Epidemic hemorrhagic fever

Introduction to epidemic hemorrhagic fever Epidemic hemorrhagic fever (epidemichemorrhagicfever, EHF) is a natural epidemic disease caused by viruses. In 1982, the World Health Organization (WHO) named hemorrhagicfever withrenalsyndromes (HFRS). The main pathological changes of this disease are extensive damage of small blood vessels and capillaries, clinical fever, hypotension, hemorrhage, and kidney damage. Etc. basic knowledge The proportion of illness: 0.0035% Susceptible people: no specific population Mode of infection: respiratory tract transmission, digestive tract transmission, contact transmission Complications: shock meningitis consciousness disorder pulmonary edema pleural effusion sepsis arrhythmia dehydration

Epidemic hemorrhagic fever

Virus infection (90%)

The pathogen of epidemic hemorrhagic fever is the Hanta virus (HV) virus of Bunyav'iridae. The pathogens that cause hemorrhagic fever of renal syndrome include Hantavirus of Hantavirus (Hantaan). Virus, HTNV), Seoul virus (SEOV), Puumala virus (PUUV), and Belgrade-Dobrava virus (BDOV), China's epidemic hemorrhagic fever Mainly caused by Hantavirus and Seoul virus, the Pumara virus mainly causes nephropathic epidemica (NE) in Europe, and the Belgrade-Dobrava virus causes more severe HFRS in Southeast Europe.

The epidemic hemorrhagic fever virus is a single-stranded negative-strand RNA virus. The shape is round or oval, with a double-layered envelope and a fiber on the outer membrane. The average diameter is 120 nm. The gene RNA can be divided into large and medium. The three small fragments, L, M and S, have molecular weights of 2.7×106, 1.2×106 and 0.6×106, respectively. Fingerprint analysis shows that the three fragments of viral RNA are unique and different strains, among which S The gene contains 1696 nucleotides and encodes a nucleocapsid protein (containing nuclear protein NP). The M gene contains 3,616 nucleotides and encodes an envelope glycoprotein, which can be divided into G1 and G2. The 1 gene encodes a polymerase with 6533 Nucleotide, nucleocapsid protein (containing nuclear protein NP) is one of the main structural proteins of the virus, which encapsulates various gene fragments of the virus, and the G1 and G2 glycoproteins constitute the envelope of the virus.

The nucleotide sequence of the M and S gene fragments of the isolated Hantavirus A9 strain in China is 84.57% homologous to the representative strain 76-118, and the amino acid homology is 96.83%. Seoul virus R22, HB55 The nucleotide homology between the strain and the representative strain Seoul, 80-39 strains were 95.3% and 95.6%, respectively, and the amino acid homology was 98.9% and 99.4%, respectively. In recent years, at least eight subtypes of HTNV have been found in China. SEOV has six subtypes and even found new genotype viruses, which may be related to gene rearrangement between Hantaviruses. Experiments have confirmed that gene rearrangements can occur between Hantavirus and Seoul virus.

The nuclear protein of epidemic hemorrhagic fever virus has strong immunogenicity and stable antigenic determinant. It is generally considered that nuclear protein contains complement-binding antigen, but does not contain neutralizing antigen. The host protein has the earliest nucleoprotein antibody, and the disease course is the first. It can be detected in 2 to 3 days, which is conducive to early diagnosis. The membrane protein contains neutralizing antigen and hemagglutination antigen, but the group-specific neutralizing antigen and hemagglutination antigen are mainly present on G2 protein, because the membrane protein has blood. The clotting activity produces low pH-dependent cell fusion, which may play an important role in adhering the virus particles to the cell surface of the infected host and subsequently entering the cytoplasm of the virus nucleating shell.

