Highly pathogenic avian influenza virus infection
Introduction
Introduction to highly pathogenic avian influenza virus infection The full name is avian influenza virus infection, which is a human acute respiratory infection caused by a strain of certain subtypes of avian influenza A virus. It is an animal infectious disease caused by a virus. It usually only infects birds, and it is rare to infect pigs. Avian influenza viruses are highly specific to specific species, but in rare cases they can infect people across species barriers. The severity of the disease varies, and severe cases can cause sepsis, shock, multiple organ failure, and Reye syndrome and other complications leading to death. basic knowledge Sickness ratio: 0.0001% Susceptible people: no specific population Mode of infection: spread through the respiratory tract, viral infection Complications: pneumonia, acute respiratory distress syndrome, pleural effusion, sepsis, shock
Cause
Causes of highly pathogenic avian influenza virus infection
(1) Causes of the disease
In 1878, avian flu first occurred in Italy, which was called chicken cockroach. It was first discovered in 1900 as a pathogen, a viral virus called true chicken prion. It was not confirmed by serology as avian flu virus until 1955. Avian influenza virus).
Avian influenza virus shape and genome (18%):
The avian influenza virus belongs to the genus of influenza A (A) type of Orthomyxovirus. It is usually spherical in shape and has a diameter of 80-120 nm, with an average of 100 nm. It has an envelope, and the newly isolated or sub-passaged virus is mostly filamentous. The length is different, up to 4000 nm, and the viral genome is a segmented single-stranded negative-strand RNA.
Classification and virulence of avian influenza virus (15):
The avian influenza virus has many subtypes depending on the antigenicity of its outer membrane hemagglutinin (HA) and neuraminidase (NA) proteins. Currently, 15 HA subtypes (H1 to H15) have been identified from poultry, 9 NA subtypes (N1 to N9), especially H5 and H7 subtypes, are highly pathogenic to birds and can cause outbreaks of severe influenza in poultry, followed by H9 and H4 subtypes, due to human influenza every The sub-pandemic is related to H1 to H3 and N1, N2. It has been considered that the avian influenza virus is not pathogenic to humans. The avian flu that has repeatedly occurred in history has included the most serious cases in the United States in 1983 and Mexico in 1995. There have been no reports of avian influenza virus infection in humans, because for specific organisms, viruses need specific genes to make surface proteins, so that they can successfully bind to proteins in the body, and different viruses can infect different organisms. It is not easy to cross the boundaries of species. However, in the case of frequent contact between humans and animals, there may be some strains that mutate and become infected with humans. In May 1997, one case of Hong Kong died of multiple organs of unknown origin. Features A strain of influenza A virus was isolated from a debilitated 3-year-old boy. In August of the same year, it was identified as H5N1 avian influenza virus by the National Influenza Center of the Netherlands and the Center for Disease Control and Prevention (CDC). This is the first time in the world that A was confirmed. Avian influenza virus H5N1 infects humans, followed by H9N2 (Hong Kong 1999) and H7N7 (Netherlands 2003) subtypes infected with humans. In December 2003 and the end of 2004, avian influenza outbreaks occurred in Southeast Asia. Reported cases of highly pathogenic avian influenza virus transmission in Thailand and Vietnam, 44 people infected with H5N1 avian influenza virus in Asia, 32 deaths, and virus antigen surface gene fragments confirmed from Vietnamese patients and H5N1 subtype The same, suggesting that people infected with H5N1 subtype are seriously ill and have a high mortality rate.
Specificity and variability of avian influenza virus (15%):
Avian influenza virus has many serosubtypes, is highly contagious, has a wide distribution, has certain host specificity, and has rapid variation. The mutation of amino acid in the outer membrane HA receptor binding central part may change its host specificity, and other type A Like influenza viruses, there are two main ways in which avian influenza viruses can be mutated, namely, antigenic drift and antigenic shift. Recently, 18 strains of avian influenza virus H5N1 isolated in Hong Kong in 1997 and 1999 were isolated. The H9N2 was found to contain no genetic fragments of mammals such as humans and pigs, indicating that it has not been genetically recombined, that is, the avian influenza virus can be directly transmitted to humans, if infected with human avian influenza virus and human influenza virus in human cells. Recombination occurs in the body to obtain human genome fragments and has the affinity for human cells, which may cause a global influenza pandemic.
Stability of avian influenza virus (15%):
The avian influenza virus is sensitive to organic solvents such as ether, chloroform and acetone. Common disinfectants such as oxidizing agents, dilute acid, sodium lauryl sulfate, halogen compounds (such as bleaching powder and iodine) are also easily inactivated. Avian influenza virus is hot. More sensitive, heating at 56 ° C for 30 min, heating at 60 ° C for 10 min, heating at 65 ~ 70 ° C for a few minutes or boiling (100 ° C) for 2 min can inactivate the virus, direct sunlight for 40 ~ 48h or direct irradiation with ultraviolet light, can quickly destroy Its infectivity, under natural conditions, the virus present in the mouth, nasal cavity and feces is extremely resistant to the protection of organic matter, such as the virus can survive in the feces for 1 week, can survive in water for 1 month, at pH It also has the ability to survive under the conditions of 4.1, and the virus has strong resistance to low temperature. It can survive for a long time at -20 ° C or under vacuum drying, and can maintain viability for more than 1 year in the case of glycerol protection.
