《傳染病學(xué)教學(xué)》7、流行性出血熱ppt課件

1、Hemorrhagic Fever with Renal Syndrome Zhang Dazhi, M.DDepartment of Infectious DiseaseThe second hospital of CMU.OverviewPathogen: Hantaviruses Clinical features: fever；renal failure；shock; hemorrhagic manifestationsHemorrhagic fever with renal syndrome(HFRS) includes a group of clinically similar i

2、llnesses Epidemic hemorrhagic fever(China)Korean hemorrhagic fever(Korean)Nephropathis epidemica(Puumala.Virology of HantaviruseBelong to the family Bun-yaviridaeSpherical enveloped viruses about 80-120 nm in diameterGenome consists of three single-stranded, negative sense RNA segments-S, M, L S (sm

3、all): encodes neucleocapsid protein M (medium): encodes envelope glycoprotein L(large): encodes polymerase.The viruses that cause hemorrhagic fever with renal syndrome include:HantaanDobrava-BelgradeSeoul PuumalaSin Nombre virus can cause hantavirus pulmonary syndrome (America)Virology of Hantavirus

4、e.Epidemiology Sources of transmission: rodent reservoirs Virus speciesReservoirEpidemic & endemic areasHantaan Striped field mouse(Apodemus agrarius) Korea, China, Eastern Russia SeoulNorway rat (Rattus norvegicus) WorldwidePuumalaBank voles (Clethrionomys glareolus)Western Europe Dobrava-Belgr

5、adeYellow-necked field mouse (Apodemus flavicollis)BalkansStriped field mouse Norway rat Bank voles Yellow-necked field mouse pOccurs mainly in Europe and Asia .Striped field mouseApodemus agrarius .Norway rat Rattus norvegicus,.Bank volesClethrionomys glareolus.Yellow-necked field mouseA. flavicoll

6、is.Epidemiology Route of transmissionExposure to aerosolized urine, droppings, or saliva of infected rodentsDirect introduction of infectious material through broken skin or onto mucous membranes Through rodent bites from infected animalsFrom mother to childTransmission from human to human is extrem

7、ely rare.Epizootic CycleRodent breeding.EpidemiologySusceptibility of populationPeople are generally susceptibleCommonly reported in male adultSubclinical infection rate is 2.54.3%Stable and persistent immunity .PathogenesisImmune mechanisms may play an major pathogenic roleViremia is only present i

8、n early stage of infection No cytopathic effectAt the time that severe symptoms begin Viremia is absentSpecific antibodies and T cells are detectedmarked cytokine production, kallikrein-kinin activation, complement pathway activation.PathogenesisBasic pathological changes Systemic microvascular endo

9、thelial edema,degeneration and necrosisThe most dramatic damage is seen in the kidneys.Immune mediated vascular endothelial injury Increased capillary permeabilityPlasma extravasationInsufficient blood volumePrimary shockoccurs before oliguric stageMassive hemorrhageorSecondary infectionorInsufficie

10、nt water-electrolyte supply during polyuric stageInsufficient blood volumeSecondary shock:occurs after oliguric stagePathogenesis: shock.Pathogenesis: hemorrhage tendencyDamage of the blood vessel wallThrombocytopenia Uremic bleeding defectsIncrease of heparinlike substances DIC .Decreased blood flo

11、w Direct injury to the kidneyPathogenesis: acute renal failure . Histopathologic changes in kidney (cortex)Small arrow: interstitial edema with mild infiltration of mononuclear cellsLarge arrow : degeneration of renal tubules Arrow head: proteinaceous casts and exudate. Histopathologic changes in ki

12、dney (medulla) Most prominent change in the medulla is welldefined necrotic lesion (asterisk)*.Intracranial hemorrhage in HFRS patient.Clinical Manifestations: overviewIncubation period: usually 1 to 2 weeksA triad of fever, hemorrhage, and renal insufficiency5 progressive stages: Febrile stage Hypo

13、tensive stage Oliguric stage Polyuric stage Convalescent stageSkipping of phase is common in atypical and mild individuals. The individual phases may overlap in severe cases. .Clinical Manifestations: Febrile stageAbrupt onset of fever lasting 3-7 daysGastrointestinal discomfort Anorexia, nausea , v

14、omiting and abdominal pain Systemic toxic symptoms Myalgia, triad of pains (Headache, lumbago and retroorbital pain).Clinical Manifestations: Febrile stageSigns of Capillary injury Congestion Hemorrhagic tendency Exudation and edema.Clinical Manifestations: Febrile stageCongestionDermathemia: triad

15、of flushings Flushing over Face, the V area of the neck (drunken face), and the backMucosal hyperemia Conjunctival suffusion, pharyngeal injection.Drunken face.Clinical Manifestations: Febrile stageHemorrhagic tendencyDermatorrhagia Petechiae often develop in areas of pressure, axilla Ecchymosis in

