Influenza, commonly known as the flu, is an acute respiratory infectious disease caused by the influenza virus. Its clinical features include sudden onset of high fever, chills, headache, fatigue, generalized muscle aches, and mild respiratory symptoms. Infants, young children, and individuals with weakened immune systems are more prone to complications such as pneumonia, which can lead to severe outcomes, including death.
Virology
Influenza viruses belong to the Orthomyxoviridae family and are single-stranded, negative-sense, segmented RNA viruses. They are classified into four types: A, B, C, and D, based on differences in nucleoproteins and matrix proteins. Influenza A viruses, particularly subtypes H1N1 and H3N2, and influenza B viruses from the Victoria and Yamagata lineages are most commonly responsible for human infections. The virus is sensitive to commonly used disinfectants such as ethanol, povidone-iodine, and tincture of iodine, as well as to ultraviolet light and heat. It becomes inactivated at 56°C within 30 minutes.
Epidemiology
Both infected individuals and asymptomatic carriers act as primary sources of transmission. Influenza viruses spread mainly via droplets from sneezing or coughing and can infect others through direct or indirect contact with mucous membranes of the mouth, nose, or eyes. Transmission is possible from the late incubation period to the acute phase. The virus is typically shed in respiratory secretions for 3–7 days, but in children, immunocompromised individuals, and critically ill patients, viral shedding can last longer than one week. The general population is universally susceptible. Vaccination can effectively prevent infection by specific influenza virus subtypes.
Pathogenesis
Influenza A and B viruses initiate infection by binding hemagglutinin (HA) to sialic acid receptors on the surface of respiratory epithelial cells. The virus enters host cells via endocytosis, and its genome undergoes transcription and replication in the cell nucleus. This leads to the production of large amounts of progeny viruses, which infect additional cells. In severe cases, influenza virus infection can trigger a cytokine storm, resulting in systemic inflammatory response syndrome. This can cause complications such as acute respiratory distress syndrome (ARDS), shock, encephalopathy, and multiple organ dysfunction syndrome.
Pathology
The main pathological changes include clustered shedding of ciliated epithelial cells in the respiratory tract, epithelial cell metaplasia, and congestion and edema of the lamina propria with infiltration of mononuclear cells. Severe cases may show evidence of pneumonia, while critically ill patients can exhibit diffuse alveolar damage. Encephalopathy-associated cases may present with diffuse congestion, edema, and necrosis in brain tissue; acute necrotizing encephalopathy is characterized by symmetrical necrotic lesions, primarily centered in the thalamus. Cardiac involvement includes findings of myocarditis, such as interstitial hemorrhage, lymphocytic infiltration, and myocardial cell swelling or necrosis.
Clinical Manifestations
The incubation period typically ranges from 1 to 7 days, most often lasting 2 to 4 days.
In children, influenza often begins abruptly, with the primary symptom being fever. Body temperature can reach 39–40°C and may be accompanied by chills or shivering. Additional systemic symptoms include headache, generalized muscle and joint pain, fatigue, and reduced appetite. Respiratory symptoms such as sore throat, dry cough, nasal congestion, runny nose, retrosternal discomfort, facial flushing, and conjunctival congestion are common. Some patients may have mild symptoms or remain asymptomatic.
Severe cases, particularly in children, may progress rapidly. Persistent high fever above 39°C can lead to the rapid onset of ARDS, sepsis, septic shock, heart failure, kidney failure, or multiple organ dysfunction. The primary causes of death are respiratory complications and influenza-associated encephalopathy or encephalitis. Secondary bacterial infections increase the risk of mortality. Common pathogens include Staphylococcus aureus, Streptococcus pneumoniae, and other streptococcal species.
Pneumonia is the most frequent complication, while other complications include neurological disorders, cardiac damage, myositis and rhabdomyolysis, and shock. Children are more prone than adults to developing complications such as laryngitis, otitis media, and bronchitis.
Pneumonia
Influenza viruses can infect the lower respiratory tract, causing primary viral pneumonia. Some severe influenza cases may also involve secondary infections with bacterial, fungal, or other pathogens. ARDS can occur in the most severe cases.
Neurological Complications
These include meningitis, encephalitis, myelitis, encephalopathy, and Guillain-Barré syndrome. Acute necrotizing encephalopathy is most commonly seen in children.