The pathogenicity of viruses carried by different hosts varies greatly, which is related to the type of host animals. In recent years, more and more data indicate that each known Hantavirus is mainly associated with a single mouse species, some As a "primary host", there is a long-term co-evolution relationship between various Hantaviruses and their unique original hosts. Jeor et al. repeatedly captured and released the same rodent vaccinated with Hantavirus and observed the natural poison in the body. In the case, it was found that the same strain of virus in the same type of rodent, during the whole process of capturing and releasing two or more, the isolated viral gene, whether M fragment, S fragment or non-coding region fragment, is completely identical, but Different species of rodents were inoculated with the same strain of virus, and the sequence of the above gene fragments was changed. Kariwa et al. also found that the Seoul virus strain isolated from the brown rats was found in different ages, and the G1 and G2 amino acid homology was greater than 99.7%. Hantavirus has its special host animal dependence. Secondly, the virulence of Hantavirus is also related to the gene of the virus itself, mainly the product encoded by the M fragment, sugar. Protein I (G1) and glycoprotein 2 (G2), different serotypes of Hantavirus, G1 coding region homology is lower than G2, cross-reaction between McAb against G1 and each serotype virus is significantly less than G2, indicating The G1 region is a coding-type antigenic determinant, while G2 is a group-specific antigenic determinant. In Bunia virus G1 is the main factor determining viral virulence and infectivity, and the homo-virus gene fragment is rearranged (rearrangment). The formation of virus mutations, changes in viral protein glycosylation patterns and gene mutations can cause changes in viral virulence. In addition, human genes play an important role in the interaction between viruses and organisms. Mustonen et al. HLA typing, found that the detection rate of HLA-B8 and DRBI0301 alleles in severe patients was significantly higher than that in the control group, in which the detection rate of shock patients was 100% (7/7), and those who needed dialysis for acute renal failure 13 For example, 9 cases (69%) were positive for HLA-B8, 8 cases were positive for DRBI0301 (62% for control group and 15% for control group). Hantavirus alleles may cause infection with Hantavirus to enhance or cause abnormal immune response. related.

Epidemic hemorrhagic fever virus is sensitive to ether solvent such as ether, chloroform, acetone and deoxycholate. It is relatively stable at 420°C, easy to inactivate above 37°C and below pH5.0, 56°C 30min or 100°C 1min. Inactivated, sensitive to UV, ethanol and iodine.

Pathogenesis

1. Pathogenesis The pathogenesis of this disease is still not fully understood. Most studies suggest that Hantavirus is the initiator of the disease. On the one hand, viral infection can cause damage to the function and structure of infected cells; It induces the immune response of the human body and the release of various cytokines, which not only has the effect of clearing the infected virus, protecting the body, but also causing damage to the body tissues.

It is generally believed that Hantavirus enters the human body and then reaches the whole body with blood flow. The virus first combines with the receptor p3 integrin expressed on the surface of platelets, endothelial cells and monocytes, and then enters the cells as well as liver, spleen, lung, kidney, etc. The tissue, after further replication, is released into the bloodstream, causing viremia, resulting in cell degeneration, necrosis or apoptosis due to viral infection and immune response induced by infection, and release of various cytokines, thereby impairing organ function. Because Hantavirus is a pan-tropic infection in humans, it can cause multiple organ damage. The mechanisms of cell and organ damage include:

(1) Direct action of the virus: The main basis is:

1 Clinically, patients have viremia and have corresponding symptoms of poisoning.

2 Different serotypes of the virus, the clinical symptoms caused by the different weight, it has different virulence to the suckling mice, indicating that the severity of clinical symptoms after EHF patients are closely related to the difference in viral antigens and virulence.

3EHF patients can detect Hantavirus antigens in almost all organ tissues, especially in vascular endothelial cells of EHF basic lesions, and cells with antigen distribution often develop lesions.

4 In normal cultured normal human bone marrow cells and vascular endothelial cells, in the absence of cellular immunity and humoral immunity, cell membrane and organelle damage occurred after infection with EHF virus, indicating that cell damage is the direct effect of Hantavirus.

(2) Immunization:

1 Injury caused by immune complex (type III allergy): The patient's serum complement is decreased in the early stage, and there is a specific immune complex in the blood circulation. In recent years, the patient's small blood vessel wall, glomerular basement membrane, renal tubule and The renal interstitial blood vessels have immune complex deposition. The immunohistochemical method proves that the antigen is an EHF virus antigen, and there is a complement cleavage fragment. Therefore, the immune complex is considered to be the cause of vascular and renal damage in this disease.

