Influenza

Introduction to influenza Influenza (infuenza), referred to as influenza, is an acute respiratory infection caused by influenza virus. The pathogens are influenza A, B, and C. The spread of influenza virus is caused by droplets and clinically high fever and fatigue. Aching and mild respiratory symptoms, short duration, self-limiting, middle-aged people and patients with chronic respiratory diseases or heart disease are prone to pneumonia. The most prominent epidemiological characteristics of influenza are: sudden outbreak, rapid spread, spread It has a wide range and has a certain seasonality (the northern part of China generally occurs in winter, while the south mostly occurs in summer and winter). basic knowledge The proportion of illness: 87% Susceptible people: no specific population Mode of infection: droplet spread Complications: sinusitis tonsillitis bacterial pneumonia toxic shock syndrome coma liver enlargement arrhythmia

Influenza cause

Virus factor (30%):

Mainly caused by influenza virus, the influenza virus is divided into three types: A, B, and C according to the difference in antigenicity of nuclear protein and M protein. The type A is divided into several subtypes according to the antigenicity of HA and NA.

Resistance decreased (20%):

Immunity is the body's own defense mechanism. It is the body's ability to recognize and destroy any foreign body invaded by foreign bodies; to deal with aging, injury, death, degeneration of self-cells, and to identify and treat mutant cells and virus-infected cells in vivo.

Other factors (20%):

1. Hemagglutinin: HA is one of the glycoprotein protuberances of the influenza virus envelope and plays an important role in influenza virus infection and replication. 1 The surface of the host cell (including red blood cells) has a hemagglutinin receptor, and the influenza virus binds to it by hemagglutinin, so that the influenza virus can be adsorbed to the host cell membrane. The adsorption of red blood cells by the influenza virus is characterized by red blood cell agglutination, hemagglutinin Therefore, after the influenza virus is adsorbed on the surface of the host cell, the fusion process between the viral envelope and the cell membrane is initiated, and the virus penetrates into the host cell membrane, and then enters into the host cytoplasm in the form of vesicles through the pinocytosis. 2 In the low pH environment in the vesicle, HA cleaves into HA-1 and HA-2 subunits, undergoes a conformational change, and the fusion sequence present at the amino acid terminus of HA-2 is exposed, activating the lytic polypeptide, so that The viral nucleocapsid that enters the host cytoplasm in the form of vesicles is released from the capsule.

2. Neuraminidase (NA): NA is another glycoprotein protuberance of the influenza virus envelope, but the amount is significantly less than hemagglutinin, which can cleave oligomeric polysaccharides and terminal neuraminic residues (ie N- The binding bond between acetylneuraminic acid (also known as citrate), the hemagglutinin receptor on the surface of the host cell contains tannic acid coupled to the oligosaccharide, and the degradation of tannic acid contained by neuraminidase Has important biological implications for viruses:

(1) The destruction of sialic acid contained in the host cell surface receptor by neuraminidase allows the influenza virus to be released from the infected cells, and the release of the extracellular flu virus is depolymerized and dispersed. Thereby facilitating its dissemination.

(2) The mucus of the respiratory mucus also contains a citrate component. The lytic activity of the neuraminidase is such that the influenza virus breaks through the mucus and is prone to spread in the respiratory mucosa.

Because of the important role played by neuraminidase in the replication of influenza virus, and the active site of neuraminidase is highly conserved in influenza A and B viruses, many new anti-influenza drugs have been developed. NA serves as a target for drug effects.

3. Nucleocapsid protein (RNP): a viral structural protein that forms a nucleocapsid with viral RNA, including nuclear protein (NP) and three polymerase proteins (PB-1, PB-2, PA), three kinds of polymerization. The enzyme protein is synthesized in the host cytoplasm and then transferred to the nucleus. Among all the structural proteins of influenza A and B viruses, PB-1 is the most homologous protein, and its function is responsible for viral mRNA synthesis. Extension after initiation, PB-2 is a viral RNA-dependent RNA polymerase that functions to recognize and bind to a cap-like structure transcribed by host cell polymerase II, which can be cleaved from the host cell and ligated to the virus. At the 5-end of specific mRNA, the cap-like structure is a primer for viral mRNA transcription, transcription of the starting RNA, and during post-transcriptional processing, PB-2 may be involved in excision of the mRNA 5-terminal cap-like structure, PA in viral RNA The role of synthesis has not been fully elucidated and may be a kinase or an unwinding protein.

