Influenza Testing
One would think that with the fizzled 2009 pandemic H1N1 (pH1N1), flu wouldn't be much of a story. In reality, the pandemic expedited FDA clearance of molecular testing options in addition to clarifying the performance parameters of the most common viral detection tests that labs or near-patient testing sites were using, such as rapid antigen tests, direct fluorescent antibody (DFA) and cell culture assays. As well, with the use of molecular respiratory virus panel assays, the diversity of viral pathogens identified as causing influenza-like-illness (ILI) or respiratory infection also increased the value of testing for viruses because of the potential for significant clinical impact in driving better patient care, including appropriate antibiotic and antiviral use, reducing hospital or emergency department (ED) length of stay, and providing valuable epidemiological information.
While memories of the pH1N1 still make some of us shudder, overall, testing for influenza and respiratory viruses was catapulted into an exciting era. Laboratories now have a variety of options for analyzing specimens not only for influenza, but a host of viruses that cause respiratory infections with sensitive molecular assays. This article focuses on some specific issues to consider when deciding how best to prepare your laboratory for the upcoming respiratory viral season.
In Retrospect
Last year approximately 250,000 visits for ILI were reported from the CDC sentinel influenza sites, but only 22% of those patients were confirmed to have influenza.1 This may seem surprising low since patients are only included in the surveillance if they presented with fever, cough, sore throat and/or headache considered the "classic" signs and symptoms of influenza.
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Click to view Figure 1.
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However, many published articles now have demonstrated that this constellation of symptoms is not specific, since only 15-45% of patients presenting with these symptoms even during the pandemic had influenza, and that the majority of patients actually had a different viral pathogen causing the respiratory infection.1 Fig. 1 shows the distribution of viral isolates within the Lifespan System over a 20-month period starting from October 2009 (the beginning of the pandemic in RI) until May 2011. Fig. 2 shows the age distribution of viral pathogens in both pediatrics and adults for the second respiratory season.
The epidemiological pattern over these two respiratory seasons gives us important information about influenza. First, it clearly shows that influenza illness is a changing entity year to year in both the age where it is most likely to be identified as well as when it appeared during the year in our area. In Fig. 1, influenza was documented in Oct.-Nov. and was almost exclusively the pH1N1 strain. A younger age group was infected as well (age data not shown) and was a unique component during the pandemic. In the second respiratory season, influenza was approximately 65% H3N2 and 35% pH1N1, as was typical of the rest of the country according to CDC statistics, but didn't show up until after December and was in an older age group, as is more typical of influenza.
Today's Tests
Some of the FDA-cleared tests for influenza or viral panel testing are shown in the Table and are representative of the assay types available. General assay parameters are described, including assay type, typical turnaround time, approximate cost and sensitivity for influenza. Footnotes highlight some important considerations such as equipment costs.
Specificity for all assays is typically high (90-100%) and is not included in the Table. Websites for each of the assays are very informative and give specific parameters. Performance data has shown that molecular methods for detecting influenza are superior to rapid influenza antigen tests and culture and cost-analysis studies have shown that implementing a viral respiratory molecular panel is more cost-effective than DFA and culture methods.2-3
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Click to view Table.
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If you're considering implementing a molecular influenza or respiratory viral panel assay into your laboratory, technical expertise and cost are still issues, though they're improving with each new FDA-cleared assay and competition in the market. In addition, options exist for both low-volume and limited technical complexity settings.
If antigen testing will be used, laboratories should consider placing a comment on negative results suggesting to physicians to ask for a molecular influenza or respiratory viral panel assay for those patients who are severely ill, are high-risk for severe influenza infection or immunocompromised.
Key Considerations
Before implementing a new technology, take into account a few key issues:
• clinical expectations by the healthcare providers and their needs for managing patients,
• logistics for movement of patients through emergency departments in peak respiratory season,
• infection control concerns and
• the laboratory issues of resources and technical capabilities.
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Click to view Figure 2.
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The following parameters should be known:
• the patient population (in-patient or outpatient [acute care] and any type of algorithm that may be in place on how patients with ILI are handled within the institution or clinic,
• age of patients (pediatric or adult),
• volume of testing (<8 or >50 specimens per day),
• days assay will be performed (daily, including weekends and all shifts or more limited) and
• technical expertise and potential additional personnel needed to perform the assays chosen.
