Rhabdoviruses

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Rhabdoviruses

• Hugh B. Fackrell
• Fackrel_at_Uwindsor.ca
• Rhabdo.ppt

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Rhabdoviruses

• Structure
• Classification
• Multiplication
• Clinical manifestations
• Epidemiology
• Diagnosis
• Control

Barons Web Site
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Structure

• Anti-sense ssRNA
• genome codes for five proteins
• bullet shaped capsid (60-180 nm)
• lipid envelope
• glycoprotein peplomers

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Rabies Virus
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Rhabdovirus proteins

• Protein L -RNA dependent RNA
  polymerase
• Protein G- surface antigen
• Protein N -RNA binding protein
• Protein NS- phosphoprotein
• Protein M-membrane/matrix protein

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Rhabdovirus G protein

• Glycoprotein in peplomer
• 64-68,000 MW
• Induces protective virus neutralizing antibody

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Rabies virus genome

• ssRNA 12 kbase
• antisense
• leader at 3 end
• intergenic region between each gene

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Multiplication

• 1903. Adelchi Negri, an Italian physician found
  negri bodies.
• in cytoplasm of CNS

Negri Body
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Multiplication

• Attaches to host via G protein
• penetration
• uncoated in cytoplasm
• Protein synthesis
• 5 complementary mRNA developed
• RNA dependent RNA polymerase
• Positive strand of RNA
• template for antisense RNA

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Rhabdo Virus Replication
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Rhabdo virus Replication
RNA polymerase
mRNA
- ss RNA
ssRNA
Cytoplasm
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Transmission

• Bite of infected animal
• Eating infected meat ( wild animals)
• Airborne transmission-
• bat caves 2 cases in USA (1950-88)
• lab workers - 2 cases in USA( 1950-1988)
• Corneal transplants - 6 cases
• no known exposure -22

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Infections from Trauma Bites

• Zoonosis Reservoir in wild animals
• Skunks, Bats, Racoons, Foxes
• Transmissible to man and domestic animals by bites

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Distribution

• Global all mammals
• Endemic in dogs in Asia, Africa,
• India 17,000 deaths/year, 3,000,000 vaccines
• Philppines canine rabies 25,000 /yr
• Mexico, Central and south America,
• Canada, U.S.A., western Europe
• Wildlife rabies -increasing
• canine rabies controlled.

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Epidemiology

• Described 5th century B.C. and 4th century B.C.
  by ancient Greeks
• Rabid dogs

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Pasteur

• evidence of infections agent in saliva, CNS,
  peripheral nerves.
• He attenuated the agent
• used it to protect against rabies Joesph
  Meister.

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Pathology of Rabies

• Virus enters local tissue through bites
• Travels along sensory nerves to CNS
• Virus multiplies in CNS neurones
• Hippocampus and cerebellum
• viremia
• Infects other organs

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Clinical Manifestations

• Fever, Malaise, Headache,
• Sensory disturbances,
• Respiratory muscle spasms ,
• Swallowing muscle spasms

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Paralytic Rabies

• Dumb rabies
• Flaccid paralysis including respiratory muscles
• Coma and Death

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Furious rabies

• excitability- CNS disturbances
• recurrent spasms of muscles involed in swallowing
• 17-50
• Hydrophobia
• choking panic
• delerium, convulsions

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Incubation Period

• usually 4-6 weeks
• severe head or neck bites -2 weeks
• range 5 days- 2 years

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Canine Rabies

• Dog acts as if it had a sore throat or something
  caught in its throat.
• Paralysed - Dumb rabies
• agitated or aggressive furious rabies
• throat muscle spasms - drooling
• Dog has difficulty swallowing
• appears to be foaming at the mouth, eventually
  becomes staperous and dies.

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Wild life rabies

• ONTARIO - Foxes, Racoons, Skunks - 59
• Bats/cave dust 14

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Diagnosis

• Clinical symptoms
• Can be detected without symptoms.
• Fluorescent antibodies -developed 1958.
• Isolate animal observe 5 days
• if symptoms disappear - not rabies -
• autopsy animal - Negri bodies - Brain cells

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Laboratory Diagnosis

• Antibodies in serial serum specimens
• virus cultured from saliva
• virus antigen
• skin biopsy
• detected by fluorescent antibody
• mouse test
• inject saliva into mouse
• isolate virus

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Treatment of Suspected Rabies

