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    Oct.11.2021

    Influenza

    Synopsis

    Key Points

    • Influenza causes seasonal epidemics of an acutely debilitating febrile respiratory illness with duration up to 2 weeks
    • During epidemics, recognition of the classic symptoms of abrupt onset of high fever, myalgia, headache, and cough is diagnostic for most patients; confirm with rapid diagnostic tests in patients with high medical risk. Laboratory testing (viral culture) is most useful in nonepidemic settings or for epidemiologic uses
    • Yearly influenza vaccination is recommended for all persons older than 6 months, with very few contraindications r1
    • Prophylactic use of neuraminidase inhibitors is indicated in some situations (eg, high medical risk)
      • Persons at higher risk for severe illness and complications (eg, viral or bacterial pneumonia) include children younger than 5 years, adults older than 65 years, pregnant patients, and those with chronic medical conditions (eg, diabetes, heart failure) r2
        • Treatment of influenza with neuraminidase inhibitors is recommended for these patients and for all patients who have severe or progressive illness or are hospitalized with influenza
      • Neuraminidase treatment is best begun within 48 hours of illness r3
    • An endonuclease inhibitor, baloxavir marboxil, is an option for treatment of acute uncomplicated influenza in patients aged 12 years or older who have been symptomatic for no more than 48 hours r4
    • Baloxavir marboxil has received FDA approval for people at high risk of developing influenza-related complications (eg, patients with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity; adults aged 65 years or older) r5
    • In November 2020, the FDA expanded the approved indication for baloxavir marboxil to include postexposure prevention of influenza for patients aged 12 years and older after contact with an individual who has influenza r6
    • Treatment is primarily supportive for persons who do not have severe disease or elevated risk of complications

    Urgent Action

    • Identify patients at higher risk of complications and start neuraminidase treatment as soon as possible
    • Hospitalize very young children, older adults, and pregnant patients if illness is severe or is rapidly worsening

    Pitfalls

    • Not all vaccine formulations are approved for all age groups; be sure to select an age-appropriate product
    • Egg allergy is not a contraindication for seasonal influenza vaccine r1
      • Persons whose allergic reaction to eggs is limited to hives may receive any age-appropriate, inactivated-virus vaccine
      • Persons who have experienced more severe reactions to eggs (eg, angioedema, respiratory distress) may receive any age-appropriate inactivated vaccine in a health care setting under supervision of a provider experienced in managing severe allergic reactions

    Terminology

    Clinical Clarification

    • Influenza is an acute, seasonally epidemic, highly contagious, and febrile respiratory illness caused by infection with influenza virus

    Classification

    • By type: r7
      • Influenza A and B cause most clinical disease in humans; type C rarely causes significant illness
        • Influenza A viruses are named according to viral surface hemagglutinin (H or HA) and neuraminidase (N or NA) antigens, geographic area of origin, isolate number, year of isolation, and virus subtype (eg, A/Texas/50/2012 for a variant of H3N2)
        • Influenza B viruses are named by lineage (eg, B/Victoria)

    Diagnosis

    Clinical Presentation

    History

    • Presentation varies from mild to profound and life-threatening illness
    • Abrupt onset of symptoms is a hallmark of influenza, beginning 1 to 4 days after exposure and lasting up to 14 days
    • First symptoms typically include:
      • Fever, chills, and diaphoresis (common) c1c2c3
      • Myalgia (may be intense) c4
      • Headache (often prominent) c5
      • Malaise and fatigue (may be profound) c6c7c8c9
      • Anorexia (common) c10
    • Subsequent symptoms may include the following respiratory tract complaints:
      • Rhinorrhea and nasal congestion, with or without sneezing (prominent) c11c12c13
      • Sore throat (common) c14
      • Deep, hacking, nonproductive cough resulting in progressive chest discomfort c15c16c17c18
      • Dyspnea may be present with influenzal pneumonia c19c20
    • Gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) occur sometimes in children but rarely in adults c21c22c23c24c25c26c27c28

