Influenza: Diagnosis and Treatment


Influenza is an acute viral respiratory infection that causes significant morbidity and mortality worldwide. Three types of influenza cause disease in humans. Influenza A is the type most responsible for causing pandemics because of its high susceptibility to antigenic variation. Influenza is highly contagious, and the hallmark of infection is abrupt onset of fever, cough, chills or sweats, myalgias, and malaise. For most patients in the outpatient setting, the diagnosis is made clinically, and laboratory confirmation is not necessary. Laboratory testing may be useful in hospitalized patients with suspected influenza and in patients for whom a confirmed diagnosis will change treatment decisions. Rapid molecular assays are the preferred diagnostic tests because they can be done at the point of care, are highly accurate, and have fast results. Treatment with one of four approved anti-influenza drugs may be considered if the patient presents within 48 hours of symptom onset. The benefit of treatment is greatest when antiviral therapy is started within 24 hours of symptom onset. These drugs decrease the duration of illness by about 24 hours in otherwise healthy patients and may decrease the risk of serious complications. No anti-influenza drug has been proven superior. Annual influenza vaccination is recommended for all people six months and older who do not have contraindications.

Influenza is an acute respiratory infection caused by a negative-strand RNA virus of the Orthomyxoviridae family. There are three distinct types of influenza viruses that infect humans: influenza A, B, and C. Influenza A infects multiple species, including humans, swine, equines, and birds. It is more susceptible to antigenic variation and, hence, is the cause of major pandemics.1,2 The surface of the virion envelope is covered with proteins hemagglutinin (HA), neuraminidase (NA), and matrix 2.1 Antigenic variation is associated with changes in the HA or NA surface proteins and is generally classified as antigenic drift or shift.1 Antigenic drift involves small, gradual amino acid substitutions of the HA or NA proteins that can result in smaller outbreaks. Antigenic shift occurs when there are significant changes in the HA or NA proteins that create novel influenza subtypes with the potential to cause widespread pandemics.1,3 Each influenza A subtype is characterized by numbering both the HA and NA proteins (e.g., H3N2, H5N1).

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The Authors

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DAVID Y. GAITONDE, MD, is a core clinical faculty member and chief of endocrinology service at Dwight D. Eisenhower Army Medical Center, Fort Gordon, Ga....

CPT. FAITH C. MOORE, USA, MC, is a resident in the Department of Internal Medicine at Dwight D. Eisenhower Army Medical Center.

MAJ. MACKENZIE K. MORGAN, USA, MC, is chief of infectious diseases service at Dwight D. Eisenhower Army Medical Center.

Address correspondence to David Y. Gaitonde, MD, Dwight D. Eisenhower Army Medical Center, 300 E. Hospital Rd., Fort Gordon, GA 30905 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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1. Taubenberger JK, Morens DM. Influenza: the once and future pandemic. Public Health Rep. 2010;125(suppl 3):16–26....

2. Barberis I, Myles P, Ault SK, et al. History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines. J Prev Med Hyg. 2016;57(3):E115–E120.

3. Iuliano AD, Roguski KM, Chang HH, et al.; Global Seasonal Influenza-associated Mortality Collaborator Network. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study [published correction appears in Lancet. 2018;391(10127):1262]. Lancet. 2018;391(10127):1285–1300.

4. Centers for Disease Control and Prevention. Influenza (flu): burden of influenza. Updated February 19, 2019. Accessed October 5, 2019.

5. Garten R, Blanton L, Elal AIA, et al. Update: influenza activity in the United States during the 2017–18 season and composition of the 2018–19 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2018;67(22):634–642.

6. Xu X, Blanton L, Abd Elal AI, et al. Update: influenza activity in the United States during the 2018–19 season and composition of the 2019–20 influenza vaccine. MMWR Morb Mortal Wkly Rep. 2019;68(24):544–551. Accessed October 7, 2019.

7. Moser MR, Bender TR, Margolis HS, et al. An outbreak of influenza aboard a commercial airliner. Am J Epidemiol. 1979;110(1):1–6.

8. Centers for Disease Control and Prevention. Influenza (flu): clinical signs and symptoms of influenza. Updated March 8, 2019. Accessed October 5, 2019.

9. Leekha S, Zitterkopf NL, Espy MJ, et al. Duration of influenza A virus shedding in hospitalized patients and implications for infection control. Infect Control Hosp Epidemiol. 2007;28(9):1071–1076.

10. Baldo V, Bertoncello C, Cocchio S, et al. The new pandemic influenza A/(H1N1)pdm09 virus: is it really “new“? J Prev Med Hyg. 2016;57(1):E19–E22.

11. 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.

12. Greenbaum A, Quinn C, Bailer J, et al. Investigation of an outbreak of variant influenza A(H3N2) virus infection associated with an agricultural fair–Ohio, August 2012. J Infect Dis. 2015;212(10):1592–1599.