2 Other immune reactions: After the EHF virus invades the human body, it can cause a series of immune responses. It is found that:

A. The specific IgG antibody increased in the early stage of the disease, and its rising level was positively correlated with the positive rate of mast cell degranulation, suggesting the presence of type I allergic reaction.

B. There are immune complexes in platelets of EHF patients. Electron microscopic observation of renal tissue in addition to granular IgG deposition, there is linear IgG deposition in the basement membrane of renal tubules, suggesting that clinical platelet reduction and tubular damage are related to type II allergic reaction.

C. Electron microscopic observation showed that lymphocytes attacked renal tubular epithelial cells, and it is believed that the virus can damage the body cells through cytotoxic T cells, suggesting the presence of type IV allergic reaction. As for the above-mentioned I, II, IV allergic reactions in this disease The status in the pathogenesis remains to be further studied.

(3) The role of various cytokines and mediators: Hantavirus can induce the release of various cytokines and mediators such as interleukin-1 (IL-1) and TH1 cytokines from macrophages and lymphocytes of the body. IFN-r, IL-2, tumor necrosis factor alpha (TNF-), TH2 cytokine IL-10, etc., cause clinical symptoms and tissue damage, such as IL-1 and TNF can cause fever, a certain amount of TNF can cause Shock and organ failure, in addition, elevated levels of endotheliolysin, thromboxane B2, and angiotensin II can significantly reduce renal blood flow and glomerular filtration rate, and promote renal failure.

2. Pathology and Physiology The pathological changes of this disease are most obvious in small blood vessels and kidneys, followed by organs such as heart, liver and brain.

The basic lesion of EHF is swelling, degeneration and necrosis of endothelial cells in small blood vessels (including small arteries, venules and capillaries). The wall of the vessel is irregularly contracted and dilated. Finally, it is fibrinous necrosis and disintegration, and there may be microscopic in the lumen. Thrombosis, due to extensive small vessel disease and plasma extravasation, edema and hemorrhage of surrounding tissues, renal fat vesicle edema, hemorrhage, renal cortex ischemia and pale, renal medulla hyperemia and hemorrhage and edema, mirror The glomerular congestion, thickening of the basement membrane, renal proximal tubule degeneration and tubular compression were narrowed or occluded, renal interstitial cells were infiltrated, and electron microscopic observation showed that the glomerular capillary endothelial cells had different degrees of swelling. In the oliguria, individual glomeruli see capillary endothelial cell necrosis, neutrophils and platelets, endothelial cells and basement membrane are filled with low electron density, and heart disease is mainly in the right atrium. Extensive hemorrhage under the membrane, myocardial fibers have different degrees of degeneration, necrosis, partial rupture, marked hyperemia of the pituitary gland, hemorrhage and coagulative necrosis, no significant changes in the pituitary gland .

(1) shock: the third to seventh days of the disease course often appear hypotension shock called primary shock, shock after the oliguria period is called secondary shock, the main cause of primary shock is due to systemic small blood vessels Widely impaired, increased vascular permeability, large amount of extravasation of plasma in loose tissues, such as retroperitoneal and organ soft tissue, which reduces blood volume. In addition, due to plasma extravasation, blood is concentrated, and blood viscosity is increased to promote diffusion. The occurrence of intravascular coagulation (DIC) leads to stasis of blood circulation and obstruction of blood flow, thus further reducing effective blood volume. The main cause of secondary shock is major bleeding, secondary infection and insufficient supplementation of water and electrolyte during polyuria, resulting in effective Insufficient blood volume.

(2) Bleeding: The factors of bleeding in EHF patients are complicated, and sometimes involve multiple factors. It is generally believed that the skin of the febrile phase, the small bleeding point of the mucous membrane is caused by capillary damage, thrombocytopenia and abnormal platelet function, and the hypotensive shock period is at most In the pre-urinary period, mainly DIC causes abnormal blood coagulation mechanism. In addition, thrombocytopenia and dysfunction, increased heparin and uremia can also cause bleeding.

