Influenza

Background

  • Human Influenza type A and B cause majority of infections. Type A has more severe disease course.

Transmission

  • Occurs in 6ft radius around infected patient who is sneezing and/or coughing
  • Viral shedding lasts ~5d (starts 24-48hr before onset of symptoms)
    • Longer duration of shedding occurs in children, elderly, patients with chronic illnesses
    • Shedding from asymptomatic individuals does not contribute significantly to transmission

Risk Factors (for complicated course)

  • Age <2 years or >65 years
  • Pregnancy through 2 weeks after delivery
  • Chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus)
  • Immunosuppression, including that caused by medications or by HIV
  • Persons younger than 19 years of age who are receiving long-term aspirin therapy
  • American Indians and Alaska Natives
  • Morbid obesity
  • Patients in nursing homes or chronic-care facilities

Vaccination Status

  • A history of influenza vaccination does not rule out influenza in an ill patient with clinical signs and symptoms compatible with influenza.
  • Therefore, vaccination status should not impede the initiation of prompt antiviral treatment.

Clinical Features

Cough and Fever

Odds that acute cough and fever are due to flu during flu season:[1]

  • Adolescents ≥ 12 yo - 79-88%
  • Children 5-12 yo - 71-83%
  • Children < 5 yo - 64%
  • Adults - unreliable predictors especially when older than 60 yo

Convalescence

  • Most gradually improve over 2-5d, although may last for one week or more
  • Some have persistent weakness lasting several weeks (postinfluenza asthenia)

Differential Diagnosis

Influenza-Like Illness

Fever

Infectious

Non-infectious

Evaluation

Workup

  • Influenza PCR preferred for inpatients (sensitivity >95%)
  • RSV/Flu/metapneumovirus test low sensitivity for adults (48-60%) and children (62-72%), with turnaround time <24 hours
  • The Viral Respiratory Panel (influenza, RSV, adenovirus, parainfluenzavirus) discouraged (sensitive 70-90%) with 3-5 days turnaround
  • Rapid tests specific but not sensitive (cannot be used to rule-out)

Evaluation

Outpatients

  • Risk factors:
    • Yes
      • Do NOT send Point of Care influenza test
      • Do NOT send diagnostic test for influenza
      • Empirically treat for influenza using antivirals if symptoms for <48 hours
    • No
      • Do NOT send Point of Care influenza test.
      • Do NOT send diagnostic test for influenza.
      • May consider treating with anti-influenza antivirals if symptoms <48 hours

Admitted Patients

  • Do not send Point of Care influenza test
  • Send diagnostic test for influenza
    • Influenza PCR preferred for inpatients
  • Empirically treat for influenza using antivirals
    • Most effective when administered when symptoms of influenza have occurred for < 48 hours
    • May be benefit when initiated in severely ill inpatients with 48 hours to 5 days of symptoms
    • No evidence of benefit after 5 days of symptoms
  • Treat empirically promptly with oseltamavir unless there is an alternative diagnosis
  • Droplet precautions (see below)

Management

Despite questions on efficacy and safety, CDC still recommends treatment for all hospitalized patients and outpatients at risk for complications[2]

Oseltamivir (Tamiflu)

Shorten duration of illness by 16.8 hrs while NNTH (number needed to harm) was 28 in regards to causing nausea/vomiting, headache and renal and psych syndromes[3]

  • Greatest benefit if within 48hrs of symptom onset[4]
    • However, may be beneficial up to 4-5 days, including in pregnant patients
    • Early treatment of hospitalized patients can reduce death

Dosing

  • Age <1 year: 3mg/kg PO BID x 5 days
  • <15kg: 30mg PO BID x 5 days
  • 15-23kg: 45mg PO BID x 5 days
  • 24-40kg: 60mg PO BID x5d
  • Adult: 75mg PO BID x 5 days

Zanamivir (Relenza)

Relatively contraindicated in patients with asthma, COPD, or pregnancy. Shorten duration of illness by 14.4 hrs with no reduction in flu-related complications[5]

Dosing

  • Age >7yo: 10mg (2 inhalations) BID x 5d
  • Prophylaxis: 10mg (2 inhalations) once daily x 7 days
    • Not for age < 5yo
Antiviral Agent Recommended For Not Recommended With Adverse Events
Oseltamivir (Tamiflu®)
  • Treatment: any age
  • Prophylaxis: >3 months
N/A
  • Adverse events: nausea, vomiting. Sporadic, transient neuropsychiatric events (self-injury or delirium) mainly reported among Japanese adolescents and adults.
Zanamivir (Relenza®)
  • Treatment: >7 yrs
  • Prophylaxis >5 years
Underlying respiratory disease (e.g., asthma, COPD)
  • Allergic reactions: oropharyngeal or facial edema.
  • Adverse events: diarrhea, nausea, sinusitis, nasal signs and symptoms, bronchitis, cough, headache, dizziness, and ear, nose and throat infections.

M2 Channel Blocker

  • Amantadine and other M2 viral proton channel blockers are no longer indicated for influenza treatment due to nearly 100% resistance

Isolation Precautions

  • Droplet precautions
    • If the patient is in an area in which they are in contact with other patients or need to be transported and thus may come in close contact (<3 feet) with staff, visitors, or other patients, the patient needs to wear a surgical mask (or N-95 respirator, if not available).

Complications

  • Pneumonia
    • Primary influenza pneumonia
      • Most severe and least common type of pneumonia
      • Rare in otherwise healthy adults
      • Consider in patients with persistent and worsening symptoms (esp high fever, shortness of breath, cyanosis)
      • CXR shows bilateral opacities with or with out superimposed consolidation
    • Secondary bacterial pneumonia
      • Exacerbation of fever and respiratory symptoms after initial improvement
        • Higher fever, productive cough, radiographic evidence of infiltrates
      • Microbiology
  • Otitis Media
    • More common in children
  • Myositis and rhabdomyolysis
    • More common in children
    • Extreme tenderness of affected muscles (most commonly in the legs)
  • Pericarditis/myocarditis
    • Rare complication

See Also

References

  1. CDC Clinical Flu
  2. Fiore AE, et al. Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). CDC. Recommendations and Reports. January 21, 2011. 60(RR01);1-24.
  3. Jefferson T, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014; 348:g2545.
  4. CDC Guidelines. 2015-2016. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
  5. Heneghan CJ, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports. BMJ. 2014; 348:g2547.