16、severe case Mucosal bleeding Petechiae in the conjunctivae, soft palateVisceral bleeding Epistaxis, bloody stool, hemoptysis, cerebral bleeding.Petechiae on axilla.Ecchymosis in severe case.Subconjunctival hemorrhage.Petechiae on the soft palate.Clinical Manifestations: Febrile stageExudation and ed

17、ema cause painPeriorbital edema, chemosis Retroperitoneal edemaAscitesAbdominal pain: Differential diagnosis?.chemosis.Clinical Manifestations: Hypotensive stageLasts approximately a few hours to 2 daysExacerbation of the disease after defervescenceFalling blood pressure and Tachycardia In severe ca

18、se shock (primary shock) .Clinical Manifestations: Oliguric stagePersists for 2-5 days Oliguria: urine output 400 ml /d Anuria: urine out put2000ml; stabilization of the azotemiaLate polyuric stage: Daily urine volume 3000ml; recover of the azotemiaFluid replacement is inadequate secondary shock.Cli

19、nical Manifestations: Convalescent stagelast for as long as 1-3 monthsDaily urine volume returns to normal.Clinical ManifestationsWhat are five progressive stages of HFRS? Febrile stage; Hypotensive stage; Oliguric stage; Polyuric stage; Convalescent stage.Laboratory findingsBlood routine testLeukoc

20、ytosis with a left shiftElevated hematocrit leverThrombocytopeniaAtypical lymphocytes Q:Viral infections causing leukocytosisHFRSInfectious mononucleosisJapanese encephalitisRabies.Laboratory findingsUrine routine testHeavy proteinuriaHematuriaCast.uMassive protein and shedded epithelial cells in ur

21、ine form Membrane-like substance.Laboratory findingsBiochemical testsElevated levels of liver enzymes, BUN, and serum creatinine Electrolyte disturbances Altered coagulation profile.Laboratory findingsEtiological diagnosisEnzyme-linked immunosorbent assay (ELISA) Antihantaviral-specific IgM1:20(+) E

22、arly diagnostic value Antihantaviral-specific IgG1:40(+) Fourfold or greater rise in IgG titer can also confirm suspected casesIsolation of virus RT-PCR: identify viral RNA.Summary of the clinical featuresA triad of fever, hemorrhage, and renal insufficiency5 progressive stages: Febrile stage Hypote

23、nsive stage Oliguric stage Polyuric stage Convalescent stageLaboratory finding: Leukocytosis and thrombocytopenia Proteinuria Elevated levels of BUN, and serum creatinine .ComplicationDigestive tract bleedingIntracranial hemorrhagesMyocardial damagePulmonary edema :ARDS, heart failure Secondary Infe

24、ctions Spontaneous kidney rupture.Treatment: overviewEarly recognition and hospitalization, bed restTreatment is supportivePrevent for secondary infectionPrevent the GI bleeding.Treatment: Febrile stageAnti-viral therapy: IV ribavirin Preferably begun within the first 4 days of illnessReduce exudate

25、: Rutosids and vitamin CManagement of the fever and toxic symptomsPhysical cooling Short course dexamethasone Prevent DIC.Treatment: Hypotensive stageSupplement of blood volumeModest crystalloid infusionHuman serum albuminPlasmaVasoactive agentsDopamine, norepinephrineCorrection of acidosis 5% Sodiu

26、m Bicarbonate Injection.Treatment: Oliguric stageMaintenance of internal environment homeostasis Restrict the volume of infusion Daily urine volume + 500-700mlControl the azotemia Supply sufficient carbohydrate to reduce the protein degradationMaintaining electrolyte balance Treatment of Hyperkalemi

27、aCorrection of acidosis 5% Sodium Bicarbonate Injection.Treatment of hyperkalemiaStop further potassium accumulationProtect the cardiac membrane Calcium gluconate 10%Shift the potassium from the blood into the cell InsulinRemoval of potassium from the body Haemodialysis, Furosemide.Treatment: Oligur

28、ic stageDiuretics: furosemideCatharsis :rheum officinaleConsider Dialysis in following conditionsSevere azotemia Fluid overload that cannot be managed with diureticsHyperkalemia refractory to medical therapySevere acid-base disturbances .TreatmentPolyuric stageMaintain fluid and electrolyte balanceP

29、revent secondary infection Antibiotics with nephrotoxic potential should be avoidedConvalescent stageMonitored in rest home.PrognosisFatality rate ranges from 5 to 15% with Hantaan virus to less than 1% for Puumala virus infectionFor survivors, convalescence can take several months but recovery is o

30、ften complete.PreventionRodent controlAvoid contact with rodent urine, droppings, saliva, and nesting materialsVaccination.Home work1 .Hantaan virus is mainly transmitted byPatients Carriers Swine Mosquitoes RodentsE.Home work2 .The most cardinal reason of bleeding in febrile period of EHF is A. DICB. Heparin-like substance increasingC. Thrombocytopenia and vas