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    Influenza

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    Mar.05.2024

    Influenza

    Synopsis

    Key Points

    • Influenza causes seasonal epidemics of an acutely debilitating febrile respiratory illness with duration of up to 2 weeks
    • During epidemics, recognition of the classic symptoms of abrupt onset of high fever, myalgia, headache, and cough is highly suggestive of influenza for most patients; confirm with rapid diagnostic tests for patients with high medical risk
    • 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 who are hospitalized with influenza
      • Treatment with neuraminidase inhibitors is most effective when begun within 48 hours of onset of illness r3
    • An endonuclease inhibitor, baloxavir marboxil, is currently approved by FDA for treatment of influenza in children aged 5 years to 12 years with no chronic medical conditions and for all patients aged 12 years and older; ideally administered within 48 hours of symptom onset r4r5
    • Baloxavir marboxil is also approved by FDA for postexposure prophylaxis of influenza for patients aged 5 years or older r5
    • Treatment is primarily supportive for persons who do not have severe disease or elevated risk of complications

    Urgent Action

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

    Pitfalls

    • Adjust dose of oseltamivir for patients with decreased creatinine clearance
    • 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 professional 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:
      • Influenza A and B cause most clinical disease in humans; type C rarely causes significant illness r6
        • Influenza A viruses are named according to viral surface hemagglutinin (H or HA) and neuraminidase (N or NA) antigensr6, 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) r6

    Diagnosis

    Clinical Presentation

    History

    • Presentation varies from mild to profound and life-threatening illness
    • Abrupt onset of symptoms and systemic signs 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) c6c7
      • Anorexia (common) c8
    • Patients may report subsequent symptoms including the following:
      • Rhinorrhea and nasal congestion, with or without sneezing (prominent) c9c10c11
      • Sore throat (common) c12
      • Deep, hacking, nonproductive cough resulting in progressive chest discomfort c13c14c15c16
      • Dyspnea may be present with influenza pneumonia c17
    • Gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) occur sometimes in children but rarely in adults c18c19c20c21c22c23c24c25

    Physical examination

    • Fever is usual but is less common in children and older adults c26c27c28
    • Tachycardia may be present if fever is high or patient is dehydrated c29
    • Tachypnea may indicate pneumonia or more severe disease c30
    • Erythema of nasal and oropharyngeal mucous membranes c31c32
    • Thin nasal discharge c33
    • Cervical adenopathy (usually posterior) c34c35
    • Lung examination usually reveals clear lungs if no involvement of lower respiratory tract; rales or rhonchi suggest viral or secondary bacterial pneumonia c36c37c38

    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 c39c40c41

    Risk factors and/or associations

    Age
    • Rates are higher among children than among adults, but all ages are affected r6c42c43
    • Older adults (eg, those aged 65 years or older) are at higher risk r6c44
    Other risk factors/associations
    • Seasonal pattern
      • Occurs from mid-fall to early spring in temperate climates c45c46c47
      • Seen sporadically throughout the year in tropical climates
    • Risk factors for severe manifestations:
      • Immunocompromised status c48
      • Comorbid chronic illness (eg, diabetes; heart failure; chronic pulmonary, renal, hepatic, hematologic, or neurologic disease) c49c50c51c52c53c54c55
      • Morbid obesity c56
      • Pregnancy c57

    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 respiratory illnesses r7c58
    • Use rapid molecular assays (ie, nucleic acid amplification tests) over rapid influenza diagnostic tests for outpatients to improve detection of influenza virus infection r2c59c60
    • Use reverse transcription polymerase chain reaction (or other molecular assays) over other influenza tests for hospitalized patients to improve detection of influenza virus infection r2c61c62
    • Use multiplex reverse transcription polymerase chain reaction assays targeting a panel of respiratory pathogens, including influenza viruses, for hospitalized patients r2c63
      • Such diagnostic testing is important for epidemiologic purposes and also to ensure that appropriate precautions (eg, droplet, contact, or airborne precautions) are implemented during patient's hospitalization to prevent spread to other hospitalized patients and health care staff
    • Do not use immunofluorescence assays for influenza virus antigen detection for 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 for 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 r8c64
      • Primarily point-of-care immunoassays; they have utility in community- and hospital-based outpatient settings and emergency departments owing to rapid processing times r2
      • Use for 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% r8
      • Specificity is 90% to 95% r8
    • Polymerase chain reaction testing for viral nucleic acid: available at commercial laboratories c65
      • Recommended for hospitalized patients,r2 especially if rapid influenza diagnostic test result is negative r8
      • Turnaround time is longer
      • Sensitivity and specificity approach 100% r9
    • Rapid molecular assays r2
      • Include nucleic acid amplification tests
      • Sensitivity is 66% to 99%
      • Specificity is 55% to 99%
      • Use over rapid influenza diagnostic tests for 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 for hospitalized patients 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
    • Viral culture c66
      • Usually not performed for clinical purposes; of no utility at point of care
      • Recommended only in unusual cases, primarily for epidemiologic purposes; turnaround time is too long for management decisions. Useful to do the following: r2r8
        • Document and characterize an outbreak
        • Determine source (eg, poultry, pigs) in nonepidemic settings
        • Determine presence of drug-resistant strains