1 small blood vessel injury: small blood vessel lesions in EH patients mainly manifested as swelling and degeneration of endothelial cells, fibrin-like necrosis in severe cases, and even disintegration of blood vessel wall, which can lead to massive blood exudation and hemorrhage. There are three reasons for the damage:

A. Hantavirus acts directly on vascular endothelial cells and damages them.

B. Hantavirus antigen and antibody complexes are deposited in small blood vessels, attract neutrophils to phagocytose antigen-antibody complexes with the participation of complement, and release proteolytic enzymes in lysosomes, thereby damaging endothelial cells.

C. Microcirculatory disorders due to shock and other causes, causing hypoxia and vascular endothelial cells to cause degeneration and necrosis.

2 thrombocytopenia and dysfunction: under normal conditions, platelets are arranged along the vessel wall, which has the function of maintaining capillary integrity, reducing capillary fragility and permeability, and the decrease of platelets leads to an increase in capillary fragility and permeability. In addition, due to platelet adhesion, aggregation and release function disorders, which affect blood coagulation, thrombocytopenia in EHF patients is associated with bone marrow megakaryocyte maturation disorders, increased platelet consumption and increased destruction.

3 abnormal blood coagulation mechanism: Because DIC consumes a large number of blood coagulation factors, in addition, DIC causes secondary fibrinolysis, increased fibrinogen degradation products, and increased heparin substances can cause coagulation abnormalities.

Reasons for A.DIC: The incidence of DIC in EHF patients can reach 35% to 70%, except in the recovery period, especially in the hypotensive shock phase and oliguria phase. This is EHF virus or immune complex. Injury of capillaries or small vascular endothelial cells, leading to the exposure of vascular basement membrane collagen, thereby activating factor XII, leading to a chain reaction that causes endogenous coagulation, in addition to extravasation of EHF patients, increased blood concentration and viscosity, and shock and Acidosis during oliguria has a role in promoting DIC.

B. Increase in heparin: 80% of EHF patients have increased heparin levels in the blood from the onset of fever, in addition to increased release of mast cells in the body, reduced heparin inactivation due to liver damage, reduced heparin excretion and plasma in renal failure A large amount of extravasation of protein and a decrease in heparin binding promoted an increase in free heparin.

(3) Acute renal failure: the reasons include:

1 renal blood flow disorder: due to plasma extravasation, blood volume reduction and blood concentration, blood flow is insufficient, resulting in a sharp decline in glomerular filtration rate.

2 Immunological damage of the kidney: The deposition of immune complexes in the glomerular basement membrane and the basement membrane of the renal tubule has been confirmed. After activation of complement, the glomerular basement membrane and renal tubular epithelial cells can be damaged, and cytotoxic T cells can also be Causes damage to the renal tubules.

3 interstitial edema and hemorrhage: renal interstitial edema caused by plasma extravasation, as well as renal medullary congestion, blood pressure to force the renal tubules, can reduce urine output.

4 renal ischemic necrosis hypotension shock and DIC lead to renal vascular microthrombus formation, which can cause ischemic necrosis of renal parenchymal cells.

5 renin, angiotensin II activation: the renal artery contraction, thus renal cortical blood flow decreased, glomerular filtration rate decreased.

6 renal tubular obstruction: renal tubule lumen can be blocked by protein, tube type, etc., urine discharge blocked.

Epidemic hemorrhagic fever prevention

(1) Rodent control and rodent control are the key to prevent the epidemic. In popular areas, the masses should be vigorously organized and rodent control should be carried out simultaneously within the prescribed time. The timing of rodent control should be selected at the peak of the disease (5-6). Before the month and October to December, the spring should focus on the house mouse, and the early winter should focus on the voles.