4. Membrane protein (MA) is one of the structural components of influenza virus envelope, including M1, M2, M1 contains 252 amino acids, is the most abundant polypeptide in virion, has type specificity, is influenza virus One of the main reasons for the type, M1 may play an important role in the progeny virus assembly, while protecting the ribonucleoprotein particles, M2 is a complete membrane protein, containing 97 amino acids, only found in influenza A virus, M2 is abundantly present on the surface of infected host cells in the form of tetramers, but has little content in virions. Its function is proton channel, which is used to control the pH value in the Golgi cavity during HA synthesis, and the process of virus decapsulation. Acidification inside the vesicles.

Pathogenesis

Influenza virus can infect and replicate in all types of cells in the respiratory tract. The main mechanism of its pathogenesis is cell damage and death caused by viral replication. Once the influenza virus enters and colonizes the respiratory epithelium, it plays through the pinocytosis and adheres. And penetrate into the airway epithelial cells and replicate in the cells for 4-6 hours. The new virus particles sprout from the cell membrane, release by the action of neuraminidase, and then infect adjacent epithelial cells, resulting in a large number of respiratory tracts in a short period of time. Epithelial cells are infected, infected cells undergo necrosis, shedding and local inflammatory reactions, and cause systemic toxic reactions such as fever, pain and leukopenia. Viral replication-induced cytopathic is the main principle of influenza, and excessive interferon may be circulating. It is related to systemic symptoms, but no viremia occurs. The pathological changes of influenza alone are mainly caused by upper and lower respiratory tract damage, tracheal involvement, degeneration of ciliated epithelial cells, necrosis and shedding, inclusion bodies in cytoplasm, mucosal congestion and edema and single Nuclear cell infiltration, but no damage to the basal cell layer, basement after 4 to 5 days of onset The cells began to proliferate, forming undifferentiated epithelial cells. After 2 weeks, the ciliated epithelial cells were formed and recovered. The pathological features of influenza virus pneumonia were extensive hemorrhage in the lungs, dark red with edema in the lungs, and bloody secretions in the trachea and bronchi. Mucosal congestion, tracheal, bronchial ciliated epithelial cell necrosis, submucosal focal hemorrhage, edema and mild inflammatory cell infiltration, alveolar fibrinogen exudation, containing neutrophils and monocytes.

Influenza prevention

1. Epidemic monitoring

As the influenza virus continues to mutate, there are flu epidemics and outbreaks around the world. Once a new strain has become popular, it may spread to the whole world. Therefore, it is necessary to monitor the flu epidemic around the world, and often master the world flu epidemic and toxicity. In order to take timely and effective preventive measures, the World Health Organization has set up international influenza research centers in London, England and Atlanta, USA. Beijing and many countries have set up their own influenza research centers. The domestic influenza epidemic and the newly identified strains of influenza virus isolated and identified are submitted to the International Influenza Research Center for further identification. The World Health Organization headquarters publishes some epidemics of the influenza every week in the epidemic weekly report, and proposes the next year's influenza in February each year. Recommendations for the selection of vaccine strains, countries should strengthen the epidemic report, the epidemic situation observation and the isolation and identification of the virus. The grassroots health units should report the epidemic prevention when the number of patients with upper respiratory tract infection increases continuously for 3 days or when multiple patients are found in one household. Stand in time Investigation and virus isolation.

2, patient isolation and treatment

Timely isolation and treatment of influenza patients is an effective measure to reduce the incidence and spread. Temporary influenza diagnosis rooms can be set up according to specific conditions, family isolation, clinical isolation room isolation, and even large-scale assembly and entertainment activities can be reduced or stopped.

3. Disinfection

The patient's tableware, utensils and masks can be boiled; the clothes can be exposed to the sun for 2 hours; the ward is sprayed with 1% chlorinated lime (bleaching powder) clarifying solution, and the public places should be ventilated during the epidemic period, lactic acid fumigation or chlorine-containing lime solution.

4, vaccine prevention

Influenza vaccine can reduce the incidence of influenza, but because of the variability of influenza virus, it affects the vaccine effect. When the influenza virus only has small mutations (antigenic drift) in the same subtype, the old strain vaccine still has some cross-immunization. Role, such as the emergence of large variations (antigenic transformation) of the subtype, the old strain vaccine is not protective, when a new subtype caused by a pandemic, the new strain can be used to prevent the pandemic , three waves and used in areas where there is no epidemic, influenza vaccines have inactivated vaccines and live attenuated vaccines.

