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Seasonal influenza A and B virus epidemics are associated with significant morbidity and mortality each year in the United States and worldwide. One study estimated that during 2010–2016, the seasonal incidence of symptomatic influenza among all ages in the United States was approximately 8% and varied from 3% to 11% 1. Most people recover from uncomplicated influenza, but influenza can cause complications that result in severe illness and death, particularly among very young children, older adults, pregnant and postpartum women within 2 weeks of delivery, people with neurologic disorders, and people with certain chronic medical conditions including chronic pulmonary, cardiac, and metabolic disease, and those who are immunocompromised 2–8. During 2010–2018, seasonal influenza epidemics were associated with an estimated 4.3–23 million medical visits, 140 000–960 000 hospitalizations, and 12 000–79 000 respiratory and circulatory deaths each year in the United States 9. A recent modeling study estimated that 291 243–645 832 seasonal influenza–associated respiratory deaths occur annually worldwide 10. Use of available diagnostic modalities and proper interpretation of results can accurately identify patients presenting with influenza. Timely diagnosis may decrease unnecessary laboratory testing for other etiologies and use of antibiotics, improve the effectiveness of infection prevention and control measures, and increase appropriate use of antiviral medications 11, 12. Early treatment with antivirals reduces the duration of symptoms and risk of some complications (bronchitis, otitis media, and pneumonia) and hospitalization, and may decrease mortality among high-risk populations 13–16. Annual vaccination is the best method for preventing or mitigating the impact of influenza, but in certain situations, chemoprophylaxis with antiviral medications can be used for preexposure or postexposure prevention and can help control outbreaks in certain populations. These clinical practice guidelines are an update of the guidelines published by the Infectious Diseases Society of America (IDSA) in 2009 17. The guidelines consider the care of children, pregnant and postpartum women, and nonpregnant adults and include special considerations for patients who are severely immunocompromised such as hematopoietic stem cell and solid organ transplant recipients. The target audience includes primary care clinicians, obstetricians, emergency medicine providers, hospitalists, and infectious disease specialists. The guidelines may be also useful for occupational health physicians and clinicians working in long-term care facilities. It adds new information on diagnostic testing, use of antivirals, and considerations of when to use antibiotics and when to test for antiviral resistance, and presents evidence on harm associated with routine use of corticosteroids. The panel followed a process used in the development of previous IDSA guidelines that included a systematic weighting of the strength of recommendations and quality of evidence based upon the US Public Health Service Grading System for ranking recommendations in clinical guidelines as utilized in the previous 2009 guidelines (Table 1) 17. Summarized below are the recommendations. A detailed description of background, methods, evidence summary, and rationale that support each recommendation, and research needs are included in the full document. Infectious Diseases Society of America–US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines Adapted from the Canadian Task Force on the Periodic Health Examination 6. Infectious Diseases Society of America–US Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines Adapted from the Canadian Task Force on the Periodic Health Examination 6. Because prevention and control of influenza is a dynamic field, clinicians should consult the website of the Centers for Disease Control and Prevention (CDC) for the latest information about influenza vaccines, influenza tests, and approved antiviral medications. 1. During influenza activity (defined as the circulation of seasonal influenza A and B viruses among persons in the local community): Clinicians should test for influenza in high-risk patients, including immunocompromised persons who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever) if the testing result will influence clinical management (A-III). Clinicians should test for influenza in patients who present with acute onset of respiratory symptoms with or without fever, and either exacerbation of chronic medical conditions (eg, asthma, chronic obstructive pulmonary disease COPD, heart failure) or known complications of influenza (eg, pneumonia) if the testing result will influence clinical management (A-III) (see Table 3). Clinicians can consider influenza testing for patients not at high risk for influenza complications who present with influenza-like illness, pneumonia, or nonspecific respiratory illness (eg, cough without fever) and who are likely to be discharged home if the results might influence antiviral treatment decisions or reduce use of unnecessary antibiotics, further diagnostic testing, and time in the emergency department, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts (see recommendations 40–42) (C-III). 