Influenza¶
Chapter 206 | Part 5: Infectious Diseases
KEY CLINICAL POINTS¶
- Influenza is a systemic respiratory illness caused by influenza A, B, and C viruses, characterized by fever, myalgia, and seasonal epidemics.
- Influenza A viruses are most clinically significant due to their segmented genome enabling antigenic shift and drift, leading to pandemics.
- Annual influenza vaccines target hemagglutinin (H) and neuraminidase (N) proteins, with trivalent/quadrivalent formulations based on WHO/CDC recommendations.
- Neuraminidase inhibitors (oseltamivir, zanamivir) are first-line antivirals for high-risk patients, effective when initiated within 48 hours of symptom onset.
- High-risk groups include children <5 years, adults ≥ 65 years, pregnant women, and immunocompromised individuals, requiring prioritization for vaccination.
1. DEFINITION & OVERVIEW¶
Influenza is a clinically defined respiratory illness with systemic symptoms (fever, myalgia, malaise) caused by orthomyxoviruses. It is distinguished by its propensity for winter epidemics, rapid transmission, and potential for global pandemics (e.g., 1918 H1N1 pandemic).
Table 206-1: Antigenic Subtypes of Influenza A Virus¶
| YEARS | SUBTYPE | EXTENT OF OUTBREAK |
|---|---|---|
| 1889–1890 | H2N8a | Severe pandemic |
| 1900–1903 | H3N8a | Moderate epidemic |
| 1918–1919 | H1N1b | Severe pandemic |
| 1933–1935 | H1N1b | Mild epidemic |
| 1946–1947 | H1N1 | Mild epidemic |
| 1957–1958 | H2N2 | Severe pandemic |
| 1968–1969 | H3N2 | Moderate pandemic |
| 1977–1978 | H1N1 | Mild pandemic |
| 2009–2010 | H1N1pdm | Pandemic |
1.1 Viral Classification¶
Influenza A, B, and C viruses are enveloped, negative-sense RNA viruses with hemagglutinin (H) and neuraminidase (N) surface glycoproteins. A viruses are most clinically significant due to their segmented genome and antigenic variability.
1.2 Pandemic Potential¶
Antigenic shift (reassortment of viral genes) can generate novel strains with pandemic potential. Historical pandemics include 1918 H1N1, 1957 H2N2, 1968 H3N2, and 2009 H1N1pdm.
2. EPIDEMIOLOGY¶
Influenza causes seasonal epidemics in temperate climates, with peak activity in winter. Global circulation patterns (e.g., Southern Hemisphere) inform Northern Hemisphere vaccine composition. Pandemic potential is influenced by viral transmissibility, host susceptibility, and antigenic match to vaccines.
Table 206-2: High-Risk Groups for Influenza Vaccination¶
| High-Risk Group |
|---|
| Children 6–59 months of age |
| Adults ‡50 years of age |
| Persons with chronic pulmonary, cardiovascular, renal, hepatic, neurologic, hematologic, or metabolic disorders |
| Immunocompromised individuals |
| Pregnant women |
| Children/adolescents on aspirin/salicylate |
| Residents of long-term care facilities |
| Extremely obese individuals (BMI ‡40) |
| Caregivers/contacts of high-risk individuals |
2.1 Seasonality and Transmission¶
Seasonal outbreaks occur during cooler months, with transmission via respiratory droplets and aerosols. Community mitigation measures (e.g., during COVID-19) significantly reduced influenza circulation in 2020.
2.2 Mortality and Burden¶
Annual mortality ranges from 4,900 to 51,000 deaths in the U.S. (2010–2023). Excess pneumonia/influenza mortality peaked in 1918, with 50 million deaths globally. Pediatric absenteeism and hospitalizations are most pronounced during epidemics.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Influenza A viruses (8-segmented RNA) cause most severe disease. Antigenic drift (point mutations) and shift (reassortment) drive immune evasion. Hemagglutinin mediates viral entry, while neuraminidase facilitates release. Swine act as mixing vessels for avian/human reassortment.
Table 206-3: Influenza Vaccines in the U.S.¶
| Route | Approved Ages | HA Content | Substrate | Number of Strains |
|---|---|---|---|---|
| Intranasal | 2–49 years | 15 µg | Eggs | 3 |
| Intramuscular (Standard) | ‡6 months | 15 µg | Eggs/cell culture | 3 |
| Intramuscular (High-Dose) | ‡65 years | 60 µg | Eggs | 3 |
| Route | Approved Ages | HA Content | Substrate | Number of Strains |
|---|---|---|---|---|
| Intramuscular (Recombinant) | ‡18 years | 45 µg | Cell culture | 3 |
| Intramuscular (Adjuvanted) | ‡65 years | 15 µg | Eggs | 3 |
3.1 Viral Structure and Replication¶
Viruses bind to sialic acid receptors via hemagglutinin, enter cells via endocytosis, and replicate in the nucleus. Neuraminidase cleavage enables viral release. Reassortment in co-infected cells generates new antigenic variants.
