Influenza Virus

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
- Up to 61 million persons infected annually in the U.S. with ~12,000 deaths (CDC 2007)
Age
- Highest occurrence in young children (up to 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 and malaise
Severe retro-orbital headache, sore throat
Upper respiratory infection signs and symptoms occur 3-4 days after initial onset
Shedding of influenza virus peaks at 24-48 hours after onset of symptoms and then rapidly declines
- In immunocompetent hosts influenza virus is usually not shed for more than 5-10 days but may be detected later in immunocompromised hosts
Complications
- Generally self-limited and uncomplicated in otherwise healthy persons
- Primary viral influenzal pneumonia
- Secondary bacterial pneumonia (Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and other organisms)
- Otitis media (common in children)
- Myositis, rhabdomyolysis
- CNS disease – encephalitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome
- Reye syndrome
- Myocarditis, pericarditis

Treatment

Current antivirals given within 48 hours of symptoms may lessen the severity of the course
- Neuraminidase inhibitors (zanamivir, oseltamivir)
- Adamantanes (amantadine, rimantadine)
- Resistant patterns of circulating influenza strains may change over time
Supportive

Prevention

Yearly vaccination for all persons >6 months of age (CDC recommendation)
- Inactivated – intramuscular
- Live attenuated – intranasal
  - Contraindicated in settings of 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 Testing

Respiratory illness consistent with influenza and usually presenting during influenza season
Diagnosed clinically
- CDC recommends testing hospitalized patients and close contacts of high-risk individuals (eg, childcare workers, healthcare workers)

Laboratory Testing

Rapid antigen detection
- Rapid detection necessary to use antivirals early
- Best specimens are 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
  - Test sensitivity ~70-80% during peak season but depends on circulating strains (95-100% specificity)
  - Test performance decreases when disease incidence is low (eg, tail-end of respiratory season)
  - Test 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 up to 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)

Tests generally appear in the order most useful for common clinical situations

Test name: Influenza A and B Antigen Test

ARUP #:

Methodology:

Use: Rapid detection of influenza

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 test results

Test name: Respiratory Viruses DFA with Reflex to Respiratory Virus Mini Panel by RT-PCR

ARUP #: 2002565

Methodology: Direct Fluorescent Antibody Stain

Use:

Rapid detection of respiratory viruses

If DFA is negative or inadequate for influenza, respiratory virus mini panel by RT-PCR will be added

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

Test name: Respiratory Viruses DFA with Reflex to Viral Culture

ARUP #: 0060281

Methodology: Direct Fluorescent Antibody Stain

Use:

Rapid detection of common respiratory viruses

Limitations:

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

Test name: Respiratory Virus Mini Panel by RT-PCR

ARUP #: 0060764

Methodology: Qualitative Reverse Transcription Polymerase Chain Reaction

Use:

Detect influenza A & B and RSV

Limitations:

May be less sensitive in children

Test name: Influenza Virus A & B DFA with Reflex to Influenza Virus A & B Rapid Culture

ARUP #: 0060284

Methodology: Direct Fluorescent Antibody Stain

Use:

Rapid detection of influenza

If DFA negative, culture is added

Limitations:

Culture less sensitive than PCR

Test name: Influenza Virus A & B DFA with Reflex to Respiratory Virus Mini Panel by RT-PCR

ARUP #: 2002643

Methodology: Direct Fluorescent Antibody Stain

Use:

Rapid detection of influenza and RSV

Limitations:

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

Test name: Influenza A H1N1 (2009) Detection by RT-PCR

ARUP #: 2004217

Methodology: Reverse Transcription Polymerase Chain Reaction

Use:

Identify 2009 H1N1 subtype in documented influenza A cases

Limitations:

Must sample from lower respiratory tract to maximize sensitivity

Additional Tests Available

Test name: Influenza Virus A & B Rapid Culture

ARUP #: 0060286

Methodology: Cell Culture/Immunofluorescence

Comments:

Diagnosis of influenza

Culture less sensitive than PCR

Test name: Respiratory Viruses Rapid Culture

ARUP #: 2001504

Methodology: Cell Culture/Immunofluorescence

Comments:

Isolates other respiratory viruses, including influenza A and B; parainfluenza types 1,2,3; adenovirus; and RSV

Test name: Respiratory Viruses DFA

ARUP #: 0060289

Methodology: Direct Fluorescent Antibody Stain

Comments:

Tests other common respiratory viruses; can help diagnose other causes of influenza-like illness

Lower sensitivity for H1N1 type

Test name: Influenza A Virus Antibody, IgG

ARUP #: 0051074