Pediatric Influenza Workup

  • Author: Itzhak Brook, MD, MSc; Chief Editor: Russell W Steele, MD   more...
 
Updated: Mar 15, 2012
 

Approach Considerations

The criterion standard for diagnosing influenza A and B is a viral culture of nasopharyngeal samples and/or throat samples.

Laboratory Studies

Isolation of influenza viruses or detection of viral antigens in respiratory secretions (eg, throat swabs, nasopharyngeal washes, sputum) can be performed during acute influenza infection. Specimens for culture should be obtained within 3 days of onset of illness.

The type of influenza virus (A or B) may be determined by immunofluorescence or hemagglutination inhibition (HAI) techniques, and the hemagglutinin subtypes of influenza A virus (H1, H2, H3) may be identified using HAI with subtype-specific antisera.

Complement-fixation (CF) and hemagglutination inhibition (HI) tests are the most common methods used to compare sera in persons with acute and convalescent infection, although these tests have low sensitivity and specificity. Rises in immunoglobulin (Ig) titer of at least fourfold are considered diagnostic of infection. Significant rises as measured by enzyme-linked immunosorbent assay (ELISA) are diagnostic of acute infection.

Viral antigens in respiratory secretions can be detected by immunofluorescence (IF) assay, time-resolved immunofluorescence assay (TRIFA), radioenzyme immunoassay, and ELISA. ELISA results can be obtained within 1 hour.

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Rapid Diagnostic Tests

The US Food and Drug Administration (FDA) has waived federal Clinical Laboratories Improvement Act (CLIA) requirements and cleared for marketing 7 rapid influenza diagnostic tests that directly detect influenza A or B virus–associated antigens or enzyme in throat swabs, nasal swabs, or nasal washes and can produce results within 30 minutes.[36] The following 3 of these tests are considered low complexity and may be used in physicians’ offices:

  • QuickVue Influenza A+B test (Quidel)
  • ZstatFlu (ZymeTx)
  • QuickVue Influenza test (Quidel)

The QuickVue tests provide results in 10 minutes or less; the ZstatFlu test provides results in 20 minutes. Because of cost, availability, and sensitivity issues, most physicians diagnose influenza based on clinical criteria alone.

Testing for avian influenza

In September 2011 the FDA approved a new kit developed by the CDC for diagnosing human infections with seasonal influenza viruses and novel influenza A viruses with pandemic potential.

The Human Influenza Virus Real-Time RT-PCR Detection and Characterization Panel (rRT-PCR Flu Panel) is an in vitro laboratory diagnostic test that can provide results within 4 hours. It is the only in vitro diagnostic test for influenza that is cleared by the FDA for use with lower respiratory tract specimens and will be given at no cost to qualified international public health laboratories.

Consisting of 3 modules, the kit can:

  • Identify and distinguish between influenza A and B viruses,

• Classify influenza A viruses by subtype, and

• Detect highly pathogenic avian influenza A (H5N1) virus infection in human respiratory tract specimens.

Other FDA-approved assays for diagnosing avian influenza include the Influenza A/H5 (Asian Lineage) Virus Real-Time Reverse Transcription–Polymerase Chain Reaction (RT-PCR) Primer and Probe Set and inactivated virus as a positive RNA control for the in vitro detection of highly pathogenic influenza virus A/H5 (Asian lineage).[37]

The CDC recommendation is to test for highly pathogenic (HP) avian influenza A/H5N1 if a patient has severe respiratory symptoms and a risk for exposure (eg, direct contact with ill, dead, or infected poultry in a country with known poultry outbreaks of HP avian influenza A/H5N1), with specific criteria included. Testing must be performed under biosafety level 3.[38, 39] Viral culture of human and animal specimens should not be performed in the same laboratory.[39]

Positive laboratory test findings must be confirmed by the CDC, which is the World Health Organization (WHO) H5 reference laboratory.