3.2 Host Factors¶
Human sialic acid receptors ( α -2,6-galactose) favor influenza A, while avian receptors ( α -2,3-galactose) favor influenza B. Swine have both, enabling interspecies transmission.
4. CLINICAL FEATURES¶
Symptoms include fever, chills, myalgia, cough, and fatigue. Complications include pneumonia, myositis, and neurological manifestations (e.g., encephalitis, Guillain-Barré syndrome). Pediatric presentations may include croup or otitis media.
4.1 Respiratory Symptoms¶
Cough, sore throat, rhinorrhea persist beyond systemic symptoms. Postinfectious pulmonary function decline is common in athletes and elderly.
4.2 Extrapulmonary Manifestations¶
Myositis (B virus), Reye syndrome (aspirin use), and neurological complications (encephalitis, transverse myelitis) occur. Postinfectious autoimmune syndromes (e.g., Guillain-Barré) are rare.
5. DIFFERENTIAL DIAGNOSIS¶
Influenza must be differentiated from other respiratory viruses (RSV, SARS-CoV-2) and bacterial infections. Clinical overlap with COVID-19 (fever, cough) necessitates testing. Seasonal patterns and epidemiologic data aid diagnosis.
5.1 Viral Mimics¶
Respiratory syncytial virus (RSV) and SARS-CoV-2 cause similar symptoms. RSV predominates in infants, while SARS-CoV-2 may present with anosmia or ageusia.
5.2 Bacterial Infections¶
Streptococcus pneumoniae and Haemophilus influenzae may cause secondary pneumonia. Differentiation relies on clinical context and diagnostic testing.
6. INVESTIGATIONS & DIAGNOSIS¶
Rapid diagnostic tests (RIDTs) detect viral antigens in 10–15 minutes. Molecular assays (NAATs) identify viral RNA. Serologic confirmation requires paired sera. Imaging (chest X-ray) aids in diagnosing pneumonia.
6.1 Diagnostic Testing¶
RIDTs (e.g., rapid influenza diagnostic tests) and NAATs (e.g., RT-PCR) are used for confirmation. Serology is less practical for acute diagnosis.
6.2 Imaging¶
Chest X-ray reveals diffuse infiltrates in viral pneumonia. CT may show ground-glass opacities in severe cases.
7. MANAGEMENT & TREATMENT¶
Antiviral therapy (oseltamivir, zanamivir) is recommended for high-risk patients within 48 hours of symptom onset. Supportive care includes hydration, rest, and monitoring for complications. Vaccination remains the primary preventive measure.
7.1 Antiviral Therapy¶
Neuraminidase inhibitors reduce viral replication and duration of illness. Resistance is rare but possible with prolonged use. Oseltamivir is preferred in hospitalized patients.
7.2 Supportive Care¶
Hydration, oxygen therapy, and corticosteroids may be used in severe cases. Antibiotics are reserved for confirmed bacterial superinfections.
8. PROGNOSIS & COMPLICATIONS¶
Mortality is highest in elderly, immunocompromised, and those with underlying cardiopulmonary disease. Complications include secondary bacterial pneumonia, myocarditis, and acute respiratory distress syndrome (ARDS).
8.1 Mortality Rates¶
Annual mortality ranges from 4,900 to 51,000 in the U.S. (2010–2023). 1918 pandemic had 50 million global deaths due to high virulence and cytokine storm.
8.2 Long-Term Effects¶
Postinfectious pulmonary function decline and myoglobinuria (rhabdomyolysis) may occur. Neurological sequelae are rare but possible.
9. SPECIAL CONSIDERATIONS¶
Pregnant women, children, and elderly require prioritization for vaccination. Aspirin use in children is contraindicated due to Reye syndrome risk. Adjuvanted vaccines may increase local reactions.
9.1 Pregnancy¶
Influenza vaccination is recommended during any trimester. Antiviral therapy (oseltamivir) is safe in pregnancy.
9.2 Pediatric Considerations¶
LAIV (live attenuated vaccine) is contraindicated in children <2 years. Aspirin use in children with influenza is prohibited.
10. KEY POINTS & CLINICAL PEARLS¶
Influenza is a systemic viral infection with seasonal epidemics. Vaccination is the most effective preventive measure. Neuraminidase inhibitors reduce morbidity/mortality in high-risk patients. Rapid diagnostic testing and antiviral therapy within 48 hours are critical for severe cases.