传染病学课件 出血热（英文）

HemorrhagicFeverwithRenalSyndromeepidemichemorrhagicfeverOverview

HFRSincludesagroupofclinicallysimilarillnessesEpidemichemorrhagicfever(China)Koreanhemorrhagicfever(Korean)Nephropathisepidemica(Puumala)OverviewHemorrhagicfeverwithrenalsyndrome(HFRS)iscausedbyanairbornecontact(mainroute)withsecretionsfromrodenthostsinfectedwithhantavirusesfromthefamilyBunyaviridaeOccursmainlyinEuropeandAsia

Characterizedbyfeverandrenalfailureassociatedwithhemorrhagicmanifestations.SupportivetherapyisthemainstayofcareforpatientswithhantavirusinfectionNaturalfocaldiseasesMainClinicalManifestationsfever,hemorrhage,andrenaldamage5progressivestages:Feverstage;Hypotensiveshockstage;Oliguricstage;Polyuricstage;ConvalescentstageVirologyofHantaviruseBelongtothefamilyBunyaviridaeSphericalenvelopedvirusesabout80-120nmindiameterGenomeconsistsofthreesingle-stranded,negativesenseRNAsegments---S,M,LS(small):encodesneucleocapsidproteinM(medium):

encodesenvelopeglycoprotein

L(large):encodespolymeraseHantaviruseG1G2LMS100nmRNASize(bp)ProteinproductsSize(KDa)L6530Polymerase247M3616Coatglycoprotein(G1)68-76Coatglycoprotein(G2)52-58S1696Nucleocapsidprotein50-54Thevirusesthatcausehemorrhagicfeverwithrenalsyndromeinclude:HantaanDobrava-BelgradeSeoulPuumalaSinNombreviruscancause

hantaviruspulmonarysyndrome(America)VirologyofHantaviruseEpidemiology

Sourcesoftransmission:rodentreservoirsVirusspeciesReservoirEpidemic&endemicareasHantaan

Stripedfieldmouse(Apodemus

agrarius)Korea,China,EasternRussiaSeoulNorwayrat(Rattus

norvegicus)WorldwidePuumalaBankvoles(Clethrionomys

glareolus)WesternEuropeDobrava-BelgradeYellow-neckedfieldmouse(Apodemus

flavicollis)BalkansStripedfieldmouse

Norwayrat

Bankvoles

Yellow-neckedfieldmouse

StripedfieldmouseApodemusagrarius

NorwayratRattusnorvegicus,BankvolesClethrionomysglareolusYellow-neckedfieldmouseA.flavicollisEpidemiology

RouteoftransmissionExposuretoaerosolizedurine,droppings,orsalivaofinfectedrodentsDirectintroductionofinfectiousmaterialthroughbrokenskinorontomucousmembranesThroughrodentbitesfrominfectedanimalsFrommothertochildTransmissionfromonehumantoanothermayoccur,butisextremelyrare.EpidemiologySusceptibilityofpopulationPeoplearegenerallysusceptibleCommonlyreportedinmaleadultTotalsubclinicalinfectionrateis2.5~4.3%;InchildrenthediseaseismildandoftensubclinicalStableandpersistentimmunityPathogenesisThepathogenesisislargelyunknownHumancellsinfectedwithhantavirusesdonotdemonstratethecytopathiceffectsofviralreplication

PathogenesisImmunemechanismsplayanimportantroleVirusispresentinbloodonlyduringtheinitialstageofinfectionandisusuallyabsentatthetimethatseveresymptomsbegin

presenceofspecificantibodiesandTcellsattheonsetofsymptomsmarkedcytokineproduction,kallikrein-kininactivation,complementpathwayactivation,orincreasedlevelsofcirculatingimmune

Immunemediatedvascularendothelialinjury

IncreasedcapillarypermeabilityPlasmaextravasationInsufficientbloodvolumePrimaryshockoccursbeforeoliguricstageMassivehemorrhageorSecondaryinfectionorInsufficientwater-electrolytesupplyduringpolyuricstageInsufficientbloodvolumeSecondaryshock:occursafteroliguricstagePathogenesis:shockPathogenesis:hemorrhageDamageofthebloodvesselwallThrombocytopenia

UremicbleedingdefectsIncreaseofheparin–likesubstancesDICDecreasedbloodflowDirectinjurytothekidneyPathogenesis:acuterenalfailure

PathologyBasicpathologicalchanges

Systemicmicrovascularendothelialedema,degenerationandnecrosisThemostdramaticdamageisseeninthekidneysRetroperitonealedemaisseenLargervisceralandcerebralhemorrhagescanoccur(e.g.,myocardium,pituitary)ClinicalManifestations:overviewIncubationperiodvariesfrom4-46days,usually1to2weeksAtriadoffever,hemorrhage,andrenalinsufficiency5progressivestages:Febrilestage;Hypotensivestage;Oliguricstage;Polyuricstage;ConvalescentstageClinicalManifestations:FebrilestageAbruptonsetoffeverlasting3-7daysGastrointestinaldiscomfort

Anorexia,nausea,vomitingandabdominalpain

Systemictoxicsymptoms

Myalgia,triadofpains(Headache,lumbagoandretroorbitalpain)SignsofCapillaryinjury

CongestionHemorrhagictendencyExudationandedemaClinicalManifestations:FebrilestageCapillaryinjury:signsofcongestionDermathemia:triadofflushings