At present, there are mechanical methods and bait methods. The mechanical method can use rodents and rat cages to kill rodents. The poison bait method mainly uses the food that the rats love to eat as bait, and the rodenticide is blended into a poison bait according to a certain proportion. In the place where the mouse hole or the mouse often appears, the common mouse is commonly used in the mouse, sodium, killing the mouse, killing the voles, zinc phosphide, poisonous rat phosphorus, venom sodium, chlorpyrifos, etc. The effect is high, but the disadvantage is that the use of carelessness can cause human and animal poisoning. Therefore, the person should be guarded within 3 days after the poison bait is placed in the field. The excess bait should be taken back and destroyed after 3 days, and the bait should be placed in the family before going to sleep at night. Because the breeding ability of rodents is extremely strong, the work of rodent control should be persevering, and it should be relaxed.

Under the premise of rodent control, at the same time, the rodent prevention work should be done at the same time. The bed should not be against the wall, sleep high, and the outside of the house should be dug to prevent the rats from entering the house and the courtyard. When building and renovating the house, the rodent-proof facilities should be installed.

(2) Defecation, anti-mite should keep the house clean, ventilated and dry, often sprayed with organophosphorus pesticides such as DDT, to remove indoor and outdoor haystacks.

(3) Strengthening food hygiene To do food hygiene, food utensil disinfection, food preservation, etc., to prevent rodent excreta from contaminating food and utensils, leftover food must be heated or cooked before consumption.

(4) Do a good job of disinfection. Blood, urine and host animal carcasses and their excretions should be disinfected to prevent environmental pollution.

(5) Pay attention to personal protection. Do not directly touch the rodents and their excrement in the affected area, do not sit on the haystack, prevent skin damage during labor, disinfect and dress after the injury, and wear socks when working in the field. Tighten the trouser legs and cuffs to prevent biting.

Epidemic hemorrhagic fever complications Complications, shock meningitis, dysfunction, pulmonary edema, pleural effusion, arrhythmia, dehydration

1. Cavity bleeding, hematemesis, blood in the stool is the most common, can cause secondary shock, abdominal bleeding, nasal and vaginal bleeding are more common.

2. Central nervous system complications include encephalitis and meningitis caused by viral invasion of the central nervous system, cerebral edema caused by shock, clotting dysfunction, electrolyte imbalance and high blood volume syndrome in shock and oliguria. Hypertensive encephalopathy and intracranial hemorrhage can cause headache, vomiting, disturbance of consciousness, convulsions, respiratory rhythm changes or hemiplegia. CT examination is helpful for the above diagnosis.

3. Pulmonary edema is a common complication of this disease, and there are two clinical cases.

(1) Acute Respiratory Distress Syndrome (ARDS): This is a pulmonary capillary injury. Increased permeability leads to massive exudation of the pulmonary interstitial. In addition, thrombosis of microvessels in the lungs and reduction of alveolar surfactant production can contribute to ARDS. The clinical manifestations are shortness of breath, 30 to 40 beats/min. There is no obvious cyanosis and lung voice in the early stage. The hair can be found in the middle stage. The lungs can smell bronchial breath sounds and dry and wet voices. X-ray films can be seen. Side spotted or flaky shadow, the lung field is shaded thick, and the edge is thin, with ground glass. Blood gas analysis arterial oxygen partial pressure (Pa02) is reduced to below 8.0 kPa (60 mmHg), and progressive reduction, alveolar arterial pressure is obvious Increased, up to 4.0kPa (30mmHg) or more, common in shock and oliguria, recent reports of Hantavirus lung syndrome in New Mexico and other places, with ARDS as the main performance, often within 2 to 6 days of onset Death due to respiratory distress leading to acute respiratory failure.

(2) Heart failure: can be caused by damage to the pulmonary capillaries, a large amount of exudate in the alveoli, or caused by high volume or myocardial damage, mainly manifested by increased breathing, cough foam-like pink sputum, cyanosis and fullness Lung sounds.

4. Hemorrhagic fever caused by pleural effusion and atelectasis is common. Kanerva examined 125 patients with PUUV-induced HFRS and found that 28% of patients had pleural effusion or atelectasis, while pulmonary edema was rare. These patients have more obvious hypoproteinemia, so it is believed that capillary leakage and inflammation may be the cause of abnormal lungs.