    Imaging

    • Chest radiograph is not indicated for patients with no clinical evidence of lower respiratory tract disease c67
      • Often, chest radiograph will show no abnormalities, even for patients with symptoms r10
    • Obtain if either primary influenza pneumonia or secondary bacterial pneumonia is suspected on clinical assessment
    • Chest radiograph findings suggestive of pneumonia due to influenza are as follows: r10
      • Peribronchial patchy interstitial infiltrates
      • Centrilobular nodules
      • Lobar ground-glass appearance
      • Consolidation

    Procedures

    c68

    Differential Diagnosis

    Most common

    • Common cold c69
      • 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
      • Differentiated by history and findings on physical examination and with influenza testing

    Diagnostic groups

    • Other respiratory tract viral infections c70
      • COVID-19 c71d1
        • Systemic infection (with a predilection for the respiratory system) caused by a coronavirus, SARS-CoV-2
        • Overlapping clinical features, so can be difficult to differentiate clinically; additionally, coinfection can occur r11r12
        • 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)
        • Testing for both viruses is recommended for all patients hospitalized with acute respiratory tract infection. For 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 r11r12
          • CDC recommends nucleic acid detection over antigen testing for both pathogens, either by multiplex or individual assays
      • Respiratory syncytial virus infection c72c73c74d2
        • Seasonality overlaps that of influenza; infection mostly affects infants and small children
        • Often nosocomial (patients develop symptoms after being in a health care setting)
        • Lower respiratory tract symptoms predominate, with prolonged expiratory phase, rales, and wheezes
        • Diagnosis is confirmed by polymerase chain reaction assay
        • Highly infectious; requires droplet and contact precautions for hospitalized patients to prevent transmission by fomites
      • Parainfluenza virus infection c75
        • 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
          • Included in most commercial multiplex assays for respiratory pathogens
      • Adenovirus infection c76c77
        • Usually not seasonal; more common in children
        • Most prominent symptoms are sore throat, hoarseness, and conjunctivitis
        • Can cause severe disease in profoundly immunocompromised patients (ie, transplant recipients); antiviral therapy with cidofovir can be considered on a case-by-case basis in this patient population
        • Diagnosis is confirmed by polymerase chain reaction assay or antigen detection test
      • Epstein-Barr virus infection (infectious mononucleosis) c78c79c80c81c82c83d3
        • 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
        • Splenomegaly may be present
        • Diagnosed by laboratory testing (mononucleosis spot test or Epstein-Barr virus antibody testing)
    • Bacterial infections c84
      • Bacterial pneumonia c85d4
        • May occur sporadically or may be a complication of influenza
        • Symptoms are similar, but cough is productive, and there is a higher 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 (or tracheal aspirate from intubated patients)
      • Meningococcal meningitis c86c87c88d5
        • 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 are initially severe headache, neck stiffness, photophobia, and vomiting
          • Rash may be present; cough is unusual
        • Patients often appear toxic
        • Confirm diagnosis by cerebrospinal fluid analysis and culture; obtain 2 sets of blood cultures
        • Notify microbiology laboratory of suspected cases of meningococcemia, as it can be an occupational hazard

    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 worsening

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

    Recommendations for specialist referral

    • Consult an infectious disease specialist and 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 have a severe allergy 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 (OTC forms of NSAIDs are often used; avoid aspirin for 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: r9r13

    • Patients with severe or progressive illness r2
    • Hospitalized patients r2
    • Patients at high risk for complications r2r14
      • 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)
        • Kidney disease
        • Liver disease
        • Hematologic conditions (including sickle cell disease)
        • Immunosuppression due to medication such as steroids or biologics, 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 greater)
        • Pregnant or recently pregnant (within 2 weeks of delivery) r2
        • American Indian or Alaska Native ancestry