    Physical examination

    • Fever is usual but is less common in children and older adults c29c30c31
    • Tachycardia may be present if fever is high or patient is dehydrated c32
    • Tachypnea may indicate pneumonia or more severe disease c33c34
    • Erythema of nasal and oropharyngeal mucous membranes c35c36
    • Thin nasal discharge c37
    • Cervical adenopathy (usually posterior) c38c39
    • Lung examination may find clear lungs; rales or rhonchi suggest viral or secondary bacterial pneumonia c40c41c42

    Causes and Risk Factors

    Causes

    • 1 or 2 strains of influenza A and B cause seasonal epidemics each year; type C strains cause only sporadic illness c43c44c45

    Risk factors and/or associations

    Age
    • Rates are higher in children than in adults, but all ages are affected r7c46c47
    • Older adults (eg, those aged 65 years or older) are also at higher risk r7c48
    Other risk factors/associations
    • Seasonal pattern
      • Occurs from mid-fall to early spring in temperate climates c49c50c51
      • Seen sporadically throughout the year in tropical climates
    • Risk factors for severe manifestations:
      • Immunocompromised status c52
      • Comorbid chronic illness (eg, diabetes; heart failure; chronic pulmonary, renal, hepatic, hematologic, or neurologic disease) c53c54c55c56c57c58c59
      • Morbid obesity c60
      • Pregnancy c61

    Diagnostic Procedures

    Primary diagnostic tools

    • Influenza can be difficult to diagnose by clinical signs and symptoms alone, which can be similar to those of other infectious agents r8c62
    • Use rapid molecular assays (ie, nucleic acid amplification tests) over rapid influenza diagnostic tests in outpatients to improve detection of influenza virus infection r2c63c64
    • Use reverse transcription polymerase chain reaction (or other molecular assays) over other influenza tests in hospitalized patients to improve detection of influenza virus infection r2c65c66
    • Use multiplex reverse transcription polymerase chain reaction assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized immunocompromised patients r2c67
      • Consider using multiplex reverse transcription polymerase chain reaction assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized patients who are not immunocompromised if results might influence care
    • Do not use immunofluorescence assays for influenza virus antigen detection in hospitalized patients except when more sensitive molecular assays are not available; perform follow-up testing with reverse transcription polymerase chain reaction or other molecular assays to confirm negative immunofluorescence test results r2
    • Do not use rapid influenza diagnostic tests in hospitalized patients except when more sensitive molecular assays are not available; perform follow-up testing with reverse transcription polymerase chain reaction or other molecular assays to confirm negative rapid influenza diagnostic test results r2

    Laboratory

    • Rapid influenza diagnostic tests r9c68c69c70c71c72
      • Primarily point of care immunoassays; they have utility in community- and hospital-based outpatient settings owing to their rapid processing times r2
      • Use in hospitalized patients only when more sensitive molecular assays are not available; perform follow-up testing with reverse transcription polymerase chain reaction or other molecular assays to confirm negative rapid influenza diagnostic test results r2
      • Performed on nasal or nasopharyngeal swab or aspirate
      • Some can distinguish influenza A from influenza B but cannot identify specific strain
      • Sensitivity is 50% to 70% r9
      • Specificity is 90% to 95% r9
    • Polymerase chain reaction testing for viral nucleic acid: available at commercial laboratories c73c74
      • Recommended for hospitalized patients,r2 especially if rapid influenza diagnostic test result is negative r9
      • Turnaround time is longer
      • Sensitivity and specificity approach 100% r10
    • Rapid molecular assays r2
      • Includes nucleic acid amplification tests
      • Sensitivity is 66% to 99%
      • Specificity is 55% to 99%
      • Use over rapid influenza diagnostic tests in outpatients to improve detection of influenza virus infection
    • Immunofluorescence assays r2
      • Require laboratory expertise and fluorescent microscope; take longer to produce results
      • Better sensitivity and specificity than rapid influenza diagnostic tests
      • Use only for influenza virus antigen detection in hospitalized patients when more sensitive molecular assays are not available; follow-up testing with reverse transcription polymerase chain reaction or other molecular assays should be performed to confirm negative immunofluorescence test results
    • Viral culture c75
      • Recommended only in unusual cases, primarily for epidemiologic purposes; turnaround time is too long for management decisions. Useful for the following: r2r9
        • Document and characterize an outbreak
        • Determine source (eg, poultry, pigs) in nonepidemic settings

