Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors
Information for Clinical Laboratory Directors
The availability and use of commercial influenza rapid diagnostic tests by laboratories and clinics have substantially increased in recent years.
- Influenza rapid diagnostic tests are screening tests for influenza virus infection.
- They can provide results within 15 minutes.
- More than 10 rapid influenza tests have been approved by the U.S. Food and Drug Administration (FDA) (see Influenza Diagnostic Table).
- Rapid tests differ in some important respects:
- Some can identify influenza A and B viruses and distinguish between them.
- Some can identify influenza A and B viruses but cannot distinguish between them.
- Some tests are waived from requirements under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
- Most tests can be used with a variety of specimen types (see Influenza Diagnostic Table), but the accuracy of the tests can vary based on the type of specimen collected (for example throat swab versus nasal swab).
- FDA approval is based upon specific specimen types.
- The rapid tests vary in terms of sensitivity and specificity when compared with viral culture or RT-PCR. Product insert information and research publications indicate that:
- Sensitivities are approximately 50-70%
- Specificities are approximately 90-95%
- Specimens to be used with rapid tests generally should be collected as close as is possible to the start of symptoms and usually no more than 4-5 days later in adults. In very young children, influenza viruses can be shed for longer periods; therefore, in some instances, testing for a few days after this period may still be useful.
Accuracy Depends Upon Prevalence
The positive and negative predictive values vary considerably depending upon the prevalence of influenza in the community.
- False-positive (and true-negative) influenza test results are more likely to occur when disease prevalence is low, which is generally at the beginning and end of the influenza season.
- False-negative (and true-positive) influenza test results are more likely to occur when disease prevalence is high, which is typically at the height of the influenza season.
Clinical Considerations of Testing When Influenza Prevalence is Low
When disease prevalence is relatively low, the positive predictive value (PPV) is low and false-positive test results are more likely. By contrast, when disease prevalence is low, the negative predictive value (NPV) is high, and negative results are more likely to be true.
|If Flu Prevalence is...||And Specificity is...||Then PPV is...||False Pos. rate is...|
|VERY LOW (2.5%)||POOR (80%)||V. POOR (6-12%)||V. HIGH (88-94%)|
|VERY LOW (2.5%)||GOOD (98%)||POOR (39-56%)||HIGH (44-61%)|
|MODERATE (20%)||POOR (80%)||POOR (38-56%)||HIGH (44-62%)|
|MODERATE (20%)||GOOD (98%)||GOOD (86-93%)||LOW (7-14%)|
The interpretation of positive results should take into account the clinical characteristics of the case. If an important clinical decision is affected by the test result, the rapid test result should be confirmed by another test, such as viral culture or polymerase chain reaction (PCR).
Clinical Considerations of Testing When Influenza Prevalence Is High
When disease prevalence is relatively high, the NPV is low and false-negative test results are more likely. When disease prevalence is high, the PPV is high and positive results are more likely to be true.
|If Flu Prevalence is...||And Sensitivity is...||Then NPV is...||False Neg. rate is...|
|MODERATE (20%)||POOR (50%)||MODERATE (86-89%)||MODERATE (11-14%)|
|MODERATE (20%)||HIGH (90%)||V. GOOD (97-99%)||V. LOW (2-3%)|
|HIGH (40%)||POOR (50%)||MODERATE (70-75%)||MODERATE (25-30%)|
|HIGH (40%)||HIGH (90%)||V. GOOD (93-94%)||LOW (6-7%)|
The interpretation of negative results should take into account the clinical characteristics of the patient. If an important clinical decision is affected by the test result, then the rapid test result should be confirmed by another test, such as viral culture or PCR.
Many factors should be considered when selecting a test, including the following:
- Tests with high sensitivity and specificity will provide better positive and negative predictive values.
- Types of specimens that provide the most accurate results.
Information about these characteristics can be found in product inserts and scientific articles, and by contacting the manufacturer.
Changes in Recommended Procedures Can Affect Test Results
Modification by the user can affect test performances and increase false-positive and/or false-negative rates. Such modifications include
- Using specimens for which the test is not optimized
- Using swabs that did not come with the rapid test kits [unless recommended (see table)].
When Is Use of Rapid Diagnostic Tests Beneficial?
- Testing during an outbreak of acute respiratory disease can determine if influenza is the cause.
