Rhabdoviruses
Rhabdoviruses
Structure
- genome codes for five proteins
- bullet shaped capsid (60-180 nm)
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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
Rhabdovirus G protein
- Induces protective virus neutralizing antibody
Rabies virus genome
- intergenic region between each gene
Multiplication
- 1903. Adelchi Negri, an Italian physician found negri bodies.
Multiplication
- Attaches to host via G protein
- Protein synthesis
- 5 complementary mRNA developed
- RNA dependent RNA polymerase
- Positive strand of RNA
- template for antisense RNA
Rhabdo Virus Replication
Rhabdo virus Replication
Transmission
- 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
Infections from Trauma Bites
- Zoonosis: Reservoir in wild animals
- Skunks, Bats, Racoons, Foxes
- Transmissible to man and domestic animals by bites
Distribution
- 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.
Epidemiology
- Described 5th century B.C. and 4th century B.C. by ancient Greeks
Pasteur
- evidence of infections agent in saliva, CNS, peripheral nerves.
- used it to protect against rabies Joesph Meister.
Pathology of Rabies
- Virus enters local tissue through bites
- Travels along sensory nerves to CNS
- Virus multiplies in CNS neurones
- Hippocampus and cerebellum
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Clinical Manifestations
- Fever, Malaise, Headache,
- Respiratory muscle spasms ,
Paralytic Rabies
- Flaccid paralysis including respiratory muscles
‘Furious’ rabies
- excitability- CNS disturbances
- recurrent spasms of muscles involed in swallowing
- 17-50%
- ‘Hydrophobia”
- choking panic
Incubation Period
- severe head or neck bites -2 weeks
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.
Wild life rabies
- ONTARIO - Foxes, Racoons, Skunks - 59%
Diagnosis
- 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
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
Treatment of Suspected Rabies
- 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
Vaccine
- Duck embryo vaccine has side effects
- Human diploid cell vaccine
Human Diploid Cell Vaccine
Pre-exposure vaccine
- lyophilized dose in syringe
- intradermal injection
- 0.1 ml
- 0,7,21,28 days
High risk Populations
- Rabies research lab workers
Postexposure Prophylaxis
- Intramuscular
- Deltoid in adults
- Thigh in children
- Days 0,3,7
- Booster day30,90
Reactions to HDCV
- Local
- % redness, induration, 24-48 hours
- General
- slight fever, malaise
- 1/10,000 type I hypersensitivity
- 1/1,000 type III 2-21 days
Single verified case of transient neuroparalytic illness after HDCV
Bernard et al 1982, JAMA 248:3136-3138
Control
Rabies free countries
- England, Australia, Japan,Sweden, Spain.
- strict import regulations.
Infections from Trauma bites
- zoonosis: Reservoir in wild animals
e.g. Skunks, Bats, Raccoons, Foxes
- Transmissible to man and domestic animals
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.
Pathology of Rabies
- Bites/ Virus enters local tissue.
- Travels along sensory nerves to CNS
- Virus multiplies in CNS neurons
- Hippocampus and cerebellum
Rabies
- Fever, Malaise, Headache,
- Respiratory muscle spasms ,
- Choking panic “ Hydrophobia”
- CNS disturbances - excitability
Rabies: Terminal Symptoms
- Flaccid paralysis including respiratory muscles
- if severe head or neck bites -2 weeks
- Isolate animal observe 5 days
- if symptoms disappear - not rabies -
- If symptoms get worse, kill animal - Negri bodies - Brain cells
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
- 4. If symptoms develop. Death very likely.
Rabies cont’d
- 1958 - Fluorescent antibodies used to detect rabies.
- Can be detected without symptoms.
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.
- ONTARIO - Foxes, Racoons, Skunks - 59%
Rabies
- Control: Pets vaccinated
- Cats, Dogs, Horses, Cattle
- Humans at risk: Veterinarians, Vaccinations - originally 14 injections - agonising.
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
Rabies
- Dog has difficulty swallowing
- appears to be foaming at the mouth, eventually becomes staperous and dies.
- Rabies free countries include: England, Australia, Japan,
- Due to vaccination and strict import regulations.