流行性乙型腦炎的教育

流行性乙型腦炎的教育第1頁/共49頁EpidemicEncephalitisB第2頁/共49頁CasereportHistorytaking：Aboy,4yearsold，borninthecountryside.Feverlastfor4days，convulsionandconfusionlastabout6hours.Physicalexamination：T40.5℃，R30bpm，P120bpm，BP100/60mmHg.Unconsciousness,conjunctivaledema,lungscanbeheardwheezes.Musclehypertonia,kneehyperreflexia,Babinskisign(+)Otherhistory?Accessoryexamination?第3頁/共49頁AbstractJapaneseencephalitis(JE),anacuteinfectiousdiseasecausedbythemosquito-borneJapaneseencephalitisvirus(JEV)andfeaturedasinflammationinbrainparenchyma.Fever,confusion,coma,convulsion,pathologicalreflexandmeningealirritation.Respiratoryfailureinseverecases,highmortality,and10%resultinpermanentneuropsychiatricsequelea.第4頁/共49頁EtiologyAsinglestrandedRNA,40-50nm,11kilobasesgenomes.RNAgenomeispackagedinthecapsidproteinformingthecoreofthevirus.Thegenomesalsoencodesseveralnonstructuralproteins(NS1,NS2a,NS3,NS4a,NS4b,andNS5)JEVcanbekilledbydisinfectant,100℃2minutesor56℃30minutes第5頁/共49頁EtiologyAntigenicstability,infectioncanproducecomplement-bindingantibodies,neutralizingantibodiesandhemagglutinationinhibitionantibodies,contributetoclinicaldiagnosisandepidemiologicalinvestigation第6頁/共49頁EpidemiologySourcesofinfection:JEisazoonosis,mosquitoesbecomeinfectedbyfeedingdomesticpigsandwildbirds

