Rabies: The Disease, The Virus, The Treatment

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Learning to Make Rabies History!

• RabiesThe Disease, The Virus, The Treatment

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Rabies The Disease

• Rabies has been around for centuries described
  as early as 2300 B.C.
• Transmission is direct, primarily via inoculation
  by bite, with infectious virus present in saliva.
• The reservoir for rabies is the animal pool that
  circulates rabies virus (diverse species of
  mammals each with a specific strain).
• Rabies is gt99 fatal once symptoms occur

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Still Considerable Concern About Rabies In The
US

• CDC estimates that more than 1 million people per
  year require medical attention for animal bites
  (far fewer than occur)
• Over 7,000 cases of rabies in animals are
  reported to the CDC annually
• Although the number of post exposure treatments
  given in the United States each year is unknown,
  it is estimated to be about 40,000

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Rabies is caused by a virus

• Family Rhabdoviridae bullet shaped
• Genus Lyssavirus
• Rabies
• Lagos bat strain
• Mokola
• Duvenhage
• EBL-1
• EBL-2
• ABLV

Picture from Centers for Disease Control and
Prevention www.cdc.gov/ncidod/dvrd/rabies
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Bullet Shaped MorphologyHelical RNP CoreRNA
Structure And Organization
Rabies Virus

• Five proteins
• Ribonucleoprotein (RNP) Core
• Nucleocapsid protein (N)
• Nucleocapsid phosphoprotein (NS or P)
• RNA polymerase (L)
• Matrix protein (M)
• Glycoprotein (G)

Cross Sectional
G protein
RNA
Envelope (membrane bilayer)
M protein
RNP
Illustrations from Centers for Disease Control
and Prevention www.cdc.gov/ncidod/dvrd/rabies
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How is rabies contracted

• Rabies is most commonly spread by bite contact
  between the rabid animal and the recipient animal
  or human
• In rabies infection, the virus present in the CNS
  and other organs
• Average incubation period (the time between an
  initial exposure to the virus and the development
  of symptoms of disease) is 4 weeks

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2 main ecologic cycles Bat all over U.S.
except Hawaii Terrestrial (ground animals)
raccoon, skunk, fox, coyote
Map from Centers for Disease Control and
Prevention www.cdc.gov/ncidod/dvrd/rabies
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Rabies Virus Distribution Worldwide
Major animal reservoirs causing human
death Africa Dog Americas Dog/Bat Asia
Dog Europe Fox
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Bats Rabies

• 80 of human rabies cases acquired in US. are
  bat-associated strains
• A history of a definite bat bite was documented
  in only 5 of these cases 60 had bat contact
  but no known bite or scratch
• Bite wounds from bats are extremely small and may
  be nearly undetectable within hours. Person
  sleeping may not wake up or otherwise be aware
  of a bite from a bat.

A small bat bite on a finger
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Rabies Infection

• Virus-laden saliva or other infectious material
  from the rabid animal must be introduced through
  a break in skin (bite) or onto mucous membranes
• Virus binds to a nerve cell migrates to spinal
  cord to brain (centripetal spread), then viral
  replication occurs produces encephalitis

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Rabies attacks the Central Nervous System

• Watch as the rabies virus from an exposure on the
  leg spreads up the spinal cord to the brain and
  throughout the rest of the body.

Rabies virus entering the body.
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Transmission/Pathogeneis

• Viral particles travel out from brain
  (centrifugal spread) via nerve cells to salivary
  glands, where further replication occurs
  secretion in saliva, rendering the person or
  animal to be infectious
• At the time it gets to the salivary glands, this
  is the end stage of the disease, and death
  usually occurs shortly thereafter within
  several days
• Incubation period Usually 4 weeks can range
  from 10 days to a year or more (??)

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Symptoms

• Headache, fever, sore throat
• Nervousness, confusion
• Pain or tingling at the site of the bite
• Hallucinations
• Seeing things that are not really there
• Hydrophobia
• Fear of water" due to spasms in the throat
• Paralysis
• Unable to move parts of the body
• Coma and death

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Rabies Human Deaths

• Annual human deaths worldwide are approximately
  55,000 every 15 minutes a patient dies of
  rabies.
• 40-70 rabies victioms are children under 15
  years of age
• Modern cell culture vaccines and animal control
  measures in developed countries have reduced the
  incidence of rabies deaths.
• In the United States, there has been a mean of 3
  deaths per year since 1990.

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Prevention steps after an animal bite

• Wash the wound well with soap and water
• Have the animal tested for rabies
• See a Doctor, even if the bite is very small.
• Contact your local health department and animal
  control officer. 

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Should Anti-Rabies Prophylaxis be Administered?

• CONSIDERATIONS
• High or lower risk animal?
• Was there an exposure?
• Likelihood timing for animal capture for
  confinement or testing?

