Guideline sources The following summarized guidelines for the evaluation and management of influenza virus infection are prepared by our editorial team based on guidelines from the Infectious Diseases Society of America (IDSA 2018; 2007) and the Association of Medical Microbiology and Infectious Disease Canada (AMMI 2012). 1 2 3 4 4 5 6 6 7 8 9 Definition Influenza is an acute viral infection of the respiratory tract caused by an influenza virus. 4 Epidemiology Two different genera of the virus family Orthomyxoviridae,influenza A and B, cause a contagious acute respiratory infection in humans. Influenza virus epidemics typically occur during the cold season in temperate regions, when low humidity and temperature ambient conditions are thought to prolong virus shedding and transmission. In subtropical and tropical regions, influenza seasons are less clearly defined, allowing recurrent infections all over the year. 4 6 Pathophysiology https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 1/7 6/24/23, 2:34 PM Influenza virus infection Pathway In the United States, the annual incidence of influenza is estimated at 5.1% (95% CI, 3.6%-6.6%) in adults and 8.7% (95% CI, 6.6%-10.5%) in children. 5 Disease course Influenza virus infection may result in pneumonia and acute respiratory failure, frequently in the setting of bacterial co-infection. Extra-pulmonary complications of influenza include viral myocarditis and viral encephalitis. 6 7 Prognosis and risk of recurrence The efficacy of the trivalent inactivated vaccine varies according to virus type and subtype. Pooled estimates suggest an estimated efficacy of 59% in adults 18-65 years of age. In patients who are hospitalized with influenza, in-hospital mortality rates are estimated at 9.4%. 8 9 Guidelines 1. Screening and diagnosis Indications for testing, flu season, outpatients and ED patients: as per IDSA 2018 guidelines, patients who present with acute onset of respiratory symptoms (with or without fever), and either exacerbation of chronic medical conditions (such as asthma, COPD, or HF) or known complications of influenza (such as pneumonia). B Show 2 more Indications for testing (flu season, hospitalized patients): patients requiring hospitalization with an acute respiratory illness, including pneumonia, with or without fever. B Show 3 more Indications for testing (low season, outpatients and ED patients): consider testing for influenza in patients with acute respiratory symptoms (with or without fever) especially in immunocompromised and high-risk patients, during low influenza activity season. C Indications for testing (low season, hospitalized patients): disease occurring in the setting of an influenza outbreak, or outbreak of acute febrile respiratory illness of uncertain cause recent travel from an area with known influenza activity. B Consider testing for influenza in patients requiring hospitalization with acute, febrile respiratory tract illness during periods of low influenza activity, especially pediatric patients and immunocompromised or high-risk adult patients, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts. C 2. Diagnostic investigations https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 2/7 6/24/23, 2:34 PM Influenza virus infection Pathway Initial diagnostic testing: use rapid molecular assays such as NAATs over rapid influenza diagnostic tests in outpatients to improve detection of influenza virus infection. B Nasopharyngeal specimens: collect upper respiratory tract specimens from outpatients for influenza testing as soon after illness onset as possible, preferably within 4 days of symptom onset. B Endotracheal specimens: collect endotracheal aspirate or BAL fluid specimens from hospitalized patients with respiratory failure receiving mechanical ventilation, including patients with negative influenza testing results on upper respiratory tract specimens, for influenza testing as soon as possible. B Other specimen sites: avoid routinely testing specimens for influenza from nonrespiratory sites such as blood, plasma, serum, CSF, urine, and stool. D Viral multiplex RT-PCR: Obtain multiplex reverse transcription PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized immunocompromised patients undergoing evaluation for influenza. B Consider using multiplex reverse transcription PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized patients who are not immunocompromised, if it might influence care (assist in cohorting decisions, reduce testing, or decrease antibiotic use). C Viral culture: avoid using viral culture to diagnose influenza, because results will not be available in a timely manner to inform clinical management. D