    Baloxavir marboxil r4r5r14

    • Not widely used at present
    • Currently approved by FDA for treatment of influenza in children aged 5 years to 12 years with no chronic medical conditions and for all patients aged 12 years or older r5
    • Also approved by FDA for postexposure prophylaxis of influenza in patients aged 5 years or older r5
      • 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 r15
    • Available as an oral suspension for children or as a tablet, given as a single dose by mouth; ideally administered within 48 hours of symptom onset r4r5
    • Not recommended for pregnant patients, breastfeeding patients, those with complicated or progressive illness, severely immunosuppressed patients, or hospitalized patients, which limits its clinical utility at present r5
    • A single study compared baloxavir with oseltamivir: a randomized controlled trial that included high-risk adolescent and adult outpatients with uncomplicated influenza r16
      • Median time to reduction in influenza symptoms was similar for patients with influenza A but 27.1 hours quicker (P = .025) with baloxavir for patients with influenza B r16
    • A randomized controlled trial involving patients older than 12 years hospitalized with severe influenza found no difference in clinical outcomes between patients treated with a neuraminidase inhibitor alone versus a neuraminidase inhibitor plus baloxavir r17

    Decision to administer therapy need not depend on test results r3

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

    Drug therapy

    • Neuraminidase inhibitors c89c90c91c92c93c94
      • May also be prescribed electively for healthy adults and children not at high risk for complications within 48 hours of illness onset r3
      • 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 hours of symptom onset r3r20
        • For hospitalized or otherwise severely ill patients, institute treatment regardless of duration of symptoms
          • Oseltamivir is favored over zanamivir in this population c95c96
          • For patients unable to absorb oseltamivir owing to gastrointestinal malfunction, IV peramivir can be administered c97
        • Standard treatment duration is 5 days; extended courses may be considered for patients who remain severely ill
      • Oseltamivir r21c98c99c100c101c102
        • 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.
        • Dosage needs to be adjusted for decreased renal function
      • Zanamivir c103c104c105c106c107
        • IV formulation not currently clinically used. No current clinical trials or compassionate use programs available to acquire IV zanamivir at present
        • 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. Administer 2 doses on the first day provided there are at least 2 hours between doses.
          • Zanamivir Inhalation powder; Adults: 10 mg by oral inhalation every 12 hours for 5 days. Administer 2 doses on the first day provided there are at least 2 hours between doses.
      • Peramivir c108c109c110c111c112
        • 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.
        • Dosage needs to be adjusted for decreased renal function
    • Endonuclease inhibitor
      • Baloxavir marboxil (treatment or postexposure prophylaxis) c113
        • Baloxavir Marboxil Oral suspension; Children 5 to 12 years weighing less than 20 kg: 2 mg/kg PO as a single dose.
        • Baloxavir Marboxil Oral suspension; Children and Adolescents 5 to 17 years weighing 20 to 79 kg: 40 mg PO as a single dose.
        • Baloxavir Marboxil Oral suspension; Children and Adolescents 5 to 17 years weighing 80 kg or more: 80 mg PO as a single dose.
        • Baloxavir Marboxil Oral tablet; Adults weighing 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 c114c115

    Procedures
    c116

    Comorbidities c117

    Special populations

    • Pregnant patients
      • Increased risk for hospitalization but not mortality r22
      • Increased risk for preterm birth and small-for-gestational-age infant status
      • All patients who are or will be pregnant during influenza season should receive an inactivated or recombinant influenza vaccine as soon as it is available r1r23
        • Any of the recommended, age-appropriate, and licensed inactivated or recombinant influenza vaccines can be given in any trimester
        • Pregnant persons in the first or second trimester should avoid vaccination in July or August unless there is concern that vaccination later in the season might not be possible r1
        • Live attenuated influenza vaccine is not recommended for use during pregnancy; however, it can be used post partum r1
      • Treat all pregnant patients with clinically suspected or confirmed influenza with antiviral medication, regardless of vaccination status or laboratory test results r23
        • Use oseltamivir or zanamivir according to current local resistance patterns; peramivir is an alternative option
        • 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 in this patient population
      • 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 or severe sepsis
      • Consider postexposure chemoprophylaxis for pregnant patients and those up to 2 weeks post partum (including after pregnancy loss) who have had close contact with anyone with influenza r23
        • Administer within 48 hours of exposure r23r24

