presentation

Report
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Rhabdoviruses
Hugh B. Fackrell
[email protected]
Rhabdo.ppt
4/13/2015
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Rhabdoviruses
Structure
Classification
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
Baron’s 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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0
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
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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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RNA polymerase
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- ss RNA
+ mRNA
+ ssRNA
Cytoplasm
Rhabdo virus Replication
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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 5 century B.C. and 4 century
B.C. by ancient Greeks
Rabid dogs
th
th
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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
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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
 <10% 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 248:3136-3138
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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
RABIESRhabdovirus
ssRNA
zoonosis: Reservoir in wild animals
e.g. Skunks, Bats, Raccoons,
Foxes
Transmissible to man and domestic animals
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2
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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3
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
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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 cont’d
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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1
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.
4/13/2015

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