• Wash bite - soap, water
• Disinfect
• quaternary ammonium
• 0.1 benzalkonium chloride
• Iodine or 70 ethanol.
• Rabies antiserum around skin of bite area
• Vaccinate with HDCV immediately
• Tetanus antiserum antibiotics

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Vaccine

• Duck embryo vaccine has side effects
• Human diploid cell vaccine
• Merieux Institute

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Human Diploid Cell Vaccine

• HDCV Merieux vaccine
• 1 allergic encephalitis

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Pre-exposure vaccine

• Merieux vaccine (HDCV)
• lyophilized dose in syringe
• intradermal injection
• 0.1 ml
• 0,7,21,28 days
• Booster every 2 years

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High risk Populations

• Rabies research lab workers
• Rabies diagnostic labs
• Spelunkers
• Veterinarians
• Animal control workers
• International travelers

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Postexposure Prophylaxis

• Intramuscular
• Deltoid in adults
• Thigh in children
• Days 0,3,7
• Booster day30,90

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Reactions to HDCV

• Local
• lt10 redness, induration, 24-48 hours
• General
• slight fever, malaise
• 1/10,000 type I hypersensitivity
• 1/1,000 type III 2-21 days

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Single verified case of transient neuroparalytic
illness after HDCV

• Bernard et al 1982, JAMA 2483136-3138

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Control

• Domestic Animal
• intradermal vaccination
• Wild animals
• oral vaccines meatballs
• Humans Vaccinations
• high risk populations

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Rabies free countries

• England, Australia, Japan,Sweden, Spain.
• Due to vaccination
• strict import regulations.
• 6 months quarantine.

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Infections from Trauma bites

• RABIES Rhabdovirus
• ssRNA
• zoonosis Reservoir in wild animals
• e.g. Skunks, Bats, Raccoons, Foxes
• Transmissible to man and domestic animals
• to man by bites

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Epidemiology

• Described 5th century B.C. and 4th century B.C.
  by ancient Greeks
• Pasteur - found evidence of infections agent in
  saliva, CNS, peripheral nerves.
• He attenuated the agent and used it to protect
  against rabies.
• 1903. Adelchi Negri, an Italian physician found
  negri bodies.

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Pathology of Rabies

• Bites/ Virus enters local tissue.
• Travels along sensory nerves to CNS
• Virus multiplies in CNS neurons
• Hippocampus and cerebellum
• viremia
• Infects other organs

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Rabies

• Clinical Course
• Fever, Malaise, Headache,
• Sensory disturbances,
• Respiratory muscle spasms ,
• Swallowing muscle spasms
• Choking panic Hydrophobia
• CNS disturbances - excitability
• Delirium, Convulsions

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Rabies Terminal Symptoms

• Flaccid paralysis including respiratory muscles
• Coma and Death
• Incubation 4-6 weeks
• if severe head or neck bites -2 weeks
• Isolate animal observe 5 days
• if symptoms disappear - not rabies -
• use fluorescent antibody
• If symptoms get worse, kill animal - Negri bodies
  - Brain cells

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Treatment of Suspected Rabies

• 1.Wash bite - soap, water, alcohol, lavage with
  Iodine.
• 2. Inject hyper immune serum around skin of bite
  area
• 3. Vaccinate immediately - Human tissue culture
  Vaccine - Duck embryo vaccine has side effects
• 1 allergic encephalitis
• 4. If symptoms develop. Death very likely.

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Rabies contd

• 1958 - Fluorescent antibodies used to detect
  rabies.
• Can be detected without symptoms.

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Rabies Incidence

• Rabies - World wide - all mammals Rabies endemic
  in dogs in Asia, Africa, Mexico, Central and
  south America,
• In Canada, U.S.A., western Europe - Rabies in
  dogs controlled.
• Wild life rabies
• ONTARIO - Foxes, Racoons, Skunks - 59
• Bats/cave dust 14

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Rabies

• Control Pets vaccinated
• Cats, Dogs, Horses, Cattle
• Humans at risk Veterinarians, Vaccinations -
  originally 14 injections - agonising.
• Now intramuscular.

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Rabies in dogs

• Dog acts as if it had a sore throat or something
  caught in its throat.
• Paralyzed - Dumb rabies
• agitated or aggressive furious rabies
• throat muscle spasms - drooling

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Rabies

• Dog has difficulty swallowing
• appears to be foaming at the mouth, eventually
  becomes staperous and dies.
• Rabies free countries include England,
  Australia, Japan,
• Sweden, Spain.
• Due to vaccination and strict import regulations.
• 6 months quarantine.