Care Process Models
are diagnosis and
treatment algorithms

Influenza (Adult and Pediatric)

Why focus on influenza?

Influenza epidemics occur almost every winter. The impact varies from year to year but it is estimated that each year up to 20% of the US population becomes ill with influenza. Attack rates are even higher in children. Rates of hospitalization for children younger than 2 with influenza equal the rate in the elderly. Annually, up to 400,000 people are hospitalized and up to 40,000 people die from influenza and related complications.

What is the definition of influenza?

Influenza is an acute respiratory illness caused by influenza A, B and C viruses. Of these, influenza A and B are thought to cause significant disease. Infections due to influenza B usually cause a milder infection. Influenza A viruses are further categorized into subtypes by the 2 major surface protein antigens: hemagglutinin (H) and neuraminidase (N). In the northern hemisphere, annual epidemics of influenza typically occur during the fall or winter months. However, the peak of influenza activity can occur as late as April or May, and the timing and duration of flu seasons remain variable.

The Centers for Disease Control and Prevention define a case of influenza-like illness as fever AND either cough or sore throat.

Additional symptoms are listed under Suspect influenza.

Who should receive antiviral prophylaxis for influenza?

Indiscriminate use of chemoprophylaxis promotes resistance to antiviral medications and reduces antiviral medication availability for treatment of persons who are severely ill. Prophylaxis with oseltamivir may be considered in the following situations:

  1. Very high-risk, asymptomatic patients if ≤48 hours have elapsed since exposure to a person with known or suspected influenza infection:
    • Highly immunosuppressed patients including:
      • Hematopoietic stem cell or organ transplant recipients
      • Patients currently receiving chemotherapy or radiation
      • HIV or other immunodeficiency with CD4 percentage <15%

    Duration of prophylaxis: 7 days

  2. Profoundly immunocompromised patients during periods of high influenza activity (with or without known exposure to persons with influenza infection):
    • Allogeneic hematopoietic stem cell transplant (SCT) patients ≤6 months after transplant or those beyond 6 months with graft-versus-host disease ≥ grade 2
    • Lung transplant recipients in the first year following transplantation or those beyond one year with augmented immune suppression or other complicating features

    Duration of prophylaxis: Continue while there is widespread influenza activity in the patient's state of residence.

Dosage of Oseltamivir for chemoprophylaxis:
  • Adults: 75mg once daily
  • Children ≥12 months
    • ≤15 kg: 30 mg once daily
    • ≥15–23 kg: 45 mg once daily
    • >23–40 kg: 60 mg once daily
    • >40 kg: 75 mg once daily
  • Infants 9-11 months: 3.5 mg/kg/dose once daily
  • Term infants 3-8 months: 3 mg/kg/dose once daily
  • Infants <3 months: antiviral prophylaxis is not recommended due to limited data in this age group
Breakthrough infections

Patients receiving prophylaxis should be instructed to seek medical evaluation if they develop a febrile respiratory illness that might indicate influenza. Infectious Diseases consultation is recommended for patients who develop influenza infection while taking or shortly after taking antiviral chemoprophylaxis.

Evaluation, Testing, Treatment, and Follow Up

  1. Suspect influenza
  2. Perform history and
    physical examination
  3. Determine need for testing
  4. Indications
    for hospitalization?
  5. Evaluate and
    hospitalize patient
    if unstable
  6. Implement
    isolation precautions
  7. Begin treatment
    with oseltamivir
  8. Order tests
  9. Instruct patient on
    respiratory etiquette
  10. High-risk patient?
  11. Ongoing contact
    with a very high-risk
    patient?
  12. Antiviral treatment
    recommended
  13. Symptomatic care
    antiviral treatment not
    recommended
  14. Condition
    improved?
  15. Follow up with
    primary provider
    for immunization
  16. Consider Infectious
    Diseases consult

Suspect influenza

Any of the following symptoms may indicate the presence of influenza:

  • Fever >38° C
    • In children younger than 12 months, this may be the only symptom
  • Muscle aches
  • Cough, dyspnea, wheezing
  • Headache
  • Malaise, fatigue
  • Sore throat
  • Gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea) may occur in children
  • In children younger than 12 months, influenza can present with sepsis-like symptoms

Perform history and physical examination

History:
  • Fever
  • Cough, dyspnea, wheezing
  • Myalgias
  • Headache
  • Malaise, fatigue
  • Sore throat
  • Gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea) may occasionally occur in children
  • In children younger than 12 months, influenza can present with sepsis-like symptoms
  • Recent influenza exposure
  • Influenza vaccination status
Physical examination:
  • Fever >38° C
  • Infants may appear systemically ill
  • Pharyngitis
  • Lungs are usually clear unless there is a secondary bacterial pneumonia

Determine need for testing

When influenza is widespread in your state (See CDC weekly US map) only test the following patients:
  • Hospitalized patients
At other times between October and May, when influenza is not widespread (See CDC weekly US map) test the following patients with influenza-like illness (fever and either cough or sore throat):
  • Hospitalized patients
  • Patients at high risk for influenza complications who appear severely ill
Acceptable samples (in order of preference): Nasopharyngeal aspirate/swab, nasal swab, throat swab

Nasopharyngeal (NP) swab or aspirate are the optimal samples for detection of Influenza. These samples can be difficult to obtain in adults and a nasal or throat swab are acceptable alternatives, although they may have slightly lower sensitivity for virus detection. NP swabs should be collected using a flexible, rayon, mini-tipped swab. Throat and nasal swabs should be collected using a regular culturette.

