1. Hemorrhagic Fever with Renal Syndrome Department of Infectious Diseases Third Affiliated Hospital of Sun Yat-sen University Lin Yang

3. Epidemic Hemorrhagic Fever ( EHF) Suggested name by WHO in 1982: Hemorrhagic Fever with Renal Syndrome (HFRS)

4. Hantan virus ▲ Member of the family of Bunyaviridae ▲ Feature of virus Single-strand negative RNA virus Circular or oval in shape 78~210 nm in diameter Envelope proteins:glycoprotein1(G1) glycoprotein2(G2) Viral genome—RNA : L M S gene ■ Etiology

6. ▲ Serologic type of Hantan virus Over twenty serologic types hantaan virus (type I, HTNV) seoul virus(type II, SEOV) puumala virus (type III,PUUV) prospect hill virus(type IV,PHV) dobrava-belgrade virus (DEOV)

7. Human HFRS : caused by four type of virus: hantaan virus (type I, HTNV) seoul virus(type II, SEOV) puumala virus (type III,PUUV) dobrava-belgrade virus(DEOV) China: Hantaan virus Seoul virus hantaan virus and DEOV show stronger pathogenecity than type II and III virus

8. ▲ Resistance of virus Low resistance: Inactivated by acid (<pH 5.0), ethanol, ether, chloroform. heat in 56 ºC for 30min or 100ºC for 1min. Be sensitive to alcohol ultraviolet rays

9. ■ Epidemiology 1. Sources of infection ▶ In our country: Apodemus agrarius Mus norvegicus Apodemus sylvaticus Citellus undulatus ▶ Laboratory Rats ▶ Other animals: cats dogs rabbits Patients:unimportant Infected field rats, house rats

10. Apodemus agrarius Mus norvegicus

16. ■ Pathogenesis Pathogenesis of HFRS is not so clear. ▲ Virus is the initiator ▲ Immune responses, humoral and cellular immune response,both involves in the pathogenesis

17. 1.Direct damage by Hantan virus Virus infection---replication in infected cells, especially in endotheliocytes of small blood vessels---damage on cells. 2. Immune-mediated damage Type III,I,II, and IV hypersensitivity reactions; CTL reaction-mediated damage; Cytokine-mediated cells damage

18. 1>Type III hypersensitivity reaction Hantan virus infection—induce specific antibodies—immune complex-activating complements-accumulation of immune complex in small blood vessels, basement of glomerulus and renal tubule--- damage

19. 2> Other hypersensitivity reaction Type I--IgE mediated damage. Type II-- linear IgG immune complex–accumulation in platelet and basement membranes of renal tubule Type IV— CD8+ cell mediated immune damage.

20. 3>.Cellular immune response: Hantan virus infection –activation of CD8 + T cells—CTL response–release lymphokines — damage 4>. Hantan virus—lymphocyte and macrophage—cytokins: such as interleukin1(IL-1), IFNr, tumor necrosis factor(TNF)—damage

38. Patient with HFRS

39. Patient with HFRS: petechia, ecchymosis

47. 2>. Early stage of diuretic phase u rine volume > 2000ml/24h no marked decrease in azotemia 3>. Late stage of diuretic phase a. urine volume > 3000ml/24h in most of cases: 4000 to 8000/24h, 15000ml/24h b. azotemia improving, BUN falling down c. Secondary shock, dehydration hypokalemia, hyponatremia

61. 2. Complication in central nervous system Encephalitis and meningitis Intracrania hemorrhage and cerebral edema

68. ■ Differential diagnosis 1. In febrile phase with common cold, influenza, Septicemia . 2. In Hypotensive phase with other infection shock 3. P yrexia, intracrania hemorrhage and cerebral edema with meningococcal meningitis

69. 4.Oliguria and renal failure with acute nephritis 5.Pyrexia and hemorrhage with Leptospirosis 6. Marked hemorrhage with: thrombocytopenic purpura, gastrointestinal bleeding caused by gastric ulcer .