5. Secondary infections are more common in oliguria and early polyuria. Pulmonary and urinary tract infections and sepsis are more common. They are caused by decreased immune function and catheterization, which may cause secondary shock and worsen the condition.

6. Spontaneous renal rupture occurs mostly in the oliguria period, due to severe renal medullary hemorrhage, often due to nausea, vomiting or cough, etc., causing a sudden increase in abdominal or thoracic pressure, causing an increase in renal blood pressure and promoting bleeding Suddenly sitting up or turning over, causing the psoas muscle to contract sharply, the kidney is squeezed and easily cause kidney rupture. The clinical manifestation is that the patient feels a sore waist or abdominal pain, severe blood pressure drops, cold sweat dripping, if blood infiltrates into the abdominal cavity, There is a peritoneal irritation sign, and there is blood in the abdomen. B-ultrasound can find a liquid level in the peri-renal and abdominal masses. If it can be operated in time to reduce the mortality rate.

7. Heart damage and heart failure Hantavirus can invade the myocardium and cause myocardial damage. Clinically, it is often bradycardia and arrhythmia. Because of high blood volume syndrome, pulmonary edema, etc., the myocardial burden is too heavy, so heart failure can occur. .

8. Liver damage 4% ~ 60% of patients with elevated ALT, a small number of patients with jaundice or significant liver damage, liver damage is more common with SEOV infection, is caused by viral damage to the liver.

9. Hyperosmolar non-ketotic coma Very few patients with HFRS have apathy, slow response, lethargy or even coma during oliguria or polyuria. Check blood glucose is significantly higher, often greater than 22.9-33.6mmol/L, blood sodium> 145mmol / L, urine ketone negative, plasma osmotic pressure > 350mmol / L, this is the HFRS patients pancreatic cells infected by the virus to reduce insulin secretion, or excessive use of glucocorticoids, intravenous sugar, excessive sodium and excessive diuretic lead to dehydration Caused.

Epidemic hemorrhagic fever symptoms Common symptoms Eyelid pain Appetite loss cheeks and upper chest congestion, dizziness, nausea, polyuria, sleepiness, mouth ulcers, abdominal pain, ascites

The incubation period is 5 to 46 days, usually 1 to 2 weeks. The disease is characterized by acute onset, fever (38 ~ 40 ° C), three pain (headache, back pain, eyelid pain) and nausea, vomiting, chest tightness, abdominal pain, diarrhea, general joint pain and other symptoms, skin and mucous membrane three red ( The face, neck and upper chest are red), the conjunctiva is congested, and the heavy one is like drunkenness. Bleeding spots or ecchymoses of different sizes appear in the oral mucosa, chest and back, under the armpits, or in the form of strips and scratches. As the disease progresses, the patient has a fever, but the symptoms worsen, followed by symptoms such as hypotension, shock, oliguria, anuria and severe bleeding. Typical hemorrhagic fever usually has fever, hypotension, oliguria, polyuria and recovery of the fifth phase. If not handled properly, the mortality rate is high. Therefore, the patient should be "four early in the morning", that is, early detection, early diagnosis, early rest, early treatment, near treatment, and reduced handling.

The early symptoms of hemorrhagic fever are mainly fever, headache, low back pain, sore throat, cough, runny nose, etc., which are easily confused with colds, causing misdiagnosis and delaying the disease; many patients are suffering from fever, headache, oliguria, edema and other symptoms. Misdiagnosed as acute nephritis or urinary tract infection; some patients may be misdiagnosed as acute gastroenteritis with nausea, vomiting or diarrhea; a few patients have fever, chills, headache, fatigue symptoms, bleeding spots on the skin and mucous membranes, or white blood cells The number is increased, which is very similar to sepsis.

(A) fever period: mainly manifested as infectious viremia and symptoms caused by systemic capillary damage.

