Influenza Workup

  • Author: Robert W Derlet, MD; Chief Editor: Burke A Cunha, MD   more...
 
Updated: Mar 8, 2012
 

Approach Considerations

The criterion standard for diagnosing influenza A and B is a viral culture of nasopharyngeal samples and/or throat samples. Rapid diagnostic tests are available, but because of cost, availability, and sensitivity issues, most physicians diagnose influenza based on clinical criteria alone.

Findings of standard laboratory studies such as a complete blood cell count (CBC) and electrolyte levels are nonspecific but helpful in the workup of influenza. Leukopenia and relative lymphopenia are typical findings in influenza. Thrombocytopenia may be present.

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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.[29] 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.

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Viral Culture

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

Obtain samples with Dacron swabs and send the samples in appropriate viral transport media (eg, multimicrobe [M4] transport media) to the laboratory to be cultured in several lines of cells.

A laboratory diagnosis of influenza is established once specific cytopathic effect is observed or hemadsorption testing findings are positive. Staining the infected cultured cell lines with fluorescent antibody confirms the diagnosis.

Polymerase chain reaction (PCR) tests

Most laboratories and hospitals now offer nucleic acid (PCR)–based studies. A nasal swab is submitted in special transport media to the laboratory, and results are reported within 24 hours. Some laboratories are able to differentiate between seasonal versus pandemic H1N1. Sensitivity for influenza is greater than 90%. These studies may be offered as respiratory panels, and they provide information on the presence of other viruses, such as respiratory syncytial virus (RSV) and adenovirus.

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Direct Immunofluorescent Tests

Some laboratories offer direct immunofluorescent tests on fresh specimens, but these tests are labor-intensive and are less sensitive than culture methods. These tests require specially trained laboratory personnel for interpretation, and these personnel generally are not available during all shifts, even in large medical centers.

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Serologic Testing

In order to overcome the expensive and time-consuming obstacle of culturing, several serologic tests have become available. In reality, many of these are not bedside tests; generally, 30-60 minutes are required to perform the test's multiple steps. Test sensitivities generally range from 60-70%.

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Testing for Avian Influenza

The standard commercially available rapid influenza A tests do not detect H5N1 avian influenza.[30] A rapid test from nasopharyngeal swab specific to H5N1 influenza (Arbor Vita Corporation) was approved by the FDA in 2009.[31]

Hematology (CBC) may be more clinically useful in avian influenza than in seasonal influenza disease. Leukopenia (white blood cell count of 454-4900 cells/µL), especially lymphopenia, is common and is observed in 50-80% of patients.[23] In at least one study, lymphopenia at presentation (absolute lymphocyte count < 1500 cells/µL) was a significant predictor of the progression to ARDS.[25] More than half of patients will have mild-to-moderate thrombocytopenia.

Liver function tests (LFTs) may be useful in differentiating illness from other febrile tropical diseases. Aminotransferase levels are elevated in more than half of all patients with avian influenza H5N1 infection.[12]

In addition to thrombocytopenia, some patients with severe disease will develop disseminated intravascular coagulation (DIC), as shown on coagulation studies.[12]

A basic metabolic panel is generally required in the care of all seriously or critically ill patients. Abnormalities in renal function may herald the progression to organ failure.

According to the 2009 CDC Recommendations,[28] clinicians should attempt to specifically identify avian H5N1 influenza in the patients with ALL of the characteristics listed below. Testing may be considered in discussion with public health authorities in patients who have only some of these characteristics. All testing should be discussed with local public health departments.

  • Severe illness requiring hospitalization or fatal, and
  • Temperature >38°C (100.4°F), and
  • Radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which an alternative diagnosis has not been established, and
  • At least one potential exposure within 7 days of symptoms onset

The CDC defines potential exposure as follows:

  • Close contact with an individual with confirmed or suspected H5N1 influenza infection, or
  • Working with H5N1 virus in laboratory, or
  • Travel to country where H5N1 influenza has been identified in birds or humans, and direct contact with a well or ill birds (poultry or wild); direct contact with surfaces with poultry parts or feces; consumption of raw or incompletely cooked poultry; or contact with H1N1 viral specimens or persons with suspected infection

If avian influenza is suspected, cultures should not be ordered without guidance from a public health laboratory. Many laboratories are not equipped to deal with the isolation needed to safely contain avian influenza (biosafety category 3+ containment, higher than that used for HIV). If a sample is sent, the laboratory may need to be shut down for decontamination.

Samples from patients with suspected avian influenza should be sent to a dedicated central reference laboratory such as at the Center for Disease Control and Prevention (CDC). The CDC laboratory can perform antiviral sensitivity testing, as well as subtyping of the virus.

The best specimens are material collected with oropharyngeal swabs, material from bronchoalveolar washes, or tracheal aspirates. Specimens from nasopharyngeal swabs are acceptable, but they may contain a low quantity of the virus. Specimens should be collected in the first 3 days of illness.

