Influenza

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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
  • Use of either N95 or plain surgical mask by healthcare professionals caring for patients with proven influenza helps to decrease rates of provider contraction of influenza.[1]

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:[2]

  • 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)

Diagnosis

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

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).

Antiviral Treatment

Despite questions on efficacy and safety, CDC still recommends treatment for all hospitalized patients and outpatients at risk for complications[3]

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.
Baloxavir marboxil (Xofluza®)
  • Treatment: >12 years
  • Prophylaxis: not yet approved for this indication
 children less than 12 or weighing less than 40kg, pregnancy, breastfeeding
  • Adverse Events: diarrhea, bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache
  • Allergic reactions: oropharyngeal or facial edema

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[4]

  • Greatest benefit if within 48hrs of symptom onset[5]
    • 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[6]

Dosing

  • Age >7yo: 10mg (2 inhalations) BID x 5d
  • Prophylaxis: 10mg (2 inhalations) once daily x 7 days
    • Not for age < 5yo

Baloxavir marboxil (Xofluza)

Only approved for patients >12 years old and >40kg in weight, no current safety data exists for pregnancy and breastfeeding.[7] More expensive but one time dosing. Genentech, its creator, states a recent phase III trial has shown it to be effective for prophylaxis but not currently FDA indicated for this.[8]

Dosing

  • Weight between 40-80kg: 40mg PO once (20 mg tab x2)
  • Weight >80kg: 80mg PO once (40mg tab x2)
  • Prophlyaxis: not yet approved for this indication by CDC or FDA

NOT Indicated

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

Disposition

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
        • Pneumococcus and S. aureus (including MRSA) most common (35% and 28%, respectively)[9]
          • MRSA associated with necrotizing cavitary infections with high mortality rate in previously healthy young people[10][11]
  • 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. ↑ SURGICAL MASK VS. N95 RESPIRATOR FOR PREVENTING INFLUENZA AMONG HEALTH CARE WORKERS Loeb, M., et al, JAMA 302(17):1865, November 4, 2009
  2. ↑ CDC Clinical Flu
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ CDC Guidelines. 2015-2016. http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm
  6. ↑ Heneghan CJ, et al. Zanamivir for influenza in adults and children: systematic review of clinical study reports. BMJ. 2014; 348:g2547.
  7. ↑ https://www.cdc.gov/flu/treatment/baloxavir-marboxil.htm
  8. ↑ https://www.gene.com/download/pdf/xofluza_prescribing.pdf
  9. ↑ Klein EY, Monteforte B, Gupta A, et al. The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses. 2016;10(5):394-403. doi:10.1111/irv.12398
  10. ↑ Centers for Disease Control and Prevention (CDC). Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza--Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep. 2007;56(14):325-329.
  11. ↑ Hageman JC, Uyeki TM, Francis JS, et al. Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006;12(6):894-899. doi:10.3201/eid1206.051141
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