1、Hemorrhagic Fever with Renal Syndrome Department of Infectious DiseaseThe second hospital of CMU整理課件OverviewPathogen: Hantaviruses Clinical features: fever；renal failure；shock; hemorrhagic manifestationsHemorrhagic fever with renal syndrome(HFRS) includes a group of clinically similar illnesses nEpi

2、demic hemorrhagic fever(China)nKorean hemorrhagic fever(Korean)nNephropathis epidemica(Puumala整理課件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, Ln S (small):

3、encodes neucleocapsid proteinn M (medium): encodes envelope glycoproteinn L(large): encodes polymerase整理課件The viruses that cause hemorrhagic fever with renal syndrome include:nHantaannDobrava-BelgradenSeouln PuumalaSin Nombre virus can cause hantavirus pulmonary syndrome (America)Virology of Hantavi

4、ruse整理課件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

5、-BelgradeYellow-necked field mouse (Apodemus flavicollis)BalkansStriped field mouse Norway rat Bank voles Yellow-necked field mouse pOccurs mainly in Europe and Asia 整理課件Striped field mouseApodemus agrarius 整理課件Norway rat Rattus norvegicus,整理課件Bank volesClethrionomys glareolus整理課件Yellow-necked field

6、 mouseA. flavicollis整理課件Epidemiology Route of transmissionnExposure to aerosolized urine, droppings, or saliva of infected rodentsnDirect introduction of infectious material through broken skin or onto mucous membranes nThrough rodent bites from infected animalsnFrom mother to childnTransmission fro

7、m human to human is extremely rare.整理課件Epizootic CycleRodent breeding整理課件EpidemiologySusceptibility of populationnPeople are generally susceptiblenCommonly reported in male adultnSubclinical infection rate is 2.54.3%nStable and persistent immunity 整理課件PathogenesisImmune mechanisms may play an major

8、pathogenic rolenViremia is only present in early stage of infection No cytopathic effectnAt the time that severe symptoms begin Viremia is absentSpecific antibodies and T cells are detectedmarked cytokine production, kallikrein-kinin activation, complement pathway activation整理課件PathogenesisBasic pat

9、hological changes Systemic microvascular endothelial edema,degeneration and necrosisThe most dramatic damage is seen in the kidneys整理課件Immune mediated vascular endothelial injury Increased capillary permeabilityPlasma extravasationInsufficient blood volumePrimary shockoccurs before oliguric stageMas

10、sive hemorrhageorSecondary infectionorInsufficient water-electrolyte supply during polyuric stageInsufficient blood volumeSecondary shock:occurs after oliguric stagePathogenesis: shock整理課件Pathogenesis: hemorrhage tendencyDamage of the blood vessel wallThrombocytopenia Uremic bleeding defectsIncrease

11、 of heparinlike substances DIC 整理課件Decreased blood flow Direct injury to the kidneyPathogenesis: acute renal failure 整理課件 Histopathologic changes in kidney (cortex)Small arrow: interstitial edema with mild infiltration of mononuclear cellsLarge arrow : degeneration of renal tubules Arrow head: prote

12、inaceous casts and exudate整理課件 Histopathologic changes in kidney (medulla) Most prominent change in the medulla is welldefined necrotic lesion (asterisk)*整理課件Intracranial hemorrhage in HFRS patient整理課件Clinical Manifestations: overviewIncubation period: usually 1 to 2 weeksA triad of fever, hemorrhag

13、e, and renal insufficiency5 progressive stages: Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stageSkipping of phase is common in atypical and mild individuals. The individual phases may overlap in severe cases. 整理課件Clinical Manifestations: Febrile stageAbrupt onset of f

14、ever lasting 3-7 daysGastrointestinal discomfort Anorexia, nausea , vomiting and abdominal pain Systemic toxic symptoms Myalgia, triad of pains (Headache, lumbago and retroorbital pain)整理課件Clinical Manifestations: Febrile stageSigns of Capillary injuryn Congestionn Hemorrhagic tendencyn Exudation an

15、d edema整理課件Clinical Manifestations: Febrile stageCongestionnDermathemia: triad of flushings Flushing over Face, the V area of the neck (drunken face), and the backnMucosal hyperemia Conjunctival suffusion, pharyngeal injection整理課件Drunken face整理課件Clinical Manifestations: Febrile stageHemorrhagic tend

16、encynDermatorrhagia Petechiae often develop in areas of pressure, axilla Ecchymosis in severe case nMucosal bleeding Petechiae in the conjunctivae, soft palatenVisceral bleeding Epistaxis, bloody stool, hemoptysis, cerebral bleeding整理課件Petechiae on axilla整理課件Ecchymosis in severe case整理課件Subconjuncti

