Description

Acute, typically self-limited, febrile infection caused by orthomyxovirus influenza types A and B marked by inflammation of nasal mucosa, pharynx, conjunctiva, and respiratory tract

Epidemiology

• Outbreaks of influenza occur annually during the fall–winter months in the Northern and Southern Hemispheres.
• Influenza virus can undergo antigenic shift (abrupt change) leading to viral strains with little immunologic resistance in a population, resulting in pandemic outbreaks. Minor seasonal variations are called antigenic drift.
• Persons of all ages are susceptible to infection. Notable demographics at risk for complications and hospitalization include:
  • Those between <2 and >65 years old; immunocompromised states, including pregnancy up to 2 weeks postpartum
  • Individuals with cardiovascular or pulmonary disease, Addison disease, or diabetes; residents of nursing homes or other long-term care facilities

Incidence
Incidence is difficult to ascertain as most individuals do not seek medical care and are therefore not diagnosed.

Prevalence
In the United States, on the 2022–2023 season, the preliminary data reveals an estimated 27 to 54 million confirmed positive cases with 12 to 26 million related medical visits, 300,000 to 650,000 hospitalizations and between 19,000 and 58,000 deaths. Since the introduction of SARS-CoV-2 into the community, influenza rates have decreased as compared to prepandemic. The 2021–2022 season remained historically low with the CDC reporting 9 million flu illnesses, 4 million flu-related medical visits, 100,000 flu-related hospitalizations, and 5,000 flu deaths. Influenza A (H3N2) was the most dominant strain of the season. The number of cases of influenza-associated illness, hospitalizations, and deaths were the lowest since the 2011–2012 season. Rates increased in 2022, likely due in part to changing isolation guidelines (i.e., increased interpersonal contact) in the context of the COVID pandemic.

Etiology and Pathophysiology

Orthomyxovirus (influenza types A [majority] and B); influenza A virus subtypes HxNx based on hemagglutinin and neuraminidase

• Incubation is 1 to 4 days; infected persons are most contagious during peak symptoms. Spread by aerosolized droplets or contact with respiratory secretions, hemagglutinin binds to columnar respiratory epithelium where replication occurs, and neuraminidase protein facilitates spread along respiratory epithelium (1).

Risk Factors

• For contracting disease:
  • Crowded environments such as nursing homes, barracks, schools, and correctional facilities
• For complications:
  • Neonates, infants, elderly; pregnancy (including 2 weeks postpartum) especially in 3rd trimester
  • Chronic pulmonary diseases; cardiovascular diseases, including valvular pathology and congestive heart failure
  • Metabolic disease, morbid obesity; hemoglobinopathies; malignancy
  • Immunosuppression; neuromuscular diseases that limit respiratory function and ability to handle secretions

General Prevention

• All persons aged ≥6 months should be vaccinated annually unless contraindication is present.
• Live attenuated influenza vaccine (LAIV) is a quadrivalent intranasal vaccine approved for healthy, nonpregnant individuals between 2 and 49 years of age.
• Inactivated influenza vaccine (IIV) is available either as trivalent (IIV3) or quadrivalent (IIV4) with either three or four strains of influenza. IIV also is available as high-dose, intradermal, cell culture–based (ccIV3), MF59-adjuvanted (aIIV3), and recombinant hemagglutinin vaccine (RIV3).
• IIV is recommended annually for all persons aged ≥6 months. Vaccine should be administered annually as soon as the vaccine is available. Protection occurs 1 to 2 weeks after immunization. Typically, mild side effects include low-grade fever and local reaction at the vaccination site. Inactivated IM dose: ≥3 years of age: 0.5 mL; children 6 to 35 months of age: 0.25 mL. Intradermal formulation for 18- to 64-year-olds uses a short 30-gauge needle in a single-use prefilled syringe with 0.1 mL vaccine; somewhat higher local reactions when given intradermal; single annual dose except for children <9 years of age, who should receive two doses (4 weeks apart) the 1st year they receive influenza vaccine
• Vaccine contraindication: Severe allergy such as anaphylaxis to IIV components, allergies from eggs are not considered a contraindication; observe all patients for 15 minutes after vaccination; no skin testing with influenza vaccine is needed in egg-allergic patients. RIV is safe in patients with an egg allergy.
• IIV-HD: high-dose quadrivalent IIV contains 4 times the antigen concentration of IIV; licensed for persons ≥65 years of age; results in higher antibody levels but somewhat higher rates of local reactions; Advisory Committee on Immunization Practices does not express a preference for/against IIV-HD.
• Antiviral prophylaxis depends on current resistance patterns each year; see https://www.cdc.gov/flu/ for patterns or check with local health department. In high-risk groups that have not been vaccinated or need additional control measures during epidemics; not a substitute for vaccination unless vaccine is contraindicated
  • During influenza season, for those with contraindications to vaccine who have been exposed to the virus
  • For staff and residents in nursing home outbreaks; for immune-deficient persons who are expected not to respond to vaccination after viral exposure

Pediatric Considerations
Vaccinate children 6 months and older annually. Recommend all household members with children aged <6 months be vaccinated. For children who need 2 doses, administer first dose as soon as available for second dose to be given before the end of October. For prophylaxis, oseltamivir dosage varies by weight and is recommended by the CDC for prophylaxis for children aged ≥3 months; zanamivir is approved for prophylaxis for children ≥5 years of age at a dosage of 2 inhalations per day. Prophylaxis treatment duration is 7 days. Currently, amantadine and rimantadine are not recommended due to resistance.

Pregnancy Considerations

• The CDC recommends vaccinating all women who will be pregnant during influenza season. If unvaccinated at the time of flu season, pregnant women should receive IIV or RIV.
• Oseltamivir, zanamivir, peramivir, rimantadine, and amantadine are pregnancy Category C medications.

Commonly Associated Conditions

Pneumonia, cardiac complications, central nervous system involvement, myositis, rhabdomyolysis, multisystem organ failure