Serologic testing: avoid using serum specimens, to diagnose influenza, because results from a single serum specimen cannot be reliably interpreted, and collection of paired (acute/convalescent) sera 2-3 weeks apart will not be available in a timely manner to inform clinical management. D Resistance testing: Consider influenza neuraminidase inhibitor resistance testing for: patients who develop laboratory-confirmed influenza while on or immediately after neuraminidase inhibitor chemoprophylaxis C patients with an immunocompromising condition and evidence of persistent influenza viral replication who remain ill during or after neuraminidase inhibitor treatment C patients with laboratory-confirmed influenza who inadvertently received subtherapeutic neuraminidase inhibitor dosing and remain ill C patients with severe influenza who do not improve with neuraminidase inhibitor treatment and have evidence of persistent influenza viral replication C 3. Medical management ICU admission criteria: consider hospitalization and admission to the ICU in patients with moderate or severe disease. C https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 3/7 6/24/23, 2:34 PM Influenza virus infection Pathway Indications for treatment: As per IDSA 2018 guidelines: Initiate antiviral treatment as soon as possible, irrespective of influenza immunization history, in patients with documented or suspected influenza who: are hospitalized with influenza, regardless of illness duration prior to hospitalization are at high risk of complications from influenza, including those with chronic medical conditions and immunocompromised patients. B Initiate antiviral treatment as soon as possible, irrespective of influenza immunization history, in patients with documented or suspected influenza who: have severe or progressive illness, regardless of illness duration are < 2 years of age or 65 years of age are pregnant women or within 2 weeks postpartum. B As per AMMI 2012 guidelines, avoid antiviral treatment for individuals with mild disease, no risk factors and illness duration > 48 hours. D Choice and duration of antiviral agent: As per IDSA 2018 guidelines, initiate antiviral treatment as soon as possible with a single neuraminidase inhibitor such as either oral oseltamivir, inhaled zanamivir, or intravenous peramivir, and avoid using a combination of neuraminidase inhibitors. A As per AMMI 2012 guidelines, initiate treatment as rapidly as possible after the onset of illness because the benefits of treatment are much greater with initiation at < 12 hours than at 48 hours. B Adjunctive corticosteroids: avoid using corticosteroids for the treatment of adults or children with suspected or confirmed seasonal influenza, influenza-associated pneumonia, respiratory failure, or ARDS, unless clinically indicated for other reasons. D Adjunctive IV immunoglobulin: avoid routinely administering IVIGs for the treatment of adults or children with suspected or confirmed seasonal influenza. D Management of bacterial co-infection: investigate and empirically treat bacterial coinfection in patients with suspected or laboratory-confirmed influenza who present initially with severe disease having extensive pneumonia, respiratory failure, hypotension, and fever, in addition to antiviral treatment for influenza. B Management of inadequate treatment response: investigate for other causes besides influenza virus infection in influenza patients who fail to improve or deteriorate despite antiviral treatment. B Management of outbreaks: implement active surveillance for additional cases as soon as possible when one healthcare-associated laboratory-confirmed influenza case is identified in a hospital or one case of laboratory-confirmed influenza is identified in a long-term care facility. B 4. Specific circumstances https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 4/7 6/24/23, 2:34 PM Influenza virus infection Pathway Intubated patients: administer oseltamivir to intubated patients with influenza illness through a nasogastric tube. B Show 4 more Pregnant patients: offer oseltamivir in standard doses for treatment of pregnant women with influenza, based on the extensive safe use of oseltamivir to treat pregnant women during the 2009 H1N1 pandemic. B Immunosuppressed patients: treat immunocompromised individuals who have uncomplicated influenza illness with oseltamivir as soon as possible without regard to the duration of illness, because they are at risk of developing severe or complicated illness. B Patients with pandemic influenza: test for H5N1 infection in patients who have an illness compatible with influenza and known exposure to poultry in areas with previous H5N1 