    Imaging

    • Chest radiograph is not indicated in most cases c76c77c78
      • Often no chest radiographic findings even in symptomatic patients r11
    • Obtain if either primary influenzal pneumonia or secondary bacterial pneumonia is suspected on the basis of physical examination findings
    • Chest radiograph findings suggestive of pneumonia due to influenza are as follows: r11
      • Peribronchial patchy interstitial infiltrates
      • Centrilobular nodules
      • Lobar ground-glass appearance
      • Consolidation

    Procedures

    c79

    Differential Diagnosis

    Most common

    • Common cold c80d1
      • Prevalent during winter months, overlapping with influenza epidemics
      • Clinically, onset is more gradual, and patient appears only mildly ill
      • Fever is absent or lower than with influenza; patients are less likely to have severe myalgia and fatigue
      • Predominant symptoms are in upper respiratory tract in common cold as opposed to lower respiratory tract (eg, cough) in influenza

    Diagnostic groups

    • Other respiratory tract viral infections c81
      • COVID-19 c82d1
        • Overlapping clinical features, so can be difficult to differentiate clinically; additionally, coinfection can occur r12r13
        • COVID-19 pandemic makes testing for SARS-CoV-2 widely indicated (eg, signs or symptoms consistent with COVID-19, known or suspected exposure to SARS-CoV-2)
        • When influenza and SARS-CoV-2 are both circulating in the community, testing for both viruses is recommended for all patients hospitalized with acute respiratory infection. In patients who present with acute respiratory illness but who do not require hospitalization, influenza testing is recommended in addition to testing for SARS-CoV-2, if influenza test results would alter management r12r13
          • CDC recommends nucleic acid detection over antigen testing for both pathogens, either by multiplex or individual assay
      • Respiratory syncytial virus infection c83c84c85d2
        • Seasonality overlaps that of influenza; infection mostly affects infants and small children
        • Often nosocomial (patients develop symptoms after being in a health care environment)
        • Lower respiratory tract symptoms predominate, with prolonged expiratory phase, rales, and wheezes
        • Diagnosis is confirmed by polymerase chain reaction assay
      • Parainfluenza virus infection c86
        • Seasonality overlaps that of influenza; infection causes both upper and lower respiratory tract disease in infants and small children and mostly upper respiratory tract disease in adults
        • Croup and hoarseness are predominant symptoms
        • Diagnosis is confirmed by polymerase chain reaction assay or antigen detection test
      • Adenovirus infection c87c88
        • Usually not seasonal; more common in children
        • Most prominent symptoms are sore throat, hoarseness, and conjunctivitis
        • Diagnosis is confirmed by polymerase chain reaction assay or antigen detection test
      • Epstein-Barr virus infection (mononucleosis) c89c90c91c92c93c94d3
        • Occurs sporadically (not seasonally); most common in adolescents and young adults
        • Most prominent symptoms are sore throat and fatigue; physical findings include pharyngeal exudates and prominent posterior cervical adenopathy; cough is not predominant symptom
        • Diagnosed by laboratory testing (mononucleosis spot test or Epstein-Barr virus antibody testing)
    • Bacterial infections c95
      • Bacterial pneumonia c96d4
        • May occur sporadically or may be a complication of influenza
        • Symptoms are similar, but cough is productive and there is more likelihood of pleuritic chest pain and dyspnea
        • Rales and rhonchi, egophony, and/or dullness to percussion suggest a pneumonic infiltrate
        • Diagnosed by chest radiograph and microscopy and culture of sputum
      • Meningococcal meningitis c97c98c99d5
        • Tends to occur in epidemics; occurs most commonly in children and young adults living in close quarters (eg, dormitories, barracks) d6
        • Begins abruptly, as influenza does, and with high fever
        • Predominant symptoms initially are severe headache, neck stiffness, photophobia, and vomiting
          • Rash may be present; cough is unusual
        • Diagnosis is confirmed by cerebrospinal fluid analysis and culture