(1) Influenza inactivated vaccine: It is a whole virus trivalent inactivated vaccine prepared according to the influenza virus strain recommended by influenza surveillance. The protection rate after subcutaneous injection can reach 80%, and the side effects are small, only 1% to 2% of the inoculation. Fever and systemic reactions occur, and about 25% of people have mild reactions in the local area, such as subunit vaccines, which have fewer side effects.

1 vaccinated subjects: mainly elderly, infants, pregnant women, chronic heart and lung disease, tumors, human immunodeficiency virus (HIV) infection, use of immunosuppressants or long-term use of salicylic acid preparations, because these people have flu after the illness Heavier, higher mortality, may also be complicated by Reye syndrome.

2 Inoculation method: The basic immunization should be inoculated twice, at intervals of 6 to 8 weeks, 1 ml per adult, subcutaneous injection, and then subcutaneous injection of 1 ml per year. If the new subtype vaccine is used, the basic immunization should be re-examined.

(2) live attenuated influenza vaccine: a live vaccine prepared by breeding an attenuated strain of influenza virus, which is inoculated into the nasal cavity of a healthy person to cause mild upper respiratory tract infection to produce immunity, which can occur 2 to 3 days after inoculation. Mild upper respiratory tract infection symptoms and mild fever, disappeared after 1 to 2 days, most observations proved that its preventive effect is similar to inactivated vaccine.

1 vaccination target: When the virus has a new subtype, the population lacks immunity. In areas or populations that are not yet prevalent, in addition to contraindications, comprehensive vaccination should be carried out. When the virus only has small mutations in the same subtype, vaccination The main targets are medical staff, childcare workers, cooks, service industry personnel, seaports and transportation personnel, etc., which are closely related to the spread of the disease. In rural areas, priority should be given to immunizing primary school students, for children aged 7 to 15 or Before the large-area inoculation, 50 to 100 people should be tested first. After 4 days without serious reaction, the inoculation should be expanded.

2 Inoculation time: It should be based on the season of the epidemic, usually inoculated within 1 to 3 months before the epidemic season.

3 inoculation method: 0.25 ml per side of the nasal spray method.

4 contraindications: the elderly, pregnant women, infants and children with severe diabetes or chronic heart, lung, kidney disease, allergies and fever.

5, drug prevention

Some drugs used to treat the flu can also be used to prevent influenza, and they can be used as a supplement to the vaccine immunization program. Individuals who are not vaccinated with flu vaccine should take drug precautions during influenza outbreaks or throughout the flu season. , then the vaccination must be carried out at the same time. The drug can be stopped after 14 days of vaccination. On the contrary, if the vaccination is not carried out, the drug should be taken continuously during the entire outbreak. Giving the patient and medical staff the help of the medical source can help control the medical source. Sexual infections are also effective for post-exposure prophylaxis in the home. The current anti-influenza A virus used in many countries is adamantan hydrochloride, including amantadine and rimantadine, during the influenza A epidemic. Prophylactic administration of amantadine or rimantadine to healthy adults or children is 70% to 90% effective in preventing influenza A virus. The two drugs can be administered within 48 hours after the onset of infection. Can reduce the disease and shorten the course of the disease, although the effectiveness of the two drugs is similar, but rimantadine is safer, especially For the elderly with impaired renal function, but it is not effective in preventing influenza B, zanamivir is another drug that can be used to prevent influenza. The effective rate of preventing infection is 82%, which can be popular. Try it for healthy adults during the period.

Influenza complications Complications sinusitis tonsillitis bacterial pneumonia toxic shock syndrome coma hepatoarrhythmia

1, secondary bacterial upper respiratory tract infection

Such as acute sinusitis or suppurative tonsillitis.

