Influenza Virus

Diagnosis

Indications for Testing

• Respiratory illness consistent with influenza and usually presenting during influenza season (usually diagnosed clinically)

Laboratory Testing

• CDC - testing recommendations
• Rapid antigen detection
  • Rapid detection necessary to use antivirals early
  • Best specimens – nasopharyngeal swabs
  • More sensitive in young children
  • Clinical Laboratory Improvement Amendments (CLIA) waived point-of-care tests – NOW Influenza A,B; QuickVue Influenza; SAS Influenza A,B; Zstat Flu
    • Sensitivity – ~70-80% during peak season depending on circulating strains
    • Specificity – 95-100%
    • Performance decreases when disease incidence is low (eg, tail-end of respiratory season)
    • Cannot differentiate H1 from H3
• Direct fluorescent antibody stain (DFA)
  • Rapid turnaround time
  • ~75% sensitivity for influenza compared to culture
• Real-time polymerase chain reaction (RT-PCR) – most sensitive
• Culture
  • Considered the gold standard
  • Conventional culture may require as many as 7-10 days

Differential Diagnosis

• Sore throat
  • Epstein-Barr virus
  • Streptococcal disease, group A
  • Other viral diseases – rhinovirus, coronavirus
• Headache
  • Meningitis
  • Encephalitis
• Cough and fever
  • Other viral disease – hantavirus
  • Atypical pneumonia (M. pneumoniae)
  • Anthrax (Bacillus anthracis)
  • Severe acute respiratory syndrome (SARS)
  • Bacterial pneumonia (Streptococcus pneumoniae)

Clinical Background

Influenza is an acute viral infection that occurs in outbreaks of varying severity mainly during the winter in temperate regions and year-round in the tropics.

Epidemiology

• Incidence – >1/1,000
  • As many as 61 million persons infected annually in U.S. with ~12,000 deaths (CDC 2007)
  • CDC weekly influenza surveillance report
• Age
  • Highest occurrence in young children – as many as 30% of children annually
  • Highest mortality in the elderly
• Transmission – respiratory droplet, airborne route
  • 10-15% transmission rate among household contacts

Organism

• Single-stranded RNA virus in the Orthomyxoviridae family
• Three types based on antigenic differences – A, B, C
  • Only A undergoes antigenic shift responsible for epidemics and pandemics
• Classified by hemagglutinin (HA)/neuraminidase (NA) activity
  • Named by H and N components (H1-15 and N1-9)
  • H1N1 was pandemic strain of 2009-2010

Risk Factors for Severe Disease

• Age – infants and elderly
• Chronic pulmonary disease (especially asthma)
• Chronic renal, cardiovascular, hematologic (eg, hemoglobinopathies), or metabolic diseases (eg, diabetes)
• Immunocompromised state
• Nursing home residents
• Pregnancy

 Clinical Presentation

• Abrupt onset of cough, fever, chills, myalgias, malaise
• Severe retro-orbital headache, sore throat
• Upper respiratory infection signs and symptoms – 3-4 days after initial onset
• Shedding of influenza virus peaks 24-48 hours after onset of symptoms and then rapidly declines
  • In immunocompetent hosts, influenza virus usually not shed for more than 5-10 days
    • May be detected later in immunocompromised hosts
• Complications
  • Generally self-limiting and uncomplicated in otherwise healthy persons 
  • Primary viral influenzal pneumonia
  • Secondary bacterial pneumonia (eg, Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae)
  • Otitis media – common in children
  • Myositis, rhabdomyolysis
  • Central nervous system disease – encephalitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome
  • Reye syndrome
  • Myocarditis, pericarditis

  Prevention

• Yearly vaccination for all persons >6 months of age (CDC recommendation)
  • Inactivated – intramuscular
  • Live attenuated – intranasal
    • Contraindicated in immunocompromised persons or households with persons who are immunocompromised
      • Antiretroviral prophylaxis with neuraminidase inhibitors when vaccination is contraindicated
• For more information on prevention, see CDC Seasonal Influenza Vaccination Resources for Health Professionals

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Influenza Virus A and B Rapid Culture 0060286 Method: Cell Culture/Immunofluorescence	Diagnose influenza Culture less sensitive than PCR
Respiratory Viruses Rapid Culture 2001504 Method: Cell Culture/Immunofluorescence	Isolates other respiratory viruses, including influenza A and B; parainfluenza types 1,2,3; adenovirus; and RSV
Respiratory Viruses DFA 0060289 Method: Direct Fluorescent Antibody Stain	Tests other common respiratory viruses; can help diagnose other causes of influenza-like illness Lower sensitivity for H1N1 type
Influenza A Virus Antibody, IgG 0051074 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Requires paired serum samples to be clinically informative
Influenza A Virus Antibody, IgM 0051081 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Antibodies appear ~2 weeks after initial inoculation
Influenza B Virus Antibody, IgG 0051080 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Requires paired serum samples to be clinically informative
Influenza B Virus Antibody, IgM 0051079 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Antibodies appear ~2 weeks after initial inoculation
Influenza A & B Virus Antibodies, IgG & IgM 0051069 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Antibodies appear ~2 weeks after initial inoculation
Influenza A Virus Antibodies, IgG & IgM 2004421 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Antibodies appear ~2 weeks after initial inoculation
Influenza B Virus Antibodies, IgG & IgM 2004422 Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay	Antibodies appear ~2 weeks after initial inoculation
Viral Culture, Respiratory, and Cytomegalovirus Rapid Culture 2006497 Method: Cell Culture/Immunofluorescence