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Influenza: Diagnosis and Management in the Emergency Department

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Influenza: Diagnosis and Management in the Emergency Department

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  About This Issue

Patients presenting to the ED with “influenza-like illness” (cough, sore throat, fever) are typical in the fall and winter. How can you tell whether a patient might have influenza and infect others with a potentially dangerous strain? Are the guidelines the same in the spring and summer?

• How do symptoms of influenza differ between adults and children?
• What are the patient groups that are at high risk for complications from influenza?
• When does rapid influenza diagnostic testing reduce costs and improve care, and when is it unnecessary?
• Does the prevalence of influenza in the community affect whether or not you should order testing?
• When is antiviral medication indicated?
• Which antiviral should be prescribed, and why?
• What about the new antiviral drug on the market, baloxavir marboxil?

  Issue Information

Author: AL Giwa MD, MBA, FACEP, FAAEM; Chinwe Ogedegbe, MD, MPH, FACEP; Charles G. Murphy, MD

Peer Reviewers: Michael K. Abraham, MD; Daniel J. Egan, MD

Publication Date: December 1, 2018

CME Expiration Date: December 1, 2021

CME Credits: 4 AMA PRA Category 1 CreditsTM, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2A or 2B CreditsIncluded as part of the 4 credits, this CME activity is eligible for 3 Pharmacotherapy CME credits.

PubMed ID: 30476430

  Issue Features
  Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Epidemiology
    1. Types of Outbreaks
    2. Seasonality and Transmission
    3. The 2017–2018 Influenza Epidemic
  6. Classification of Influenza Viruses
    1. Antigen Variations
  7. Pathophysiology
    1. Vaccination
  8. Differential Diagnosis
  9. Prehospital Care
  10. Emergency Department Evaluation
  11. Diagnostic Studies
  12. Treatment
    1. The Neuraminidase Inhibitors
      1. Oseltamivir
      2. Zanamivir
      3. Peramivir
    2. The Adamantane Derivatives
    3. Baloxavir Marboxil
    4. Antiviral Resistance
    5. Chemoprophylaxis for Influenza
      1. Chemoprophylaxis in Institutional Settings
      2. Antiviral Use in Pregnant Patients
  13. Controversies and Cutting Edge
    1. Efficacy of Treatment With Antiviral Medications
  14. Disposition
  15. Summary
  16. Risk Management Pitfalls For Managing Influenza in the Emergency Department
  17. Time- and Cost-Effective Strategies
  18. Case Conclusions
  19. Clinical Pathways
    1. Clinical Pathway for Managing a Patient Who Presents to the ED With an Influenza-Like Illness
    2. Clinical Pathway for Managing a Patient Who Presents to the ED With an Influenza-like Illness When There is Low Regional Prevalence of Disease
  20. Tables and Figures
    1. Table 1. Influenza Pandemics Over the Past 100 Years
    2. Table 2. Yearly Vaccine Effectiveness
    3. Table 3. Online Resources for Evaluation/Management of Influenza
    4. Table 4. Most Frequent Clinical Symptoms of Seasonal Influenza, by Age Group
    5. Table 5. Complications Associated With Influenza Infection in Adults
    6. Table 6. Clinical Considerations of Testing When Influenza Prevalence is Low
    7. Table 7. Clinical Considerations of Testing When Influenza Prevalence Is High
    8. Table 8. CDC Antiviral Treatment Recommendations
    9. Table 9. CDC Recommendations for Antiviral Medications for Treatment and Chemoprophylaxis of Influenza
    10. Figure 1. Schematic Diagram of an Influenza Virion
    11. Figure 2. Seasonal Impact of Influenza
  21. References



Emergency clinicians must be aware of the current diagnostic and therapeutic recommendations for influenza and the available resources to guide management. This comprehensive review outlines the classification of influenza viruses, influenza pathophysiology, the identification of high-risk patients, and the importance of vaccination. Seasonal variations of influenza are discussed, as well as the rationale for limiting testing during periods of high prevalence. Differences between strains of influenza are discussed, as well as the challenges in achieving optimal vaccine effectiveness. Recommendations for use of the currently available oral, intranasal, and intravenous antiviral treatments are provided, as well as utilizing shared decision-making with patients regarding risks and benefits of treatment.