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High Risk Animals

• Raccoon
• Skunk
• Groundhog
• Fox
• Bat
• free-roaming cats

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Intermediate Risk Animals

• Dogs
• Cats vaccinated or non-roaming
• Livestock horses, cattle, pigs
• Other non-rodent wild animal species
• i.e, opossum, bear, deer, coyote, etc

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Low Risk Animal

• Squirrels, chipmunks
• Rats
• Mice, voles
• Indoor small caged pet rodents
• Logomorphs

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WHO Definition of Exposure
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Was There An Exposure?

• A bite (penetration of the skin by teeth) from a
  known or suspect rabid animal
• Scratches, abrasions, open wounds (bleeding
  within 24 hrs), or mucous membranes (eyes)
  contaminated with saliva or other potentially
  infectious material from a known or suspect rabid
  animal
• Other contact - such as petting an animal or
  contact with urine, feces or skunk spray - does
  NOT constitute an exposure

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Can The Biting Animal Be Confined Observed?

• Healthy dogs, cats, ferrets and livestock may be
  confined and observed for 10 14 days
• Raccoons, skunks, fox, groundhogs and other
  wildlife may excrete rabies virus while
  asymptomatic for extended periods and cannot be
  safely confined observed. Testing of the
  animal - or prophylaxis of bite victim - is
  always recommended

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10 Day Confinement Observation Period

• In domestic animals the virus usually appears in
  the saliva at the onset of clinical signs so if
  animal healthy, probably not rabid
• Rarely, the virus can appear in the saliva 1 to 3
  days prior to onset of illness, so thus an
  observation period created
• Clinical course usually less than 7 days -
  animal dead before end of 10 days

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Rabies Vaccination Status Of Animal

• Lower risk if animal has been regularly
  vaccinated
• But NO vaccine is 100 effective
• Put as much weight on animal behavior health
  status

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Animal Behavior/Health Risk Factors To Consider

• Was the bite or exposure provoked?
• Did the animal escape in a normal manner?
• Rabies is characterized by abnormal behavior with
  neurologic impairment.
• There is often a period of aggression that
  progresses to paralysis, although aggression may
  not always occur

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Rabies Virus Survival

• If saliva or other material potentially
  containing the rabies virus is dry to the touch,
  the virus can be considered noninfectious.
• Stability of the virus in the environment
• Strong soaps, detergents, acids and alkalis all
  inactivate the virus
• Heat inactivates the virus
• Radiation destroys the virus
• Lipid solvents inactivate the virus

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WHO Recommended Post-exposure prophylaxis

• Immediate flushing and washing of the wound with
  soap and water, or other detergent
• If soap or detergent are not available, flush
  extensively with water
• Passive immunization Administration of Rabies
  immune globulin for Category III
  contacts/exposures
• Active immunization Administration of tissue
  culture vaccine according to one of WHO regimens

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Rabies Postexposure (PEP)

• Two biologics are administered
• Human Rabies Immunoglobulin (HRIG) confers
  immediate protection with antibodies vs rabies
• Rabies Vaccine - patient develops antibodies over
  a 2 to 4 week period

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Preexposure Vaccination

• Recommended for veterinarians, veterinary
  technicians, animal control officers, animal
  shelter workers, rabies lab personnel and person
  working with wildlife.
• Provides protection from unapparent exposures and
  when treatment is delayed
• Also recommended for persons spending 1 month or
  more in countries with endemic dog rabies and in
  which PEP would likely be significantly delayed
  to geographic distances/ lack of medical
  infrastructure

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Pre-exposure Vaccination Protocol

• Three doses of vaccine administered on days 0, 7
  and 21 or 28
• Dosage 1.0 ml administered IM in the upper
  deltoid
• Test serum every 2 years to determine if an
  adequate antibody level persists. If absent,
  administer booster

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Rabies Specimen Testing

• Only the head or brain of an animal larger than 2
  pounds (squirrel) should be submitted
• Brain tissue to include Brain Stem, Cerebellum,
  Hippocampus
• Submitted specimens cannot be returned
• Specimen should be kept refrigerated but not
  frozen

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Diagnoses provides surveillance data Surveillance
data helps PEP decisions
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Resources

• World Rabies Day Website
• www.worldrabiesday.org
• US Centers for Disease Control and Prevention
  (CDC) Rabies Website
• www.cdc.gov/rabies
• World Health Organization
• www.who.int
• Pan American Health Organization
• http//www.paho.org/english/ad/dpc/vp/rabia.htm
• Alliance for Rabies Control
• www.rabiescontrol.net
• Kansas State University Rabies Laboratory
• www.vet.ksu.edu/depts/dmp/service/rabies/index.htm