Influenza

Aka: Influenza

1. See Also
   1. Upper Respiratory Infection
   2. Avian Influenza
2. Epidemiology
   1. Annual Periodicity
      1. Temperate Climate
         1. Onset as early as October
         2. Peaks in late December to March
      2. Tropical Climate: Occurs year round
   2. Transmission
      1. Small-large particle aerosol from cough and sneeze
   3. Course
      1. Incubation: 2-3 days (may be as long as 7 days)
      2. Infectivity (Viral shedding)
         1. Begins within 1 day of symptom onset
         2. Peaks with illness severity
         3. Declines over 4-5 days
         4. Absent after 10 days
      3. Acute symptoms resolve in 4-5 days
      4. Persistent symptoms may not clear for 3 or more weeks
         1. Fatigue or malaise
         2. Persistent non-productive cough
   4. Attack rate:
      1. Epidemics (antigenic drift): 20-30%
      2. Pandemics (antigenic shift): 50%
   5. Ages affected
      1. Children
         1. Highest attack rate
      2. Elderly (over age 65 years)
         1. Lowest attack rate
         2. Highest risk of complication
            1. Relative risk of hospitalization: 5-10
            2. Relative risk of mortality: 5
         3. Highest mortality (80% of deaths are in elderly)
   6. Incidence (worldwide)
      1. Severe Influenza: 3 to 5 million people annually
      2. Influenza-related deaths: Up to 500,000 annually
3. Pathophysiology
   1. Classification
      1. Single-stranded DNA virus in the Orthomyxovirus Family
   2. Vaccines directed at critical viral surface antigens
      1. Hemagglutinin
      2. Neuraminidase
   3. Antigenic drift
      1. Minor genetic mutations result in epidemics
      2. Influenza A most commonly involved
   4. Antigenic shift
      1. Major genetic changes result in pandemic
      2. Major Pandemics
         1. 1918: "Spanish flu" 20 Million deaths worldwide
         2. 1957: Asian Flu
         3. 1968: Hong Kong flu 34,000 deaths
      3. Recent Antigenic Shifts
         1. 1976: Swine flu isolated
         2. 1997: Hong Kong H5N1 (avian) Influenza
         3. 2009: H1N1 Novel Influenza
            1. Reported April 12, 2009 in Veracruz, Mexico and WHO declared pandemic by April 27, 2009
            2. Chimera of swine flu, avian flu, and human flu
            3. (2009) N Engl J Med 361:674-9
4. Types
   1. Influenza A
      1. Major outbreaks result from antigenic shifts
      2. See Avian Influenza
      3. Re-assortment of genomic expression
         1. Neuraminidase and Hemagglutinin
   2. Influenza B
      1. Less variation than Influenza A
      2. Outbreaks in Schools and Military camps
   3. Influenza C
5. Symptoms
   1. Abrupt illness onset
   2. Viral prodrome
      1. High fever to 104 F (fever lasts 4-5 days)
      2. Chills
      3. Severe myalgias (lasts for first 3 days)
      4. Severe Headache (most severe in first 2 days)
   3. Eye
      1. Photophobia
      2. Red, Burning eyes
   4. Nose
      1. Coryza or profuse Nasal discharge (lasts 6-7 days)
         1. Often onset with fever and no other symptoms
      2. Rhinitis
      3. Nasal congestion or "stuffiness"
   5. Throat
      1. Sore Throat or dry throat (lasts for first 3 days)
   6. Chest
      1. Severe dry cough (lasts for first 3 days)
      2. Chest discomfort
   7. Other Constitutional symptoms
      1. Anorexia (may persist for first week)
      2. Fatigue persists weeks
      3. Severe Malaise (may persist for more than a week)
   8. Less common symptoms (20-40%)
      1. Nausea or Vomiting
      2. Dizziness
6. Signs
   1. Fever up to 104 F (40 C)
   2. Non-exudative Pharyngitis
   3. Muscle tenderness
   4. Less Common Influenza signs
      1. Conjunctivitis
