Rhabdoviruses by Ma5vn8

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    Rhabdoviruses
            Hugh B. Fackrell

        Fackrel@Uwindsor.ca

                 Rhabdo.ppt
                               8/7/2012
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                   Rhabdoviruses

    Structure
    Classification
    Multiplication
    Clinical manifestations
    Epidemiology
    Diagnosis
    Control
                Baron’s Web Site   8/7/2012
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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


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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




                           8/7/2012
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- ss RNA                    + mRNA




            + ssRNA

     Cytoplasm


           Rhabdo virus Replication   8/7/2012
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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
                 th                th



     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.   8/7/2012
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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          8/7/2012
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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
       Deltoidin 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

    RABIES Rhabdovirus
       ssRNA

    zoonosis: Reservoir in wild animals
             e.g. Skunks, Bats, Raccoons,
     Foxes

    Transmissible to man and domestic animals
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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.
                                              8/7/2012
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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             8/7/2012
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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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                         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.                      8/7/2012

								
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