    Treatment

    Goals

    • Relieve symptoms
    • Prevent complications (eg, viral pneumonia) in patients at higher risk

    Disposition

    Admission criteria

    Admit pregnant patients, children younger than 5 years, and adults older than 65 years who have severe illness or moderate illness that appears to be rapidly worsening

    Criteria for ICU admission
    • High likelihood of needing ventilator support
      • Severe or rapidly progressive illness with dyspnea and/or hypoxia
      • Bilateral diffuse pneumonia
    • Hemodynamic instability

    Recommendations for specialist referral

    • Refer to an infectious disease specialist, pulmonologist, or critical care specialist for severe illness requiring hospitalization
    • Consider consultation with an allergist for high-risk patients who would benefit from immunization but are allergic to the vaccine

    Treatment Options

    Supportive care with rest and maintenance of adequate hydration

    • Common symptomatic treatments involve relief of fever, pain, and nasal congestion (eg, OTC forms of NSAIDs are often used; avoid aspirin in children owing to risk of Reye syndrome)

    Neuraminidase inhibitors are recommended as soon as possible with confirmed or suspected influenza for the following 3 groups of patients: r10r14

    • Patients with severe or progressive illness r2
    • Hospitalized patients r2
    • Patients at high risk of complications r2r15
      • Children younger than 5 years (especially those younger than 2 yearsr2)
      • Adults aged 65 years or older r2
      • Residents of nursing homes and other long-term care facilities
      • Persons with certain medical conditions or demographic characteristics, as follows:
        • Asthma and other chronic pulmonary diseases
        • Cardiovascular disease (except hypertension alone)
        • Renal disease
        • Hepatic disease
        • Hematologic conditions (including sickle cell disease)
        • Immunosuppression due to medication, HIV infection, or other causes
        • Long-term aspirin therapy if younger than 19 years
        • Metabolic disorders (including diabetes mellitus)
        • Neurologic and neurodevelopmental conditions
        • Morbid obesity (BMI of 40 kg/m² or more)
        • Pregnant or recent (within 2 weeks) postpartum status r2
        • Native American or Alaska Native ethnicity

    Baloxavir marboxil r4r15

    • A more recent option is a single dose for the treatment of acute uncomplicated influenza in patients aged 12 years or older
    • Approved in 2018 for treatment of acute uncomplicated influenza in patients aged 12 years or older who have been symptomatic for no more than 48 hours r4
    • Received FDA approval in October 2019 for people at high risk of developing influenza-related complications (eg, patients with asthma, chronic lung disease, diabetes, heart disease, or morbid obesity; adults aged 65 years or older) r5
    • In November 2020, the FDA expanded the approved indication for baloxavir marboxil to include postexposure prevention of influenza for patients aged 12 years and older after contact with an individual who has influenza r6
      • A 2020 randomized controlled trial reported that single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza r16

    Decision to administer therapy need not depend on test results r3

    • In very ill patients or those at high risk, in particular, do not delay treatment while awaiting test results

