Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus

Swine flu (H1N1) virus will be making a comeback in just a few weeks.
Here is a recent update on Influenza Testing from the CDC.

IN SUMMARY

1. These results showed that, although the Rapid Influenza Diagnostic Tests ( RIDT) were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus

2. Please place patients on isolation- Droplet and Contact Precautions with eye protection (surgical mask with eye shield, gown and gloves) when H1N1 is suspected with negative rapid test results.

Evaluation of Rapid Influenza Diagnostic Tests for Detection of Novel Influenza A (H1N1) Virus --- United States, 2009
The recent appearance and worldwide spread of novel influenza A (H1N1) virus (1,2) has highlighted the need to evaluate commercially available, widely used, rapid influenza diagnostic tests (RIDTs) for their ability to detect these viral antigens in respiratory clinical specimens. As an initial assessment, CDC conducted an evaluation of multiple RIDTs. Sixty-five clinical respiratory specimens collected during April--May 2009* that had previously tested positive either for novel influenza A (H1N1) or for seasonal influenza A (H1N1) or A (H3N2) viruses by real-time reverse transcription--polymerase chain reaction (rRT-PCR) assay were used in the evaluation. The results showed that, although the RIDTs were capable of detecting novel A (H1N1) virus from respiratory specimens containing high levels of virus (as indicated by low cycle threshold [Ct] values), the overall sensitivity was low (40%--69%) among all specimens tested and declined substantially as virus levels decreased (and Ct values increased). These findings indicate that, although a positive RIDT result can be used in making treatment decisions, a negative result does not rule out infection with novel influenza A (H1N1) virus. Patients with illnesses compatible with novel influenza A (H1N1) virus infection but with negative RIDT results should be treated empirically based on the level of clinical suspicion, underlying medical conditions, severity of illness, and risk for complications. If a more definitive determination of infection with influenza virus is required, testing with rRT-PCR or virus isolation should be performed. Additional evaluations of the accuracy of RIDTs in detecting novel influenza A (H1N1) virus should be conducted.

Overall, for the 45 specimens that had tested positive for novel influenza A (H1N1) by rRT-PCR, the sensitivity of the three RIDT tests was 40% for BinaxNOW Influenza A&B, 49% for Directigen EZ Flu A+B,** and 69% for QuickVue Influenza A+B.

Sensitivity of the RIDTs was generally greater for seasonal influenza A (H1N1) and (H3N2) than for novel influenza A (H1N1), although the number of specimens tested was small, especially for seasonal influenza A (H1N1). None of the specimens had a Ct value <20. Compared with rRT-PCR, the three tests demonstrated sensitivity ranging from 60% to 80% for seasonal A (H1N1) and from 80% to 83% for seasonal A (H3N2)

Reported by: A Balish, et al. Influenza Div, National Center for Immunization and Respiratory Diseases, CDC.

Editorial Note:
The sensitivity of RIDTs to detect seasonal influenza viruses compared with virus isolation or rRT-PCR varies among commercial kits and has been shown to be low in some reports (3--5). In this evaluation, the sensitivity of three RIDTs to detect novel influenza A (H1N1) viral antigen in clinical specimens ranged from 40% to 69% and declined substantially with lower viral titers (as determined by Ct values). These findings are compatible with other recent studies, which reported that the sensitivity of some RIDTs to detect novel influenza A (H1N1) in clinical specimens ranged from 10% to 51% (6,7). Overall, the findings in this report demonstrate that these RIDTs are capable of detecting novel influenza A (H1N1) in respiratory specimens, but that many infections will be missed, especially in specimens with low viral titers.

RIDTs do not distinguish among influenza A virus subtypes, and RIDT sensitivity might vary by subtype of influenza A (4,6,8). Therefore, when using a positive RIDT result to help determine the appropriate course of clinical treatment or other action, the result should always be interpreted in the context of currently circulating strains. Conversely, as indicated by the results of this and other studies, a negative RIDT result should not be interpreted as indicating the absence of infection. In this analysis, the sensitivity of all three assays evaluated declined as the viral titer in the specimen decreased. The amount of virus found in respiratory specimens can be affected by timing of the specimen collection; viral titers are highest in the first 3 days of illness. Other factors that can affect the amount of virus in the specimen include age (e.g., children generally shed more virus and for longer periods than adults), type of specimen collected, and transportation and storage of the specimen before testing. Testing with rRT-PCR or virus isolation should be performed if a more definitive determination of the presence of influenza virus is required. In the titered cultured virus results presented in this report, all three RIDTs detected the cultured novel H1N1 influenza A/California/4/2009 virus with a lower limit of detection between 104.5 and 105.5 TCID50, slightly higher TCID50 levels than for detection of seasonal influenza viruses. These findings are consistent with the analytical sensitivities of RIDTs to detect novel influenza A (H1N1) virus described in one report (9), but higher than those described in another report (10).

The results described in this report should be viewed as preliminary. More data are needed on the clinical performance of all RIDTs to detect novel influenza A (H1N1) virus in different respiratory specimens. Because of the limitations of RIDTs and until additional data are available, all results from RIDTs, both positive and negative, when used for clinical decision-making in a patient with suspected novel influenza A (H1N1) virus infection, should be interpreted in the context of circulating influenza virus strains in the patient's community, level of clinical suspicion, severity of illness, and risk for complications. Additional CDC guidance on interpretation of RIDTs for testing of patients with suspected novel influenza A (H1N1) virus infection is available at http://www.cdc.gov/h1n1flu/guidance/rapid_testing.htm.

References
1. Dawood FS, Jain S, Finelli L, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009;360:2605--15.
2. CDC. Update: novel influenza A (H1N1) virus infections---worldwide May 6, 2009. MMWR 2009;58:453--8.
3. Uyeki TM. Influenza diagnosis and treatment in children: a review of studies on clinically useful tests and antiviral treatment for influenza. Pediatr Infect Dis J 2003;22:164--77.
4. Hurt AC, Alexander R, Hibbert J, Deed N, Barr IG. Performance of six influenza rapid tests in detecting human influenza in clinical specimens. J Clin Virol 2007;39:132--5.
5. Uyeki TM, Prasad R, Vukotich C, et al. Low sensitivity of rapid diagnostic test for influenza. Clin Infect Dis 2009;48:e89.
6. Faix DJ, Sherman SS, Waterman SH. Rapid-test sensitivity for novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; e-published ahead of print.
7. Ginocchio CC, Zhang F, Manji R, et al. Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak. J Clin Virol 2009;45:191--5.
8. Carrat F, Vergu E, Ferguson NM, et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. Am J Epidemiol 2008;167:775--85.
9. Hurt AC, Baas C, Deng YM, Roberts S, Kelso A, Barr IG. Performance of influenza rapid point-of-care tests in the detection of swine lineage A (H1N1) influenza viruses. Influenza Other Respi Viruses 2009;3:171--6.
10. Chan KH, Lai ST, Poon LL, Guan Y, Yuen KY, Peiris JS. Analytical sensitivity of rapid influenza antigen detection tests for swine-origin influenza virus (H1N1). J Clin Virol 2009;45:205--7.



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