Case Presentations

A 20-month-old boy presents to the ED with a cough and fever for 3 days. He has no past medical history, and his routine vaccinations are up-to-date. His parents say he has been eating less than usual; however, his urine output is normal, and he has had no vomiting or diarrhea. Vital signs are: temperature, 39.6˚C (103.2°F); heart rate, 156 beats/min; respiratory rate, 32 breaths/ min; and oxygen saturation, 100% on room air. He is well-appearing, although his left tympanic membrane is erythematous and bulging, with apparent middle-ear purulence. You make the diagnosis of otitis media in the setting of a presumed viral upper respiratory infection. While preparing the discharge papers, you consider the many patients you’ve seen during the current flu epidemic and wonder whether treatment for influenza would be appropriate . . .

Your next patient is a 32-year-old man with the same chief complaints: cough and fever. His maximum temperature over the past 5 days was 40˚C (103.9°F). He has been taking over-the-counter cold remedies without relief, and today he is markedly short of breath. The patient has no regular primary care provider and has no significant past medical history. His initial vital signs are: temperature 39.2˚C (102.5°F); heart rate, 118 beats/min; respiratory rate, 28 breaths/min; blood pressure, 134/78 mm Hg; and oxygen saturation, 88% on room air. On examination, he appears uncomfortable, with notable tachypnea. The oropharynx is clear and the neck supple. Crackles are noted in the right lower lung field, without any wheezing. The abdomen is soft and nontender. The patient is given oxygen via face mask, with an improvement in saturation to 100%. Chest x-ray reveals a right lower lobar pneumonia with a small pleural effusion. You start IV antibiotics and request an inpatient bed, as he is hypoxic with his pneumonia. You wonder whether influenza testing is indicated, and if so, what type of test, and how reliable would it be?



During the 1918–1919 influenza pandemic, approximately one-third of the world’s population was infected and approximately 50 million people died.1 At that time, influenza pandemics were not new occurrences, but their mortality and morbidity had not been well documented and the causative organisms had not been identified. Fifty years later, it was estimated that the 1968 “Hong Kong” influenza pandemic (H3N2) caused between 1 and 4 million deaths worldwide. Despite advances in diagnostic and treatment strategies, mortality from influenza continues to increase, with over 30,000 deaths annually in the United States, partly related to the aging of the population.2 With globalization, the need to contain regional influenza outbreaks has assumed more urgency to prevent an emerging pandemic. The emergency department (ED) plays a key role in disease outbreaks, since containment of a potential epidemic relies on early and rapid identification, treatment, and—in some cases—prophylaxis.

The medical costs and lost wages from influenza are substantial. According to the United States Centers for Disease Control and Prevention (CDC), influenza epidemics cost $10.4 billion per year in direct medical expenses and an additional $16.3 billion in lost earnings annually in the United States.3,4 An influenza epidemic is responsible for 3.1 million hospitalized days, and 31.4 million outpatient visits annually (during the epidemic), with a total economic burden of $87.1 billion in the United States alone.4

As the public health community commemorates the 50th and 100th anniversaries of historic and tragic influenza pandemics, this issue of Emergency Medicine Practice presents an update based on a critical appraisal of the most current literature on influenza. Recent studies on clinical presentation, diagnosis, and treatment are reviewed, and recommendations on the evaluation and management of patients with suspected symptoms of influenza are provided.


Critical Appraisal of the Literature

PubMed, ISI Web of Knowledge, and the Cochrane Database of Systematic Reviews resources from 2012 to 2018 were accessed using the keywords: emergency department, epidemic, pandemic, influenza, novel H1N1, and H3N2. The CDC5 and the World Health Organization (WHO)6 websites were accessed. Guidelines from the American College of Emergency Physicians (ACEP),7 the Infectious Diseases Society of America (IDSA),8 and the American Academy of Pediatrics (AAP)9 were also reviewed. References from the literature were searched to identify additional content.


Risk Management Pitfalls For Managing Influenza in the Emergency Department

2. “The patient had an infiltrate on chest x-ray, so bacterial pneumonia appeared to be the clear diagnosis.”

Numerous secondary complications can stem from a primary influenza infection. When addressing and treating these complications, do not overlook the possibility of a primary influenza infection and the need for medical management. In certain clinical situations, treatment with antiviral medications as well as antibacterial medications may be indicated.

5. “My patient is pregnant and has influenza. The side-effect profile of antiviral medications concerns me, so I feel better treating her with supportive care.”

