1 5/13/2015 Streptococcus Hugh B. Fackrell Filename:Strept.ppt.
15/13/2015 Rhabdoviruses Hugh B. Fackrell [email protected].
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Transcript of 15/13/2015 Rhabdoviruses Hugh B. Fackrell [email protected].
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RhabdovirusesRhabdoviruses
Hugh B. FackrellHugh B. Fackrell
[email protected]@Uwindsor.ca
Rhabdo.pptRhabdo.ppt
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RhabdovirusesRhabdoviruses
StructureStructureClassificationClassificationMultiplicationMultiplicationClinical manifestationsClinical manifestationsEpidemiologyEpidemiologyDiagnosisDiagnosisControlControl
Baron’s Web Site
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StructureStructure
Anti-sense ssRNAAnti-sense ssRNAgenome codes for five proteinsgenome codes for five proteinsbullet shaped capsid (60-180 nm)bullet shaped capsid (60-180 nm)lipid envelopelipid envelopeglycoprotein peplomersglycoprotein peplomers
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Rhabdovirus proteinsRhabdovirus proteins
Protein L -RNA dependent RNA Protein L -RNA dependent RNA polymerase polymerase
Protein G- surface antigenProtein G- surface antigenProtein N -RNA binding proteinProtein N -RNA binding proteinProtein NS- phosphoproteinProtein NS- phosphoproteinProtein M-membrane/matrix proteinProtein M-membrane/matrix protein
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Rhabdovirus G proteinRhabdovirus G protein
Glycoprotein in peplomerGlycoprotein in peplomer 64-68,000 MW64-68,000 MW
Induces protective virus neutralizing Induces protective virus neutralizing antibodyantibody
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Rabies virus genomeRabies virus genome
ssRNA 12 kbasessRNA 12 kbaseantisense antisense leader at 3’ endleader at 3’ endintergenic region between each geneintergenic region between each gene
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MultiplicationMultiplication
1903. Adelchi 1903. Adelchi Negri, an Italian Negri, an Italian physician found physician found negri bodies.negri bodies.
in cytoplasm of in cytoplasm of CNSCNS
Negri Body
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MultiplicationMultiplication
Attaches to host via G proteinAttaches to host via G proteinpenetrationpenetrationuncoated in cytoplasmuncoated in cytoplasmProtein synthesisProtein synthesis
5 complementary mRNA developed5 complementary mRNA developed RNA dependent RNA polymeraseRNA dependent RNA polymerase
Positive strand of RNAPositive strand of RNA template for antisense RNAtemplate for antisense RNA
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+ mRNA
+ ssRNA
- ss RNA
RNA polymerase
Cytoplasm
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TransmissionTransmission
Bite of infected animalBite of infected animalEating infected meat ( wild animals)Eating infected meat ( wild animals)Airborne transmission-Airborne transmission-
bat caves 2 cases in USA (1950-88)bat caves 2 cases in USA (1950-88) lab workers - 2 cases in USA( 1950-1988)lab workers - 2 cases in USA( 1950-1988)
Corneal transplants - 6 cases Corneal transplants - 6 cases no known exposure -22%no known exposure -22%
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Infections from Trauma BitesInfections from Trauma Bites
Zoonosis: Zoonosis: Reservoir in wild animalsReservoir in wild animalsSkunks, Bats, Racoons, FoxesSkunks, Bats, Racoons, Foxes
Transmissible to man and domestic animals Transmissible to man and domestic animals by bitesby bites
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DistributionDistribution
GlobalGlobal all mammals all mammals Endemic in dogs in Asia, Africa,Endemic in dogs in Asia, Africa,
India 17,000 deaths/year, 3,000,000 vaccinesIndia 17,000 deaths/year, 3,000,000 vaccines Philppines canine rabies 25,000 /yr Philppines canine rabies 25,000 /yr
Mexico, Central and south America,Mexico, Central and south America,Canada, U.S.A., western Europe Canada, U.S.A., western Europe
Wildlife rabies -increasingWildlife rabies -increasing canine rabies controlled.canine rabies controlled.