Most of them suddenly have chills and fever, and the body temperature can reach 39 to 40 °C within 1 to 2 days. The heat type is mostly relaxation heat and heat retention, which lasts for 3 to 7 days. Symptoms of systemic poisoning, high fatigue, body aches, headaches and severe low back pain, eyelid pain, known as "three pains."

(B) hypotension period : mainly for the performance of plasma loss of hypovolemic shock. Generally, on the 4th to 6th day of fever, when the body temperature starts to drop or shortly after the fever, the patient has hypotension, and the severe person suffers from shock.

(C) oliguria : there is often no clear boundary between oliguria and hypotension.

(D) polyuria: renal tissue damage gradually repair, but because the renal tubular back absorption function has not fully recovered, resulting in a significant increase in urine output.

(5) Recovery period : With the gradual recovery of renal function, when the urine volume is reduced to below 3000 ml, it will enter the recovery period. The urine dilution and concentration function gradually recovered, the spirit and appetite gradually improved, and the physical strength gradually recovered.

Epidemic hemorrhagic fever

[Laboratory Inspection]

Blood routine

(1) White blood cell count: Most of the first to second disease days are normal, and gradually increase after the third disease day, up to (15 ~ 30) × 109 / L, a small number of critically ill patients can reach (50 ~ 100) × 109 / L .

(2) Classification of white blood cells: early stage of neutrophil enlargement, left shift of the nucleus, poisoning granules, severe cases showed immature leukemia reaction in naive cells, lymphocytes increased after 4th to 5th disease days, and more atypical lymphoids appeared. Cells, because atypical lymphocytes can also occur in other viral diseases, can not be used as the main basis for disease diagnosis.

(3) Hemoglobin and red blood cells: As blood extravasation leads to blood concentration, the number of hemoglobin and red blood cells increases from the late stage of fever to the hypotensive shock period, reaching 150 g/L and 5.0×10 12 /L or more.

(4) Platelets are reduced from the second disease day, generally around (50 ~ 80) × 109 / L, and visible platelets.

2. Urine routine

(1) Urine protein: It can appear on the second disease day. The urine protein is often reached on the 4th to 6th day, and a large amount of urine protein suddenly appears, which is helpful for diagnosis. In some cases, there is a membrane in the urine, which is a large amount. Agglomerates of urine protein mixed with red blood cells and exfoliated epithelial cells.

(2) Microscopic examination: red blood cells, white blood cells and casts can be seen. In addition, huge fusion cells can be found in the urine sediment. This is the fusion of the urinary exfoliated cells of the EHF virus envelope glycoprotein under acidic conditions. EHF virus antigen can be detected.

3. Blood biochemical examination

(1) Blood urea nitrogen and creatinine: Most patients in the hypotensive shock phase, a small number of patients in the late fever, urea nitrogen and creatinine began to rise, peaked at the end of the transition period, began to decline in the late polyuria.

(2) Blood acidity and alkalinity: Blood gas analysis during fever is more common in respiratory alkalosis, which is related to fever and hyperventilation. Metabolic acidosis is the main stage of shock and oliguria.

(3) Electrolytes: blood sodium, chlorine and calcium are mostly decreased in all stages of the disease, while phosphorus and magnesium are increased. Blood potassium is in the fever phase, the shock phase is at a low level, the oliguria phase is elevated, and the polyuria phase is increased. Lower, but a small number of patients still have hypokalemia during oliguria.

(4) Coagulation function: thrombocytopenia begins during the febrile phase, and its adhesion, aggregation and release function are reduced. If the DIC platelet is often reduced to less than 50×109/L, the clotting time is shortened during the hypercoagulable period of DIC, and the consumptive low coagulation period is observed. The fibrinogen is reduced, prothrombin is prolonged and thrombin is prolonged, and fibrinolytics (FDP) are elevated during the fibrinolysis phase.

4. Special inspection

(1) Virus isolation: Hantavirus can be isolated from serum, blood cells and urine samples from patients with fever during the inoculation of Vero-E6 cells or A549 cells.