infectedwiththeJEV.JEVisamplifiedinthebloodsystemsofthedomesticpigsandwildbirds.Pigsaretheimprotantamplifiedandreservoirs.Otherreserviorincludescow,sheep,horse,duck,gooseandchicken.第7頁/共49頁EpidemiologyRouteoftransmission:thebiteofaninfectedmosquito,primarilyCulexspecies.Humansareadead-endhostintheJEVtramsmissioncycle.JEVisnottransmittedfromperson-to-person.OnlydomesticpigsandwildbirdsarecarriersoftheJEV.第8頁/共49頁Epidemiology.Susceptiblepopulation:Generallysusceptible,especiallyresidentsofruralareasinendemiclocation,mostlyasymptomatic.Theratioofpatientsandlatentinfectionwas1:1000-2000.Pre-existingantibodies.CountriesthatstillhaveperiodicepidemicsincludeIndia,Cambodia,Nepalandsoon.第9頁/共49頁Epidemiology.Epidemicfeature:mostcasesintemperateandsubtropicalareasoccurfromJunetoSeptember,whileintropicalareasoccurthroughouttheyear.Fivegenotypes:genotypesI,II,III,IV,V.GenotypesIandIIIoccurprincipallyintemperate,epidemicareas,andgenotypeIIandIVoccurprincipallyintropical,endemicregions.第10頁/共49頁第11頁/共49頁第12頁/共49頁PathogenesisandPathologyJEVMononuclearmacrophagesmultiplyviremiaInvadetheCNSNotinvadetheCNSIncidenceLatentinfection第13頁/共49頁ThissectionofbrainwastakenfromapatientwithJapaneseencephalitis,andshowsthegrosspathologyfoundinallofthearbovirusencephalitides.Thechanges,whichconsistofperivascularcongestionandhemorrhage,maybediffuseorfocal,buttheyareseenpredominantlyincorticalgrayanddeepgraymatter第14頁/共49頁PathogenesisandPathologyJEVDirectinvasionAntigen-antibodybindingtotheimmuneattackNervecelllesionsVascularsheathformationThalamus,basalganglia,brainstem,cerebellum,hippocampus,cerebralcortexGlialcellproliferation第15頁/共49頁Showsofteninglesions,oval-shapedlightpalearea,thestructurewasloosemesh第16頁/共49頁ClinicalmanifestationsIncubationperiodof5-15days.thevastmajorityofinfectionsareasymptomatic,only1in250infectionsdevelopintoencephalitis.Typicalmanifestation:therearefourstagesTheprimarystage(1-3days):onsetwassuddenwithhighfever,upto39-41℃in1-2daysaccompaniedheadacheandmalaise.Anorexia,nausea,orabdominalpain.Apathyandneckrigidity.第17頁/共49頁ClinicalmanifestationsTheproximitystage(fourthtotenthdays)HyperthermiaConsciousdisturbanceConvulsionRespiratoryfailureOthernervoussymptomsandsignsCirculationfailure第18頁/共49頁ClinicalmanifestationsTheproximitystage：Hyperthermia:acuteonset;morethan40℃,lasts7-10daysgenerallyandsomegravecasescanlastfor3weeks.Thehighertemperature,thelongercourse,themoreseriousofJE.第19頁/共49頁ClinicalmanifestationsTheproximitystageConsciousdisturbance：Lethargy,delirium,coma,anddisorientationaremainpresentationsAppearsmostlyatthe3-8days,lastingforalmost1weekApositivecorralationbetweentheseriousandthelastingtimeofcomaandthegravityofJEandprognosis第20頁/共49頁ClinicalmanifestationsTheproximitystageConvulsion：Causes:highfever,cerebraledema,brainparenchymalinflammationOneormorefocal/asymmetricsignsappearinginthefirstfewdaysLight:theface,lips,localconvulsions,severecasesofthebodyAbout30%ofsurvivorshavefrankpersistentmotorlanguageimpairment.第21頁/共49頁ClinicalmanifestationsRespiratoryfailure:causedbyinflammatoryofbrainparenchyma,hypoxia,cerebraledema,acuteintracranialhypertensionandcerebralherniaCerebralhenia：Spittingvomiting,convulsionsComaincreasedPupilchanges.Anteriorfontanelbulging,papilledema第22頁/共49頁ClinicalmanifestationsTheproximitystage：Circulationfailure:rarely,tachycardia,hyperorhypotensionandrarelyECGevidenceofpericarditis.Othernervoussymptomsandsigns:superficialreflexdisappearsorweakens;deepreflexaccentuationsfirstandthedisappearsandtherearesymptomsandmeningealirritation.第23頁/共49頁ClinicalmanifestationshyperthermiaconvulsionRespiratoryfailureArecriticalpresentationsofJEandrespiratoryfailureistheleadingcauseofdeath第24頁/共49頁ClinicalmanifestationsTheconvalescencestage：DefervescenceoffeverandneurologicimprovementItusuallylastsforatleasttwoweeks第25頁/共49頁ClinicalmanifestationsThesequelaestage：theexistenceofneuropsychiatricsymptomsafter6months。Theincidenceofabout5%to20%.第26頁/共49頁AxialT2weighted(TR/TE=2500/90)image.(A)Hyperintenselesionsatbilateralthalami(arrows)wereshownonthe14thdaysafteronset.(B)Smallhyperintenselesionsatbilateralthalami(arrows)onthe60thdayafteronsetClinicalmanifestations第27頁/共49頁LaboratoryexaminationsWhitebloodcell:growsupto10~20×109/L,neutrophiloccupiedmorethan80%.SomepatientshavenormalWBCcounts.Cerebrospinalfluid(CSF)：lumbarpuncturetoobtainCSFsamples.第28頁/共49頁LaboratoryexaminationsCerebrospinalfluid(CSF)：Theopeningpressureisusuallynormalbutmayberaised.Mononuclearwhitebloodcellsmaybe50~500×106/L;Glucoselevelsarenormal;Proteinlevelsaremildlyelevatedinmostcases,oftenlessthan900mg/dl第29頁/共49頁LaboratoryexaminationsAntibobydetection:SpecificIgMantibodiesisthestandarddiagnostictestforJE,nearly100%sensitivity;IgMantibodylevelsmaybefoundevenwithin7daysofsymptoms.False-negativeresultsmayoccurifthesamplesaretestdtooearly.Somecross-reactivitymayarisefromotherflavivirusesandfromJEandyellowfevervaccinations第30頁/共49頁LaboratoryexaminationsNucleicaciddetection:detectionofviralgenomebyRT-PCRiseasiertoperformandhighlyreliablewith100%sensitivity,JEVhasbeenisolateduptoevenalmost4monthsafterclinicalsymptomshavebegunInmagingstudies:MRIandCT第31頁/共49頁DiagnosisEpidemiologydata:rigorousseasonality:summerandautumn;lessthan10yearsoldaremoresusceptiblebutmoreadultpatientsareseennowClinicalfeatures：acuteonsetheadache,vomitting,hyperthermia,convulsionandpositivepathologicreflexandmeningealirritationsign第32頁/共49頁DiagnosisLaboratoryexaminations：peripheralbloodpicture,CSF,serumantibodies,EEG,CTandMRI,brainbiopsyVirologicalinvestigation:JEVisdifficulttobeseparatedfrombloodandCSF.JEVantigencanbedetectedinsuchbodyfluidusingPCR.第33頁/共49頁DifferentialdiagnosisToxicbacillarydysenteryTuberculousmeningitisPurulentmeningitisEncephalitisbOnsetAcute，24hourpeakChronic,longcourse1-2peak1-2peakSeasonSummertoautumnNon-seasonalwinterandspringSummertoautumnCSFNormalChlorideandglucosearelow,highprotein,cellcount50*106/LChlorideandglucosearelow,highprotein,cellcount1000*106/LChlorideandglucosearenormal,highprotein,cellcount50~500*106/LPathogenAnusdrysmearofpuscells,bloodculturesofShigellaCSFfilmsmearTBCSFsmearstainingbacteriaCSFbacterialtestingwasnegative.SpecificIgMantibodies第34頁/共49頁TreatmentGeneraltreatmentSymptomatictreatment