17、val hemorrhage整理課件Petechiae on the soft palate整理課件Clinical Manifestations: Febrile stageExudation and edema cause painnPeriorbital edema, chemosis nRetroperitoneal edemanAscitespAbdominal pain: Differential diagnosis?整理課件chemosis整理課件Clinical Manifestations: Hypotensive stageLasts approximately a few

18、 hours to 2 daysExacerbation of the disease after defervescenceFalling blood pressure and Tachycardia In severe case shock (primary shock) 整理課件Clinical Manifestations: Oliguric stagePersists for 2-5 days Oliguria: urine output 400 ml /d Anuria: urine out put2000ml; stabilization of the azotemianLate

19、 polyuric stage: Daily urine volume 3000ml; recover of the azotemiaFluid replacement is inadequate secondary shock整理課件Clinical Manifestations: Convalescent stagelast for as long as 1-3 monthsDaily urine volume returns to normal整理課件Clinical ManifestationsWhat are five progressive stages of HFRS? Febr

20、ile stage; Hypotensive stage; Oliguric stage; Polyuric stage; Convalescent stage整理課件Laboratory findingsBlood routine testnLeukocytosis with a left shiftnElevated hematocrit levernThrombocytopenianAtypical lymphocytes Q:Viral infections causing leukocytosisuHFRSuInfectious mononucleosisuJapanese ence

21、phalitisuRabies整理課件Laboratory findingsUrine routine testnHeavy proteinurianHematurianCast整理課件uMassive protein and shedded epithelial cells in urine form Membrane-like substance整理課件Laboratory findingsBiochemical testsnElevated levels of liver enzymes, BUN, and serum creatinine n Electrolyte disturban

22、cesn Altered coagulation profile整理課件Laboratory findingsEtiological diagnosisnEnzyme-linked immunosorbent assay (ELISA) Antihantaviral-specific IgM1:20(+) Early diagnostic value Antihantaviral-specific IgG1:40(+) Fourfold or greater rise in IgG titer can also confirm suspected casesnIsolation of viru

23、s nRT-PCR: identify viral RNA整理課件Summary of the clinical featuresA triad of fever, hemorrhage, and renal insufficiency5 progressive stages: Febrile stage Hypotensive stage Oliguric stage Polyuric stage Convalescent stageLaboratory finding:n Leukocytosis and thrombocytopenian Proteinurian Elevated le

24、vels of BUN, and serum creatinine 整理課件ComplicationDigestive tract bleedingIntracranial hemorrhagesMyocardial damagePulmonary edema :ARDS, heart failure Secondary Infections Spontaneous kidney rupture整理課件Treatment: overviewEarly recognition and hospitalization, bed restTreatment is supportivePrevent

25、for secondary infectionPrevent the GI bleeding整理課件Treatment: Febrile stageAnti-viral therapy: IV ribavirin Preferably begun within the first 4 days of illnessReduce exudate: Rutosids and vitamin CManagement of the fever and toxic symptomsnPhysical cooling nShort course dexamethasone Prevent DIC整理課件T

26、reatment: Hypotensive stageSupplement of blood volumenModest crystalloid infusionnHuman serum albuminnPlasmaVasoactive agentsnDopamine, norepinephrineCorrection of acidosisn 5% Sodium Bicarbonate Injection整理課件Treatment: Oliguric stageMaintenance of internal environment homeostasis nRestrict the volu

27、me of infusion Daily urine volume + 500-700mlnControl the azotemia Supply sufficient carbohydrate to reduce the protein degradationnMaintaining electrolyte balance Treatment of HyperkalemianCorrection of acidosis 5% Sodium Bicarbonate Injection整理課件Treatment of hyperkalemiaStop further potassium accu

28、mulationProtect the cardiac membrane Calcium gluconate 10%Shift the potassium from the blood into the cell InsulinRemoval of potassium from the body Haemodialysis, Furosemide整理課件Treatment: Oliguric stageDiuretics: furosemideCatharsis :rheum officinaleConsider Dialysis in following conditionsnSevere

29、azotemia nFluid overload that cannot be managed with diureticsnHyperkalemia refractory to medical therapynSevere acid-base disturbances 整理課件TreatmentPolyuric stageMaintain fluid and electrolyte balancePrevent secondary infection Antibiotics with nephrotoxic potential should be avoidedConvalescent st

30、ageMonitored in rest home整理課件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 often complete整理課件PreventionRodent controlAvoid contact with rodent urine, droppings, saliva, an

31、d nesting materialsVaccination整理課件Home work1 .Hantaan virus is mainly transmitted byA. Patients B. Carriers C. Swine D. Mosquitoes E. Rodents（E）整理課件Home work2 .The most cardinal reason of bleeding in febrile period of EHF is A. DICB. Heparin-like substance increasingC. Thrombocytopenia and vascular injuryD. Azo