Influenza

Basics

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 this 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, during the 2019 to 2020 season, prevalence was estimated to be at 38 million positive tests with 18 million related medical visits, 400,000 hospitalizations, and 22,000 deaths, 199 of these in the pediatric population. The proportion of positive tests ranged from 26% to 30%. The 2020 to 2021 season was historic due to its setting during the COVID-19 pandemic. The CDC reported a positive test rate of just 0.2%. A single influenza-related pediatric death was reported. A record number of vaccinations were given, at least 25 million more doses than previous seasons. Concurrent COVID-19 precautionary measures such as social distancing, face masking, and school closures likely contributed to the mitigation of influenza spread. The 2021 to 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 to 2012 season. Rates increase in 2022, likely due in part to changing isolation guidelines in the context of the COVID-19 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 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 as 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 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 2 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 aged ≥6 months 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. For prophylaxis, the dosage of amantadine and of rimantadine is 5 mg/kg/day up to 150 mg in 2 divided doses. 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

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