2, secondary bacterial pneumonia

Influenza patients may have the following three kinds of pneumonia: in addition to the primary influenza virus pneumonia, there may be secondary bacterial pneumonia, or mixed pneumonia with virus and bacteria, influenza virus infection leads to necrosis of airway epithelial cells, cilia shedding And mucus secretion dysfunction, local defense function is reduced, easy to secondary bacterial infection, manifested as acute bronchitis and pneumonia, common flu secondary bacterial vaginal pneumonia is more common than influenza virus pneumonia, mostly by Streptococcus pneumoniae, golden yellow Staphylococcus, Haemophilus influenzae, etc., secondary bacterial pneumonia and primary viral pneumonia can often be distinguished by clinical features, secondary bacterial pneumonia occurs after the influenza condition has improved, and then the body temperature rises again, accompanied by Symptoms and signs of bacterial pneumonia; bacterial pneumonia can also coexist with influenza virus pneumonia, patients mostly elderly, or patients with chronic heart and lung disease, metabolism or other diseases, usually with simple influenza, 2 ~ After 3 days, the condition worsened, the body temperature was higher than before, and it was accompanied by chills. The symptoms of systemic poisoning were obvious and the cough was intensified. Pus sputum, accompanied by chest pain, patients with difficulty breathing, cyanosis, lungs full of voices, physical examination and chest X-ray can be found with local consolidation, can also be associated with pleurisy, pleural effusion or empyema, white blood cell count and The proportion of neutrophils is significantly increased. Gram staining and sputum culture of sputum smear can show related pathogenic bacteria. Those with severe disease can cause toxic shock syndrome after influenza.

3, Reye syndrome (encephalopathy - hepatic steatosis syndrome)

Is a liver infected with influenza A or B virus, neurological complications, nausea, frequent vomiting, lethargy, coma and convulsions, neurological symptoms, liver enlargement, no jaundice, liver function after several days of acute respiratory infection Mild damage, histological changes are characterized by liver, kidney, and cardiac steatosis. The cause of Reye syndrome is unknown. In recent years, it may be related to long-term use of aspirin.

4, other complications

A small number of patients may have myositis. Children are more common than adults. They are pain and tenderness of the gastrocnemius and soleus muscles. They can cause paralysis of the lower extremities. In severe cases, they cannot walk. The influenza B virus is more likely to develop this complication than the type A. The content of acid phosphokinase increased temporarily, and the patient recovered completely after 3 to 4 days. It has been reported that very few patients may have myoglobinuria and renal failure, and also have myocardial damage, which is characterized by abnormal electrocardiogram, arrhythmia, myocardial enzyme content. Increased, etc., pericarditis is rarely reported.

Influenza symptoms Common symptoms Sore throat, dry throat and burning sensation, nasal congestion, high fever, cold war, cough, hoarseness, nausea, fever, chills, sneezing, tonsil congestion

Clinical symptoms

Acute chills, high fever, headache, dizziness, body aches, fatigue and other symptoms of poisoning, may be accompanied by sore throat, runny nose, tears, cough and other respiratory symptoms, a few cases of loss of appetite, accompanied by abdominal pain, bloating, vomiting and diarrhea Equal gastrointestinal symptoms, the clinical symptoms of infant flu are often atypical, showing febrile seizures; some children with laryngotracheal bronchitis, severe airway obstruction; neonatal flu, although rare, once often appear sepsis Such as lethargy, refusal to milk, apnea, etc., often accompanied by pneumonia, high mortality.

classification

1, typical flu

It can be expressed as chills, fever, body temperature can be as high as 39-40 ° C, while the patient feels headache, body aches, weakness, and often dry eyes, dry throat, mild sore throat, some patients may have sneezing, rogue , nasal congestion, sometimes visible gastrointestinal symptoms, plus nausea, vomiting, diarrhea and so on.

Fever and the above symptoms generally peak in 1-2 days, heat retreat within 3-4 days, symptoms disappear, fatigue and cough can last for l-2 weeks.

2, light flu

Acute onset, mild onset, systemic symptoms and respiratory symptoms are very light.

3, pneumonia flu

That is, influenza virus pneumonia, the condition is rapidly aggravated within 24 hours, manifested as high fever, fatigue, irritability, severe cough, difficulty breathing, cyanosis, cough and blood stasis, double lungs dense wet rales and wheezing, pulse is weak and weak, and the mortality rate is higher. High, such patients are less common, mainly in the original heart disease, chronic lung disease patients or pregnant women.

4, encephalitis flu

The patient has a sudden onset of illness, which is very serious at first, often manifested as high fever, unconsciousness, neck stiffness, convulsions and other symptoms of encephalitis.

Influenza check

1, blood

The total number of white blood cells decreased, lymphocytes increased, and eosinophils disappeared. When combined with bacterial infection, the total number of white blood cells and neutrophils increased.

2. Immunofluorescence or immunoenzymatic staining for antigen detection

Taking the labeled specimen of mucosal epithelial cells in the nasal wash of the patient, and detecting the antigen by fluorescent or enzyme-labeled influenza virus immune serum, the result is fast, the sensitivity is high, and it is helpful for early diagnosis, such as using monoclonal antibody to detect antigen. Can identify influenza A, B, C.

