Influenza Virus

Influenza, commonly referred to as the flu, is an acute viral infection that is highly transmissible, leading to outbreaks of varying severity during the winter in temperate regions. Laboratory testing methods include rapid point of care testing, direct fluorescent antibody stain (DFA), PCR, and culture. Choice of testing depends upon several factors, including whether or not the patient is hospitalized or immunocompromised.

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

Indications for Testing

Abrupt onset of fever, chills, myalgia, headache, cough, sore throat, nasal congestion, and malaise

Laboratory Testing

  • CDC – testing recommendations
  • Rapid antigen detection
    • Point of care testing – multiple Clinical Laboratory Improvement Amendments (CLIA)-waived tests available
    • Rapid detection – ~15 minute turnaround time assists with decision to use antivirals
    • Interpretation of results should include clinical picture and incidence of influenza in community (see CDC Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests)
    • Sensitivity
      • ~50-70% (CDC, 2016) – negative results should be viewed with caution if clinical suspicion is high
      • Dependent on viral strain and titer, collection technique and quality of sample, duration of illness, and disease incidence in community (Abraham, 2015)
    • Specificity – ~90-95% (CDC, 2016)
    • Recommended specimens
      • Nasopharyngeal swabs
      • Nasal washes/aspirates may be necessary in children
  • Direct fluorescent antibody stain (DFA)
    • Rapid turnaround time
    • ~75% sensitivity for influenza compared to culture
    • Strategy combining DFA with reflex to culture or polymerase chain reaction (PCR) increases sensitivity
  • PCR
    • Slower turnaround time
    • Most sensitive and specific
  • Culture
    • Considered the gold standard
    • Slow turnaround times
    • Conventional culture may require as many as 7-10 days

Differential Diagnosis

Epidemiology

  • Incidence – >1/1,000
  • Age
    • Highest occurrence in children
    • Highest mortality in the elderly
  • Transmission
    • Respiratory droplet, airborne route
    • 10-15% transmission rate among household contacts

Organism

  • Single-stranded RNA virus in Orthomyxoviridae family
    • Aquatic birds considered reservoir for influenza A
  • 3 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)

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

  • Abrupt onset of fever, chills, myalgia, headache, cough, sore throat, nasal congestion, and malaise
  • Shedding of influenza virus peaks 24-48 hours after onset of symptoms and then rapidly declines
    •  Immunocompromised hosts may have delayed and prolonged viral shedding – virus is usually not shed for more than 5-10 days
  • Generally self limited and uncomplicated in healthy persons 
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 Viruses DFA with Reflex to Viral Culture, Respiratory 0060281
Method: Direct Fluorescent Antibody Stain/Cell Culture

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 depends on adequacy of specimen; if specimen contains <20 cells, then DFA result will be reported as inadequate

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 

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

Influenza A Virus H1/H3 Subtype by PCR 2007469
Method: Qualitative Polymerase Chain Reaction

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

Explify Respiratory Pathogens by Next Generation Sequencing 2013694
Method: Massively Parallel Sequencing

Guidelines

Influenza Vaccination: Information for Healthcare Professionals. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Nov 2016; Accessed: Jul 2017]

U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Manual for the Surveillance of Vaccine-Preventable Diseases. Centers for Disease Control and Prevention. Atlanta, GA [Last updated: Apr 2016; Accessed: Aug 2017]

General References

Abraham MK, Perkins J, Vilke GM, Coyne CJ. Influenza in the Emergency Department: Vaccination, Diagnosis, and Treatment: Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee. J Emerg Med. 2016; 50(3): 536-42. PubMed

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. 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: Mar 2016; Accessed: Jul 2017]

Hessen MT. 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 MR, 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

Nelson RE, Stockmann C, Hersh AL, Pavia AT, Korgenksi K, Daly JA, Couturier MR, Ampofo K, Thorell EA, Doby EH, Robison JA, Blaschke AJ. Economic analysis of rapid and sensitive polymerase chain reaction testing in the emergency department for influenza infections in children. Pediatr Infect Dis J. 2015; 34(6): 577-82. 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

Content Reviewed: 
July 2017

Last Update: November 2017