13. Duwell MM, Blythe D, Radebaugh MW, et al. Influenza A(H3N2) variant virus outbreak at three fairs - Maryland, 2017. MMWR Morb Mortal Wkly Rep. 2018;67(42):1169–1173.

14. Harfoot R, Webby RJ. H5 influenza, a global update. J Microbiol. 2017;55(3):196–203.

15. Grohskopf LA, Alyanak E, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2019–20 influenza season. MMWR Recomm Rep. 2019;68(RR-3):1–21.

16. American Academy of Family Physicians. Prevention and control of seasonal influenza with vaccines. Accessed May 7, 2019.

17. Erlikh IV, Abraham S, Kondamudi VK. Management of influenza. Am Fam Physician. 2010;82(9):1087–1095. Accessed September 5, 2019.

18. Centers for Disease Control and Prevention. Influenza (flu): for clinicians: antiviral medication. Updated Decemebr 27, 2018. Accessed February 24, 2019.

19. Centers for Disease Control and Prevention. Influenza (flu): guide for considering influenza testing. Updated March 4, 2019. Accessed October 5, 2019.

20. Stoeckle J, Cunningham A, Diaz V, et al. Back to basics: five steps to better influenza vaccination rates. Fam Pract Manag. 2017;24(6):30–33. Accessed September 5, 2019.

21. Fogarty CT, Crues L. How to talk to reluctant patients about the flu shot. Fam Pract Manag. 2017;24(5):6–8. Accessed September 5, 2019.

22. Centers for Disease Control and Prevention. Influenza (flu): immunogenicity, efficacy, and effectiveness of influenza vaccines. Updated August 23, 2018. Accessed January 22, 2019.

23. DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635–645.

24. DiazGranados CA, Robertson CA, Talbot HK, et al. Prevention of serious events in adults 65 years of age or older: a comparison between high-dose and standard-dose inactivated influenza vaccines. Vaccine. 2015;33(38):4988–4993.

25. Peteranderl C, Herold S, Schmoldt C. Human influenza virus infections. Semin Respir Crit Care Med. 2016;37(4):487–500.

26. 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;11(5):372–393.

27. von Ranke FM, Zanetti G, Hochhegger B, et al. Infectious diseases causing diffuse alveolar hemorrhage in immunocompetent patients: a state-of-the-art review. Lung. 2013;191(1):9–18.

28. 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;68(6):895–902.

29. Ebell MH, Afonso AM, Gonzales R, et al. Development and validation of a clinical decision rule for the diagnosis of influenza. J Am Board Fam Med. 2012;25(1):55–62.

30. Dale AP, Ebell M, McKay B, et al. Impact of a rapid point of care test for influenza on guideline consistent care and antibiotic use. J Am Board Fam Med. 2019;32(2):226–233.

31. Merckx J, Wali R, Schiller I, et al. Diagnostic accuracy of novel and traditional rapid tests for influenza infection compared with reverse transcriptase polymerase chain reaction: a systematic review and meta-analysis. Ann Intern Med. 2017;167(6):394–409.

32. Muthuri SG, Myles PR, Venkatesan S, et al. Impact of neuraminidase inhibitor treatment on outcomes of public health importance during the 2009–2010 influenza A(H1N1) pandemic: a systematic review and meta-analysis in hospitalized patients. J Infect Dis. 2013;207(4):553–563.

33. Jefferson T, Jones MA, Doshi P, et al. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014;(4):CD008965.

34. Muthuri SG, Venkatesan S, Myles PR, et al.; PRIDE Consortium Investigators. Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data. Lancet Respir Med. 2014;2(5):395–404.

35. Louie JK, Yang S, Samuel MC, et al. Neuraminidase inhibitors for critically ill children with influenza. Pediatrics. 2013;132(6):e1539–e1545.

36. Lee N, Leo YS, Cao B, et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J. 2015;45(6):1642–1652.

37. Heo YA. Baloxavir: first global approval. Drugs. 2018;78(6):693–697.

38. Hayden FG, Sugaya N, Hirotsu N, et al.; Baloxavir Marboxil Investigators Group. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med. 2018;379(10):913–923.

39. Jefferson T, Jones M, Doshi P, et al. Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments. BMJ. 2014;348:g2545.

40. Centers for Disease Control and Prevention. Interim guidance for influenza outbreak management in long-term care and post-acute care facilities. Reviewed February 12, 2019. Accessed October 5, 2019.

41. Montalto NJ. An office-based approach to influenza: clinical diagnosis and laboratory testing. Am Fam Physician. 2003;67(1):111–118. Accessed September 5, 2019.

42. Montalto NJ, Gum KD, Ashley JV. Updated treatment for influenza A and B. Am Fam Physician. 2000;62(11):2467–2476. Accessed September 5, 2019.

Published online November 11, 2019



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