- During influenza season, testing of selected patients presenting with respiratory illnesses compatible with influenza can help establish whether influenza is present in a specific patient population and help health-care providers determine how to use their clinical judgment for diagnosing and treating respiratory illness. (Testing need not be done for all patients.)
- Otherwise, rapid tests do not address the public health need for influenza virus isolated that can only be obtained through the collection of specimens for viral culture. Influenza virus isolates are essential for determining the match between circulating influenza viruses and those viruses contained in the vaccine and for aiding in the selection of new vaccine strains.
Table 1: Influenza Virus Testing Methods
|Method1||Types Detected||Acceptable Specimens3||Test Time3||CLIA Waived|
|Viral cell culture (conventional)||A and B2||NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum||3-10 days||No|
|Rapid cell culture (shell vials; cell mixtures)||A and B2||As above||1-3 days||No|
|Immunofluorescence, Direct (DFA) or Indirect (IFA) Antibody Staining||A and B2||NP swab or wash, bronchial wash, nasal or endotracheal aspirate||1-4 hours||No|
|RT-PCR4 (singleplex and multiplex; real-time and other RNA-based) and other molecular assays||A and B2||NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum||Varied (Generally 1-6 hours)||No5|
|Rapid Influenza Diagnostic Tests6||A and B||NP swab, (throat swab), nasal wash, nasal aspirate||<30 min.||Yes/No|
- Serologic (antibody detection) testing is not recommended for routine patient diagnosis.
- May be adapted to identification of specific subtypes
- Ref: Leland, et al. 2007, Clin Micro Rev 20: 49-78. Approved respiratory specimens vary among FDA cleared influenza assays.
- Reverse transcriptase polymerase chain reaction, including FDA-approved test systems, reference laboratory testing using ASR or lab-developed reagents
- Random-access, single cartridge tests may be moderately complex
- Immunochromatographic lateral flow and membrane-based immunoassays
Table 2: Characteristics of Rapid Influenza Diagnostic Tests1
|Approved Specimens1||Test Time|
|3M™ Rapid Detection|
Flu A+B Test4,6
|A and B||NP2 swab/aspirate|
|Alere Influenza A & B5,6|
|A and B||Nasal swab||15 minutes|
|BD Veritor System for Rapid Detection of Flu A+B CLIA-waived5,6,8|
|A and B||NP2 swab/nasal swab||10 minutes|
|BD Veritor System for Rapid Detection of Flu A+B Moderately Complex4,6,8|
|A and B||NP2 wash/aspirate/swab||10 minutes|
|BinaxNOW® Influenza A&B5,6|
|A and B||NP2 swab,|
|BioSign® Flu A+B4,6|
|A and B||NP2 swab/aspirate/wash, nasal swab||15 minutes|
|Directigen™ EZ Flu A+B4,6|
|A and B||NP2 wash/aspirate/swab|
|OSOM® Influenza A&B4,6|
|A and B||Nasal swab||10 minutes|
|QuickVue® Influenza Test3,5|
|A or B||Nasal wash/aspirate/swab||10 minutes|
|QuickVue® Influenza A+B Test5,6|
|A and B||NP2 swab|
|SAS™ FluAlert A&B4,6|
|A and B||Nasal wash/aspirate||15 minutes|
|SAS™ FluAlert A3,5|
|A only||Nasal wash/aspirate||15 minutes|
|SAS™ FluAlert B3,5|
|B only||Nasal wash/aspirate||15 minutes|
|Sofia Influenza A+B 5,6,7,8|
|A and B||NP2 aspirate/swab/wash|
|A and B||NP2 aspirate/swab|
|XPECT™ Flu A&B4,6|
|A and B||Nasal wash/swab|
- List may not include all test kits approved by the U.S. Food and Drug Administration. Discontinued tests not included. Approved respiratory specimens according to manufacturer's package insert. Note that test performance may vary if other respiratory specimens are used.
- NP = nasopharyngeal.
- Does not distinguish between influenza A and B virus infections when used alone.
- Moderately complex test – requires specific laboratory certification.
- CLIA-waived test. Can be used in any office setting. Requires a certificate of waiver or higher laboratory certification.
- Distinguishes between influenza A and B virus infections.
- Immunofluorescence assay.
- Requires use of a separate analyzer reader device.
Disclaimer: Use of trade names or commercial sources is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention or the Department of Health and Human Services.