Cardiac Complications
Cardiac damage primarily manifests as myocarditis and pericarditis, with abnormalities detectable through cardiac biomarkers, electrocardiography, and echocardiography. Severe cases may progress to heart failure. Additionally, infection with the influenza virus significantly increases the risk of myocardial infarction, ischemic heart disease-related hospitalization, and mortality.
Myositis and Rhabdomyolysis
These complications involve muscle pain, muscle weakness, and elevated serum creatine kinase and myoglobin levels. Severe cases can lead to acute kidney injury.
Laboratory Examinations
Complete Blood Count (CBC)
Peripheral white blood cell counts are generally normal or decreased, with a significant reduction in lymphocyte count in severe cases.
Biochemical Tests
Elevations in aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and creatinine levels may occur. A minority of patients may exhibit increased creatine kinase levels. Electrolyte imbalances such as hypokalemia may also manifest in some cases.
Arterial Blood Gas Analysis
Severe cases may exhibit decreases in partial pressure of oxygen (PaO2), oxygen saturation, and oxygenation index, along with acid-base imbalances.
Cerebrospinal Fluid (CSF) Analysis
In cases involving the central nervous system, cell counts and protein levels in CSF may be normal or elevated. Acute necrotizing encephalopathy typically presents with normal cell counts and elevated protein levels.
Virological Tests
Viral nucleic acid testing is highly sensitive and specific. RT-PCR can detect influenza virus nucleic acids in respiratory specimens and can differentiate between virus subtypes. Influenza virus can also be cultured and isolated from respiratory specimens. Retrospective diagnosis is supported by observing a fourfold or greater increase in influenza-specific IgG antibody levels between the acute and recovery phases. The sensitivity and specificity of IgM antibody testing are relatively low.
Imaging Studies
In cases of pneumonia, chest X-rays may reveal patchy infiltrates in the lungs. Chest CT scans may show ground-glass opacities, bilateral or multilobar exudative lesions, or consolidation. Pleural effusion may be present in a small number of patients.
Diagnosis and Differential Diagnosis
The diagnosis of influenza can be established based on an epidemiological history and characteristic clinical features, along with one or more positive laboratory findings: detection of influenza virus nucleic acid, positive antigen testing, isolation of the virus through culture, or a fourfold or greater increase in influenza virus-specific IgG antibody levels between the acute and recovery phases.
Differentiation from other conditions is necessary, including the common cold, respiratory infections caused by other pathogens, novel coronavirus infections, and viral encephalopathy or encephalitis caused by other viruses.
Treatment
For children with severe influenza or those at high risk of severe complications, early initiation of antiviral therapy within 48 hours of symptom onset is crucial. Clinical and confirmed cases should undergo isolation and treatment as early as possible.
Antiviral Therapy
Oseltamivir
For infants ≤8 months: 6 mg/(kg·day).
For infants aged 9–11 months: 7 mg/(kg·day).
For children ≥1 year:
- ≤15 kg: 60 mg/day.
- 16–23 kg: 90 mg/day.
- 24–40 kg: 120 mg/day.
- 40 kg: 150 mg/day.
These doses are divided into two oral administrations per day, with a treatment course of 5 days.
Zanamivir
For children >7 years: 10 mg inhalation, twice daily, for 10 days.
Peramivir
Dose: 10 mg/(kg·day), with a maximum dose of 600 mg per day, administered intravenously for 5–10 days.
Management of Complications and Severe Cases
Appropriate treatment of primary conditions and prevention, as well as management of complications, should be undertaken. Effective organ protection and functional support are required. In cases where any of the following occur, bacterial coinfection should be suspected, and further investigations and empiric antimicrobial treatment should be initiated alongside antiviral therapy:
- Early signs of severe influenza.
- Worsening of symptoms after initial clinical improvement with early antiviral treatment.
- Lack of improvement after 3–5 days of antiviral therapy.
Prevention
Adopting good personal hygiene practices is critical for preventing influenza and other respiratory infections. Measures include frequent handwashing, avoiding crowded places, and minimizing contact with individuals who have respiratory symptoms. When a family member is infected with influenza, efforts to reduce close contact with others are important.
Annual influenza vaccination is the most effective strategy for preventing influenza and reducing the risk of severe complications. Children older than 6 months benefit from influenza vaccine protection against the virus. Antiviral prophylaxis cannot replace vaccination. Post-exposure prophylaxis is recommended for close contacts at high risk of severe influenza, ideally within 48 hours of exposure. Oseltamivir or Zanamivir can be used for such prophylaxis.