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U.S. Department of Health and Human Services

Medical Devices

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Performance and Cautions in Using Rapid Influenza Virus Diagnostic Tests

FDA has cleared for marketing 7 rapid influenza diagnostic tests that can produce results within 30 minutes. These tests directly detect influenza A or B virus associated antigens or enzyme in throat swabs, nasal swabs, or nasal washes.

For the various products that have been FDA cleared for marketing Becton Dickinson’s Directogen Flu A test can detect only antigens associated with influenza A virus. Binax’s NOW Flu A, Binax’s NOW Flu B, and Becton Dickinson’s Directogen Flu A+B can detect and distinguish between influenza A and B virus antigens. Quidel’s QuickVue Influenza and Thermo BioStar FLU OIA can detect but do not distinguish between influenza A and B antigens. ZymeTx's ZstatFlu test can detect neuraminidase the presence of which denotes a high probability that infectious virions are present; it also does not distinguish between influenza A and B.

The Quidel Quick Vue and ZymeTx’s ZstatFlu and Quidel’s QuickVue influenza tests are considered low complexity and may be used in physicians’ offices. The other five tests mentioned above are considered moderately complex and are for use in a hospital or clinical reference laboratories.

If performed on individuals with signs and symptoms consistent with influenza, rapid influenza diagnostic tests appear to be moderately to reasonably accurate for detecting influenza virus dependent on when testing is performed during the influenza season. Potentially the rapid time for results can be very useful for managing patients with suspected influenza and for detection of institutional influenza outbreaks. However, positive testing must not be used alone to determine the cause of an individual’s symptoms. Often an individual may be co-infected with another pathogen that is the underlying cause of the symptom. Use of rapid influenza virus testing and missing an underlying cause was the subject of a public health advisory from the Centers for Drugs Evaluation and Research. [1] [2] The basis for this advisory were several deaths where individuals were treated with antiviral medication but died from an underlying bacterial infection.

Laboratories should make sure that physicians using these rapid test results understand the limitations of the tests, use clinical experience, further laboratory testing, and consider local surveillance data about circulating influenza viruses when interpreting test results.

The accuracy of an influenza test is determined by the sensitivity and specificity of the test to detect influenza virus antigens/enzyme compared with a reference method (cell culture) and the prevalence of influenza in the population being tested. Sensitivity is the percentage of culture confirmed influenza virus isolates detected by a test. Specificity is the percentage of virus negative cell cultures with negative rapid test results. Positive predictive value (PPV) of a test is the percentage of rapid test positive patients that have influenza virus isolated from cell culture. Negative predictive value (NPV) is the percentage of rapid test negative patients that do not have influenza virus isolated from cell culture.

Although the sensitivity and specificity of a test are unaffected by the prevalence of disease, the PPV and the NPV of a test are affected by disease prevalence. An influenza test will have the highest PPV (and lowest NPV) during peak influenza activity and the lowest PPV (and highest NPV) during periods of low influenza prevalence, i.e., at the beginning and ending of the influenza season.

Diagnostic antigen/enzyme tests for influenza are more likely to produce false positive results when the prevalence of influenza virus infections is low, such as during the late spring, summer, and early fall in North America. Confirming positive test results with viral culture is particularly important during this time period. Even when a positive test result reflects true influenza virus infection, this does not rule out the possibility of other co-existing infections. Persons with influenza are at risk for bacterial superinfections, and coincidental dual infections with other pathogens. Since some bacterial infections may have a fulminant course requiring urgent intervention, a positive test for influenza should not be used as a reason for withholding antibacterial therapy if clinical evaluation suggests a need.

False negative test results will be more common during periods of high influenza activity, such as during the winter in North America. Clinical judgment and local influenza surveillance data should be utilized to guide patient management. When compared to culture, FDA has found that the majority of rapid influenza virus assays have sensitivity ≥ 80 and ≤ 90%, and specificity in the same range. Most of these studies were performed during influenza season in the U.S. or the Southern Hemisphere.

Proper sample collection is the major determinant for obtaining accurate results. It has been reported in the literature and shown during studies conducted by companies that throat swabs are the poorest specimen source with properly collected nasal swabs or washes being the best. The adequacy of samples being tested should be carefully monitored before performing rapid tests and should be factored into interpretation of results.

FDA reminds users that life threatening or potentially threatening adverse device failures should be reported to the agency through the MEDWATCH medical device reporting system. This may be done by visiting the MedWatch web site or calling 1-800-FDA-1088. Less serious adverse device failures may be reported to the FDA by simply sending an e-mail to fdalabtests@cdrh.fda.gov.

For additional information on using rapid tests for detecting influenza A viruses go to Cautions in Using Rapid Tests for Detecting Influenza A Viruses

Literature Cited

[1]Public Health Advisory, Food And Drug Administration Public Health Advisory Subject: Safe And Appropriate Use Of Influenza Drugs, 12 January 2000

[2]FDA Talk Paper, FDA Reminds Prescribers of Important Considerations Before Prescribing Flu Drugs, January 12, 2000 

General References

Covalciuc KA, Webb KH, Carlson CA. Comparison of four clinical specimen types for detection of Influenza A and B viruses by optical immunoassay (FLU OIA Test) and cell culture methods. J Clin Micro 1999; 37:3971-3974.

Boivin G, Hardy I, Kress A. Evaluation of a rapid optical immunoassay for influenza viruses (FLU OIA Test) in comparison with cell culture and reverse transcription-PCR. J Clin Micro 2002; 39:730-732.

Schultze D, Thomas Y, Wunderli W. Evaluation of an optical immunoassay for the rapid detection of influenza A and B viral antigens. Eur J Clin Microbiol Infect Dis 2001; 20:280-382.

Tucker SP, Cox C, Steaffens J. A flu optical immunoassay (ThermoBioStar’s FLU OIA): a diagnostic tool for improved influenza management. Philos Trans R Soc Lond B Biol Sci 2001; 356:1915-1024.

Yamazaki M, Mitamura K, Kimura K, Komiyama O. et al. Clinical evaluation of an immunochromatography test for rapid diagnosis of influenza. Kansenshogaku Zasshi. 2001; 75:1047-1053.

Rodriguez WJ, Schwartz RH, Thorne MM. Evaluation of diagnostic tests for influenza in a pediatric practice. Pediatr Infect Dis J 2002; 21:193-196.

Reina J, Padilla E, Alonso F, Ruiz DGE et al. Evaluation of a new dot blot enzyme immunoassay (Directigen flu A+B) for simultaneous and differential detection of influenza A and B virus antigens from respiratory samples. J Clin Micro 2002;40:3513-3517.

Uyeki TM. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatric Infect. Dis. J 2003; 22:164-177.