2. During low influenza activity without any link to an influenza outbreak: Clinicians can consider influenza testing in patients with acute onset of respiratory symptoms with or without fever, especially for immunocompromised and high-risk patients (B-III). Clinical Manifestations and Complications Associated With Influenza Adapted from Jani AA, Uyeki TM. Chapter 46. Influenza. In: Emergency management of infectious diseases. 2nd ed. Chin RL, ed. Cambridge, UK: Cambridge University Press, 2018. Clinical Manifestations and Complications Associated With Influenza Adapted from Jani AA, Uyeki TM. Chapter 46. Influenza. In: Emergency management of infectious diseases. 2nd ed. Chin RL, ed. Cambridge, UK: Cambridge University Press, 2018. 3. During influenza activity: Clinicians should test influenza on admission in all patients requiring hospitalization with acute respiratory illness, including pneumonia, with or without fever (A-II). Clinicians should test for influenza on admission in all patients with acute worsening of chronic cardiopulmonary disease (eg, COPD, asthma, coronary artery disease, or heart failure), as influenza can be associated with exacerbation of underlying conditions (A-III). Clinicians should test for influenza on admission in all patients who are immunocompromised or at high risk of complications and present with acute onset of respiratory symptoms with or without fever, as the manifestations of influenza in such patients are frequently less characteristic than in immunocompetent individuals (A-III). Clinicians should test for influenza in all patients who, while hospitalized, develop acute onset of respiratory symptoms, with or without fever, or respiratory distress, without a clear alternative diagnosis (A-III). 4. During periods of low influenza activity: Clinicians should test for influenza on admission in all patients requiring hospitalization with acute respiratory illness, with or without fever, who have an epidemiological link to a person diagnosed with influenza, an influenza outbreak or outbreak of acute febrile respiratory illness of uncertain cause, or who recently traveled from an area with known influenza activity (A-II). Clinicians can consider testing for influenza in patients with acute, febrile respiratory tract illness, especially children and adults who are immunocompromised or at high risk of complications, or if the results might influence antiviral treatment or chemoprophylaxis decisions for high-risk household contacts (see recommendations 41–43) (B-III). 5. Clinicians should collect upper respiratory tract specimens from outpatients for influenza testing as soon after illness onset as possible, preferably within 4 days of symptom onset (A-II). Nasopharyngeal specimens should be collected over other upper respiratory tract specimens to increase detection of influenza viruses (A-II). If nasopharyngeal specimens are not available, nasal and throat swab specimens should be collected and combined together for influenza testing over single specimens from either site (particularly over throat swabs) to increase detection of influenza viruses (A-II). Mid-turbinate nasal swab specimens should be collected over throat swab specimens to increase detection of influenza viruses (A-II). Flocked swab specimens should be collected over nonflocked swab specimens to improve detection of influenza viruses (A-II). 6. Clinicians should collect nasopharyngeal (optimally, as for outpatients), mid-turbinate nasal, or combined nasal–throat specimens from hospitalized patients without severe lower respiratory tract disease for influenza testing as soon as possible (A-II). 7. Clinicians should collect endotracheal aspirate or bronchoalveolar lavage 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 (A-II). 8. Clinicians should not collect or routinely test specimens for influenza from nonrespiratory sites such as blood, plasma, serum, cerebrospinal fluid, urine, and stool (A-III). 9. Clinicians should not collect serum specimens, including single or paired sera, for serological diagnosis of seasonal influenza virus infection for clinical management purposes (A-III). 10. Clinicians should use rapid molecular assays (ie, nucleic acid amplification tests) over rapid influenza diagnostic tests (RIDTs) in outpatients to improve detection of influenza virus infection (A-II) (see Table 6). 11. Clinicians should use reverse-transcription polymerase chain reaction (RT-PCR) or other molecular assays over other influenza tests in hospitalized patients to improve detection of influenza virus infection (A-II) (see Table 6). 12. Clinicians should use multiplex RT-PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized immunocompromised patients (A-III). 