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EPIDEMIC HEMORRHAGIC FEVER ( Hemorrhagic fever with renal syndrome )

EPIDEMIC HEMORRHAGIC FEVER ( Hemorrhagic fever with renal syndrome ). Department of infectious disease Huang Fen. DEFINITION. 1. The disease is caused by hantan virus, hemorrhagic fever with renal syndrome (HFRS) 2. The clinical characteristic:

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EPIDEMIC HEMORRHAGIC FEVER ( Hemorrhagic fever with renal syndrome )

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  1. EPIDEMIC HEMORRHAGIC FEVER( Hemorrhagic fever with renal syndrome ) Department of infectious disease Huang Fen

  2. DEFINITION 1. The disease is caused by hantan virus, hemorrhagic fever with renal syndrome (HFRS) 2. The clinical characteristic: three cardinal symptoms: fever, suffusion, bleeding, renal injury.

  3. DEFINITION five clinical phases: febrile period, hypotensive-shock period, oliguric period, diuretic period , convalescent period .

  4. ETIOLOGY 1.Pathogen:EHFV; Hantavirus, the family Bunyaviridae, genus Hantavirus. 2.Morphology: RNA virus, circular or ovoid shape, diameter: 80~115nm.

  5. ETIOLOGY 3. Biologic characteristics: 4. Serotypes: Hantavirus: • in world : 11serotypes I type Hantann virus II type Seoul virus III type Puumala virus

  6. ETIOLOGY IV type Prospect hill virus Belgrade - Dobrava virus • in china: Hantann virus (wild rat type) Seoul virus (house rat type)

  7. EPIDEMIOLOGY 1.Source of infection: rodents Apodemus agrarius Mus norvegicus Apodemus sylvaticus

  8. EPIDEMIOLOGY 2 . Routes of transmission • respiratory tract spread • alimentary tract spread • contact transmission • spread from mother to child • insect - borne

  9. EPIDEMIOLOGY 3. Epidemic features • geographic distribution • seasonal distribution November~January,March~June • distribution of population • 20~40 years old • male>female

  10. EPIDEMIOLOGY • farmer,worker in forest, soldier 4. Susceptibility of population • universal susceptibility, • stable and persistent immunity • subclinical infection:2.5~4.3%

  11. PATHOGENESIS 1. Pathogenesis of disease: • direct injury of virus: viremia toxic symptoms serum types difference organs EHFV antigen bone marrow cells, endothelial cells injury

  12. PATHOGENESIS • immunity injury : • allergic reaction of type III • allergic reaction of type I II IV • cytokine and medium injury (IL1 ,TNFa)

  13. PATHOGENESIS 2. Pathogenesis of symptoms: • shock: EHFV injury of blood vessels vascular permeability exudation of plasma effective blood volume shock

  14. PATHOGENESIS • hemorrhage: vascular injury fragility thrombocytopenia DIC heparin like substance

  15. PATHOGENESIS • acute renal failure : glomerular filtration rate immunity injury of kindney cast obstruction in renal tubules interstitial edema pressing renal tubules

  16. PATHOLOGY • basic pathologic lesion: extensive lesion of the systemic small blood vessels. • internal organs: kidney, heart , brain , liver etc.

  17. PATHOLOGY • pathological diagnosis: • typical lesion of kidney • hemorrhage in right cardiac atrium • adenohypophysis lesion • retroperitoneal gelatinous edema

  18. CLINICAL MANIFESTATIONS Incubation period:4~46 days, usually 7~14 days. 1. febrile period: fever, suffusion and bleeding, renal impairment. • fever: 3~7 days. • three pains : headache; lumbago; orbital pain.

  19. CLINICAL MANIFESTATIONS • trilogy: anorexia, vomiting, abdominal pain • three reds: conjunctival suffusion ; flush over face; flush over neck and upper chest ; drunken face

  20. CLINICAL MANIFESTATIONS • hemorrhage mucosa: conjunctivae, palate: petechiae skin: axillary folds, chest and back, petechiae internal organs :

  21. CLINICAL MANIFESTATIONS • exudative edema chemosis ; eyelid edema ; • renal injury : proteinuria , hematuria or cast .

  22. CLINICAL MANIFESTATIONS 2. hypotension-shock period: 4~6 day after illness , last 1~3 days. hypotension: systolic pressure <90mmHg; shock: systolic pressure <70mmHg

  23. CLINICAL MANIFESTATIONS 3. oliguric period about 5~8 days , last 2~5d; oliguria: urine volume in 24h<500 ml anuria: urine volume in 24h <50 ml

  24. CLINICAL MANIFESTATIONS • uremia: • symptoms of digestive tract : anorexia, nausea, vomiting, diarrhea, hiccup; • symptoms of nervous system headache, lethargy dysphoria ect.