Preferred test for persons ≥2 years of age (PCR for influenza A/B)
Preferred test for persons <2 years of age (PCR for influenza A/B and RSV, can be done on a single swab)
Alternative test: Rapid antigen tests

PCR for influenza A/B has a reported sensitivity of 100% and a specificity of 98.6% for influenza A and 100% sensitivity and specificity for influenza B, respectively. Tracheal aspirates are not acceptable for testing due to the viscous nature of these specimens.

If PCR is not readily available, rapid antigen tests for influenza A and B may be used. However, the sensitivity of the rapid antigen tests is low so false-negative results are very common.

Culture and serologic testing have no role in the primary diagnosis of acute disease.

Time range between onset of symptoms and utility of testing

Testing is most likely to detect influenza in the first 1-3 days after symptom onset, when the the highest levels of virus are shed but PCR can be positive for as long as 7 days following onset. When influenza is widespread, treatment decisions should be based on clinical presentation rather than test results.

Indications for hospitalization

Adults:
  • Hypotension
  • Dehydration
  • Renal failure
  • Respiratory distress
  • Altered mental status
  • Social concerns (elderly, living alone)
Children:
  • Dehydration
  • Respiratory distress
  • Suspicion of bacterial pneumonia
  • Children younger than 12 months who are more than mildly ill-appearing

Use clinical judgment when determining if patient is unstable and in need of hospitalization.

Implement isolation precautions

For hospitalized patients with suspected or confirmed seasonal influenza the appropriate isolation precautions are:

  • Adults: Droplet precautions
  • Children: Contact precautions and Droplet precautions

Duration of isolation:

  • Children and immunosuppressed patients: duration of hospitalization
  • All others: 7 days after illness onset or until 24 hours after resolution of fever and respiratory symptoms, whichever is longer

For additional information contact your health care facility's Infection Prevention and Control.

Teaching Point: Preventing the spread of influenza

The best way to prevent influenza is to get the vaccine each year. Other precautions that can help to prevent the spread of influenza include:

  • Handwashing
  • Respiratory etiquette, covering your cough/sneeze (See CDC Cover Your Cough)
  • Staying at home when sick
  • Appropriate isolation of hospitalized patients
  • Avoiding contact with infected persons

Begin treatment with oseltamivir

All hospitalized patients and out-patients at high risk for complications from influenza should receive oseltamivir.

Adult oseltamivir dosing:
  • CrCl ≥30 ml/min:
    • 75 mg PO bid for 5 days
  • CrCl <30 ml/min:
    • 75 mg PO once daily for 5 days
Pediatric oseltamivir dosing:
  • Children ≥12 months
    • ≤15 kg: 30 mg twice daily for 5 days
    • ≥15–23 kg: 45 mg twice daily for 5 days
    • >23–40 kg: 60 mg twice daily for 5 days
    • >40 kg: 75 mg twice daily for 5 days
  • Infants 9-11 months: 3.5 mg/kg/dose BID for 5 days
  • Term infants 0-8 months: 3 mg/kg/dose BID for 5 days
  • Dosing in premature infants:
    • <38 weeks’ postmenstrual age (gestational age + chronological age): 1 mg/kg/dose BID for 5 days
    • 38 through 40 weeks’ postmenstrual age: 1.5 mg/kg/dose BID for 5 days
    • >40 weeks’ postmenstrual age: 3 mg/kg/dose BID for 5 days

Order tests

The following tests should be ordered for severely ill or hospitalized patients.

  • Influenza Virus Type A/B PCR - nasopharynx swab, nasal swab or throat swab (these are in order of preference)
    • For children <2, consider obtaining a PCR for influenza A/B and RSV, which can be done on a single swab
    • For most children ≥2, testing only for influenza A/B by PCR is sufficient
  • Complete blood count (CBC) w/differential
  • Electrolyte Panel
  • Blood Gas (ABGs) (if low oxygen saturation)
  • Chest PA & Lateral (X-ray)

Instruct patient on respiratory etiquette

The best way to prevent influenza is to get the vaccine each year. Other precautions that can help to prevent the spread of influenza include:

  • Handwashing (using alcohol hand rub or soap and water)
  • Respiratory etiquette, covering your cough/sneeze (See CDC Cover Your Cough)
  • If you have influenza, you should stay home from daycare/work/school for at least 24 hours after fever has resolved
Teaching Point: Outpatient precautions

If a patient needs to be seen in the outpatient clinic:

  • Instruct the patient/caregiver to notify the staff on arrival at the clinic that patient has a febrile respiratory illness
  • Desk staff should be alerted that the patient should be masked with a surgical-style mask and further instructed on respiratory etiquette and hand hygiene. The patient should then be placed in an examining room as soon as possible or in a separate area of the waiting room away from other patients
  • When examining the patient or while taking a nasopharyngeal swab, put on gloves and a droplet mask (mask that covers mouth and nose and also provides eye protection)

High-risk patient?