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EpidemiologyEpidemiology
Described 5Described 5 th th century B.C. and 4century B.C. and 4 th th century century B.C. by ancient GreeksB.C. by ancient Greeks
Rabid dogsRabid dogs
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Pasteur Pasteur
evidence of infections agent in saliva, CNS, evidence of infections agent in saliva, CNS, peripheral nerves.peripheral nerves.
He attenuated the agentHe attenuated the agent used it to protect against rabies Joesph used it to protect against rabies Joesph
Meister. Meister.
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Pathology of RabiesPathology of Rabies
Virus enters local tissue through bitesVirus enters local tissue through bitesTravels along sensory nerves to CNSTravels along sensory nerves to CNS Virus multiplies in CNS neuronesVirus multiplies in CNS neurones Hippocampus and cerebellumHippocampus and cerebellumviremiaviremiaInfects other organsInfects other organs
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Clinical ManifestationsClinical Manifestations
Fever, Malaise, Headache, Fever, Malaise, Headache, Sensory disturbances, Sensory disturbances, Respiratory muscle spasms , Respiratory muscle spasms , Swallowing muscle spasmsSwallowing muscle spasms
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Paralytic RabiesParalytic Rabies
‘‘Dumb’ rabiesDumb’ rabiesFlaccid paralysis including respiratory Flaccid paralysis including respiratory
musclesmusclesComa and DeathComa and Death
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‘Furious’ rabies‘Furious’ rabies
excitability- CNS disturbancesexcitability- CNS disturbancesrecurrent spasms of muscles involed in recurrent spasms of muscles involed in
swallowingswallowing 17-50%17-50% ‘‘Hydrophobia”Hydrophobia” choking panicchoking panic
delerium, convulsionsdelerium, convulsions
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Incubation Period Incubation Period
usually 4-6 weeksusually 4-6 weekssevere head or neck bites -2 weekssevere head or neck bites -2 weeks range 5 days- 2 yearsrange 5 days- 2 years
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Canine RabiesCanine Rabies
Dog acts as if it had a sore throat or something Dog acts as if it had a sore throat or something caught in its throat.caught in its throat.
Paralysed - “Dumb” rabiesParalysed - “Dumb” rabiesagitated or aggressive furious rabiesagitated or aggressive furious rabiesthroat muscle spasms - droolingthroat muscle spasms - droolingDog has difficulty swallowingDog has difficulty swallowing appears to be foaming at the mouth, eventually appears to be foaming at the mouth, eventually
becomes staperous and dies.becomes staperous and dies.
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Wild life rabiesWild life rabies
ONTARIO - Foxes, Racoons, Skunks - ONTARIO - Foxes, Racoons, Skunks - 59% 59%
Bats/cave dust 14%Bats/cave dust 14%
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DiagnosisDiagnosis
Clinical symptomsClinical symptomsCan be detected without symptoms.Can be detected without symptoms. Fluorescent antibodies -developed 1958.Fluorescent antibodies -developed 1958.Isolate animalIsolate animal observe 5 daysobserve 5 days
if symptoms disappear - not rabies -if symptoms disappear - not rabies -autopsy animal - Negri bodies - Brain autopsy animal - Negri bodies - Brain
cellscells
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Laboratory DiagnosisLaboratory Diagnosis
Antibodies in serial serum specimensAntibodies in serial serum specimensvirus cultured from salivavirus cultured from saliva virus antigenvirus antigen
skin biopsyskin biopsy detected by fluorescent antibodydetected by fluorescent antibody
mouse testmouse test inject saliva into mouseinject saliva into mouse isolate virusisolate virus
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Treatment of Suspected Rabies Treatment of Suspected Rabies
Wash bite - soap, waterWash bite - soap, waterDisinfect Disinfect
quaternary ammoniumquaternary ammonium 0.1% benzalkonium chloride 0.1% benzalkonium chloride Iodine or 70% ethanol.Iodine or 70% ethanol.