(two) pathogenesis
After dissecting two of the six deaths in Hong Kong in 1997 and one of the death veterinarians in the Netherlands in 2003, the lungs were congested and edema, and the cut surface was dark red, hard, cystic, focal and hemorrhagic, severe. Diffuse lesions, accompanied by septal fibrosis, similar to viral pneumonia with sequelae of hyperbaric ventilation, 3 patients with lung tissue using immunohistochemical methods did not find influenza virus antigen, nor found secondary bacterial pneumonia, Epithelial cell regeneration can be seen in the lung tissue of Dutch patients. Atypical lung epithelial cells and ciliated epithelial cells are scattered in the alveolar septum and bronchial wall. These atypical cells are large in shape, with large cell nuclei, rough chromatin and distinct nucleoli, Hong Kong. The pathological examination of 2 death patients also showed that the blood and lymphoid tissue system is characterized by reactive hemophagocytic syndrome. A large number of iron particles are deposited in the tissue cells, and multiple lymph nodes in the body can be seen in the enlarged medullary cavity. Red blood cell phenomenon, mild expansion of the spleen with white pulp atrophy, and extensive hepatic lobular necrosis and acute tubular necrosis The levels of soluble IL-2 receptor, IL-6, and interferon in the blood are elevated. It is speculated that the target cells of the virus are in the respiratory tract, and after the virus replicates in the respiratory tract, the cytokine levels are sharply increased by reactive hemophagocytic syndrome. It suggests that the pathogenesis of avian influenza H5N1 virus infection may be different from human influenza virus H1H3 subtype infection. Due to the limited data, the pathogenesis needs further study.
Prevention
Highly pathogenic avian influenza virus infection prevention
1. Monitor and control the source of infection
The health department cooperates with the agricultural sector to carry out surveillance of human and poultry H5N1 epidemics, exchange information, strengthen quarantine, and prevent the introduction of avian influenza virus, especially highly pathogenic avian influenza virus, into China. In particular, attention should be paid to strengthening countries or countries that are endemic from animal epidemics. Anti-epidemic disinfection of transportation vehicles in the region, prohibiting passengers from carrying or mailing related animals and their products into the country, insisting on the feeding method of all-in and out-out poultry, strengthening disinfection in time, doing a good job of immunization against general diseases, and improving the resistance of poultry. The flu epidemic must be handled in accordance with the relevant provisions of the Animal Quarantine Law. Early diagnosis should be carried out. If highly pathogenic strains such as H5 and H7 are found and diagnosed, the diseased chickens will be strictly isolated, blocked, and culled. Destruction, comprehensive cleaning, cleaning and thorough disinfection of the chicken farm. The current measures are to cull chickens in all chicken farms within 3km of the source of the disease, and to force immunization of chickens within 5km, farmers and all Relevant personnel should do protective work and strengthen monitoring. When flu-like symptoms appear in such personnel, they should be immediately separated. And report the epidemic situation, and conduct epidemiological investigations to prevent the deterioration of the disease and the expansion of the epidemic. Collect the patient's nose, pharyngeal secretions, mouthwash, sputum or tracheal aspirate and serum to the designated experiment while isolating the patients. Room, virus isolation and antibody detection, as soon as possible to confirm the diagnosis.
2, cut off the route of transmission
In the event of a human bird flu epidemic, the poultry farms, commercial poultry stalls, slaughterhouses and patient units, households should be thoroughly disinfected, dead poultry and poultry waste should be destroyed or buried deeply; hospital outpatients and wards Do isolation and disinfection to prevent patient excretion and blood from polluting the hospital environment and medical supplies; medical personnel should do personal protection. Patients who are exposed to bird flu should wear masks, gloves, and gowns. Wash hands after contact, strengthen test specimens and In the laboratory management of avian influenza virus strains, the laboratory for avian influenza virus isolation should meet the P3 standard and strictly enforce the operation rules to prevent infection and spread of nosocomial infections and laboratories.
3. Promote a healthy lifestyle
Usually strengthen physical exercise, avoid overwork, pay attention to nutrition, do not smoke, wash hands frequently, pay attention to food hygiene, do not drink raw water, when the epidemic is found, people should try to avoid contact with poultry, chicken and other foods should be thoroughly cooked, do not eat Raw or semi-cooked animal foods keep fresh air in the room. For close contacts, oral anti-influenza drugs such as amantadine and oseltamivir can be used for prevention.
