Influenza laboratory findings
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For more information about non-human (variant) influenza viruses that may be transmitted to humans, see Zoonotic influenza
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
Overview
Diagnostic tests available for influenza include viral culture, serology, rapid antigen testing, polymerase chain reaction (PCR), immunofluorescence assays, and rapid molecular assays. Sensitivity and specificity of any test for influenza might vary by the laboratory that performs the test, the type of test used, and the type of specimen tested. Among respiratory specimens for viral isolation or rapid detection, nasopharyngeal specimens are typically more effective than throat swab specimens. As with any diagnostic test, results should be evaluated in the context of other clinical and epidemiologic information available to health-care providers.
Laboratory Findings
- A number of tests can help in the diagnosis of influenza, however tests do not need to be performed in all patients.
- For individual patients, tests are most useful when they are likely to give results that will help with diagnosis and treatment decisions.
- During a respiratory illness outbreak in a closed setting, such as hospitals, nursing home, cruise ship testing for influenza can be very helpful in determining if influenza is the cause of the outbreak.
- Preferred respiratory samples for influenza testing include nasopharyngeal or nasal swab, and nasal wash or aspirate, depending on which type of test is used.
- Samples should be collected within the first 4 days of illness.
- Rapid influenza diagnostic tests provide results within 15 minutes or less; viral culture provides results in 3-10 days.
- Most of the rapid influenza diagnostic tests that can be done in a physician’s office are approximately 50-70% sensitive for detecting influenza and approximately greater than 90% specific.
The following table shows routine laboratory findings that may be present among some patients, but normal laboratory findings are also seen.[1]
| Test | Findings |
|---|---|
| White blood cell count | Leucopenia Lymphocytopenia |
| Platelets | Thrombocytopenia |
| Liver function tests | Elevated aspartate aminotransferase |
| Other tests | Elevated C-reactive protein Elevated LDH |
Influenza Virus Testing Methods
| Method | Types Detected | Acceptable Specimens | Test Time |
|---|---|---|---|
| Viral culture (conventional) | A and B |
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3-10 days |
| Rapid cell culture (shell vials; cell mixtures) | A and B |
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1-3 days |
| Immunofluorescence, Direct (DFA) or Indirect (IFA) Antibody Staining | A and B |
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1-4 hours |
| RT-PCR (singleplex and multiplex; real-time and other RNA-based) and other molecular assays | A and B |
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Varied (Generally 1-6 hours) |
| Rapid Influenza Diagnostic Tests (Immunochromatographic lateral flow and membrane-based immunoassays) |
A and B |
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<30 min. |
| Table adapted from CDC Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests [2] | |||
Rapid Diagnostic Testing
| Rapid Influenza Diagnostic Tests |
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- Reverse transcription polymerase chain reaction (RT-PCR) is best. Use a nasopharyngeal swab or aspirate
- Sensitivities of some rapid diagnostic tests are approximately 50-70% when compared with viral culture or reverse transcription polymerase chain reaction (RT-PCR), and specificities of rapid diagnostic tests for influenza are approximately 90-95%.
- Sensitivity of rapid nucleic acid amplification tests [NAATs]) are over 90%[3]
- The reliability of rapid diagnostic tests depends largely on the conditions under which they are used.
- False-positive (and true-negative) results are more likely to occur when disease prevalence in the community is low, which is generally at the beginning and end of the influenza seasons.
- False-negative (and true-positive) results are more likely to occur when disease prevalence is high in the community, which is typically at the height of the influenza season.
- Some tests are approved for use in any outpatient setting, whereas others must be used in a moderately complex clinical laboratory.
- 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.
Clinical Considerations of Testing When Influenza Prevalence is Low[4]
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 Positive 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[4]
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 Specificity is: | Then PPV is: | False Positive 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.
Serologic Testing
- Routine serological testing for influenza requires paired acute and convalescent sera, does not provide results to help with clinical decision-making, is only available at a limited number of public health or research laboratories and is not generally recommended, except for research and public health investigations.
- Serological testing results for human influenza on a single serum specimen is not interpretable and is not recommended.
References
- ↑ Gao, Hai-Nv; Lu, Hong-Zhou; Cao, Bin; Du, Bin; Shang, Hong; Gan, Jian-He; Lu, Shui-Hua; Yang, Yi-Da; Fang, Qiang; Shen, Yin-Zhong; Xi, Xiu-Ming; Gu, Qin; Zhou, Xian-Mei; Qu, Hong-Ping; Yan, Zheng; Li, Fang-Ming; Zhao, Wei; Gao, Zhan-Cheng; Wang, Guang-Fa; Ruan, Ling-Xiang; Wang, Wei-Hong; Ye, Jun; Cao, Hui-Fang; Li, Xing-Wang; Zhang, Wen-Hong; Fang, Xu-Chen; He, Jian; Liang, Wei-Feng; Xie, Juan; Zeng, Mei; Wu, Xian-Zheng; Li, Jun; Xia, Qi; Jin, Zhao-Chen; Chen, Qi; Tang, Chao; Zhang, Zhi-Yong; Hou, Bao-Min; Feng, Zhi-Xian; Sheng, Ji-Fang; Zhong, Nan-Shan; Li, Lan-Juan (2013). "Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection". New England Journal of Medicine. 368 (24): 2277–2285. doi:10.1056/NEJMoa1305584. ISSN 0028-4793.
- ↑ "CDC Guidance for Clinicians on the Use of Rapid Influenza Diagnostic Tests".
- ↑ Merckx J, Wali R, Schiller I, Caya C, Gore GC, Chartrand C; et al. (2017). "Diagnostic Accuracy of Novel and Traditional Rapid Tests for Influenza Infection Compared With Reverse Transcriptase Polymerase Chain Reaction: A Systematic Review and Meta-analysis". Ann Intern Med. 167 (6): 394–409. doi:10.7326/M17-0848. PMID 28869986.
- ↑ 4.0 4.1 "Rapid Diagnostic Testing for Influenza: Information for Clinical Laboratory Directors".