Meeting Patient Population's Needs
"One-size-fits-all" is not probable for influenza testing with the variety of healthcare settings and, in fact, one assay may not work within one institution. At Lifespan, which services four hospitals, three emergency centers as well as clinics and outreach, we have adjusted our influenza testing each of the last three respiratory seasons. While we were able to implement a full respiratory molecular panel just prior to the pH1N1 outbreak, we limited viral testing to the panel test only due to limited laboratory resources and no rapid testing for influenza was performed.
While the panel was used effectively for inpatients, allowing a statistically significant adjustment in antiviral treatment, hospital stay and cohorting of patients, the daily turnaround time was not user friendly for ED physicians. They expressed concerns about excessive workups for possible sepsis and pneumonia in patients presenting with ILI, as well as overuse of antibiotics, antivirals, utilization of ED bed space and other hospital resources. All of these are legitimate concerns; data with other rapid test methods have shown that having a rapid viral result will decrease length of stay, reduce antibiotics and lab costs.3-10
As a result, this year's respiratory virus menu for Lifespan will include a rapid molecular influenza assay to diagnose influenza as the first line assay and if negative, the specimen will reflex to a full molecular panel for patients being admitted. Because only about 20% of patients with ILI will have influenza, this will mean an increase in workload for the laboratories doing both the rapid molecular assay for influenza and the panel for respiratory viruses or any other virologic methodology. Our volume will clearly increase due to increased demand for acute care patients, so we made sure to address concerns about volume and resources. Of note, this algorithm was designed in conjunction with the Emergency Departments, Hospital Acquired Infections Committee, Quality Improvements and Patient Safety Committee and nursing, then presented to hospital administration for support. While the effort was considerable, this multi-disciplinary approach not only took the laboratory out of the "black box" in their contribution to healthcare but allowed all the stakeholders in the process to have a say.
Planning and Precautions
Prevention is still the best medicine for keeping influenza at bay. Vaccination, which will be the same viral components as last year, is available for anyone >6 months. The clear cut standbys of hand hygiene and cough etiquette help as well.
As more assays become available for influenza and virus panel testing, laboratories can expect that change may be possible again for next year-just like that genetically drifting and shifting influenza virus.
Dr. Chapin is director of Microbiology, Lifespan Academic Medical Centers, and professor of Pathology and Medicine, The Brown Alpert Medical School, Providence, RI.
References
1. MMWR Weekly Aug 7, 2009/58(30); 826-829.
2. Operational Simplicity and Cost Effectiveness of the Luminex xTAGTM Respiratory Viral Panel. Dundas, N et al, 2011, J of Molecular Diagnostics, vol 13, No 2, p 175-179.
3. Multiplex PCR Theranostics of Severe Respiratory Infections, Pozzetto B, et al, Expert Rev. Anti Infect. Ther. 8(3) 251-253.
4. Lee, B.Y., et al., To test or to treat? An analysis of influenza testing and antiviral treatment strategies using economic computer modeling. PLoS One, 2010. 5(6): p. e11284.
5. Robinson, C.C., The value of RVP in children's hospitals. J Clin Virol, 2007. 40 Suppl 1: p. S51-2.
6. Ginocchio C, Zhang F, Manji R et al. Evaluation of multiple test methods for the detection of novel 2009 influenza A (H1N1) during the New York City outbreak. Journal of Clinical Virology, 45(3), 191-195 (2009).
7. Mahony J, Blackhouse G, Babwah J et al. Cost analysis of multiplex PCR testing for diagnosing respiratory virus infections. Journal of Clinical Microbiology, 47(9), 2812-2817 (2009).
8. McCulloh R, Andrea SB, Dennehy P, Chapin KC. Implementing a Multiplex PCR Respiratory Viral Panel (RVP) Assay: Insights Into Epidemiology During Peak 2009 H1N1 Influenza Incidence and Effect On Antiviral Prescription Practices. In: IDSA. (Ed.^(Eds) (Vancouver, British Columbia, Canada 2010)
9. CDC Data 2010-11 Influenza Season
10. Surveillance Sites (http://www.cdc.gov/mmwr)