4, vaccine
The current H1N1, H3N2 and influenza B vaccines cannot prevent H5N1, H7N7 and H9N2 infections. The H9N2 vaccine has been clinically tested in human phase I. It is initially considered to have certain safety and tolerability. Recently, WHO is organizing. Each laboratory conducted a safety and immunogenicity test of the H5N1 vaccine.
Complication
Highly pathogenic avian influenza virus infection complications Complications pneumonia acute respiratory distress syndrome pleural effusion septic shock
Most of the mild cases have a good prognosis and no sequelae. In some cases (especially those with H5N1 infection), the disease develops rapidly, severe pneumonia, acute respiratory distress syndrome, pulmonary hemorrhage, pleural effusion, whole blood cell reduction, multiple organs Failures such as dysfunction, sepsis, shock and Reye syndrome can lead to death. In 1997, 8 of 18 patients in Hong Kong had mild upper respiratory tract infections, 4 had severe pneumonia, and eventually recovered after receiving respiratory support. Six patients died of various complications after monitoring.
Symptom
Symptoms of highly pathogenic avian influenza virus infection Common symptoms Nasal congestion, high fever, cough, sore throat, nausea, soreness, diarrhea, shock, abdominal pain
1. Incubation period
Not yet accurately reported, currently estimated to be within 7 days, usually 1 to 3 days.
2, clinical symptoms
H5N1 virus infections are mostly acute onset, early manifestations similar to common influenza, mainly fever, body temperature mostly lasts above 39 °C, heat range 1 to 7 days, usually 3 to 4 days, may be accompanied by salivation, nasal congestion , cough, sore throat, headache, muscle aches and general malaise, some patients may have nausea, abdominal pain, diarrhea, watery stools and other gastrointestinal symptoms, most of the mild cases have a good prognosis, severe cases of rapid development, pneumonia, Acute respiratory distress syndrome, pulmonary hemorrhage, pleural effusion, whole blood cell reduction, renal failure, sepsis, shock and Reye syndrome, etc., severe cases can cause death, if the body temperature continues to exceed 39 °C during treatment, be vigilant Severe tendency, H7N7 infected patients with mild symptoms, most patients may have conjunctivitis, a small number of patients with mild flu-like symptoms, H9N2 infected only caused transient flu symptoms, no deaths reported.
3, signs
Severe patients may have signs of lung consolidation.
Examine
Highly pathogenic avian influenza virus infection check
1. Peripheral blood and bone marrow
The total number of white blood cells is generally not high or decreased, platelets are normal, and the number of white blood cells and lymphocytes are decreased in severe patients. Bone marrow cytology shows that cells proliferate actively, and reactive histiocytosis with hemorrhagic phagocytosis.
2. Viral antigen and gene detection
The patient's respiratory specimens were taken and the influenza A virus nucleoprotein antigen (NP) and the avian influenza virus H subtype antigen were detected by immunofluorescence (or enzyme-linked immunosorbent assay). The avian influenza virus subtype specificity can also be detected by RT-PCR. H antigen gene, recently Lau et al. used a nucleic acid sequence amplification technology (NASBA) to rapidly detect H5 and H7, which has high sensitivity and specificity, and can distinguish between pathogenic and non-pathogenic diseases to some extent. Sexual avian influenza virus.
3, virus separation
Avian influenza virus is isolated from patient respiratory specimens such as nasopharyngeal secretions, oral sputum, tracheal aspirate or airway epithelial cells.
4, serological examination
Collect double serum at the onset and recovery period, use hemagglutination inhibition test, complement binding test or enzyme-linked immunosorbent assay to detect anti-avian influenza virus antibody. If the titer is 4 times or more, it can be used as a retrospective diagnosis. reference indicator.
Chest X-ray examination of severe patients can show unilateral or bilateral pneumonia, and a small number of patients with pleural effusion.
Diagnosis
Diagnosis and identification of highly pathogenic avian influenza virus infection
Diagnostic criteria
The diagnosis is based on the human bird flu treatment plan (Trial) of the People's Republic of China, that is, according to the epidemiological history, clinical manifestations and laboratory test results, after the exclusion of other diseases, the diagnosis of human avian influenza can be made.
1. Medical observation cases: There is a history of epidemiology, clinical manifestations appear within 1 week, and there is a close contact history with human avian influenza patients, and clinical manifestations appear within 1 week.
2, suspected cases: epidemiological history and clinical manifestations, patients with respiratory secretion specimens using influenza A virus and H subtype monoclonal antibody antigen detection positive.
3, confirmed cases: epidemiological history and clinical manifestations, from the patient's respiratory secretions specimens to isolate specific viruses or RT-PCR detection of avian influenza H subtype virus genes, and the initial stage and recovery period of double serum The anti-avian influenza virus antibody titer is increased by 4 times or more.
Differential diagnosis
Clinical attention should be paid to influenza, common cold, bacterial pneumonia, chlamydia pneumonia, mycoplasma pneumonia, infectious atypical pneumonia, enterovirus infection, cytomegalovirus infection, leptospirosis, infectious mononucleosis and other diseases. Perform a differential diagnosis.
