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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: three cardinal symptoms: fever, suffusion, bleeding, renal injury.
DEFINITION five clinical phases: febrile period, hypotensive-shock period, oliguric period, diuretic period, convalescent period.
ETIOLOGY 1.Pathogen: EHFV; Hantavirus, the family Bunyaviridae, genus Hantavirus. 2.Morphology: RNA virus, circular or ovoid shape, diameter: 80~115nm.
3. Biologic characteristics: 4. Serotypes: Hantavirus: in world : 11serotypes I type Hantann virus II type Seoul virus III type Puumala virus ETIOLOGY
IV type Prospect hill virus Belgrade - Dobrava virus in china: Hantann virus (wild rat type) Seoul virus (house rat type) ETIOLOGY
EPIDEMIOLOGY 1.Source of infection: rodents Apodemus agrarius Mus norvegicus Apodemus sylvaticus
EPIDEMIOLOGY 2. Routes of transmission respiratory tract spread alimentary tract spread contact transmission spread from mother to child insect - borne
EPIDEMIOLOGY 3. Epidemic features geographic distribution seasonal distribution November~January,March~June distribution of population 20~40 years old male>female
EPIDEMIOLOGY farmer,worker in forest, soldier 4. Susceptibility of population universal susceptibility, stable and persistent immunity subclinical infection:2.5~4.3%
PATHOGENESIS 1. Pathogenesis of disease: direct injury of virus: viremia toxic symptoms serum types difference organs EHFV antigen bone marrow cells, endothelial cells injury
PATHOGENESIS immunity injury : allergic reaction of type III allergic reaction of type I II IV cytokine and medium injury (IL1,TNFa)
PATHOGENESIS 2. Pathogenesis of symptoms: shock: EHFV injury of blood vessels vascular permeability exudation of plasma effective blood volume shock
PATHOGENESIS hemorrhage: vascular injury fragility thrombocytopenia DIC heparin like substance
PATHOGENESIS acute renal failure : glomerular filtration rate immunity injury of kindney cast obstruction in renal tubules interstitial edema pressing renal tubules
PATHOLOGY basic pathologic lesion: extensive lesion of the systemic small blood vessels. internal organs: kidney, heart, brain, liver etc.
PATHOLOGY pathological diagnosis: typical lesion of kidney hemorrhage in right cardiac atrium adenohypophysis lesion retroperitoneal gelatinous edema
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.
CLINICAL MANIFESTATIONS trilogy: anorexia, vomiting, abdominal pain three reds: conjunctival suffusion ; flush over face; flush over neck and upper chest ; drunken face
CLINICAL MANIFESTATIONS hemorrhage mucosa: conjunctivae, palate: petechiae skin: axillary folds, chest and back, petechiae internal organs :
CLINICAL MANIFESTATIONS exudative edema chemosis ; eyelid edema ; renal injury : proteinuria, hematuria or cast.
CLINICAL MANIFESTATIONS 2. hypotension-shock period: 4~6 day after illness, last 1~3 days. hypotension: systolic pressure <90mmHg; shock: systolic pressure <70mmHg
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
CLINICAL MANIFESTATIONS uremia: symptoms of digestive tract : anorexia, nausea, vomiting, diarrhea, hiccup; symptoms of nervous system headache, lethargy dysphoria ect.
CLINICAL MANIFESTATIONS Hemorrhage: petechiae or ecchymosis hemoptysis, hematemesis hematochezia,hematuria, even intracranial bleeding.
CLINICAL MANIFESTATIONS metabolic acidosis : disturbance of water and electrolyte balance: hyperkalemia, hyponatremia, exudative edema : chemosis, edema of eyelid, ascites ect.
CLINICAL MANIFESTATIONS high blood volume syndrome venous engorgement, pulse enlargement, pulse pressure increase, severe edema (heart failure, pulmonary edema) hypertension.
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
CLINICAL MANIFESTATION early period of diuresis 2000ml~3000ml/24h azotemia symptoms late period of diuresis >3000ml/24h dehydration hyponatremia, hypokalemia
CLINICAL MANIFESTATION secondary infection secondary shock 5.convalescent period: (1~3m) urine volume<2000ml
CLINICAL TYPES mild type moderate type severe type dangerous severe type non-typical type
LABORATORY FINDINGS 1. blood routine examination WBC: 15~30×10 9 /L thrombocytopenia heteromorphic lymphocyte
LABORATORY FINDINGS WBC > 50×10 9 /L or leukemoid thrombocytopenia <20×10 9 /L heteromorphic L >15%
LABORATORY FINDINGS 2. Urine routine examination proteinuria hemoturia RBC cast membranoid substance large diffuse cell
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
LABORATORY FINDINGS 4.pathagenic examination isolation of virus PCR: RNA 5.other examination BuN Cr, K Na Cl, DIC etc.
COMPLICATION 1. bleeding of internal organs 2. complications of CNS meningitis or encephalitis brain edema Intracranial bleeding
COMPLICATION 3. pulmonary edema: ARDS pulmonary edema of heart failure 4. Other: liver injury secondary infection, spontaneous rupture of kidney
DIAGNOSIS 1. epidemiologic data 2. clinical features 3. Lab findings : specific IgM antibody specific IgG antibody 4 fold rise PCR: EHFV RNA
DIFFERENTIAL DIAGNOSIS 1. fever: Influenza, septicemia 2. shock: other infectious shock 3. oliguria: acute glomerulonephritis 4.hemorrhage: thrombopenic purpura 5.abdominal pain :
TREATMENT 1. febrile period controlling infection: ribavirin decreasing exudation: liquid treatment: “ balance ” balanced salt solution 1000~1500ml/24h vitamin C 20% mannitol 125~250ml
TREATMENT improvement of toxic symptoms: high fever: physical cooling ect. toxic symptoms: dexamethason prevention of DIC: dextran heparin 0.5~1mg/kg 6~12h
TREATMENT 2. hypotensive period: supplement of blood volume: early, fast, suitable volume. crystalloid solution plus colloidal solution correction of acidosis: 5% NaHCO 3
TREATMENT vaso-active agent: Dopamine: 10~20mg/100ml 654-2: 0.3~0.5mg/kg cardiotonics: cedilanid adrenocortical hormone: Dexamethason 10~20mg
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
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
eccoprotic and phlebotomy: high blood volume syndrome, hyperkalemia, mannitol magnesium rhubarb. TREATMENT
dialysis therapy : BUN >28.56mmol/L BUN> 7.14mmol/L/day high blood volume syndrome K > 6 mmol/L peritoneal dialysis blood dialysis. TREATMENT
4.diuretic period : supplement of fluid and electrolyte, treatment or prevention of secondary infection. 5.convalescent period: supplement of nutrition; rest months. TREATMENT
PREVENTION 1.killing and preventing rats; 2.personal protective measures; 3.vaccine has been utilizing for prevention the disease. 88~94%.
H F R S Hemorrhagic Fever with Renal Syndrome (Epidemic Hemorrhagic Fever)
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