      2. Cervical adenopathy
7. Diagnosis
   1. Findings most suggestive of Influenza
      1. Sudden onset of classic Influenza symptoms
      2. High fever to 104 F with chills, sweats, rigors
      3. Severe malaise, Fatigue, and anorexia
      4. Severe myalgias
      5. Moderate to severe Headache
      6. Onset of symptoms within 3 days of office visit
   2. Findings most suggestive of other diagnosis
      1. Systemic symptoms absent
      2. Cough absent
      3. Not confined to bed
      4. Able to perform daily activities without difficulty
   3. References
      1. Ebell (2004) J Am Board Fam Pract 17:1-5
8. Differential Diagnosis
   1. Common Cold viruses
      1. Respiratory Syncytial Virus (RSV)
      2. Parainfluenza
      3. Adenovirus
   2. Factors suggesting Common Cold
      1. Findings suggestive of Influenza (see diagnosis above) are absent
      2. Gradual onset of more mild symptoms
      3. Upper respiratory symptoms predominate
9. Complications
   1. Primary Influenza Pneumonia (1% of adults)
      1. Increased risk with cardiac disease (Mitral Stenosis)
      2. Occurs 1 week after Influenza symptom onset
      3. Occasionally fatal even in young adults
   2. Bacterial tracheobronchitis (occurs in 30% of adults)
      1. Increased risk in Tobacco smoking
   3. Acute Sinusitis (5-10%)
   4. Secondary Bacterial Pneumonia
      1. Occurs one week after Influenza symptom onset
      2. Etiologies
         1. Streptococcal Pneumonia
         2. Staphylococcal Pneumonia
         3. Haemophilus Influenzae
      3. Risk factors
         1. Older than 65 years old
         2. Chronic renal disease
         3. Diabetes Mellitus and other endocrine disease
         4. Hematologic disease or Immunodeficiency
         5. Cardiopulmonary disease
   5. Rare Neurologic Complications
      1. Meningoencephalitis
      2. Transverse myelitis
      3. Reye's Syndrome
      4. Guillain-Barre Syndrome
      5. Myositis or Rhabdomyolysis
   6. Other rare complications
      1. Myoglobinuric Renal Failure
      2. Myocarditis
      3. Pericarditis
      4. Glomerulonephritis
      5. Parotitis
10. Labs: Diagnosis
    1. General
       1. Influenza diagnosis should be made clinically (lab testing is only needed in certain groups)
       2. Rapid Influenza Testing has poor Test Sensitivity and does not exclude Influenza if negative
       3. High risk groups should still be treated without delay if high clinical suspicion despite negative testing
    2. Indications for testing
       1. Influenza-like illness in patients or workers in the hospital, Nursing Home or daycare
    3. Initial testing at point of care
       1. Rapid Influenza Test (Influenza Immunoassay)
          1. Sample site varies between products
          2. Test Sensitivity 10-70% (very high false negative rate)
          3. Test Specificity >95%
    4. Confirmatory Testing
       1. Real Time Reverse Transcriptase PCR (RT-PCR) for RNA detection (preferred)
          1. Test Sensitivity: 86 to 100%
          2. Requires 24 hours to run test
          3. If Rapid Influenza Test negative despite high suspicion, consider PCR (especially in Nursing Home)
       2. Influenza Culture (48-72 hours required for isolation)
          1. Nasopharyngeal swab
          2. Throat swab
          3. Sputum
       3. Serology (diagnostic if four fold rise over 10-14 days)
          1. Hemagglutination inhibition
          2. Complement fixation titers
11. Labs: Other
    1. Complete Blood Count
       1. Leukopenia or slight Leukocytosis (up to 15,000)
       2. Relative Lymphopenia
12. Management
    1. Symptomatic treatment
       1. Acetaminophen