Pregnancy is a risk factor for a more severe disease course during an influenza infection. Initial CDC epidemiologic data from the last 10 influenza seasons indicate that some of the highest rates of morbidity and mortality are among pregnant women, which confirms the necessity of antivirals in this population.

7. “Flu is everywhere. I don’t have the time to consult the CDC website. I will just give oseltamivir to my patient and be done with it.”

Even in times of epidemic influenza infection, numerous strains can be circulating at a given time within a particular region. In past epidemics, there have been reports of influenza strains resistant to oseltamivir. Thus, without knowing the prevalence of local strains, one might mistakenly choose an antiviral agent that will prove less effective on those strains. Treatment with more than 1 agent may even be indicated in some regions until more formal strain-specific diagnostic testing can be undertaken. Since certain medications are effective against only influenza type A, the local prevalence of any type B influenza should be determined in order to select the appropriate drug therapy.


Tables and Figures

influenza - antiviral - oseltamivir - prevalence - Table 1. Influenza Pandemics Over the Past 100 Years



Table 3. Online Resources for Bioterrorism and Children

Up-to-date information on influenza
Weekly flu activity and surveillance
Influenza infection in pregnancy
Antiviral medication treatment recommendations and susceptibility information
American College of Emergency Physicians
Strategic plan for ED management of outbreaks of novel H1N1 influenza
National Highway Traffic Safety Administration
Strategic plan for prehospital evaluation and management of an influenza pandemic
Abbreviations: CDC, United States Centers for Disease Control and Prevention; ED, emergency department.



Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

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  2. Thompson WW. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179. (Retrospective study)
  3. CDC Foundation. Business pulse: how CDC protects the health of your business. Available at: Accessed November 10, 2018. (CDC website)
  4. Molinari N-AM, Ortega-Sanchez IR, Messonnier ML, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086-5096. (Epidemiologic surveillance study)
  5. Centers for Disease Control and Prevention. Influenza activity. Available at: Accessed November 10, 2018. (CDC website)
  6. World Health Organization. 2009 influenza A pandemic statement. Available at: Accessed November 10, 2018. (WHO website)
  7. American College of Emergency Physicians. National strategic plan for emergency department management of outbreaks of novel H1N1 influenza. Available at: Accessed November 10, 2018. (ACEP strategic plan)
  8. Harper Scott A, Bradley John S, Englund Janet A, et al. Seasonal influenza in adults and children—diagnosis, treatment, chemoprophylaxis, and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(8):1003-1032. (Clinical practice guideline)
  9. American Academy of Pediatrics Working Group. Novel influenza A (H1N1) virus and children with underlying medical conditions. Available at: Accessed November 10, 2018. (Clinical guideline)
  10. Centers for Disease Control and Prevention. Public health response to severe influenza. Available at: Accessed November 10, 2018. (CDC website)
  11. Centers for Disease Control and Prevention. Influenza surveillance. Available at: Accessed November 10, 2018. (CDC website)
  12. Itoh Y, Shinya K, Kiso M, et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009;460(7258):1021-1025. (Basic science research)
  13. Monto AS. Epidemiology of influenza. Vaccine. 2008;26:D45-D48. (Epidemiologic history)
  14. Cox NJ, Subbarao K. Global epidemiology of influenza: past and present. Annu Rev Med. 2000;51(1):407-421. (Epidemiologic history)
  15. McNeil D. This flu season is the worst in nearly a decade. The New York Times. Available at: Accessed November 10, 2018. (News story)
  16. Ducharme J. Here’s why the flu is especially bad this year. Time. Available at: Accessed November 10, 2018. (News story)
  17. McNeil D. Over 80,000 Americans died of flu last winter, highest toll in years. The New York TImes. Available at: Accessed November 10, 2018. (News story)
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  19. Centers for Disease Control and Prevention. Situation report: summary of weekly FluView Report. Available at: Accessed November 10, 2018. (CDC website)
  20. CBS News. Hospitals struggle to battle peak flu season amid widespread IV bag shortage. Time. Available at: Accessed November 10, 2018. (News story)
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  23. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. 2006;12(1):9-14. (Review article)
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  25. Dawood FS, Iuliano AD, Reed C, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12(9):687-695. (Epidemiologic surveillance study)
  26. Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of multidrug-resistant influenza A virus in an immunocompromised patient. N Engl J Med. 2003;348(9):867-868. (Case report)
  27. Sato M, Hosoya M, Kato K, et al. Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors. Pediatr Infect Dis J. 2005;24(10):931-932. (Prospective study; 63 patients)
  28. Centers for Disease Control and Prevention. Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia associated with influenza--Louisiana and Georgia, December 2006-January 2007. MMWR Morb Mortal Wkly Rep. 2007;56(14):325-329. (CDC research)
  29. Shapiro ED, Ward JI. The epidemiology and prevention of disease caused by Haemophilus influenzae type B. Epidemiol Rev. 1991;13(1):113-142. (Epidemiologic history)
  30. Barry J. The Great Influenza: The Epic Story of the Deadliest Plague in History. New York: Penguin Group; 2004. (Book)
  31. Rolfes M, Foppa I, Garg S, et al. Estimated influenza illnesses, medical visits, hospitalizations, and deaths averted by vaccination in the United States. Available at: Accessed November 10, 2018. (CDC website)
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  36. Centers for Disease Control and Prevention. Influenza infection control. Available at: Accessed November 10, 2018. (CDC website)
  37. VanWormer JJ, Sundaram ME, Meece JK, et al. A cross-sectional analysis of symptom severity in adults with influenza and other acute respiratory illness in the outpatient setting. BMC Infectious Diseases. 2014;14(1):231. (Prospective study; 2374 patients)
  38. Monto AS, Gravenstein S, Elliott M, et al. Clinical signs and symptoms predicting influenza infection. Arch Intern Med. 2000;160(21):3243. (Retrospective study; 3744 patients)
  39. Silvennoinen H, Peltola V, Lehtinen P, et al. Clinical presentation of influenza in unselected children treated as outpatients. Pediatr Infect Dis J. 2009;28(5):372-375. (Prospective study; 2231 patients)
  40. Peltola V, Ziegler T, Ruuskanen O. Influenza A and B virus infections in children. Clin Infect Dis. 2003;36(3):299-305. (Retrospective study; 15,420 patients)
  41. Lim WS. Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic. Thorax. 2007;62(suppl1):1-46. (Clinical practice guidelines – UK)
  42. Centers for Disease Control and Prevention. Influenza antiviral medications. Available at: Accessed November 10, 2018. (CDC website)
  43. Bonner AB, Monroe KW, Talley LI, et al. Impact of the rapid diagnosis of influenza on physician decision-making and patient management in the pediatric emergency department: results of a randomized, prospective, controlled trial. Pediatrics. 2003;112(2):363-367. (Randomized prospective controlled trial; 418 patients)
  44. Noyola DE, Demmler GJ. Effect of rapid diagnosis on management of influenza A infections. Pediatr Infect Dis J. 2000;19(4):303-307. (Retrospective study; 1530 patients)
  45. Esposito S. Effect of a rapid influenza diagnosis. Arch Dis Child. 2003;88(6):525-526. (Randomized controlled trial; 957 patients)
  46. D’Heilly SJ, Janoff EN, Nichol P, et al. Rapid diagnosis of influenza infection in older adults: influence on clinical care in a routine clinical setting. J Clin Virol. 2008;42(2):124-128. (Retrospective study; 311 patients)
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  48. Benito-Fernandez J, Vazquez-Ronco MA, Morteruel-Aizkuren E, et al. Impact of rapid viral testing for influenza A and B viruses on management of febrile infants without signs of focal infection. Pediatr Infect Dis J. 2006;25(12):1153-1157. (Prospective study; 206 patients)
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  50. Grijalva CG, Poehling KA, Edwards KM, et al. Accuracy and interpretation of rapid influenza tests in children. Pediatrics. 2007;119(1):e6-e11. (Prospective study; 2797 patients)
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  74. American Academy of Pediatrics. Prevention of influenza: recommendations for influenza immunization of children, 2008-2009. Pediatrics. 2008;122(5):1135-1141. (Clinical policy statement)
  CME Information

Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME.

Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 3 Pharmacotherapy CME credits, subject to your state and institutional approval.

Faculty Disclosures: It is the policy of EB Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Dr. Giwa, Dr. Murphy, Dr. Ogedegbe, Dr. Abraham, Dr. Egan, Dr. Mishler, Dr. Toscano, and their related parties report no significant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation. Dr. Jagoda made the following disclosures: Consultant, Daiichi Sankyo Inc; Consultant, Pfizer Inc; Consultant, Banyan Biomarkers Inc.

Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support.

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