Influenza

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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 influenza infection. Notable demographics at risk for complications and hospitalization include the following:
    • Those between <2 years old and >65 years old, pregnancy
    • Individuals with cardiovascular or pulmonary disease, Addison disease, or diabetes
    • Residents of nursing homes or other long-term care facilities
    • Individuals who identify as American Indian or Alaska Native
    • Pregnant women and women up to 2 weeks postpartum

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

Prevalence
In the United States, the Centers for Disease Control and Prevention (CDC) provides yearly surveillance data. During the 2019 to 2020 season, prevalence was estimated to be at 38,000,000 with 18,000,000 related medical visits, 400,000 hospitalizations, and 22,000 deaths.

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, especially in 3rd trimester
    • Chronic pulmonary diseases
    • Cardiovascular diseases, including valvular pathology and congestive heart failure (CHF)
    • Metabolic disease, morbid obesity
    • Hemoglobinopathies
    • Malignancy; immunosuppression
    • Neuromuscular diseases that limit respiratory function and ability to handle secretions

General Prevention

  • Vaccination: All persons ≥6 months should be vaccinated annually unless contraindication present. The CDC does not express preference for any type of vaccine over another.
  • 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 recommended annually for the following:
    • 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 [A]
    • During influenza season, for those with contraindications to vaccine who have been exposed to the virus [A]
    • 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 <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 ≥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.

Commonly Associated Conditions

Bacterial pneumonia

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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 influenza infection. Notable demographics at risk for complications and hospitalization include the following:
    • Those between <2 years old and >65 years old, pregnancy
    • Individuals with cardiovascular or pulmonary disease, Addison disease, or diabetes
    • Residents of nursing homes or other long-term care facilities
    • Individuals who identify as American Indian or Alaska Native
    • Pregnant women and women up to 2 weeks postpartum

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

Prevalence
In the United States, the Centers for Disease Control and Prevention (CDC) provides yearly surveillance data. During the 2019 to 2020 season, prevalence was estimated to be at 38,000,000 with 18,000,000 related medical visits, 400,000 hospitalizations, and 22,000 deaths.

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, especially in 3rd trimester
    • Chronic pulmonary diseases
    • Cardiovascular diseases, including valvular pathology and congestive heart failure (CHF)
    • Metabolic disease, morbid obesity
    • Hemoglobinopathies
    • Malignancy; immunosuppression
    • Neuromuscular diseases that limit respiratory function and ability to handle secretions

General Prevention

  • Vaccination: All persons ≥6 months should be vaccinated annually unless contraindication present. The CDC does not express preference for any type of vaccine over another.
  • 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 recommended annually for the following:
    • 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 [A]
    • During influenza season, for those with contraindications to vaccine who have been exposed to the virus [A]
    • 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 <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 ≥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.

Commonly Associated Conditions

Bacterial pneumonia

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