传染病学课件：肾综合症出血热（英文版）

HemorrhagicFeverwithRenalSyndromeOverviewPathogen:HantavirusesClinicalfeatures:

fever；renalfailure；shock;hemorrhagicmanifestationsHemorrhagicfeverwithrenalsyndrome(HFRS)includesagroupofclinicallysimilarillnessesEpidemichemorrhagicfever(China)Koreanhemorrhagicfever(Korean)Nephropathisepidemica(PuumalaWhatishemorrhagicfeverwithrenalsyndrome?

Hemorrhagicfeverwithrenalsyndrome(HFRS)isagroupofclinicallysimilarillnessescausedbyhantavirusesfromthefamilyBunyaviridae.

VirologyofHantaviruseBelongtothefamilyBunyaviridaeSphericalenvelopedvirusesabout80-120nmindiameterEHFVGenomicGenomeconsistsofthreesingle-stranded,

negativesenseRNAsegments---S,M,LS(small):

encodesneucleocapsidproteinM(medium):

encodesenvelopeglycoproteinL(large):

encodespolymeraseThevirusesthatcausehemorrhagicfeverwithrenalsyndromeinclude:Hantaan(Ⅰ)Dobrava-BelgradeSeoul(Ⅱ)Puumala(Ⅲ)SinNombrevirus(V)

cancause

hantaviruspulmonarysyndrome(America)VirologyofHantaviruseEpidemiology

Sourcesoftransmission:rodentreservoirsStripedfieldmouse

Norwayrat

Bankvoles

Yellow-neckedfieldmouse

OccursmainlyinEuropeandAsiaStripedfieldmouseApodemusagrarius

NorwayratRattusnorvegicus,BankvolesClethrionomysglareolusYellow-neckedfieldmouseA.flavicollisEpidemiology

RouteoftransmissionExposuretoaerosolizedurine,droppings,orsalivaofinfectedrodentsDirectintroductionofinfectiousmaterialthroughbrokenskinorontomucousmembranesThroughrodentbitesfrominfectedanimalsFrommothertochildTransmissionfromhumantohumanisextremelyrare.EpizooticCycleRodentbreedingEpidemiologySusceptibilityofpopulationPeoplearegenerallysusceptibleCommonlyreportedinmaleadultSubclinicalinfectionrateis2.5~4.3%StableandpersistentimmunityPathogenesisImmunemechanismsmayplayanmajorpathogenicroleViremiaisonlypresentinearlystageofinfection

NocytopathiceffectAtthetimethatseveresymptomsbegin

ViremiaisabsentSpecificantibodiesandTcellsaredetectedmarkedcytokineproduction,kallikrein-kininactivation,complementpathwayactivationPathogenesisBasicpathologicalchanges

Systemicmicrovascularendothelialedema,degenerationandnecrosisThemostdramaticdamageisseeninthekidneysImmunemediatedvascularendothelialinjury

IncreasedcapillarypermeabilityPlasmaextravasationInsufficientbloodvolumePrimaryshockoccursbeforeoliguricstageMassivehemorrhageorSecondaryinfectionorInsufficientwater-electrolytesupplyduringpolyuricstageInsufficientbloodvolumeSecondaryshock:occursafteroliguricstagePathogenesis:shockPathogenesis:hemorrhagetendencyDamageofthebloodvesselwallThrombocytopenia

UremicbleedingdefectsIncreaseofheparin–likesubstancesDICDecreasedbloodflowDirectinjurytothekidneyPathogenesis:acuterenalfailure

Pathologicanatomypathologicanatomy

Histopathologicchangesinkidney(cortex)Smallarrow:interstitialedemawithmildinfiltrationofmononuclearcellsLargearrow:degenerationofrenaltubules

Arrowhead:proteinaceouscastsandexudate

Histopathologicchangesinkidney(medulla)

Mostprominentchangeinthemedullaiswell–definednecroticlesion(asterisk)*IntracranialhemorrhageinHFRSpatientClinicalManifestations:overviewIncubationperiod:usually1to2weeksAtriadoffever,hemorrhage,andrenalinsufficiency5progressivestages:Febrilestage→Hypotensivestage→Oliguricstage→Polyuricstage→ConvalescentstageSkippingofphaseiscommoninatypicalandmildindividuals.Theindividualphasesmayoverlapinseverecases.ClinicalManifestations:FebrilestageAbruptonsetoffeverlasting3-7daysGastrointestinaldiscomfort

Anorexia,nausea,vomitingandabdominalpainSystemictoxicsymptoms

Myalgia,triadofpains(Headache,lumbagoandretroorbitalpain)ClinicalManifestations:FebrilestageSignsofCapillaryinjury

CongestionHemorrhagictendencyExudationandedemaClinicalManifestations:FebrilestageCongestionDermathemia:triadofflushings

FlushingoverFace,theVareaoftheneck(drunkenface),andthebackMucosalhyperemia

Conjunctivalsuffusion,pharyngealinjectionDrunkenfaceClinicalManifestations:FebrilestageHemorrhagictendencyDermatorrhagia①Petechiaeoftendevelopinareasofpressure,axilla②Ecchymosisinseverecase

Mucosalbleeding

Petechiaeintheconjunctivae,softpalateVisceralbleeding

Epistaxis,bloodystool,hemoptysis,cerebralbleedingPetechiaeonaxillaEcchymosisinseverecaseSubconjunctivalhemorrhagePetechiaeonthesoftpalateClinicalManifestations:FebrilestageExudationandedema→causepainPeriorbitaledema,chemosisRetroperitonealedemaAscitesAbdominalpain:Differentialdiagnosis?chemosis发热期临床表现发热三红酒醉貌，头眼腰痛像感冒，腋腭鞭击出血点，恶心呕吐蛋白尿。“发热、三痛、三红、一水肿、肾损害”ClinicalManifestations:HypotensivestageLastsapproximatelyafewhoursto2daysExacerbationofthediseaseafterdefervescenceFallingbloodpressureandTachycardiaInseverecaseshock(primaryshock)