If other test findings are negative, paired avian influenza virus serologies can be performed at the CDC. However, reagents may not be widely available, and acute and convalescent serum analysis requires time to allow a 4-fold increase in antibody.

Other laboratory tests include the following:

  • Blood culture
  • Complete blood count (CBC) with differential
  • Electrolyte level measurement
  • Liver enzyme assay
  • Blood urea nitrogen (BUN) and creatinine level measurement

Lumbar puncture is indicated in selected patients. Very rarely, central nervous system involvement is documented by viral isolation from cerebrospinal fluid (CSF) and blood in patients who present with seizure and coma.[40]

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Radiography

Chest radiography may be necessary to exclude the diagnosis of pneumonia. In avian influenza, chest radiography, both posteroanterior and lateral views, may reveal patchy or diffuse infiltrates, an interstitial pattern, and lobar consolidation revealing air bronchogram or an acute respiratory distress syndrome (ARDS)–like picture.

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Histologic Findings in Avian Influenza

Histologic findings may include pulmonary changes with alveolar damage similar to seasonal influenza. Fibrinous exudate membrane formation and lymphocyte infiltrates are noted in postmortem analysis of patients who had avian influenza.

Necrosis is noted in organs such as the liver and kidney. The spleen may be depleted of lymphoid cells. Bone marrow demonstrates hemophagocytosis.[14]

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Contributor Information and Disclosures
Author

Itzhak Brook, MD, MSc  Professor, Department of Pediatrics, Georgetown University School of Medicine

Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society

Disclosure: Nothing to disclose.

Coauthor(s)

Hakan Leblebicioglu, MD  Chairman, Professor, Department of Infectious Diseases and Clinical Microbiology, Ondokuz Mayis University School of Medicine, Turkey

Hakan Leblebicioglu, MD is a member of the following medical societies: American Society for Microbiology and European Society of Clinical Microbiology and Infectious Diseases

Disclosure: Nothing to disclose.

Anthony R Sambol, MA, SM, (NRM), SV(ASCP)  Assistant Professor, Department of Pathology and Microbiology, University of Nebraska Medical Center; Assistant Professor, Division of Clinical Laboratory Science, School of Allied Health Professions, University of Nebraska Medical Center; Assistant Director of Nebraska Public Health Laboratory; Manager of Special Pathogens/Biosecurity Preparedness Lab for Biological, Chemical, and Radiological Preparedness

Disclosure: Nothing to disclose.

Meera Varman, MD  Associate Professor, Department of Pediatrics, Section of Pediatric Infectious Diseases, Creighton University Medical Center

Meera Varman, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: phamaceutical companies Honoraria speaker; phamaceutical companies Grant/research funds clinical trials research

Specialty Editor Board

Robert W Tolan Jr, MD  Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine

Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility

Disclosure: Novartis Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Leslie L Barton, MD  Professor Emerita of Pediatrics, University of Arizona College of Medicine

Leslie L Barton, MD is a member of the following medical societies: American Academy of Pediatrics, Association of Pediatric Program Directors, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Joseph Domachowske, MD  Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD  Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

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Swine influenza virus. Colorized transmission electron micrograph (37,800X) of the A/New Jersey/76 (Hsw1N1) virus under plate magnification. Image taken during the virus' first developmental passage through a chicken egg. Courtesy of the CDC/Dr. E. Palmer; R.E. Bates.
Colorized transmission electron micrograph shows avian influenza A/H5N1 viruses (gold) grown in Madin-Darby canine kidney (MDCK) cells (green). Image courtesy of Centers for Disease Control and Prevention.
Transmission electron micrograph (original magnification X 150,000) shows ultrastructural details of an avian influenza A/H5N1 virion, a subtype of avian influenza A. Note the stippled appearance of the roughened surface of the proteinaceous coat encasing the virion. Image courtesy of Centers for Disease Control and Prevention.
 
 
 
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