Treatment plan for human H7N9 avian influenza infection

  Human H7N9 avian influenza is an acute respiratory infectious disease caused by the H7N9 subtype of avian influenza virus. Since February 2013, cases of severe pneumonia of unknown origin have occurred in Shanghai, Anhui Province and Jiangsu Province, of which 3 cases of human H7N9 avian influenza were confirmed and 2 cases died. 3 cases were disseminated and no epidemiological association between the 3 cases has been found.
  I. Pathogenesis
  Avian influenza virus belongs to the genus influenza A virus of the family Orthomyxoviridae. Avian influenza A virus particles are polymorphic, including spherical 80-120 nm in diameter, with a capsule membrane. The genome is segmented single-stranded negative-stranded RNA. based on its outer membrane hemagglutinin (H) and neuraminidase (N) protein antigenicity, currently can be divided into 16 H subtypes (H1 ~ H16) and 9 N subtypes (N1 ~ N9).
  In addition to infecting birds, avian influenza A viruses can also infect humans, pigs, horses, mink and marine mammals. The subtypes of avian influenza viruses that can infect humans are H5N1, H9N2, H7N7, H7N2, H7N3, and the one reported this time is the human H7N9 avian influenza virus. The virus is a novel reassortant virus with internal genes derived from the H9N2 avian influenza virus.
  Avian influenza viruses are generally heat-sensitive and resistant to low temperatures, and can be inactivated by heating at 65°C for 30 minutes or boiling (100°C) for more than 2 minutes. The virus can survive for 1 week at a lower temperature in feces and for 1 month in water at 4°C. It is resistant to an acidic environment and has some survivability at pH 4.0. In the presence of glycerol can remain viable for more than 1 year.
  II. Epidemiology
  (A) The source of infection. It is not clear, based on past experience and epidemiological investigation of this case, it is presumed that the birds carrying H7N9 avian influenza virus and their secretions or excretions.
  (B) Transmission route. Spread by respiratory tract, but also through close contact with infected avian secretions or excretions, etc. Be infected, direct contact with the virus can also be infected. There is no definite evidence of human-to-human transmission.
  (C) susceptible populations. There is no conclusive evidence that humans are susceptible to the H7N9 avian influenza virus. The existing confirmed cases are all adults.
  (D) High-risk populations . At this stage, they are mainly engaged in poultry breeding, sales, slaughtering, processing industry, and those who have been in contact with poultry within 1 week before the onset of the disease.
  III. Clinical manifestations
  According to the incubation period of influenza and the findings of existing cases of H7N9 avian influenza virus infection, the incubation period is generally within 7 days.
  (i) General manifestations.
  Patients generally present with flu-like symptoms, such as fever, cough, little sputum, which may be accompanied by headache, muscle aches and general discomfort. Severely ill patients develop rapidly and show severe pneumonia, with body temperature mostly persisting above 39℃, respiratory distress, and may be accompanied by hemoptysis; acute respiratory distress syndrome, mediastinal emphysema, sepsis, shock, impaired consciousness and acute kidney injury may appear in rapid progress.
  (B) Laboratory tests.
  1, blood routine. Total white blood cell count is generally not high or reduced. Severely ill patients mostly have total leukocyte and lymphocyte reduction, and have reduced platelets.
  2, blood biochemical examination. Most of them have elevated creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, elevated C-reactive protein, and myoglobin may be elevated.
  3, pathogenic testing.
  (1) Nucleic acid detection. The H7N9 avian influenza virus nucleic acid was detected by real time PCR (or RT-PCR) on the patient’s respiratory specimens (such as nasopharyngeal secretions, oral gargle, tracheal aspirates or respiratory epithelial cells).
  (2) Virus isolation. H7N9 avian influenza virus was isolated from the patient’s respiratory specimen.
  (3) Chest imaging. Pneumonia occurs in patients with lamellar images in the lungs. In severe cases, the lesions progress rapidly, showing multiple ground glass images of both lungs and solid lung images, which may be combined with a small amount of pleural effusion. When ARDS occurs, the lesions are widely distributed.
  (IV) Prognosis. The prognosis of patients with severe human H7N9 avian influenza infection is poor. Factors affecting prognosis may include patient age, underlying diseases, comorbidities, etc.
  IV. Diagnosis and differential diagnosis
  (A) Diagnosis. The diagnosis of human H7N9 avian influenza can be made based on epidemiological contact history, clinical manifestations and laboratory test results. In cases where the epidemiological history is unknown, the diagnosis can be made based on clinical manifestations, ancillary examinations and laboratory test results, especially if the H7N9 avian influenza virus is isolated from the patient’s respiratory secretion specimen, or if the H7N9 avian influenza virus is tested positive for nucleic acid.
  1, epidemiological history. History of contact with birds and their secretions and excretions within 1 week before the onset of the disease.
  2, diagnostic criteria.
  (1) suspected cases: consistent with the above clinical symptoms and blood routine, biochemical and chest imaging features, positive for influenza A virus universal primer and excluded seasonal influenza, can have a history of epidemiological exposure.
  (2) Confirmed cases: meet the diagnostic criteria for suspected cases, and H7N9 avian influenza virus was isolated from respiratory secretion specimens or H7N9 avian influenza virus nucleic acid test positive.
  Serious cases: pneumonia combined with respiratory failure or other organ failure is a serious case.