ClinicalManifestations:OliguricstagePersistsfor2-5daysOliguria:urineoutput<400ml/dAnuria:urineoutput<50ml/dHemorrhagictendenciescontinueOnsetofrenalfailureSymptomsassociatedwithuremiaWater-sodiumretention

Hypentension;pulmonaryedema;ascitesAcidosis,electrolyteimbalance,BUN↑，Cr↑↑ClinicalManifestations:

PolyuricstageLastforacoupleofdaysuptoweeksCharacterizedbydiuresisandhyposthenuriaMigratorystage:dailyurinevolumeincreasesfrom400mlto2000ml;exacerbationoftheazotemiaEarlypolyuricstage:Dailyurinevolume>2000ml;stabilizationoftheazotemiaLatepolyuricstage:Dailyurinevolume>3000ml;recoveroftheazotemiaFluidreplacementisinadequate→secondaryshockClinicalManifestations:Convalescentstagelastforaslongas1-3monthsDailyurinevolumereturnstonormalClinicalManifestationsWhatarefiveprogressivestagesofHFRS?Febrilestage;Hypotensivestage;Oliguricstage;Polyuricstage;ConvalescentstageLaboratoryfindingsBloodroutinetestLeukocytosiswithaleftshiftElevatedhematocritleverThrombocytopeniaAtypicallymphocytes

Q:ViralinfectionscausingleukocytosisHFRSInfectiousmononucleosisJapaneseencephalitisRabiesLaboratoryfindingsUrineroutinetestHeavyproteinuriaHematuriaCastMassiveproteinandsheddedepithelialcellsinurineformMembrane-likesubstanceLaboratoryfindingsBiochemicaltestsElevatedlevelsofliverenzymes,BUN,andserumcreatinineElectrolytedisturbancesAlteredcoagulationprofileLaboratoryfindingsEtiologicaldiagnosisEnzyme-linkedimmunosorbentassay(ELISA)

①Antihantaviral-specificIgM＞1:20(+)

Earlydiagnosticvalue②Antihantaviral-specificIgG＞1:40(+)

FourfoldorgreaterriseinIgGtitercanalsoconfirmsuspectedcasesIsolationofvirusRT-PCR:identifyviralRNASummaryoftheclinicalfeaturesAtriadoffever,hemorrhage,andrenalinsufficiency5progressivestages:Febrilestage→Hypotensivestage→Oliguricstage→Polyuricstage→ConvalescentstageLaboratoryfinding:

LeukocytosisandthrombocytopeniaProteinuriaElevatedlevelsofBUN,andserumcreatinineComplicationDigestivetractbleedingIntracranialhemorrhagesMyocardialdamagePulmonaryedema:ARDS,heartfailureSecondaryInfectionsSpontaneouskidneyruptureTreatment:overviewEarlyrecognitionandhospitalization,bedrestTreatmentissupportivePreventforsecondaryinfectionPreventtheGIbleedingTreatment:FebrilestageAnti-viraltherapy:IVribavirinPreferablybegunwithinthefirst4daysofillnessReduceexudate:

RutosidsandvitaminCManagementofthefeverandtoxicsymptomsPhysicalcoolingShortcoursedexamethasone

PreventDICTreatment:HypotensivestageSupplementofbloodvolumeModestcrystalloidinfusionHumanserumalbuminPlasmaVasoactiveagentsDopamine,norepinephrineCorrectionofacidosis5%SodiumBicarbonate

InjectionTreatment:OliguricstageMaintenanceofinternalenvironmenthomeostasisRestrictthevolumeofinfusion

Dailyurinevolume+500-700mlControltheazotemiaSupplysufficientcarbohydratetoreducetheproteindegradationMaintainingelectrolytebalance

TreatmentofHyperkalemiaCorrectionofacidosis5%SodiumBicarbonate

InjectionTreatmentofhyperkalemiaStopfurtherpotassiumaccumulationProtectthecardiacmembrane

Calciumgluconate10%ShiftthepotassiumfromthebloodintothecellInsulinRemovalofpotassiumfromthebodyHaemodialysis,FurosemideTreatment:OliguricstageDiuretics:furosemideCatharsis:rheumofficinaleConsiderDialysisinfollowingconditionsSevereazotemiaFluidoverloadthatcannotbemanagedwithdiureticsHyperkalemiarefractorytomedicaltherapySevereacid-basedisturbancesTreatmentPolyuricstageMaintainfluidandelectrolytebalancePreventsecondaryinfection

AntibioticswithnephrotoxicpotentialshouldbeavoidedConvalescentstageMonitoredinresthomePrognosisFatalityraterangesfrom5to15%withHantaanvirustolessthan1%forPuumalavirusinfectionForsurvivors,convalescencecantakeseveralmonthsbutrecoveryisoftencompletePreventionRodentcontrolAvoidcontactwithrodenturine,droppings,saliva,andnestingmaterialsVaccinationHomework1.HantaanvirusismainlytransmittedbyPatientsCarriersSwineMosquitoesRodents（E）Homework2.ThemostcardinalreasonofbleedinginfebrileperiodofEHFisA.DICB.Heparin-likesubstanceincreasingC.Thrombocytopeniaandvascular