3. Polymerase chain reaction (PCR) for the determination of influenza virus RNA

It is a direct, rapid and sensitive method for detecting viral RNA directly from patient secretions. The current application of PCR-ELIA directly detects influenza virus RNA, which is much more sensitive and rapid than virus culture. The measurement is performed directly.

4, virus separation

The sputum containing the acute phase is inoculated into the amniotic sac or allantoic fluid of the chicken embryo for virus isolation.

5, serological examination

The blood coagulation resistance test, the complement fixation test, etc. are used to determine the antibodies in the serum of the acute phase and the recovery phase, and if it is increased by 4 times or more, it is positive, and the neutralizing antibody can be detected by the neutralization immunoassay, and the neutralizing antibody can be detected. These all contribute to retrospective diagnosis and epidemiological investigations.

6. PCR detection of influenza virus genes

Since the 5th and 3rd ends of each RNA segment of all influenza virus genomes are conserved, synthetic primers can be designed accordingly for PCR detection. PCR technology can detect influenza virus genes directly from patient secretions, which is more sensitive and rapid than virus culture method; however, it should be noted that false positives may occur, and myocardial damage may occur, which is manifested as abnormal electrocardiogram.

Influenza diagnosis

diagnosis

Epidemiological data is one of the main basis for the diagnosis of influenza. It is not difficult to diagnose with typical clinical manifestations. However, in the early stage of epidemics, the diagnosis of sporadic or light cases is difficult. The diagnosis often requires laboratory examination. The main diagnosis is as follows:

1. Epidemiological history: During the epidemic season, a large number of patients with upper respiratory tract infections or hospital outpatients appeared in one unit or region, and patients with emergency upper respiratory tract infections increased significantly.

2, clinical symptoms: acute chills, high fever, headache, dizziness, body aches, fatigue and other symptoms of poisoning, may be accompanied by sore throat, runny nose, tears, cough and other respiratory symptoms, a few cases have loss of appetite, accompanied by abdominal pain, Digestive symptoms such as bloating, vomiting and diarrhea, the clinical symptoms of infant flu are often atypical, showing febrile seizures; some children present with laryngotracheal bronchitis, severe airway obstruction; although neonatal flu is rare, once it occurs It is characterized by sepsis, such as lethargy, refusal of milk, apnea, etc., often accompanied by pneumonia, and high mortality.

3. Laboratory inspection:

(1) Peripheral blood: The total number of white blood cells is not high or decreased, and lymphocytes are relatively increased.

(2) Virus isolation: Influenza virus is isolated from nasopharyngeal secretions or oral sputum.

(3) Serological examination: The serum anti-influenza antibody titer of the serum at the initial stage and the recovery period is increased by 4 times or more, which is helpful for retrospective diagnosis.

(4) The patient's respiratory epithelial cells were positive for influenza virus antigen.

(5) The specimen was positive for influenza virus antigen after being propagated for 1 generation by sensitive cells overnight.

4. Diagnostic classification: Suspected cases: with epidemiological history and clinical symptoms; confirmed cases: suspected cases at the same time laboratory tests meet 2 or 3 or 4 or 5.

Differential diagnosis

1, respiratory infections: slow onset, mild symptoms, no obvious symptoms of poisoning, serological and immunofluorescence tests can be clearly diagnosed.

2, epidemic cerebrospinal encephalitis (flowing brain): early symptoms of meningitis are often similar to the flu, but the flow of the brain has obvious seasonality, more common in children, early severe headache, meningeal irritation, sputum, cold sores, etc. Can be differentiated from the flu, cerebrospinal fluid examination can confirm the diagnosis.

3, Legionnaires' disease: This disease is more common in summer and autumn, clinical manifestations of severe pneumonia, increased white blood cells, and liver and kidney complications, but mild cases like influenza, erythromycin, rifampicin and gentamicin and other antibiotics It is effective for this disease, and the diagnosis will help the pathogen examination.

4. Mycoplasmal pneumonia: Mycoplasma pneumonia is similar to X-ray findings of primary viral pneumonia, but the former is milder, and the condensation test and MG streptococcal agglutination test can be positive.

5, acute bacterial tonsillitis: tonsil redness and exudation, culture may isolate pathogenic bacteria.

6, leptospirosis: a certain regional, mostly occurred in the harvest rice season, farmers more common, gastrocnemius pain, tenderness or inguinal lymphadenopathy and so on as the identification points.

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