For high-risk patients, test if possible but do not delay treatment for test results.

Factors that increase risk for significant disease and complications:

  • Age <12 months or >65 years
  • Patient <19 years on daily aspirin therapy
  • Resident of nursing home
  • Hospitalized patients
  • Pregnancy or lactation
  • Postpartum (within first 14 days)
  • Morbid obesity (body mass index ≥40)
  • Pulmonary disease (including asthma)
  • Cardiovascular disease (excluding hypertension)
  • Liver or renal disease
  • Neurologic or neurodevelopmental disorders
  • Airway abnormalities
  • Chronic metabolic disease (including diabetes)
  • Hemoglobinopathies
  • Immunodeficiency
    • HIV or other immunodeficiency with CD4 percentage <15% or <200 cells/mm3
    • Solid organ transplant or stem cell transplant
    • Chronic steroid or other immunosuppressant use

Ongoing contact with a very high-risk patient?

Very high risk patients include:
  • Infants <6 months
  • Highly immunosuppressed patients including:
    • Hematopoietic stem cell or organ transplant recipients
    • Patients currently receiving chemotherapy or radiation
    • HIV or other immunodeficiency with CD4 percentage <15%

Consider prophylaxis for very high-risk immunosuppressed contacts.

Symptomatic care; antiviral treatment not recommended

  • Encourage hydration
  • Activity as tolerated
  • Acetaminophen or NSAIDs for fever, headache, myalgias
  • Avoid aspirin in patients ≤18 years of age
Teaching Point: Previously healthy persons with mild-to-moderate symptoms do not require antivirals

Testing and treatment for influenza is not likely to provide significant benefit to previously healthy individuals even if within 48 hours from onset of symptoms. Provide symptomatic treatment and reevaluate if symptoms worsen.

Condition improved?

Treatment goals for influenza:

  • Resolution of fever
  • Prevent influenza complications (eg, respiratory failure, secondary bacterial pneumonia, prolonged hospitalization, death)
Return to daycare, school, and/or work

Patients with influenza should be excluded from daycare, school, and/or work until at least 24 hours after fever resolution (without the use of fever-reducing medicines).

Health care workers caring for hematopoietic stem cell transplant patients in protective environment: Exclude from work for 7 days from symptom onset or until 24 hours after the resolution of fever, whichever is longer. Alternatively consider temporary re-assignment to other areas.

Follow up with primary provider for immunization

  • No routine tests or referrals are needed for influenza follow up
  • Ensure that an influenza vaccine is administered during the current season, if not already administered, and annually (See CDC: Seasonal Influenza Vaccination Resources for Health Professionals). Influenza vaccine protects against multiple strains of influenza, therefore, vaccination is indicated even after an illness with influenza to protect against the other strains.
Patient Education:

Influenza (CDC.gov)

Consider Infectious Diseases consult

If symptoms persist despite treatment of influenza, or delayed exacerbation of symptoms, consider Infectious Diseases referral.

Influenza complications
in high-risk patients

For Infectious Diseases Experts
  1. Expert treatment plan
    and follow up
  2. Condition
    improved?
  3. Follow up with
    primary provider
    for immunization

Expert treatment plan and follow up

  • Re-evaluate influenza diagnosis
  • Assess need for antibiotic treatment of bacterial infection of the respiratory tract
  • Evaluate for acute lung injury

The above algorithm does not replace clinical judgment and should be modified as needed for individual patients.

Primary Authors: Larry M. Baddour, MD, Thomas Boyce, MD, W. Charles Huskins, MD, Priya Sampathkumar, MD, and Pritish Tosh, MD

Input and Recommendations: Brenda Anderson, RN, Ritu Banerjee, MD, PhD, Matthew Binnicker, PhD, Walter Cook, MD, Chris Derauf, MD, Walter Hellinger, MD, Robert V. Johnson, MD, Michael R. Keating, MD, Shimon Kusne, MD, Robert D. Noyce, MD, Robert Orenstein, DO, Siobhan Pittock, MD, Stacey Rizza, MD, Andi Selby, DO, Maria Seville, MD, Jill M. Smith, RN, CNP, Dennis Spano, MD, Stephanie Starr, MD, Rodney L. Thompson, MD, Maria Valdes, MD, Abinash Virk, MD, and John W. Wilson, MD

Secondary Author: Jane Linderbaum, RN, CNP and Deborah Rhodes, MD