Influenza, also known as flu, is an acute respiratory infectious disease caused by influenza virus, and is characterized by acute onset, high fever, headache, malaise, conjunctivitis, generalized myalgia, and mild respiratory catarrh. The virus is mainly transmitted through contact and air droplets. The disease is seasonal and the general population is susceptible.
Etiology
Influenza virus belongs to the family Orthomyxoviridae, and is RNA virus. There is a lipid capsule with glycoprotein protrusions composed of hemagglutinin and neuraminidase on the surface of the virus. According to the different antigenicity of the internal antigen nucleoprotein, influenza virus can be divided into type A, B, C, and D. According to the difference in the antigenicity of the external antigen hemagglutinin and neuraminidase, influenza A virus is divided into different subtypes. Antigenic variation is the most significant feature of influenza virus. Influenza A virus is very prone to mutation, mainly mutation of hemagglutinin (H) and neuraminidase (N). There are 18 types of H and 11 types of N. Influenza viruses can have antigenic drift and shift. The former is a quantitative change due to the changes in antigenic sites resulting from the accumulation of point mutations in the genes encoding surface antigens (HA, NA), while the latter is a qualitative change as a result of the emergence of new subtypes resulting from the rearrangement of the genome. Influenza A virus can have large mutations (both H and N mutations), subtype mutations (large H mutation, no or small N mutation), and variant mutations (small H and small N mutations). Depending on the antigenic mutation scales, the original immunity of the human body may be completely or partially ineffective against the mutated new virus, thereby causing influenza epidemics. Influenza B virus is also prone to variant mutations, influenza C virus generally does not mutate, and the mutation of influenza D virus is still under study. The prevalence of influenza is closely related to the binding efficiency of the viral hemagglutinin to α2,6-sialic acid expressed by respiratory epithelial cells and transcriptional synthesis efficiency within host cells.
Influenza A virus often causes severe disease and pandemics, influenza B and C viruses cause sporadic cases and epidemics, and Influenza D virus mainly infects cattle and other animals. On account of the rapid change in the antigenicity of influenza viruses, humans cannot obtain lasting immunity. There is no apparent seasonality in epidemics, and sporadic cases are more common in winter and spring. Patients are mostly children and older adults. In recent influenza epidemics, H5N1 occurred mainly in older adults, H1N1 occurred in children, and H7N9 occurred in older adults, particularly those with diabetes and chronic obstructive pulmonary disease.
Pathogenesis and pathology
Influenza virus is mainly transmitted through viral particles in the air or close contact. Influenza virus invades the ciliated columnar epithelial cells of the respiratory tract and replicates there. After the RNA of the influenza virus is transported into the host cell nucleus, with the participation of viral transcriptase and cellular RNA polymerase, the viral RNA is transcribed, forming complementary RNA bound to ribosomes, which is mRNA; with the participation of replicase, the viral RNA is replicated using nucleotides of the host and then migrates to the cytoplasm for assembly; finally, the new viruses are released from the cells through the action of neuraminidase, and invade other epithelial cells, causing lesions. In case of concurrent pneumonia, there are symptoms of bronchopneumonia such as pulmonary congestion and edema, and fibrin and exudate in the alveoli. Some influenza patients have severe pneumonia which may rapidly progress to acute respiratory distress syndrome (ARDS).
Clinical manifestations
The incubation period is generally 1 - 7 days, mostly 2 - 4 days.
The symptoms are fever, headache, myalgia, malaise, and body temperature up to 39°C - 40°C in the early stage, followed by chills and rigors, often accompanied by generalized myalgia and arthralgia, fatigue, and anorexia. Pharyngeal pain, dry cough, nasal obstruction, nasal discharge, retrosternal discomfort, facial flushing, and conjunctival congestion are also often present. Some patients are mild or asymptomatic.
In children, fever is usually severe, and digestive tract symptoms such as nausea, emesis, and diarrhea are more common in influenza B. In neonates, hypersomnia, milk refusal, and apnea are apparent.
In patients without complications, since the disease is self-limiting, fever gradually subsides and the systemic symptoms improve 3 - 5 days after onset, but cough relief and physical recovery often take a long time.
Laboratory examination
The total peripheral white blood cell count is normal or decreased, and lymphocytes are reduced. Nasopharyngeal secretions, lower respiratory tract secretions, and oral fluid can be used to isolate the influenza virus. A 4-fold increase in serum anti-influenza virus antibody titer between early stage and convalescent stage is helpful for retrospective diagnosis. Rapid nasopharyngeal swab examination or serum virus PCR examination is helpful for early diagnosis, with high sensitivity and specificity, and is currently widely used in the diagnosis of clinical influenza and other respiratory viruses.
Diagnosis
Diagnosis is mainly based on epidemiology, clinical manifestations, and etiological examination, and false positives and false negatives of viral antigen detection should be considered.
Treatment
Suspected and confirmed patients should be isolated.
Antipyretics, analgesics, anti-inflammatory agents, antitussives, and expectorants can be used.
Antiviral medications should be administered within 48 hours after onset. The new influenza antiviral drug baloxavir marboxil is a cap-dependent endonuclease inhibitor, which can inhibit the transcription of influenza virus mRNA. Moreover, administration of single dose (40 - 80mg) within 48 hours after onset can inhibit viral replication. Neuraminidase inhibitors can inhibit influenza virus replication, reduce pathogenicity, relieve symptoms, shorten the course of the disease, and reduce complications. These drugs have low toxicity, less resistance, and good tolerance. Other treatment regimen includes oral oseltamivir 75mg twice a day for at least 5 days in adults, or until two negative virus tests in severe patients; intravenous peramivir 300 - 600mg once a day; and inhaled zanamivir 5mg twice a day for 5 days in adults and adolescent patients over age 12. The hemagglutinin inhibitor arbidol is also used for the treatment of influenza. In addition, M2 ion channel blocker amantadine and rimantadine are basically not used clinically due to their high resistance and side effects.
Attention should be paid to good rest, adequate water intake, rehydration, and correction of electrolyte disturbances. Complications should be prevented. Respiratory supportive treatment is given in case of respiratory failure, and extracorporeal membrane oxygenation (ECMO) can be used if necessary. Antibiotics should be used promptly in case of secondary bacterial infection.
Prognosis
Prognosis is associated with the virulence of viruses and autoimmune of humans. The older adults and infirm individuals are susceptible to influenza pneumonia and have a high mortality. Simple influenza presents good prognosis. Influenza vaccination, especially in children and older patients, can alleviate secondary influenza symptoms.
Prevention
Vaccination
Vaccination is the most effective means of preventing influenza, and can reduce the risk of influenza infection and serious complications. It is recommended that older adults age 60 and above, children age 6 months to 5 years, pregnant women, family members and caregivers of children under 6 months of age, patients with chronic diseases, and medical staff get vaccinated every year.
Antiviral prophylaxis
Antiviral prophylaxis cannot replace vaccination. It is recommended that postexposure prophylaxis should be administered in unvaccinated persons in close contact with high risk factors for severe influenza within 48 hours after exposure. The prophylaxis plan is oseltamivir or zanamivir for 7 days, and the dose is consistent with that of treatment.