    Drug therapy

    • Neuraminidase inhibitors c100c101c102c103c104c105c106c107c108c109c110c111c112c113c114c115c116c117c118c119c120c121c122c123c124
      • May be prescribed electively for healthy adults and children not at high risk of complications; associated with small decrease in length of illness in adults, but results in children are inconsistent r17
      • Observational studies of hospitalized children and adults suggest that significant decrease in mortality is most pronounced when an inhibitor is started within 48 hoursr18r19
      • If treatment is elected, start antiviral treatment as soon as possible after illness onset,r2 ideally within 48 hoursof symptom onset r3r20
        • In hospitalized or otherwise severely ill patients, institute treatment regardless of duration of symptoms
          • Oseltamivir is favored over zanamivir in this population c125
          • For patients unable to absorb oseltamivir owing to gastrointestinal malfunction, IV peramivir may be administered c126
          • If oseltamivir resistance is suspected, IV zanamivir (an investigational formulation) is an option
        • Extended courses may be considered for patients who remain severely ill
      • Oseltamivir r21c127c128c129c130c131c132c133c134c135c136c137c138c139c140c141c142c143c144c145c146c147c148c149c150
        • Oseltamivir Phosphate Oral suspension; Premature Neonates younger than 38 weeks postmenstrual age†: 1 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Premature Neonates 38 to 40 weeks postmenstrual age†: 1.5 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Premature Neonates older than 40 weeks postmenstrual age† and Term Neonates 0 to 13 days†: 3 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Term Neonates 14 to 29 days: 3 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Infants 1 to 8 months: 3 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Infants 9 to 11 months: 3.5 mg/kg/dose PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Children weighing 15 kg or less: 30 mg PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Children weighing 16 to 23 kg: 45 mg PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral suspension; Children weighing 24 to 40 kg: 60 mg PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral capsule; Children and Adolescents weighing more than 40 kg: 75 mg PO twice daily for 5 days.
        • Oseltamivir Phosphate Oral capsule; Adults: 75 mg PO twice daily for 5 days.
      • Zanamivir c151c152c153c154c155c156c157c158c159c160c161c162c163c164c165c166c167c168c169c170c171c172c173c174
        • Inhaled
          • Infants and children younger than 7 years: safety and efficacy have not been established. Clinical studies have indicated that young children do not produce the peak inspiratory flow rates needed for the proper use of dry powder inhalers such as the Diskhaler device, which limits the systemic absorption and clinical efficacy of zanamivir.
          • Zanamivir Inhalation powder; Children and Adolescents 7 to 17 years: 10 mg by oral inhalation every 12 hours for 5 days.
          • Zanamivir Inhalation powder; Adults: 10 mg by oral inhalation every 12 hours for 5 days.
        • IV
          • Available only through enrollment in an ongoing clinical trial or through a compassionate use program; follow dosage recommendations from the clinical trial or provided by the manufacturer
          • Emergency investigative new drug application must be obtained for usage. Contact GlaxoSmithKline to obtain emergency investigative new drug forms: +1-919-315-5215 (24/7), then contact FDA: +1-301-796-1500 (business day) or +1-301-796-9900 (after hours)
      • Peramivir c175c176c177c178c179c180c181c182c183c184c185c186c187c188c189c190c191c192c193c194c195c196c197c198
        • Peramivir Solution for injection; Infants and Children 6 months to 12 years: 12 mg/kg/dose (Max: 600 mg/dose) IV as a single dose.
        • Peramivir Solution for injection; Adolescents: 600 mg IV as a single dose.
        • Peramivir Solution for injection; Adults: 600 mg IV as a single dose.
    • Endonuclease inhibitor
      • Baloxavir marboxil (treatment or postexposure prophylaxis) c199
        • Baloxavir Marboxil Oral tablet; Children and Adolescents 12 to 17 years weighing less than 80 kg: 40 mg PO as a single dose.
        • Baloxavir Marboxil Oral tablet; Children and Adolescents 12 to 17 years weighing 80 kg or more: 80 mg PO as a single dose.
        • Baloxavir Marboxil Oral tablet; Adults less than 80 kg: 40 mg PO as a single dose.
        • Baloxavir Marboxil Oral tablet; Adults weighing 80 kg or more: 80 mg PO as a single dose.

    Nondrug and supportive care

    Rest and adequate fluid intake are recommended to offset insensible losses during fever c200c201

    Procedures
    c202

    Comorbidities c203

    Special populations

    • Pregnant patients
      • Increased risk for hospitalization but not mortality r22
      • Increased risk of preterm birth and small-for-gestational-age infant status
      • All patients who are or will be pregnant during influenza season should receive an inactivated influenza vaccine as soon as it is available r1r23
        • Any of the recommended, age-appropriate, inactivated influenza vaccines can be given in any trimester
        • Live attenuated influenza vaccine is not recommended for use during pregnancy
      • All pregnant patients with clinically suspected or confirmed influenza should be treated with antiviral medication, regardless of vaccination status or laboratory test results r24
        • Use oseltamivir or zanamivir according to current local resistance patterns
        • Start treatment within 48 hours of symptom onset if possible
          • However, it is recommended that these drugs be started even if the 48-hour mark has passed
      • Hospitalize pregnant patients if illness appears to be severe or is worsening, with a low threshold for admitting to ICU with signs of respiratory distress
      • Consider postexposure chemoprophylaxis in pregnant patients and those up to 2 weeks postpartum (including after pregnancy loss) who have had close contact with anyone with influenza r24
        • Administer within 48 hours of exposure r25