Rabies antiserum around skin of bite areaRabies antiserum around skin of bite areaVaccinate with HDCV immediatelyVaccinate with HDCV immediatelyTetanus antiserum & antibioticsTetanus antiserum & antibiotics
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Vaccine Vaccine
Duck embryo vaccine has side effectsDuck embryo vaccine has side effectsHuman diploid cell vaccine Human diploid cell vaccine
Merieux InstituteMerieux Institute
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Human Diploid Cell VaccineHuman Diploid Cell Vaccine
HDCV =Merieux vaccineHDCV =Merieux vaccine1% allergic encephalitis1% allergic encephalitis
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Pre-exposure vaccinePre-exposure vaccine
Merieux vaccine (HDCV)Merieux vaccine (HDCV)lyophilized dose in syringelyophilized dose in syringe
intradermal injection intradermal injection 0.1 ml0.1 ml0,7,21,28 days0,7,21,28 days
Booster every 2 yearsBooster every 2 years
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High risk PopulationsHigh risk Populations
Rabies research lab workersRabies research lab workersRabies diagnostic labsRabies diagnostic labsSpelunkersSpelunkersVeterinariansVeterinariansAnimal control workersAnimal control workersInternational travelersInternational travelers
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Postexposure ProphylaxisPostexposure Prophylaxis
IntramuscularIntramuscular Deltoid in adultsDeltoid in adults Thigh in childrenThigh in children Days 0,3,7Days 0,3,7 Booster day30,90 Booster day30,90
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Reactions to HDCVReactions to HDCV
LocalLocal<10% redness, induration, 24-48 hours<10% redness, induration, 24-48 hours
GeneralGeneral slight fever, malaiseslight fever, malaise1/10,000 type I hypersensitivity1/10,000 type I hypersensitivity1/1,000 type III 2-21 days1/1,000 type III 2-21 days
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Single verified case of transient neuroparalytic illness after
HDCV
Single verified case of transient neuroparalytic illness after
HDCV
Bernard et al 1982, JAMA 248:3136-3138Bernard et al 1982, JAMA 248:3136-3138
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ControlControl
Domestic AnimalDomestic Animal intradermal vaccinationintradermal vaccination
Wild animalsWild animals oral vaccines meatballsoral vaccines meatballs
Humans Vaccinations Humans Vaccinations high risk populationshigh risk populations
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Rabies free countries Rabies free countries
England, Australia, Japan,Sweden, Spain.England, Australia, Japan,Sweden, Spain.Due to vaccination Due to vaccination strict import regulations.strict import regulations.6 months quarantine. 6 months quarantine.
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RABIESRABIES RhabdovirusRhabdovirus
ssRNAssRNA
zoonosis: Reservoir in wild animalszoonosis: Reservoir in wild animals
e.g. Skunks, Bats, Raccoons, Foxese.g. Skunks, Bats, Raccoons, Foxes
Transmissible to man and domestic animalsTransmissible to man and domestic animals
to man by bitesto man by bites
Infections from Trauma bitesInfections from Trauma bites
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EpidemiologyEpidemiology
Described 5th century B.C. and 4th century Described 5th century B.C. and 4th century B.C. by ancient GreeksB.C. by ancient Greeks
Pasteur - found evidence of infections agent Pasteur - found evidence of infections agent in saliva, CNS, peripheral nerves.in saliva, CNS, peripheral nerves.
He attenuated the agent and used it to He attenuated the agent and used it to protect against rabies. protect against rabies.
1903. Adelchi Negri, an Italian physician 1903. Adelchi Negri, an Italian physician found negri bodies.found negri bodies.
