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

3. 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.

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

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

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

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

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

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

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

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

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

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

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

15. PATHOGENESIS  hemorrhage: vascular injury fragility thrombocytopenia DIC heparin like substance

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

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

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

19. 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.

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

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

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

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

24. 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

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

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

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

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

29. 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

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

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

32. CLINICAL TYPES  mild type  moderate type  severe type  dangerous severe type  non-typical type

33. LABORATORY FINDINGS 1. blood routine examination WBC: 15~30×10 9 /L thrombocytopenia heteromorphic lymphocyte

34. LABORATORY FINDINGS WBC > 50×10 9 /L or leukemoid thrombocytopenia <20×10 9 /L heteromorphic L >15%

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

36. 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

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

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

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

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

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

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

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

44. TREATMENT 2. hypotensive period:  supplement of blood volume: early, fast, suitable volume. crystalloid solution plus colloidal solution  correction of acidosis: 5% NaHCO 3

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

46. 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 TREATMENT

47.  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 TREATMENT

48.  eccoprotic and phlebotomy: high blood volume syndrome, hyperkalemia, mannitol magnesium rhubarb. TREATMENT

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

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

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