Peter Conner, MD, Pathology Resident
Larissa May, MD, Professor, Emergency Medicine
Nam Tran, PhD, Associate Professor and POCT Director

Introduction:

Summer is not a time when we think about influenza; however, “flu season” is not far away—often beginning in October of each year. During every flu season, there is a surge in diagnostic testing for influenza and/or respiratory pathogens.1 In a previous UC Davis Lab Best Practices Blog on point-of-care influenza testing, UC Davis Health developed guidelines based on national recommendations for the management of specific populations such as patients in the clinic, pregnant women, and children. In this blog, we expand on this discussion and provide additional recommendations for stratifying patients into high or low risk categories and the appropriate diagnostic test, if any, has the most clinical utility for both high and low risk populations.2

Stratifying patients:

Quickly and correctly differentiating high-risk versus low-risk is one of the key facets of clinical medicine. Should these patients be admitted or are we safe to send them home with/without treatment? However, this task is rarely simple, and often requires clinical experience and gestalt in parallel to following established guidelines to optimally prepare and prioritize care. As influenza is a significant contributor to morbidity and mortality in the United States and worldwide each year, many organizations have provided recommendations on which populations are at particular risk of complications due to influenza. As reported by the Centers for Disease Control (CDC) and the Infectious Disease Society of America (IDSA), the populations at greatest risk for complications and resulting in severe illness or death due to influenza include: very young children (<2 years of age), older adults (>=65 years of age), pregnant and post-partum women within 2 weeks of delivery, people with neurologic disorders, chronic medical conditions such chronic obstructive pulmonary disease, heart disease and diabetes, as well as the morbidly obese and immunocompromised.3

Lab Best Practice:

As of January 2018, UC Davis Health has converted over to molecular flu testing. In this section we will provide an update on how to optimize and prioritize molecular testing based on different clinical settings (Figure 1).

Figure 1. Best Practices for Influenza Testing

Outpatient Clinic or Emergency Department

Low-risk: If the patient is presenting with typical or atypical symptoms of influenza and/or upper respiratory disease, and the clinician feels that testing for influenza will influence clinical management, then they should consider focused molecular POC influenza tests to assist in diagnosing the patient and guiding management. Antigen-based rapid influenza tests are no longer available at UC Davis Health since they have been shown to have unacceptable sensitivity and specificity. However, if the clinician does not plan on changing management, regardless of the test results, then no further influenza testing is necessary.3 In fact, the CDC recommends against molecular influenza testing for outpatients when disease prevalence is high (i.e., influenza season) since diagnosis can be made by signs and symptoms alone.4 Multiplex testing during influenza season, in particular, has been shown to be excessive in terms of cost and having limited clinical value.5

High-Risk: We recommend rapid molecular testing for high-risk patients. Clinicians can consider using multiplex respiratory pathogen panels which will include influenza viruses; however, these tests should be reserved as an initial test for the immunocompromised or those with severe comorbidities. For other high-risk patients presenting during influenza season, more focused molecular testing is reasonable and more cost-effective.3 Pregnant women presenting with signs and symptoms of influenza combined with other risk factors (e.g., asthma, pre-term labor, difficulty breathing, etc.) should be empirically treated as recommended by the American College of Obstetricians and Gynecologists.6

Hospitalized patients

Patients with severe enough acute respiratory disease to need hospitalization should be considered high risk and clinicians should test for influenza on admission. If it is during the time of year where influenza is “in season,” then clinicians can use focused molecular testing for influenza. If it during the time of year where Influenza is not “in season”, the clinicians can consider using the multiplex panel as a first-line test to determine if a broader range of pathogens is affecting their patient.3