  (B) Differential diagnosis. Attention should be paid to the differential diagnosis of human infection with highly pathogenic H5N1 avian influenza, seasonal influenza (including influenza A H1N1), bacterial pneumonia, infectious atypical pneumonia (SARS), novel coronavirus pneumonia, adenovirus pneumonia, chlamydial pneumonia, mycoplasma pneumonia and other diseases. The differential diagnosis mainly relies on pathogenetic examination.
  V. Treatment
  (a) Patients with clinical diagnosis and confirmation should be treated in isolation.
  (B) Symptomatic treatment. Oxygen, antipyretics, cough expectorants, etc. can be applied.
  (C) Anti-viral treatment. Anti-influenza virus drugs should be applied as early as possible.
  1, neuraminidase inhibitors: can choose oseltamivir (Oseltamivir) or zanamivir (Zanamivir), clinical applications show that the avian influenza virus H5N1 and H1N1 infection, etc. effective, presumably for human infection with H7N9 avian influenza virus should be effective. Oseltamivir adult dose 75mg twice daily, the dose can be doubled in severe cases, the course of treatment 5-7 days. Zanamivir adult dose of 10mg, twice daily inhalation.
  2, ion channel M2 blockers: the current laboratory data suggest that amantadine (Amantadine) and amantadine (Rimantadine) resistance, not recommended for use alone.
  (D) Chinese medicine treatment.
  1.Epidemic toxin offends the lung, and the lung loses its propagation and descent
  Symptoms: fever, cough, little phlegm, headache, muscle and joint pain.
  Treatment: clearing heat and promoting the lung
  Reference prescription.
  Mulberry leaf, honeysuckle, forsythia, fried almonds, gypsum, rehmannia, artemisia, scutellaria, raw licorice.
  Decoction with water, 1-2 doses daily, taken orally every 4-6 hours.
  Add or subtract: add loquat leaves and zhebei mu if the cough is severe.
  Chinese patent medicines: Shufeng detoxification capsule, Lianhua Qingfei capsule, Qingkailing injection can be chosen.
  2.Epidemic toxin congestion in the lung, internal closure and external release
  Symptoms: high fever, cough, little sputum, breathlessness, shortness of breath, hemoptysis, warmth at the end of the day, cold sweat, restlessness, or even delirium.
  Treatment: Clearing the lung and detoxifying the toxin, supporting the righteousness and fixing the detoxification.
  Reference prescription.
  Roasted ephedra, fried almonds, raw gypsum, Zhi Mu, fishy grass, scutellaria
  Fried gardenia, tiger scepter, cornelian, ginseng
  Decoction with water, 1-2 doses daily, taken orally or intranasally every 4-6 hours.
  Add and subtract: for those with high fever, confusion, or even faint delirium, take An Gong Niu Huang Wan above; for those with cold extremities and dripping sweat, add ginseng, cannon root, calcined keel, calcined oyster; for those with hemoptysis, add red peony, Xian He Cao, and Phellodendron leaf; for those with cyanosis of mouth and lips, add Panax ginseng, motherwort, astragalus, and angelica tail.
  Proprietary Chinese medicine: Ginseng and wheat injection, raw vein injection can be chosen.
  (E) Strengthen supportive treatment and prevent complications. Pay attention to rest, drink more water, increase nutrition, and give an easily digestible diet. Observe closely, monitor and prevent complications. Antibacterial drugs should be used when secondary bacterial infection is clear or when there is sufficient evidence to suggest secondary bacterial infection.
  (vi) Treatment of critically ill patients. Critically ill patients should be admitted to the hospital, and those who develop respiratory dysfunction should be given oxygen and other appropriate respiratory support, and those who develop other complications should be actively treated accordingly.
  1.Respiratory function support.
  (1) Mechanical ventilation: The condition of critically ill patients progresses rapidly and can develop into acute respiratory distress syndrome (ARDS) relatively quickly. In severe cases requiring mechanical ventilation, the principles of ARDS mechanical ventilation can be referred to.
  = 1 * GB3 ① Non-invasive positive pressure ventilation: In patients presenting with respiratory distress and/or hypoxemia, non-invasive ventilation may be attempted early. However, in severe cases, non-invasive ventilation is not effective and early consideration of invasive ventilation is required.
  = 2 * GB3 ② Invasive positive pressure ventilation: Given that some patients are more prone to air pressure injury, an ARDS protective ventilation strategy should be used.
  (2) Extracorporeal membrane oxygenation (ECMO): When conventional mechanical ventilation cannot maintain satisfactory oxygenation and/or ventilation, ECMO is recommended when available.
  (3) Others: When satisfactory oxygenation cannot be maintained by conventional mechanical ventilation, prone position ventilation or high frequency oscillatory ventilation (HFOV) can be considered.
  2. Other treatment: In addition to respiratory function support treatment, attention should be paid to the monitoring and treatment of other organs’ functional status; prevention and timely treatment of various complications, especially hospital-acquired infections.
  VI. Other
  Strictly standardize hospital infection control measures for medical institutions that admit patients with human H7N9 avian influenza. Follow the principles of standard prevention, according to the disease transmission route to take preventive and control measures. Specific measures based on the “Technical Guidelines for Prevention and Control of Human Infection with H7N9 Avian Influenza Hospital Infection (2013 Edition)” of the relevant provisions.