Influenza Virus

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

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 (12-36 hours after illness onset) necessary to use antivirals early
    • Recommended specimens – nasal washes/aspirates may be necessary in young children; 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
    • Less rapid turnaround time
  • Culture
    • Considered the gold standard
    • Conventional culture may require as many as 7-10 days

Differential Diagnosis

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
  • Age
    • Highest occurrence in young children
    • 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
    • Aquatic birds considered reservoir for influenza A
  • Three types based on antigenic differences – A, B, C
    • Only A undergoes antigenic shift responsible for epidemics and pandemics
    • C causes only mild illness
  • Classified by hemagglutinin (HA)/neuraminidase (NA) activity
    • Named by H and N subtypes (H1-16 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 residency
  • Pregnancy

Clinical Presentation

  • Upper respiratory infection signs and symptoms – 3-4 days after initial onset
    • Abrupt onset of cough, fever, chills, myalgias, malaise
    • Severe retro-orbital headache, sore throat
  • 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
      • Immunocompromised hosts may have delayed and prolonged viral shedding
  • Complications

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

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.

Influenza A and B Antigen Test

Limitations

Time-sensitive test

Negative rapid influenza virus test does not rule out an infection with influenza A or B; 70% sensitive, 95% specific

Rapid tests administered within 4 weeks after vaccination with live, attenuated influenza virus vaccines may produce false-positive results

Respiratory Virus Mini Panel by PCR 0060764
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Limitations

May be less sensitive in children

Respiratory Viruses DFA with Reflex to Viral Culture, Respiratory 0060281
Method: Direct Fluorescent Antibody Stain/Cell Culture

Limitations

DFA is specific and sensitive in children; may not be as sensitive in adults

Influenza Virus A and B DFA with Reflex to Influenza Virus A and B Rapid Culture 0060284
Method: Direct Fluorescent Antibody Stain/Cell Culture

Limitations

Sensitivity of DFA methodology is dependent upon adequacy of the specimen; if specimen contains fewer than 20 cells, then the DFA result will be reported as "inadequate”

Culture less sensitive than PCR

Influenza Virus A and B DFA with Reflex to Respiratory Virus Mini Panel by PCR 2002643
Method: Direct Fluorescent Antibody Stain/Qualitative Polymerase Chain Reaction

Limitations

DFA is specific and sensitive in children; may not be as sensitive in adults

Sensitivity of DFA methodology is dependent upon adequacy of the specimen; if the specimen contains fewer than 20 cells, then DFA results will be reported as inadequate

Influenza A Virus H1/H3 Subtyping by Real-Time RT-PCR 2007469
Method: Qualitative Reverse Transcription Polymerase Chain Reaction

Respiratory Viruses DFA with Reflex to Respiratory Virus Mini Panel by PCR 2002565
Method: Direct Fluorescent Antibody Stain/Qualitative Polymerase Chain Reaction

Limitations

DFA is specific and sensitive in children; may not be as sensitive in adults

Sensitivity of DFA is dependent upon adequacy of specimen; if <20 cells, DFA will be reported as inadequate

Related Tests

General References

Bennett J, Dolin R, Blaser M. Influenza virus. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier, 2014.

Brady RC. Influenza. Adolesc Med State Art Rev. 2010; 21(2): 236-50, viii. PubMed

Charles PG P. Early diagnosis of lower respiratory tract infections (point-of-care tests). Curr Opin Pulm Med. 2008; 14(3): 176-82. PubMed

Chung EY, Chiang VW. Influenza vaccination, diagnosis, and treatment in children. Pediatr Emerg Care. 2011; 27(8): 760-9; quiz 770-1. PubMed

Clark NM, Lynch JP. Influenza: epidemiology, clinical features, therapy, and prevention. Semin Respir Crit Care Med. 2011; 32(4): 373-92. PubMed

Flu Activity & Surveillance. Centers for Disease Control and Prevention. Atlanta, GA [Last updated Oct 2015; Accessed: Nov 2015]

Hessen MTrexler. In the clinic. Influenza. Ann Intern Med. 2009; 151(9): ICT5-1-ICT5-15; quiz ICT5-16. PubMed

McGeer AJ. Diagnostic testing or empirical therapy for patients hospitalized with suspected influenza: what to do? Clin Infect Dis. 2009; 48 Suppl 1: S14-9. PubMed

Peaper DR, Landry ML. Rapid diagnosis of influenza: state of the art. Clin Lab Med. 2014; 34(2): 365-85. PubMed

Petrozzino JJ, Smith C, Atkinson MJ. Rapid diagnostic testing for seasonal influenza: an evidence-based review and comparison with unaided clinical diagnosis. J Emerg Med. 2010; 39(4): 476-490.e1. PubMed

Sullivan SJ, Jacobson RM, Dowdle WR, Poland GA. 2009 H1N1 influenza. Mayo Clin Proc. 2010; 85(1): 64-76. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Couturier MRoger, Barney T, Alger G, Hymas WC, Stevenson JB, Hillyard D, Daly JA. Evaluation of the FilmArray® Respiratory Panel for clinical use in a large children's hospital. J Clin Lab Anal. 2013; 27(2): 148-54. PubMed

Hymas WC, Hillyard DR. Evaluation of Nanogen MGB Alert Detection Reagents in a multiplex real-time PCR for influenza virus types A and B and respiratory syncytial virus. J Virol Methods. 2009; 156(1-2): 124-8. PubMed

Taggart EW, Hill HR, Martins TB, Litwin CM. Comparison of complement fixation with two enzyme-linked immunosorbent assays for the detection of antibodies to respiratory viral antigens. Am J Clin Pathol. 2006; 125(3): 460-6. PubMed

Medical Reviewers

Last Update: April 2016