infection. B 5. Patient education General counseling: consider counseling together with arrangements for contacts to have medication on hand as an early treatment strategy. C Clinician education: be informed on current CDC and WHO surveillance data on the frequency and geographic distribution of neuraminidase inhibitor-resistant influenza viruses during influenza season, and with the latest CDC antiviral treatment recommendations. B 6. Preventative measures Influenza vaccination: offer inactivated influenza vaccine to all patients 50 years of age, others at risk for influenza complications, household contacts of high-risk persons, and healthcare workers. A Pre-exposure prophylaxis: As per IDSA 2018 guidelines, consider antiviral chemoprophylaxis for the duration of the influenza season for patients 3 months of age who are at very high risk of developing complications from influenza and for whom influenza immunization is contraindicated, unavailable, or expected to have low effectiveness (e.g., persons who are significantly immunocompromised). C As per AMMI 2012 guidelines, favor early therapy over routine seasonal pre-exposure prophylaxis. B Post-exposure prophylaxis: As per IDSA 2018 guidelines, consider postexposure antiviral chemoprophylaxis for asymptomatic patients 3 months of age who are at very high risk of developing complications from influenza, including: patients who are severely immunocompromised https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 5/7 6/24/23, 2:34 PM Influenza virus infection Pathway patients in whom influenza immunization is contraindicated or unavailable patients in whom influenza immunization is expected to have low effectiveness after household exposure to influenza. C As per AMMI 2012 guidelines, favor early therapy over post-exposure prophylaxis due to concerns regarding drug resistance. B Likelihood Ratios Pertinent positives The following findings increase the probability of influenza virus infection in adults. -1 Finding LR+ Value History of fever and cough of acute onset 5.4 (3.8-7.7) Positive rapid influenza test 4.7 (3.6-6.2) Presence of fever and leukocytosis 3.8 (2.8-5.0) History of chills 2.6 (2.0-3.2) Show 1 more Pertinent negatives The following findings decrease the probability of influenza virus infection in adults. -1 Finding LR- Value Negative rapid influenza test 0.06 (0.03-0.12) No history of sneezing 0.47 (0.24-0.92) References 1. Uyeki TM, Bernstein HH, Bradley JS 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. Clin Infect Dis. 2018 Dec 19. Open 2. Fred Y Aoki, MD FRCPC, Upton D Allen et al. The use of antiviral drugs for influenza: Guidance for practitioners 2012/2013. Can J Infect Dis Med Microbiol. 2012 Winter; 23 4 e79 e92. Open 3. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2 S27 72. Open 4. Moghadami M. A Narrative Review of Influenza: A Seasonal and Pandemic Disease. Iran J Med Sci. 2017 Jan;42 1 2 13. Open 5. Tokars JI, Olsen SJ, Reed C. Seasonal Incidence of Symptomatic Influenza in the United States. Clin Infect Dis. 2018 May 2;66 10 1511 1518. Open 6. Peteranderl C, Herold S, Schmoldt C. Human Influenza Virus Infections. Semin Respir Crit Care Med. 2016 Aug;37 4 487 500. Open https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 6/7 6/24/23, 2:34 PM Influenza virus infection Pathway 7. Sellers SA, Hagan RS, Hayden FG et al. The hidden burden of influenza: A review of the extra-pulmonary complications of influenza infection. Influenza Other Respir Viruses. 2017 Sep;11 5 372 393. Open 8. Uyeki TM. Influenza. Ann Intern Med. 2017 Sep 5;167 5 ITC33 ITC48. Open 9. Pawelka E, Karolyi M, Daller S et al. Influenza virus infection: an approach to identify predictors for in- hospital and 90-day mortality from patients in Vienna during the season 2017/18. Infection. 2019 Jun 15. Open 10. COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2018 2019. Pediatrics. 2018 Oct;142 4 . pii: e20182367. Open 11. American Society for Clinical Pathology. Choosing Wisely ASCP recommendations. Choosing Wisely. 2019. Open 12. Uyeki TM, Bernstein HH, Bradley JS 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. Clin Infect Dis. 2019 Mar 5;68 6):e1-e47. Open 13. American Academy of Allergy, Asthma & Immunology. Choosing Wisely AAAAI recommendations. Choosing Wisely. 2012. Open 14. Winston K Cheung, John Myburgh, Ian M Seppelt et al. A multicentre evaluation of two intensive care unit triage protocols for use in an influenza pandemic. Med J Aust. 2012 Aug 6;197 3 178 81. Open 15. Christine C Ginocchio, Frank Zhang, Ryhana Manji 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 Jul;45 3 191 5. Open https://web.pathway.md/diseases/recP4grBZ6PWuxFVg 7/7