FlushingoverFace,theVareaoftheneck(drunkenface),andthebackMucosalhyperemia

Conjunctivalsuffusion,pharyngealinjectionDrunkenfaceClinicalManifestations:FebrilestageCapillaryinjury:signsofhemorrhagictendencyDermatorrhagia①Petechiaeoftendevelopinareasofpressure,axilla②Ecchymosisinseverecase

Mucosalbleeding

Petechiaeintheconjunctivae,softpalateVisceralbleeding

Epistaxis,bloodystool,hemoptysis,cerebralbleedingPetechiaeonaxillaEcchymosisinseverecaseSubconjunctivalhemorrhagePetechiaeonthesoftpalateClinicalManifestations:FebrilestageCapillaryinjury:SignsofexudationandedemaPeriorbitaledema,chemosisRetroperitonealedemaAsciteschemosisClinicalManifestations:FebrilestageAbruptonsetoffeverlasting3-7daysGastrointestinaldiscomfort

Anorexia,nausea,vomitingandabdominalpain

Systemictoxicsymptoms

Myalgia,triadofpains(Headache,lumbagoandretroorbitalpain)SignsofCapillaryinjury

CongestionHemorrhagictendencyExudationandedemaClinicalManifestations:HypotensivestageLastsapproximatelyafewhoursto2daysExacerbationofthediseaseafterdefervescenceFallingbloodpressureandTachycardiaInseverecaseshock(primaryshock)

ClinicalManifestations:OliguricstageTheoliguriapersistsfor2-5days(maylastingaslongas10days)Oliguria:urineoutput<500ml/dAnuria:urineoutput<50ml/dHemorrhagictendenciescontinueOnsetofrenalfailureSymptomsassociatedwithuremiaAcidosisandelectrolyteimbalanceWater-sodiumretention

Hypentension;pulmonaryedema;ascitesClinicalManifestations:PolyuricstageLastforacoupleofdaysuptoweeksCharacterizedbydiuresisandhyposthenuriaMigratorystage:dailyurinevolumeincreasesfrom500mlto2000ml;exacerbationoftheazotemiaEarlypolyuricstage:Dailyurinevolume>2000ml;stabilizationoftheazotemiaLatepolyuricstage:Dailyurinevolume>3000ml;recoveroftheazotemia

Rapidsignsofdehydrationandsevereshockcanoccurduringthisstageiffluidreplacementisinadequate(secondaryshock)ClinicalManifestations:Convalescentstagelastforaslongas1-3monthsDailyurinevolumereturnstonormalSymptomsbegintoimproveClinicalManifestationsWhatarefiveprogressivestagesofHFRS?Febrilestage;Hypotensivestage;Oliguricstage;Polyuricstage;ConvalescentstageSkippingofphaseiscommoninatypicalandmildindividuals.Theindividualphasesmayoverlapinseverecases.PrognosisFatalityraterangesfrom5to15%withHantaanvirustolessthan1%forPuumalavirusinfectionForsurvivors,convalescencecantakeseveralmonthsbutrecoveryisoftencompleteLaboratoryfindingsBloodroutinetestLeukocytosiswithaleftshiftElevatedhematocritlevelThrombocytopeniaAtypicallymphocytes

UrineroutinetestHeavyproteinuriaHematuriaCastMassiveproteinandsheddedepithelialcellsinurineformMembrane-likesubstanceLaboratoryfindingsBiochemicaltestsElevatedlevelsofliverenzymes,BUN,andserumcreatinine

ElectrolytedisturbancesAlteredcoagulationprofileProlongedprothrombintime(PT)Activatedpartialthromboplastintime(aPTT)orbleedingtimeElevatedfibrin-degradationproductslevelsLaboratoryfindingsEtiologicaldiagnosisEnzyme-linkedimmunosorbentassay(ELISA)

①Antihantaviral-specificIgM＞1:20(+)

Earlydiagnosticvalue②Antihantaviral-specificIgG＞1:40(+)

FourfoldorgreaterriseinIgGtitercanalsoconfirmsuspectedcasesIsolationofvirusRT-PCR:identifyviralRNAComplicationDigestivetractbleedingIntracranialhemorrhagesMyocardialdamagePulmonaryedema:ARDS,heartfailureSecondaryInfectionsspontaneouskidneyruptureDiagnosisEpidemiologicdataComesintocontactwithrodentsthatcarryhantavirusClinicalfeaturesAtriadoffever,hemorrhage,andrenalinsufficiencyFiveprogressivestagesLaboratoryfindingsBloodroutine:leukocytosiswithaleftshift,thrombocytopeniaandatypicallymphocytesUrineroutine:proteinuriaBiochemicaltests:elevatedBUN,andserumcreatinineEtiologicaldiagnosis:specificserumIgMantibodiesTreatment:overviewGenaralprinciplesEarlyadmissiontoanearbyhospitalEarlyrecognitionanddiagnosisofthediseaseEarlyandeffectivetherapy

TreatmentissupportiveStandardprecautionsforinfectioncontrolshouldbeusedwhencaringforpatientsPreventtheGIbleedingwithH2receptorantagonistsorprotonpumpinhibitorTreatment:FebrilestageAnti-viraltherapy:IVribavirinIntravenousribavirin,preferablybegunwithinthefirst4daysofillness,hasbeenshowntoshortenillnessanddecreasetheriskfordeathReduceexudate:

vitaminCImprovetoxicsymptomsPhysicalcoolingShortcoursedexamethasone

PreventDICTreatment:HypotensivestageSupplementofbloodvolumeModestcrystalloidinfusion,IVuseofhumanserumalbuminorplasmaExcessiv