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Diagnostic Testing for 2009 Pandemic Influenza A (H1N1) Virus Infection in Hospitalized Patients

Tim Uyeki, M.D., M.P.H.

N Engl J Med 2009; 361:e114December 17, 2009

Article

Establishing a diagnosis of 2009 pandemic influenza A (H1N1) virus infection in hospitalized patients can be challenging, especially in patients presenting late in their clinical course. Although real-time reverse-transcriptase polymerase chain reaction (RT-PCR) is the most sensitive testing method to detect 2009 H1N1 virus in respiratory specimens,1 results are not accessible right away. Influenza antigen–detection tests produce quick results, but reported sensitivities of rapid influenza diagnostic tests (RIDTs) to detect 2009 H1N1 virus infection in upper respiratory specimens as compared with real-time RT-PCR range from 10 to 70%; therefore, false negative RIDT results are common2 and also occur with direct immunofluorescence assay (DFA).3 One study reported lower RIDT detection for 2009 H1N1 virus than for seasonal influenza viruses.4

Anecdotal reports indicate that some hospitalized patients did not receive antiviral treatment at admission because of a negative result of RIDT or immunofluorescence testing of upper respiratory tract specimens, with later confirmation of 2009 H1N1 by real-time RT-PCR. Empirical antiviral treatment should be started as soon as possible for hospitalized patients with suspected 2009 H1N1 and not withheld, because a negative RIDT or DFA result does not exclude 2009 H1N1 virus infection. Nor should treatment be delayed until real-time RT-PCR results are available.

Several factors in addition to specimen-acquisition issues can influence influenza test results in a patient with suspected 2009 H1N1. The optimal clinical specimen for identification of 2009 H1N1 virus infection in a hospitalized patient is not yet known, and detection may vary according to multiple factors, such as the patient's age and immune status, the time from illness onset, the concentration and duration of viral shedding, the specimen source and quality, clinical complications, and specimen processing. The 2009 H1N1 virus infects upper respiratory tract epithelial cells, but it can also infect lower respiratory tract tissue.5 Ideally, upper respiratory tract specimens (nasopharyngeal swab, aspirate, or wash; nasal swabs, or combined nasal and throat swabs) should be tested as close to illness onset as possible.

Some patients with severe lower respiratory tract disease tested negative by real-time RT-PCR on upper respiratory tract (nasopharyngeal) specimens but tested positive by real-time RT-PCR on endotracheal specimens because of presumed prolonged viral shedding in the lower respiratory tract.6 One study reported that systemic corticosteroid therapy was associated with prolonged detection of viral RNA in upper respiratory specimens from hospitalized patients with seasonal influenza.7 Clinicians treating patients with respiratory failure and suspected 2009 H1N1 that has not been diagnosed by tests of upper respiratory tract specimens should consider testing lower respiratory tract specimens (endotracheal aspirate, bronchoalveolar lavage) by real-time RT-PCR.8 The limitations of available influenza diagnostic tests need to be understood in interpreting results for patients with suspected 2009 H1N1. Patients with suspected influenza and negative RIDT or DFA results should have appropriate respiratory specimens tested for 2009 H1N1 by real-time RT-PCR.

Tim Uyeki, M.D., M.P.H.
Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA

No potential conflict of interest relevant to this article was reported.

This article (10.1056/NEJMopv0911052) was published on December 2, 2009, at NEJM.org.

References

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   Americo Testa, Gino Soldati, Roberto Copetti, Rosangela Giannuzzi, Grazia Portale, Nicolo Gentiloni-Silveri. (2012) Early recognition of the 2009 pandemic influenza A (H1N1) pneumonia by chest ultrasound. Critical Care 16:1, R30
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   J. S. Bradley, C. L. Byington, S. S. Shah, B. Alverson, E. R. Carter, C. Harrison, S. L. Kaplan, S. E. Mace, G. H. McCracken, M. R. Moore, S. D. St Peter, J. A. Stockwell, J. T. Swanson. (2011) The Management of Community-Acquired Pneumonia in Infants and Children Older Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clinical Infectious Diseases 53:7, e25-e76
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   Haitao Chu, Eric T. Lofgren, M. Elizabeth Halloran, Pei F. Kuan, Michael Hudgens, Stephen R. Cole. (2011) Performance of rapid influenza H1N1 diagnostic tests: a meta-analysis. Influenza and Other Respiratory Virusesno-no
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   Carrye Cost, Evangeline Brock, Beverley Adams-Huet, Jane D. Siegel, Monica I. Ardura. (2011) 2009 pandemic influenza a (H1N1) virus infection in pediatric oncology and hematopoietic stem cell transplantation patients. Pediatric Blood & Cancer 56:1, 127-133
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   Samer Homsi, Natasa Milojkovic, Yamen Homsi. (2010) Clinical Pathological Characteristics and Management of Acute Respiratory Distress Syndrome Resulting from Influenza A (H1N1) Virus. Southern Medical Journal 103:8, 786-792
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   M.A. Bürkle, L. Frey, B. Zwißler. (2010) Neue Influenza-A/H1N1-2009-Virus-Pandemie. Der Anaesthesist 59:1, 11-22
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