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Pathology of RabiesPathology of Rabies
Bites/ Virus enters local tissue.Bites/ Virus enters local tissue.Travels along sensory nerves to CNSTravels along sensory nerves to CNS Virus multiplies in CNS neuronsVirus multiplies in CNS neuronsHippocampus and cerebellumHippocampus and cerebellumviremiaviremiaInfects other organsInfects other organs
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RabiesRabies
Clinical Course: Clinical Course: Fever, Malaise, Headache, Fever, Malaise, Headache, Sensory disturbances, Sensory disturbances, Respiratory muscle spasms , Respiratory muscle spasms , Swallowing muscle spasmsSwallowing muscle spasmsChoking panic “ Hydrophobia”Choking panic “ Hydrophobia”CNS disturbances - excitability CNS disturbances - excitability Delirium, ConvulsionsDelirium, Convulsions
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Rabies: Terminal SymptomsRabies: Terminal Symptoms
Flaccid paralysis including respiratory musclesFlaccid paralysis including respiratory musclesComa and DeathComa and DeathIncubation: 4-6 weeksIncubation: 4-6 weeksif severe head or neck bites -2 weeksif severe head or neck bites -2 weeksIsolate animalIsolate animal observe 5 daysobserve 5 daysif symptoms disappear - not rabies -if symptoms disappear - not rabies - use fluorescent antibodyuse fluorescent antibodyIf symptoms get worse, kill animal - Negri bodies - Brain If symptoms get worse, kill animal - Negri bodies - Brain
cellscells
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Treatment of Suspected RabiesTreatment of Suspected Rabies
1.Wash bite - soap, water, alcohol, lavage with 1.Wash bite - soap, water, alcohol, lavage with Iodine.Iodine.
2. Inject hyper immune serum around skin of bite area2. Inject hyper immune serum around skin of bite area3. Vaccinate immediately - Human tissue culture 3. Vaccinate immediately - Human tissue culture
Vaccine - Vaccine - Duck embryo vaccine has side effectsDuck embryo vaccine has side effects 1% allergic encephalitis1% allergic encephalitis
4. If symptoms develop. Death very likely.4. If symptoms develop. Death very likely.
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Rabies cont’dRabies cont’d
1958 - Fluorescent antibodies used to detect rabies.1958 - Fluorescent antibodies used to detect rabies.Can be detected without symptoms.Can be detected without symptoms.
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Rabies: IncidenceRabies: Incidence
Rabies - World wide - all mammals Rabies Rabies - World wide - all mammals Rabies endemic in dogs in Asia, Africa, Mexico, endemic in dogs in Asia, Africa, Mexico, Central and south America,Central and south America,
In Canada, U.S.A., western Europe - Rabies in In Canada, U.S.A., western Europe - Rabies in dogs controlled.dogs controlled.
Wild life rabiesWild life rabiesONTARIO - Foxes, Racoons, Skunks - 59% ONTARIO - Foxes, Racoons, Skunks - 59% Bats/cave dust 14% Bats/cave dust 14%
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Rabies Rabies
Control: Pets vaccinatedControl: Pets vaccinated Cats, Dogs, Horses, CattleCats, Dogs, Horses, Cattle
Humans at risk: Veterinarians, Vaccinations - Humans at risk: Veterinarians, Vaccinations - originally 14 injections - agonising.originally 14 injections - agonising. Now intramuscular.Now intramuscular.
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Rabies in dogs:Rabies in dogs:
Dog acts as if it had a sore throat or Dog acts as if it had a sore throat or something caught in its throat.something caught in its throat.
Paralyzed - “Dumb” rabiesParalyzed - “Dumb” rabiesagitated or aggressive furious rabiesagitated or aggressive furious rabiesthroat muscle spasms - droolingthroat muscle spasms - drooling
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RabiesRabies
Dog has difficulty swallowingDog has difficulty swallowing appears to be foaming at the mouth, eventually appears to be foaming at the mouth, eventually
becomes staperous and dies.becomes staperous and dies.Rabies free countries include: England, Australia, Rabies free countries include: England, Australia,
Japan,Japan,Sweden, Spain.Sweden, Spain.Due to vaccination and strict import regulations.Due to vaccination and strict import regulations.6 months quarantine.6 months quarantine.