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

EPIDEMIOLOGY3. 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: 15~30×109/L thrombocytopenia heteromorphic lymphocyte

LABORATORY FINDINGS

WBC > 50×109/L or leukemoid

thrombocytopenia <20×109/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 FINDINGS4.pathagenic examination

isolation of virus PCR: RNA

5.other examination BuN Cr, K Na Cl, DIC etc.

COMPLICATION

1. bleeding of internal organs2. 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% NaHCO3

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 in

fection .5.convalescent period: supplement of nutrition; rest 1 - 2 months.

TREATMENT

PREVENTION

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