hyperthermia,convulsion,respiratoryfailure

第35頁/共49頁TreatmentGeneraltreatmentComapatientsshouldpayattention：OralcleaningPreventsecondarybacterialinfectionPreventbedsoresoccurProtectthecorneaAnti-fallingbedpreventthetonguebittenNotethatwater,electrolytes,acid-basebalance,butnottoomuchinfusionvolumetopreventbrainedema第36頁/共49頁Treatmenthyperthermia：LowertheroomtemperaturePhysicalcooling:iceoralcoholcoolsalineWithconvulsions:hibernationtherapy(chlorpromazine+promethazine)第37頁/共49頁Treatmentconvulsion：Cerebraledema:dehydration,20%mannitol1-2g/Kg,intravenousinfusion,4-6htime,whilecombinedwithadrenalcortexhormones,furosemide,50%GS,toreducevascularpermeability,PreventionofbrainedemaanddehydrationagentreboundapplicationRespiratoryblockage:suction,oxygen,ifnecessary,tracheotomy第38頁/共49頁TreatmentRespriatoryfailure：Brainedema:dehydratingagentCentralrespiratoryfailure:availablerespiratorystimulantsImprovemicrocirculation,reducecerebraledema:vasodilators第39頁/共49頁TreatmentRespriatoryfailure：RespiratorysecretionsInfarct:suction,atomizationinhalationofα-chymotrypsin;withbronchospasmmaybe0.25%-0.5%isoproterenolinhalation.Andappropriatetreatmentwithantibioticssuchasbacterialinfection.Ifnecessary,endotrachealintubationorincision,artificialrespirationventilation第40頁/共49頁TreatmentRecoveryandsequelaeoftreatment:acupuncture,physicaltherapy,hyperbaricoxygentherapy第41頁/共49頁prognosisControlthesourceofinfection:VaccinethepigsbeforetheepidemicseasonCutoffthetransmission:anti-mosquito,mosquitocontrol.Protectionofsusceptiblepopulations,vaccinationinjections第42頁/共49頁prognosisVaccinationinjections:

thecurrentdosingscheduleforpatientsaged3yearsorolderis1mlsubcutaneouslyondays0,7,and30(0.5mlinpatientsaged1-2y).Administerthelastdoseofvaccineatleast10dayspriortotravelinanendemicarea.Adversereactionsincludelocalpainandredness,fever,gastrointestinalsymptoms,headache第43頁/共49頁CasereportHistorytaking：Aboy,4yearsold，borninthecountryside.Feverlastfor4days，convulsionandconfusionlastabout6hours.Physicalexamination：T40.5℃，R30bpm，P120bpm，BP100/60mmHg.Unconscious