    Complications and Prognosis

    Complications

    • Direct influenza virus complications
      • Influenzal pneumonia is the most common viral complication c204
      • Rarely, the following may occur:
        • Aseptic meningitis and/or encephalitis c205c206
        • Myositis and/or rhabdomyolysis c207c208
        • Transverse myelitis c209
    • Suppurative complications
      • Secondary bacterial pneumonia c210
      • Otitis media c211
      • Sinusitis c212
    • Worsening of comorbid conditions
      • Asthma c213
      • Chronic obstructive pulmonary disease c214
      • Congestive heart failure c215

    Prognosis

    • For patients in low-risk groups who do not develop complications, prognosis is good and full recovery is expected
    • Patients in high-risk groups have increased incidence of severe illness, hospitalization, and death
    • Overall mortality is 1.8 deaths per 100,000 population in the United States r26

    Screening and Prevention

    Screening c216

    Prevention

    • Vaccination
      • Seasonal influenza vaccine is recommended yearly, in autumn, for all persons aged 6 months and older (including pregnant patients) for whom there is no contraindication r1r27c217c218
      • Children aged 6 months through 8 years require 2 doses of influenza vaccine (administered 4 or more weeks apart) during their first season of vaccination to optimize immune response r1
        • Children aged 6 months through 8 years who have received 2 or more doses of trivalent or quadrivalent influenza vaccine previously (regardless of whether they were given during the same season or consecutive seasons) do not require 2 doses of vaccine r1
        • Children who have received only 1 vaccine dose in a previous season should receive the 2-dose initial regimen; the interval between the 2 doses should be at least 4 weeks r1
      • 3 types of vaccines are produced in the United States r1
        • Inactivated influenza virus vaccine, available in quadrivalent forms: primarily for patients aged 6 months and older r1c219
          • One vaccine (Flucelvax Quadrivalent) is approved for persons aged 2 years and older r1
          • Not all commercially available vaccines are approved for all age groups r1
          • For some influenza vaccines, the dosage for children aged 6 through 35 months differs from that for older children and adults; be sure to administer the appropriate dose of an age-appropriate product r1
          • High-dose quadrivalent and adjuvanted quadrivalent forms are available for adults aged 65 years or older r1c220c221c222
        • Recombinant influenza vaccine r1c223
          • 1 quadrivalent formulation expected to be available during the 2021-2022 influenza season r1
          • For patients aged 18 years or older r1
        • Live attenuated influenza vaccine, quadrivalent (administered intranasally) r1c224
          • A single live attenuated influenza vaccine is expected to be available during the 2021-2022 influenza season r1
          • An option for healthy, nonpregnant persons aged 2 through 49 years r1
      • Egg allergy is not a contraindication to influenza vaccine r1
        • Persons with a history of egg allergy, regardless of severity, may receive any of the recommended age-appropriate influenza vaccines r1
        • In persons who have experienced reactions more severe than urticaria (eg, angioedema, respiratory distress, lightheadedness, recurrent emesis) or who required epinephrine or similar intervention, the vaccine should be administered in a medical setting and supervised by a clinician able to manage severe allergic reactions r1
      • For egg-based quadrivalent inactivated influenza vaccines and quadrivalent live attenuated influenza vaccines, history of severe allergic reaction (eg, anaphylaxis) to any influenza vaccine is a contraindication to future receipt of all egg-based quadrivalent inactivated influenza vaccines and quadrivalent live attenuated influenza vaccines; also contraindicated in patients with severe allergic reaction (eg, anaphylaxis) to any vaccine component r1
      • For cell culture–based quadrivalent inactivated influenza vaccine: r1
        • History of a severe allergic reaction (eg, anaphylaxis) to any egg-based inactivated influenza vaccine, recombinant influenza vaccine, or live attenuated influenza vaccine of any valency is a precaution to using cell culture–based quadrivalent inactivated influenza vaccine; if administered, vaccination should occur under the supervision of a health care provider who can identify and manage severe allergic reactions r1
