

    • No history of bat exposure for the remaining victims


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Disease Principals

  • Rabies is not a zoonosis: Animals that get infected will die.

    • Death occurs within 3-9 days after they first begin secreting virus in their saliva. They can transmit the virus at this point.

    • Exceptions: Some animals can get sick before virus is found in saliva or may not become ill until several days after virus is secreted.


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Disease Principals

  • Bats can live 10 days after infection

  • Has been suggested dogs can become asymptomatic carriers, but transmission from one has never been documented

  • In U.S. all rabid dogs die within 8 days of becoming ill; median 3 days.



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Animal Behavior

  • Classic Picture of rabid, mangy dog foaming at the mouth…not often seen, signs frequently more subtle.

  • Animals can display aggressive behavior, ataxia, irritability, anorexia, lethargy or excessive salivation.


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Animal Behavior

  • Cats are more likely to be aggressive than dogs

  • Animals exhibit change in instinctive behavior: nocturnal animal walking around in daylight (i.e. raccoons)

  • Unprovoked bites


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Transmission

  • Almost all transmission is by bite

  • 50 times greater risk than a scratch

  • One human case may have been acquired in a laboratory (transmitted by aerosol)


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Transmission

  • In wild animals: Rabies can be transmitted transplacentally

  • Transplants in human- possible

  • Human-to-human: Never has been confirmed

  • Rabies virus never isolated from blood


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Virus lifestyle

  • Virus replicated in muscle cells near site of bite for most of incubation time.

    • Incubation time 30-90 days. Latency up to 7 years

  • Then ascends along motor and sensory axons at rate of 12-100mm/day and has predilection for brainstem and medulla

  • Enters salivary glands after replication in CNS.


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Rabies virus

  • Risk of developing rabies after a bite: 5-80%.

    • Depends upon….

      • Severity of exposure

      • Location of the bite

      • The biting animal

      • **Bites on head and neck have shorter incubation time (as short as 15 days) because of rich peripheral nerve supply


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Clinical Features

  • Prodrome: HA, fever, rhinorrhea, sore throat, myalgias, GI upset. *Back pain and muscle spasms.

  • Agitation and anxiety may result in diagnosis of psychosis or intoxication

  • Paresthesias, pain or severe itching at site may be the first neurological symptom.


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Clinical Features

  • Over several days symptoms progress

  • Rabies takes two forms:

    “Furious”/Encephalitic form: agitation, hydrophobia, extreme irritability, hyperexcitability periods fluctuate with lucidity.

    • Vitals abnormal: tachycardia, tachypnea, fever


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Encephalitic Form

  • Hydrophobia: Patient can’t swallow because violent jerky contraction of diaphragm and accessory muscles of inspiration when pt attempts to swallow liquids

    - Patients will be terrified during this reaction and may even experience this at the sight of water or if water touches their face.


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Encephalitic Form

  • Aerophobia: an extreme fear of air in motion can be elicited from some patients. This can also cause violent muscle spasms in the neck and pharynx.

  • Hallucinations, seizures, ataxia, focal weakness and arrhythmias can occur.


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Paralytic Rabies

  • Other form is “dumb” or paralytic rabies. Similar to Guillain-Barre.

    • Prominent limb weakness. Consciousness initially spared

  • Two forms can overlap or progress from one to the other

  • Coma after one week of neuro symptoms with death a few days after.


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Management

  • Once symptoms occur: fatal in 3-10 days

  • ICU support: can prolong 4 months.

  • Six patients have survived clinical rabies: 5 had pre or postexposure prophylaxis before onset of symptoms


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Clinical Case

  • In Wisconsin 2004: 15 year old girl bitten on left index finger by a bat after picking it up off a floor and releasing it outside of her church.

  • Pt cleaned wound with hydrogen peroxide but did not seek help because the belief that sick/rabid bats could not fly.


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Clinical Case

  • 1 month after bite, c/o fatigue, parasthesias in left hand. Two days later: unsteady, diploplia, nausea/vomiting.

  • Referred to neuro from pediatrician: MRI/MRA normal and sent home.


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Clinical Case

  • Fourth day of illness: symptoms cont’d. Admitted for LP and supportive care.

    • CSF: wbc 23 cells

    • 93% lymphocytes

    • RBC 3 cells

    • Protein 50 mg/dL

    • Glucose 58 mg/dL


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Clinical Case

  • Over next 36 hours: slurred speech, nystagmus, tremors in left arm, lethargy, temp of 102.

  • Sixth day: bat-bite history reported and rabies considered in differential and transferred to tertiary care center.

  • Upon arrival: Temp 100.9, impaired muscle coordination, difficulty speaking, double vision, muscle twitching, tremors, obtunded.


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Clinical Case

  • Blood, CSF, nuchal skin samples, saliva submitted to CDC.

  • Pt developed hypersalivation and was intubated.

  • Rabies-virus specific antibodies were detected in serum and CSF. No evidence found in nuchal skin biopsies and saliva.


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Clinical Case

  • Management: drug-induced coma and ventilator support for 7 days

  • IV ribavirin

  • CSF antirabies IgG: from 1:32 to 1:2,048

  • Meds tapered, on 33rd day of illness, extubated, 3 days later transferred to rehab.

  • Unable to speak, could walk with assistance and feed herself.

  • Prognosis for her full recovery is unknown.


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Management

  • No effective treatment exists.

  • Postexposure Prophylaxis/PEP: 3 steps

    • 1. Wound care: immediate thorough washing with soap and water and a virucidal agent such as povidine-iodine or 1-2% benzalkonium chloride.

      • Shown to be protective if performed within 3 hours of exposure

      • If puncture, swab deeply in wound and around edges


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PEP

  • 2. Passive Immunization: Human rabies immunoglobulin (HRIG) 20 IU/kg ASAP, but not longer than 7 days after vaccine given. Infiltrate entire dose around wound, any remaining IG inject IM at a site distant from the vaccine.

  • 3. Human diploid cell vaccine (HDCV): 1 ml (deltoid) on days 0,3,7,14,28.


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PEP

  • Vaccine: do not give in gluteal. If injected into fat, no antibodies formed.

  • HRIG and HDCV: give in different anatomical sites and never in the same syringe.


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PEP

  • Local Reactions: itching, erythema, pain, swelling

  • Systemic: HA, myalgia, nausea.

  • Anaphylaxis: .1% of cases

  • Guillain-Barre: 3 cases

  • Angiodema: 6% of pts who receive boosters.

  • Can give PEP during pregnancy


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Who should get PEP?

  • Type of exposure

  • Location of incident (head/neck)

  • Species of biting animal (common carrier of rabies?)





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Significant Exposure

  • Bites are significant

  • Nonbite exposures that involve contamination of either mucous membrane or open wound (bled within 24 hours) with saliva

  • Not significant: petting a rabid animal, contact with its blood, urine, feces.

    • Skunk spray

    • Dry virus: NOT INFECTIOUS


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Animals in captivity

  • Wild animals that are caught should by euthanized immediately and head sent under refrigeration to an appropriate lab for testing.

  • Domestic animals that are apparently healthy should be observed for 10 days. If animal doesn’t become ill, victim does not require treatment.

    • If animal gets sick, euthanize and test immediately.


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References

  • Chapter 129: Rabies. Rosen’s Emergency Medicine

  • CDC : http://www.cdc.gov/ncidod/dvrd/rabies

    http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5350a1.htm

  • WHO:

    http://www.who.int/mediacentre/factsheet/fs099/en


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