72. ▲ Treatment  Supportive treatment  Anti-viral therapy  Symptomatic treatment

74. 2. Treatment in febrile phase Principle of treatment a>.Anti-virus therapy b>.Reduce exudation of plasma c>.Reduce intoxicating symptoms d>.Preventing from DIC

75. 1 >.Anti-viral therapy: important giving anti-virus drug in early stage. (Ribavirin(virazole) 1.0g iv drip with 10%GS qd for 3-5 days 2>.Reduce permeability of small vessel and exudation Lutin and Vitamin C

77. 4>.Prevention from DIC a>. Reduce the blood viscosity Danshen solution, Dextran 40 b>. anti-coagulation therapy Heparin should be given once the CT is less than 3 min or APTT less than 34 seconds.

78. 3.Treatment in Hypotensive phase Principle of treatment: ► Supplement blood volume ► Correct acidosis 1>.Supplement blood volume A.Principle: early rapidly adequate

79. 1>.Supplement blood volume A.Principle: early rapidly adequate B:kinds of fluids: Crystalloid fluids and Colloid fluids containing suitable glucose, electrolytes and vitamins: Ringer’s Solution Normal saline solution Dextran, 20% Mannitol Plasma, albumin, Artificial plasma.

80. 2>Correct metabolic acidosis 5% sodium bicarbonate solution. The amount calculated according to CO 2 CP value. 3>.Blood vessel activating drugs for hypotension and shock: aramine, dopamine, 654-2

81. 4>.Corticosteroids Reduce severe toxemia, Reduce permeation of small vessel Improving microcirculation of tissue. 10~20mg of Dexamethason is given by intravenous drip.

82. 4.Treatment in oliguric phase Principle of treatment : ► Balance intra-environment ► Diuretic therapy ► Catharsis therapy for preventing from hypervolemia ► Dialysis therapy

83. 1>.Balance intra-environment a>.Correct imbalance of fluid electrolytes, acid- base Closely observe and record urine volume. Examine blood biochemical parameter and renal function adjusting amount of fluid and electrolytes

84. b>. Reducing protein degradation and control of azotemia. Food containing high vitamins high carbohydrate, low protein. For the serious patient : Supplement glucose 200~300g every day by intravenous drip 20-25% GS with insulin.

85. 2>.Diuretic for oliguria 20%Mannitol solution. lasix (furosemide) 3>Catharsis therapy for hypervolemia inducing diarrhea to take out fluids by intestinal. 50% Magnesium Sulfate solution 20%Mannitol solution

86. Reducing blood volume therapy For hypervolemia with cardiac failure and pulmonary edema, taking out 300ml ~400ml blood may be useful. used rare now

89. 5 . Treatment in Diuretic phase a. Keeping balance of fluid and electrolytes. b.Preventing and treatment secondary infection: antibiotics

90. 6.Convalescent phase a:Supplement nutrition food. b:Examination renal function, blood pressure, pituitary function at regular interval.

91. 7.Complications treatment 1>. Hemostatics therapy for heavy bleeding such as gastrointestinal hemorrhage treatment of DIC: according to different phase of DIC, giving EACA, protamine ,respectively.

92. 2>.Treatment ARDS a: Control of amount of intravenous infusion. b: Giving oxygen, or mechanical ventilation: positive end expiratory pressure. c.Corticosteroids: 20 to 30mg of dexamethasone d. Cedilanid for cardiac failure.

93. 3>.Treatment of central nervous system complications a> Diazepam for tics b>.Cerebral edema and high intracranial pressure: 20% of mannitol or/and lasix dripped intravenously.

94. 4>. Prevention and treatment of secondary infections: Antibiotics 5>. Spontaneous rupture of the kidneys Surgery therapy

97. THANKS!!!

102. THANKS!!!