  25. CLINICAL MANIFESTATIONS • Hemorrhage: petechiae or ecchymosis hemoptysis , hematemesis hematochezia ,hematuria, even intracranial bleeding.

  26. CLINICAL MANIFESTATIONS • metabolic acidosis : • disturbance of water and electrolyte balance: hyperkalemia, hyponatremia, exudative edema : chemosis , edema of eyelid, ascites ect.

  27. CLINICAL MANIFESTATIONS • high blood volume syndrome • venous engorgement , • pulse enlargement, • pulse pressure increase, • severe edema (heart failure, pulmonary edema) • hypertension .

  28. CLINICAL MANIFESTATIONS 4 .diuretic period 9-14 d after illness, lasts 7~14 d diuresis: urine volume >2000ml/24h. • transitional phase urine volume : 500~2000ml/24h azotemia symptoms

  29. CLINICAL MANIFESTATION • early period of diuresis 2000ml~3000ml/24h azotemia symptoms • late period of diuresis >3000ml/24h • dehydration • hyponatremia, hypokalemia

  30. CLINICAL MANIFESTATION • secondary infection • secondary shock 5.convalescent period: (1~3m) urine volume<2000ml

  31. CLINICAL TYPES • mild type • moderate type • severe type • dangerous severe type • non-typical type

  32. LABORATORY FINDINGS 1. blood routine examination WBC: 15~30×109/L thrombocytopenia heteromorphic lymphocyte

  33. LABORATORY FINDINGS • WBC > 50×109/L or leukemoid • thrombocytopenia <20×109/L • heteromorphic L >15%

  34. LABORATORY FINDINGS 2. Urine routine examination • proteinuria • hemoturia RBC • cast • membranoid substance • large diffuse cell

  35. LABORATORY FINDINGS 3. serological examination • specific antigen serum, WBC, urine cell. direct immunofluorescence, ElisA • specific antibody IgM antibody 1:20 positive IgG antibody 1:40 positive four fold rise

  36. LABORATORY FINDINGS 4.pathagenic examination • isolation of virus • PCR: RNA 5.other examination BuN Cr, K Na Cl, DIC etc.

  37. COMPLICATION 1. bleeding of internal organs 2. complications of CNS • meningitis or encephalitis • brain edema • Intracranial bleeding

  38. COMPLICATION 3. pulmonary edema: • ARDS • pulmonary edema of heart failure 4 . Other: • liver injury • secondary infection, • spontaneous rupture of kidney

  39. DIAGNOSIS 1. epidemiologic data 2. clinical features 3. Lab findings : specific IgM antibody specific IgG antibody 4 fold rise PCR: EHFV RNA

  40. DIFFERENTIAL DIAGNOSIS 1. fever: Influenza, septicemia 2. shock: other infectious shock 3. oliguria: acute glomerulonephritis 4.hemorrhage: thrombopenic purpura 5.abdominal pain :

  41. TREATMENT 1. febrile period • controlling infection: ribavirin • decreasing exudation: • liquid treatment: “balance” balanced salt solution 1000~1500ml/24h • vitamin C • 20% mannitol 125~250ml

  42. TREATMENT • improvement of toxic symptoms: • high fever: physical cooling ect. • toxic symptoms: dexamethason • prevention of DIC: • dextran • heparin 0.5~1mg/kg 6~12h

  43. TREATMENT 2. hypotensive period: • supplement of blood volume: early, fast, suitable volume. crystalloid solution plus colloidal solution • correction of acidosis: 5% NaHCO3

  44. TREATMENT • vaso-active agent: Dopamine: 10~20mg/100ml 654-2: 0.3~0.5mg/kg • cardiotonics: cedilanid • adrenocortical hormone: Dexamethason 10~20mg

  45. TREATMENT 3.oliguric period : • Stabilization of internal environment • control of azotemia: Glucose 200g~300g/day • maintaining fluid-electrolyte balance limitation of liquid: urine volume + 500~700ml electrolyte: K Na Cl

  46. TREATMENT • maintaining acid-base balance: • stabilization of blood pressure: • diuresis: early phase: 20%mannitol 125ml Furosemide: 40~100mg/time 654-2: 10~20mg ivdrop, 2~3time/d

  47. TREATMENT • eccoprotic and phlebotomy: high blood volume syndrome, hyperkalemia, mannitol magnesium rhubarb.

  48. TREATMENT • dialysis therapy : • BUN >28.56mmol/L BUN> 7.14mmol/L/day • high blood volume syndrome • K > 6 mmol/L • peritoneal dialysis • blood dialysis.

  49. TREATMENT 4.diuretic period : • supplement of fluid and electrolyte, • treatment or prevention of secondary infection . 5.convalescent period: supplement of nutrition; rest 1 - 2 months.

  50. PREVENTION 1.killing and preventing rats; 2.personal protective measures; 3.vaccine has been utilizing for prevention the disease . 88~94%.

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