    Complications and Prognosis

    Complications

    • Direct influenza virus complications
      • Influenzal pneumonia is the most common viral complication c118
      • Very rarely, the following may occur:
        • Aseptic meningitis and/or encephalitis c119c120
        • Myositis and/or rhabdomyolysis c121c122
        • Transverse myelitis c123
        • Pericarditis or myocarditis
    • Suppurative complications
      • Secondary bacterial pneumonia c124
      • Otitis media c125
      • Sinusitis c126
    • Exacerbation of comorbid conditions
      • Asthma c127
      • Chronic obstructive pulmonary disease c128
      • Congestive heart failure c129

    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 0.2 deaths per 100,000 population in the United States r25

    Screening and Prevention

    Screening c130

    Prevention

    • Vaccination
      • Seasonal influenza vaccine is recommended yearly, in autumn, for all persons aged 6 months or older (including pregnant patients) for whom there is no contraindication r1r26c131c132
      • 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; they require only 1 dose 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 or older r1c133
          • 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 r1c134c135c136c137
        • Recombinant influenza vaccine r1c138
          • One quadrivalent formulation is available during the 2023-2024 influenza season for patients aged 18 years or older r1
        • Live attenuated influenza vaccine, quadrivalent (administered intranasally) r1c139
          • A single live attenuated influenza vaccine is available during the 2023-2024 influenza season. It is a quadrivalent vaccine covering 2 strains of influenza A (H1N1 and H3N2) and 2 strains of influenza Br27r1
          • An option for healthy, nonpregnant persons aged 2 through 49 years who would like to avoid an injection r1r27
      • High-dose influenza vaccination is recommended for adults aged 65 years or older; the following formulations are preferred: r28
        • Fluzone high-dose quadrivalent vaccine
        • Flublok quadrivalent recombinant flu vaccine
        • Fluad quadrivalent adjuvanted flu vaccine
      • Egg allergy is not a contraindication to administration of influenza vaccine r1
        • Persons with a history of egg allergy, regardless of severity, may receive any of the recommended age-appropriate influenza vaccines that are otherwise appropriate 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 for 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, recombinant, or live attenuated influenza vaccine of any valency is a precaution when using cell culture–based quadrivalent inactivated influenza vaccine; if administered, vaccination should occur under supervision of a health care professional 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 for 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, cell culture–based inactivated, or live attenuated influenza vaccine of any valency is a precaution when using quadrivalent recombinant influenza vaccine; if administered, vaccination should occur under the supervision of a health care professional who can identify and manage severe allergic reactions r1
        • History of severe allergic reaction (eg, anaphylaxis) to any recombinant influenza vaccine is a contraindication to future receipt of quadrivalent recombinant influenza vaccine; also contraindicated for 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: r2c140c141c142
        • 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 r2c143c144c145
        • To protect unvaccinated high-risk patients and their household contacts with recent exposure to influenza r2c146c147c148
        • To protect immunocompromised patients who cannot develop an antibody response to vaccine r2c149c150c151
        • To prevent or control large outbreaks in closed settings r2c152c153c154
      • Begin postexposure prophylaxis within 48 hours of exposure r13
      • 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 of the vaccine 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 during the 5 days (peramivir) or 17 days (baloxavir) preceding vaccination and up to 2 weeks after (both) r1
          • Persons who receive these medications during these periods before or after vaccination with the live vaccine should be revaccinated with another appropriate influenza vaccine (eg, inactivated or recombinant formulations) r1
      • Zanamivir dosage for prophylaxis is the same as for treatment; oseltamivir prophylaxis is given once daily at half the total daily treatment dosage r13
      • Duration of chemoprophylaxis varies with the circumstances, as follows: r13
        • Postexposure prophylaxis is usually maintained for 10 days after most recent exposure
        • For 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, whichever is later
      • Baloxavir marboxil is approved by FDA for postexposure prophylaxis of influenza in patients aged 5 years and older r5
        • 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 r15
    • Other preventive measures r29
      • Frequent handwashing with soap and water c155c156
      • Avoiding contact with infected persons and limiting contact with others while sick (by staying home for at least 24 hours after flulike symptoms appear) c157
      • Covering one's nose and mouth with a tissue while coughing or sneezing and throwing the tissue in the trash after use c158c159
      • Wearing a mask
      • Avoiding touching mucosal surfaces such as the mouth, nose, and eyes c160
      • Cleaning and disinfecting surfaces c161c162
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