Pneumatic tubing is not recommended for transport; hand transport using a leak-proof specimen bag is preferred. The specimen should be clearly labeled as "suspected AI," and the person who transports the specimen should use appropriate protective equipment.

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Radiography

In elderly or high-risk patients with pulmonary symptoms, perform chest radiography to exclude pneumonia. Early radiographic findings include no or minimal bilateral symmetrical interstitial infiltrates. Later, bilateral symmetrical patch infiltrates become visible. Focal infiltrates indicate superimposed bacterial pneumonia.

With avian influenza, pulmonary infiltrates are seen in almost all patients. The wide variety of radiographic characteristics range from diffuse or patchy infiltrates to lobar multilobar consolidation. Effusions and lymphadenopathy are also observed, as well as cystic changes (see the image below).

Chest radiograph of severe lung disease in a patieChest radiograph of severe lung disease in a patient with avian influenza.

In avian influenza, the severity of radiologically apparent disease is a good predictor of mortality, including findings consistent with acute respiratory distress syndrome (ARDS), such as a diffuse, bilateral ground-glass appearance.

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Other Tests

Alveolar-arterial gradient

Severe hypoxemia is present in severe cases of influenza. The alveolar-arterial (A-a) gradient may be increased (>35 mm Hg).

Lumbar puncture

Patients with physical examination findings compatible with meningitis should undergo lumbar puncture.

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Contributor Information and Disclosures
Author

Robert W Derlet, MD  Professor of Emergency Medicine, University of California at Davis School of Medicine; Chief Emeritus, Emergency Department, University of California at Davis Health System

Robert W Derlet, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Association for the Advancement of Science, Infectious Diseases Society of America, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Nicholas John Bennett, MB, BCh, PhD,  Assistant Professor in Pediatrics, Division of Infectious Diseases, Connecticut Children's Medical Center

Nicholas John Bennett, MB, BCh, PhD, is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

Disclosure: Nothing to disclose.

Ethan E Bodle, MD, MPH  Associate Physician, Department of Emergency Medicine, Kaiser Permanente East Bay Medical Center

Ethan E Bodle, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and American Public Health Association

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.

Jon Mark Hirshon, MD, MPH  Associate Professor, Department of Emergency Medicine, University of Maryland School of Medicine

Jon Mark Hirshon, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Public Health Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Edmond A Hooker II, MD, DrPH, FAAEM  Assistant Professor, Department of Emergency Medicine, University of Cincinnati College of Medicine; Associate Professor, Department of Health Services Administration, Xavier University

Edmond A Hooker II, MD, DrPH, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American Public Health Association, Society for Academic Emergency Medicine, and Southern Medical Association

Disclosure: Nothing to disclose.

Hien H Nguyen, MD, MS  Associate Clinical Professor, Division of Infectious Diseases and Pulmonary/Critical Care Medicine, Infectious Diseases Consultant and Hospitalist, University of California, Davis, Health System; Medical Director, Acute Infections Management Service, Antimicrobial Infusion Service; Medical Director, Electronic Health Records of University of California, Davis, Health System

Hien H Nguyen, MD, MS is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Frederick Burton Rose, MD, FACP  Professor, Department of Medicine, University Hospital Epidemiologist, State University of New York Upstate Medical University

Frederick Burton Rose, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Christian E Sandrock, MD, MPH, FCCP  Associate Professor of Clinical Medicine, Division of Pulmonary/Critical Care Medicine, Division of Infectious Diseases, Department of Internal Medicine, University of California, Davis Medical Center

Christian E Sandrock, MD, MPH, FCCP is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, and Infectious Diseases Society of America

Disclosure: Pfizer Honoraria Speaking and teaching; Pfizer Honoraria Consulting; therevance Honoraria Consulting; GSK Honoraria Speaking and teaching

David Yew, MD  Assistant Clinical Professor, Department of Surgery, University of Hawaii, John A Burns School of Medicine; Medical Director and Flight Physician, Hawaii Life Flight, AirMed International

David Yew, MD is a member of the following medical societies: Air Medical Physician Association and American College of Emergency Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Klaus-Dieter Lessnau, MD, FCCP  Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Joseph F John Jr, MD, FACP, FIDSA, FSHEA  Clinical Professor of Medicine, Molecular Genetics and Microbiology, Medical University of South Carolina College of Medicine; Associate Chief of Staff for Education, Ralph H Johnson Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Charles V Sanders, MD  Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center

Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD  Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Ruth Lawrence, MD, to the development and writing of the source article.

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Chest radiograph of severe lung disease in a patient with avian influenza.
Global map of countries where avian influenza (bird and human infections) has been reported. Image courtesy of PandemicFlu.gov.
Colorized transmission electron micrograph shows avian influenza A H5N1 viruses (gold) grown in MDCK cells (green). Image courtesy of Centers for Disease Control and Prevention.
Transmission electron micrograph (original magnification 150,000X) 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.
Photograph shows police officers during the 1918 Spanish flu pandemic. Image courtesy of US National Archives.
Avian H5N1 influenza in humans, annual case counts from the World Health Organization.
 
 
 
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