(2) Antigen examination: serum of early patients, peripheral blood neutrophils, lymphocytes and monocytes, and urine and urine sediment cells, using Hantavirus polyclonal or monoclonal antibodies, can detect Hantan Viral antigens, commonly used in immunofluorescence or ELISA, colloidal gold is more sensitive.

(3) Specific antibody detection: including detection of specific IgM or IgG antibody in serum, IgM antibody is positive at 1:20, can be detected on the second day of onset, IgG 1:40 is positive, and titer rises after 1 week 4 It has diagnostic value. It is believed that the detection of nucleoprotein antibodies is conducive to early diagnosis, while the detection of G2 antibody is beneficial to prognosis. Recently, the rapid immunoassay of immunochromatography has used recombinant nucleoprotein (NP) as antigen to detect patients. IgM antibody can produce results in 5 min with sensitivity and specificity of 100%.

(4) PCR technology: RT-PCR method for detection of Hantavirus RNA, high sensitivity, for early diagnosis.

Film degree exam

1. Liver function: Serum alanine aminotransferase (ALT) is elevated in about 50% of patients, and serum bilirubin is elevated in a small number of patients.

2. Electrocardiogram: There may be sinus bradycardia, conduction block and other arrhythmia and myocardial damage, in addition to high blood potassium, T wave high tip, U blood wave appears when hypokalemia.

3. Intraocular pressure and fundus: In some patients, the intraocular pressure is increased, and the intraocular pressure is obviously increased. It is often indicated as severe. Patients with cerebral edema can see optic disc edema and venous congestion and dilatation.

4. Chest X-ray: About 30% of patients have pulmonary edema and congestion, and about 20% of patients have pleural effusion and pleural reaction.

Diagnosis of epidemic hemorrhagic fever

diagnosis

Based on epidemiological data, clinical findings and laboratory findings can be diagnosed.

(1) Epidemiology includes epidemic areas, epidemic seasons, direct and indirect contact with rodents, and entry into epidemic areas or within two months of epidemic areas.

(B) clinical manifestations of acute onset, fever, headache, eyelid pain, low back pain, thirst, vomiting, drunkenness, conjunctival edema, congestion, bleeding, soft palate, bleeding under the armpits, rib pain in the rib angle .

(3) Laboratory inspection

1. General laboratory examination of the total number of white blood cells increased, the classification of lymphocytes increased, and abnormal lymphocytes, the number of platelets decreased, urine test protein, red blood cells, white blood cells, casts and so on.

2. Specific experimental diagnosis In recent years, the application of serological methods has been helpful for early diagnosis of patients. It is especially helpful for the diagnosis of patients with clinical atypical. The detection methods include indirect immunofluorescence test, enzyme-linked immunosorbent assay, and enzyme-labeled SPA group. Chemical test, hemagglutination inhibition test, immunoadhesive blood coagulation test, solid phase immunoglobulin adsorption test and solid phase radioimmunoassay, etc., specific IgM positive or early stage and recovery period of serum-specific IgG antibody titer increase 4 More than double, there is a diagnosis value, the virus can be isolated from the blood or urine of the patient or the virus antigen can be detected. Recently, the polymer antigen is directly detected by polymerase chain reaction (PCR), which is helpful for pathogen diagnosis.

Differential diagnosis

The fever period should be differentiated from upper respiratory tract infection, influenza, sepsis, typhoid fever, leptospirosis, acute gastroenteritis and dysentery. Patients with skin hemorrhage should be distinguished from thrombocytopenic purpura. Proteinuria should be associated with acute pyelonephritis. Nephritis, acute glomerulonephritis, abdominal pain should be distinguished from acute appendicitis, acute cholecystitis, gastrointestinal bleeding should be different from ulcer bleeding, hemoptysis should be differentiated from bronchiectasis, tuberculosis hemoptysis, shock and other infections Sexual shock identification, oliguria is differentiated from acute nephritis and other causes of acute renal failure, bleeding is obvious with peptic ulcer bleeding, thrombocytopenic purpura and other causes of DIC identification, the disease has typical clinical manifestations And unique period of time, as well as serological testing, etc., are helpful to identify.

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