References

  1. “Frequently Asked Flu Questions 2018-2019 Influenza Season | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/flu/season/flu-season-2018-2019.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Fabout%2Fseason%2Fflu-season-2018-2019.htm.
  2. Tran, Nam K, et al. “Molecular Pathogen Detection at the Point of Care: Next Generation Flu Testing!” Laboratory Best Practice Blog, 2017, blog.ucdmc.ucdavis.edu/labbestpractice/index.php/2017/11/16/molecular-pathogen-detection-at-the-point-of-care-next-generation-flu-testing/.
  3. Uyeki, Timothy M, et al. “Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza.” Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, U.S. National Library of Medicine, 5 Mar. 2019, www.ncbi.nlm.nih.gov/pubmed/30566567.
  4. “Information on Rapid Molecular Assays, RT-PCR, and Other Molecular Assays for Diagnosis of Influenza Virus Infection | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, cdc.gov/flu/professionals/diagnosis/molecular-assays.htm.
  5. Green DA, Hitoaliaj L, Kotansky B, Campbell SM, Peaper DR. Clinical Utility of On-Demand Multiplex Respiratory Pathogen Testing among Adult Outpatients. J Clin Microbiol. 2016;54(12):2950–2955. doi:10.1128/JCM.01579-16
  6. Influenza Season Assessment and Treatment for Pregnant Women With Influenza-Like Illness. American College of Obstetrics and Gynecology, 2017.
  7. https://jcm.asm.org/content/54/11/2763, Direct Comparison of Alere i and cobas Liat Influenza A and B Tests for Rapid Detection of Influenza Virus Infection
  8. Mason J. Point-of-Care Testing for Influenza. 2016 Nov 3. In: CADTH Issues in Emerging Health Technologies. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2016-. 149. Available from: https://www.ncbi.nlm.nih.gov/books/NBK401783/
  9. https://www.who.int/influenza/resources/documents/RapidTestInfluenza_WebVersion.pdf, WHO recommendations on the use of rapid testing for influenza diagnosis July 2005
  10. https://www.cdc.gov/flu/professionals/diagnosis/molecular-assays.htm, Information on Rapid Molecular Assays, RT-PCR, and other Molecular Assays for Diagnosis of Influenza Virus Infection
  11. https://www.cdc.gov/flu/professionals/diagnosis/consider-influenza-testing.htm, Guide for considering influenza testing when influenza viruses are circulating in the community
  12. https://www.cdc.gov/flu/professionals/diagnosis/algorithm-results-not-circulating.htm, Algorithm to assist in the interpretation of influenza testing results and clinical decision-making during periods when influenza viruses are NOT circulating in the community
  13. http://www.roche-diagnostics.ch/content/dam/corporate/roche-dia_ch/documents/broschueren/molecular_diagnostics/parameter/07-cobas-liat-system/cobas_Liat_Assay_Influenza_AB_RSV.pdf
  14. Point-Counterpoint: Large Multiplex PCR Panels Should Be First-Line Tests for Detection of Respiratory and Intestinal Pathogens, Paul C. Schreckenberger, Alexander J. McAdam, Journal of Clinical Microbiology Sep 2015, 53 (10) 3110-3115; DOI: 10.1128/JCM.00382-15
  15. Mahony JB, Blackhouse G, Babwah J, et al. Cost analysis of multiplex PCR testing for diagnosing respiratory virus infections. J Clin Microbiol. 2009;47(9):2812-7.
  16. Dugas AF, Valsamakis A, Atreya MR, et al. Clinical diagnosis of influenza in the ED. Am J Emerg Med. 2015;33(6):770–775. doi:10.1016/j.ajem.2015.03.008
  17. Green DA, Hitoaliaj L, Kotansky B, Campbell SM, Peaper DR. Clinical Utility of On-Demand Multiplex Respiratory Pathogen Testing among Adult Outpatients. J Clin Microbiol. 2016;54(12):2950–2955. doi:10.1128/JCM.01579-16
  18. “Information on Rapid Molecular Assays, RT-PCR, and Other Molecular Assays for Diagnosis of Influenza Virus Infection | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 2019, www.cdc.gov/flu/professionals/diagnosis/molecular-assays.htm.