狂犬病學習培訓課件

1RabiesVirus2LearningobjectivesWhenwefinishthislecture,youshouldbeableto:1Describethebiologicalpropertiesofrabiesvirus;23Listtheappropriatelabtestsfordiagnosis,andknowhowtotreat,prevent,andcontrolrabiesviralinfection.Describetheepidemiology,explainthepathogenesisandtheclinicalcourseofrabies;case

Abatwasfoundina4-yearboy'sbedroom.Apparentlyitwasthereflyingaroundallnight.Thechildwasnotbittennorhadanycontactwiththebat.Fourweekslater,theboydevelopedachangeinbehavior,becomingirritableandagitated.Soonafter,hebecameconfusedwithuncontrollablethrashingabout,andinabilitytohandlehissecretions.Hebecamecomatoseandeventuallydiedfromrespiratoryarrest.Whatdidthechildhave?Rabies!4

Rabies

anacuteinfectionofthecentralnervoussystem,alwaysfatal.causedbyrabiesvirus.majorlyspreadfromaninfectedanimaltohumanthroughabite.aclassiczoonoticinfectionwithabiganimalreservoir.

Biologicalproperties6StructuresVirionBullet-shaped,75nm×180nmEnvelopeprotrudingspikes,trimersofviralglycoproteinGenomeLinear,-ssRNAencodesfor5proteins:glycoprotein(G),nucleoprotein(N),phosphoprotein(P),matrixprotein(M),largepolymeraseprotein(L)Replicationreplicationinthecytoplasm;virionsbudfromplasmamembrane.Rhabdovirueses/rabies/diagnosis/electron_microscopy.html/rabies-virus/#Structure_of_Rabies_Virusapproximately12,000nucleotides

linear,-ssRNAs,

non-segmentedencodesthe5differentviralproteins

nucleoprotein(N):helicalcapsid

phosphoprotein(P):protectstheRNAfromdigestion

largepolymeraseprotein(L):RNA-dependentRNApolymerase

matrixprotein(M):involvedinvirionstructureglycoprotein(G):attachmenttoreceptors(AChR,NCAM,orothermolecules，stimulatesthehostgeneratesneutralizingAbsGenomeofRabiesVirusRNP

PathogenesisandImmunity

PathogenesisRabiesisusuallyfromthebiteofarabidanimal.MedicalMicrobiology(7thedition),PatrickMurray,KenRosenthal,MichaelPfallerClinicalmanifestationsRabiesisanacute,fulminant,fatalencephalitis.

dividedinto3stages:IncubationperiodProdromalphaseNeurologicphase

Theincubationperiodinhumans

isdependenton:thedistancebetweensiteofbiteandCNSsizeofinoculumageofhostimmunestatusofhostviralstraininvolvedClinicalmanifestations

Incubationperiod(typically1–3months;beasshortastwodaysoraslongas6years)VirusreplicatesinthemuscleatthesiteofthebitewithminimalornosymptomsThepictureoriginatesfromtheinternet.ClinicalmanifestationsProdromalphase(2-10days)

shownonspecificsymptomsfevermalaiseheadachepainornumbnessatthesiteofthebitegastrointestinalsymptomsfatigueanorexiaphotophobiaNeurologicphase:typicalsymptoms

nervoussystemdysfunction:disorientation,andhallucinationsgeneralsympatheticoveractivity:increasedtears,sweatandsalivaproduction

Hydrophobia(fearofwater),themostcharacteristicComaaftertheneurologicphaseDeath(resultingfromneurologicandpulmonarycomplications)Hospitalizedhumanrabiesvictiminrestraints.whenswallowingwater,intenseandpainfulspasmsofthethroatandchestmusclesoccur.ClinicalmanifestationsRecoveryandsurvivalareextremelyrare.ProgressionofRabiesDiseaseDiseasestagesIncubationphaseProdromephaseNeurologicphaseComaanddeathSymptomsasymptomaticfever,nausea,GIproblems,headache,lethargy,painatsiteofbitehydrophobia,pharyngealspasms,hyperactivity,anxiety,depressionCNSsymptoms:lossofcoordination,paralysis,confusion,deliriumcoma,hypotension,hypoventilation,secondaryinfections,cardiacarrestLastingTime(Days)60-3652-102-70-14Siteofvirus

inmuscleinCNSandbraininbrainandothersitesvirusinbrainandothersitesImmune

responsedetectableantibodyinserumandCNSEpidemiology16EpidemiologyZoonosisspreadfromanimalstohumansReservoirs:wildanimals,

unvaccinateddogsandcatsSources：

major:

fromsalivaofaninfectedanimal

minor:fromaerosolinanenclosedenvironmentcontainingrabidbatsThepicturesoriginatefromtheinternet.Transmissionroutesusuallyfromthebiteofarabidanimalbyscratches,abrasions,oropenwoundsthatareexposedtosalivaorotherpotentiallyinfectiousmaterialfromarabidanimalthroughinhalationofaerosolizedvirus(asmaybefoundinbatcaves)intransplantedinfectedtissue(e.g.,cornea)18Whoisatrisk?VeterinariansandanimalhandlersPersonbittenbyarabidanimalInhabitantsofcountrieswithnopetvaccinationprogramLabDiagnosis20Spicimencollection：

-saliva

-serum

-spinalfluid

-skin

-biopsymaterialfromthenapeoftheneck,

-brainbiopsy

-autopsymaterial

-impressionsmearsofcornealepithelialcellsNegriBodyinneuroncell

intracytoplasmicinclusionbodyconsistingofaggregatesofviralnucleocapsids(Negribodies)inaffectedneurons.DetectionofNegribodiesThepicturesoriginatefromtheinternet.Viralantigenandgenomedetection21Antigendetection：usingdirectimmunofluorescence(DFA)

genomedetection：usingRT-PCR-relativelyquickandsensitivePositiveresultofDFAtestAntibodydetection

usingimmunofluorescenceorELISAVirusisolationThepictureoriginatesfromtheinternet.

Management,PreventionandControl23Vaccinationofanimals(petvaccinationprogram)PreexposureprophylaxisVaccinePostexposureprophylaxislocalwoundtreatmenthumanrabiesimmunoglobulin(HRIG)killed-virusvaccine(HDCV)Noeffectivetreatmentinclinicaluse.

SupportivecareManagement,PreventionandControlPreventionandControlManagementThepictureoriginatesfromtheinternet.case

Abatwasfoundtoflyina

4-yearboy'sbedroom.Itwasthereapparentlyallnight.Therewasnobitewoundorcontact,andthebatwasfinallyreleased.Fourweekslater,thechildpresented

achangeinbehavior,becomingirritableandagitated.Thisstatequicklydevelopedtoconfusion,uncontrollablethrashingabout,andinabilitytohandlehersecretions.Heeventuallybecamecomatoseanddiedfromrespiratoryarrest.Whatwasthedisease?How