Epidemiology

In the Third World: An estimated 4070,000 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

Epidemiology

World wide: Dogs most commonly infected and cause more transmission to humans Bats: An important source in North & South America and Mexico.

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.

Animal Behavior

Animal Behavior

Classic Picture of rabid, mangy dog foaming at the mouthnot often seen, signs frequently more subtle. Animals can display aggressive behavior, ataxia, irritability, anorexia, lethargy or excessive salivation.

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

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)

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

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.

Rabies virus

Risk of developing rabies after a bite: 580%.

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

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.

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

Encephalitic Form

Hydrophobia: Patient cant 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.

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.

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.

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

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.

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.

Clinical Case

Fourth day of illness: symptoms contd. Admitted for LP and supportive care.
CSF: wbc 23 cells 93% lymphocytes RBC 3 cells Protein 50 mg/dL Glucose 58 mg/dL

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.

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.

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.

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

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.

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.

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

Who should get PEP?

Type of exposure Location of incident (head/neck) Species of biting animal (common carrier of rabies?)

WHAT IS A SIGNIFICANT EXPOSURE?

Significant Exposure

Significant Exposure

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

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 doesnt become ill, victim does not require treatment.
If animal gets sick, euthanize and test immediately.

References
Chapter 129: Rabies. Rosens 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