       2. Pharyngitis Symptomatic Treatment
       3. Cough Symptomatic Treatment
       4. Consider antiviral agent below if ill <48 hours
          1. Shorten course of illness (~1 day)
          2. No evidence that antivirals prevent complications
    2. Influenza A
       1. Neuraminidase Inhibitors
          1. See Zanamivir (Relenza)
          2. See Oseltamivir (Tamiflu)
       2. Resistance to Adamantanes (Amantadine, Rimantadine) is common (esp. H1N1)
          1. Consider using Rimantadine 100 mg daily for 5 days for treatment in combination with Neuraminidase Inhibitors in Nursing Home
          2. Due to resistance, not used for chemoprophylaxis
       3. Course: 5 days or 48 hours after symptoms resolve
    3. Influenza A or B: Neuraminidase Inhibitors
       1. See Zanamivir (Relenza)
       2. See Oseltamivir (Tamiflu)
    4. Avoid Salicylates in patients younger than 16 years
       1. Risk of Reye's Syndrome
13. Management: Hospitalization Indications (findings suggestive of severe case)
    1. Chest Pain
    2. Altered Level of Consciousness
    3. Seizures
    4. Severe weakness
    5. Hemoptysis
    6. Hypoxia, cyanosis, labored breathing or Shortness of Breath
    7. Decreased urine output, Hypotension or dehydration
    8. High fever or progressive worsening after first 72 hours
14. Prevention
    1. Influenza Vaccine yearly
       1. Immunize all high risk groups
          1. See Influenza Vaccine for indications
          2. Nursing Home residents and staff
          3. Comorbid illness
          4. Pregnant women after first trimester
       2. Efficacy (depends on vaccine components)
          1. Healthy younger patients: 70-90%
          2. Elderly: 30-40%
    2. Flumist
       1. Live virus intranasal vaccine
       2. May be used in healthy patients aged 5 to 49 years
    3. Postexposure prophylaxis in high risk groups
       1. Start within 48 hours of exposure
       2. Nursing Home: Treat for at least 2 weeks and for at least 7 days after the last infected case
       3. Amantadine Or Rimantadine prophylaxis is no longer recommended for Influenza A due to resistance (use Neuraminidase Inhibitors)
       4. Neuraminidase Inhibitors
          1. See Zanamivir (Relenza)
          2. See Oseltamivir (Tamiflu)
    4. Other measures
       1. Respiratory isolate hospitalized Influenza patients
       2. Isolate Nursing Home residents with Influenza to room
       3. Isolate Nursing Home residents on prophylaxis to room
          1. Risk of virus shedding
15. Prevention: Pandemic Preparedness
    1. Federal, State and Local Planning
    2. Influenza Surveillance via WHO worldwide (CDC in US)
       1. Local Vital Statistics offices report deaths weekly
    3. Maximize Vaccine development and delivery
    4. Develop limited antiviral (Amantadine) indications
    5. Emergency medical, hospital and backup preparedness
    6. Ensure communication networks are in place
       1. Internet, Health Alert Network, Telephone
16. Resources
    1. Is it the cold or the flu
       1. http://www.naid.nih.gov/publications/cold/sick.htm
    2. CDC Influenza Surveillance
       1. http://www.cdc.gov/ncidod/diseases/flu/weekly.htm
    3. CDC Influenza Information
       1. http://www.cdc.gov/ncidod/diseases/flu
    4. American Lung Association Influenza Information
       1. http://www.lungusa.org/diseases/luninfluenz.html
    5. National Foundation Infectious Disease on Influenza
       1. http://www.nfid.org/factsheets/inflfacts.html
17. References
    1. (1999) Preparing Next Influenza Pandemic Teleconf, CDC
    2. Hayden (2000) N Engl J Med 343:1282-9
    3. Welliver (2001) JAMA 285:748-54
    4. Erlikh (2010) Am Fam Physician 82(9):1087-95