        • History of severe allergic reaction (eg, anaphylaxis) to any cell culture–based inactivated influenza vaccine of any valency is a contraindication to future receipt of cell culture–based quadrivalent inactivated influenza vaccine; also contraindicated in patients with severe allergic reaction (eg, anaphylaxis) to any vaccine component r1
      • For quadrivalent recombinant influenza vaccine: r1
        • History of a severe allergic reaction (eg, anaphylaxis) to any egg-based inactivated influenza vaccine, cell culture–based inactivated influenza vaccine, or live attenuated influenza vaccine of any valency is a precaution to using quadrivalent recombinant influenza vaccine; if administered, vaccination should occur under the supervision of a health care provider who can identify and manage severe allergic reactions r1
        • History of severe allergic reaction (eg, anaphylaxis) to any recombinant influenza vaccine of any valency is a contraindication to future receipt of quadrivalent recombinant influenza vaccine; also contraindicated in patients with severe allergic reaction (eg, anaphylaxis) to any vaccine component r1
      • Persons with history of Guillain-Barré syndrome occurring within 6 weeks of influenza vaccination should not receive influenza vaccine unless they are at high risk for complications from influenza, in which case benefit may outweigh risk; antiviral prophylaxis is an alternative r1
    • Antiviral prophylaxis
      • Pre- or postexposure chemoprophylaxis with the neuraminidase inhibitors oseltamivir and zanamivir may be given to adults and children aged 3 months or older for the following reasons: r2c225c226c227
        • In conjunction with prompt administration of inactivated influenza vaccine, to protect patients who are at high risk of developing complications from influenza in whom influenza vaccination is expected to be effective (but not yet administered) when influenza activity has been detected in the community r2c228c229c230
        • Protect unvaccinated high-risk patients and their household contacts with recent exposure to influenza r2c231c232c233
        • Protect immunocompromised patients who cannot develop an antibody response to vaccine r2c234c235c236
        • Prevent or control large outbreaks in closed settings r2c237c238c239
      • Begin postexposure prophylaxis within 48 hours of exposure r14
      • Antiviral drugs may be given concurrently with inactivated influenza virus vaccine or quadrivalent recombinant influenza vaccine r1
        • Influenza antiviral medications may reduce effectiveness of live attenuated influenza vaccine (quadrivalent) if given within the interval from 48 hours before to 14 days after administration r1
        • Newer influenza antivirals peramivir and baloxavir have longer half-lives than oseltamivir and zanamivir (approximately 20 hours for peramivir and 79 hours for baloxavir) and could potentially interfere with the replication of live attenuated influenza vaccine (quadrivalent) if administered more than 48 hours before vaccination r1
      • Zanamivir dosage for prophylaxis is the same as for treatment; oseltamivir prophylaxis is given once daily at half the total daily treatment dosage r14
      • Duration of chemoprophylaxis varies with the circumstances, as follows: r14
        • Postexposure prophylaxis is usually maintained for 10 days after most recent exposure
        • In persons at high risk who cannot be immunized, continue preexposure prophylaxis for duration of influenza season
        • For management of institutional outbreaks, continue prophylaxis for a minimum of 2 weeks and for at least 10 days after onset of illness in the last patient
      • In November 2020, the FDA expanded the approved indication for baloxavir marboxil to include postexposure prevention of influenza for patients aged 12 years and older after contact with an individual who has influenza r6
        • A 2020 randomized controlled trial found that single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza r16
    • Other preventive actions r28
      • Handwashing with soap and water c240c241
      • Avoiding contact with infected persons and limiting contact with others while sick (by staying home for at least 24 hours after flulike symptoms appear) c242
      • Covering one's nose and mouth with a tissue while coughing or sneezing and throwing the tissue in the trash after use c243
      • Avoiding touching mouth, nose, and eyes c244
      • Cleaning and disinfecting surfaces c245c246
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