13. Clinicians can consider using multiplex RT-PCR assays targeting a panel of respiratory pathogens, including influenza viruses, in hospitalized patients who are not immunocompromised if it might influence care (eg, aid in cohorting decisions, reduce testing, or decrease antibiotic use) (B-III). 14. Clinicians should not use immunofluorescence assays for influenza virus antigen detection in hospitalized patients except when more sensitive molecular assays are not available (A-II), and follow-up testing with RT-PCR or other molecular assays should be performed to confirm negative immunofluorescence test results (A-III). 15. Clinicians should not use RIDTs in hospitalized patients except when more sensitive molecular assays are not available (A-II), and follow-up testing with RT-PCR or other molecular assays should be performed to confirm negative RIDT results (A-II). 16. Clinicians should not use viral culture for initial or primary diagnosis of influenza because results will not be available in a timely manner to inform clinical management (A-III), but viral culture can be considered to confirm negative test results from RIDTs and immunofluorescence assays, such as during an institutional outbreak, and to provide isolates for further characterization (C-II). 17. Clinicians should not use serologic testing for diagnosis of influenza because results from a single serum specimen cannot be reliably interpreted, and collection of paired (acute/convalescent) sera 2–3 weeks apart are needed for serological testing (A-III). Influenza Diagnostic Tests for Respiratory Specimens Negative results may not rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s package insert for the specific test for the approved respiratory specimen(s). Most US Food and Drug Administration (FDA)–cleared influenza diagnostic tests are approved for upper respiratory tract specimens but not for sputum or lower respiratory tract specimens. Specificities are generally high (>90%) for all tests compared to RT-PCR. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments (CLIA)–waived; most FDA-cleared rapid influenza molecular assays are CLIA-waived, depending on the specimen. Abbreviation: RT-PCR, reverse-transcription polymerase chain reaction. Influenza Diagnostic Tests for Respiratory Specimens Negative results may not rule out influenza. Respiratory tract specimens should be collected as close to illness onset as possible for testing. Clinicians should consult the manufacturer’s package insert for the specific test for the approved respiratory specimen(s). Most US Food and Drug Administration (FDA)–cleared influenza diagnostic tests are approved for upper respiratory tract specimens but not for sputum or lower respiratory tract specimens. Specificities are generally high (>90%) for all tests compared to RT-PCR. FDA-cleared rapid influenza diagnostic tests are Clinical Laboratory Improvement Amendments (CLIA)–waived; most FDA-cleared rapid influenza molecular assays are CLIA-waived, depending on the specimen. Abbreviation: RT-PCR, reverse-transcription polymerase chain reaction. 18. Clinicians should start antiviral treatment as soon as possible for adults and children with documented or suspected influenza, irrespective of influenza vaccination history, who meet the following criteria: Persons of any age who are hospitalized with influenza, regardless of illness duration prior to hospitalization (A-II). Outpatients of any age with severe or progressive illness, regardless of illness duration (A-III). Outpatients who are at high risk of complications from influenza, including those with chronic medical conditions and immunocompromised patients (A-II). Children younger than 2 years and adults ≥65 years (A-III). Pregnant women and those within 2 weeks postpartum (A-III). 19. Clinicians can consider antiviral treatment for adults and children who are not at high risk of influenza complications, with documented or suspected influenza, irrespective of influenza vaccination history, who are either: Outpatients with illness onset ≤2 days before presentation (C-I). Symptomatic outpatients who are household contacts of persons who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (C-III). Symptomatic healthcare providers who care for patients who are at high risk of developing complications from influenza, particularly those who are severely immunocompromised (C-III). 20. Clinicians should start antiviral treatment as soon as possible with a single neuraminidase inhibitor (NAI) (either oral oseltamivir, inhaled zanamivir, or intravenous peramivir) and not use a combination of NAIs (A-1). 21. Clinicians should not routinely use higher doses of US Food and Drug Administration–approved NAI drugs for the treatment of seasonal influenza (A-II). 22. Clinicians should treat uncomplicated influenza in otherwise healthy ambulatory patients for 5 days with oral oseltamivir or inhaled zanamivir, or a single dose of intravenous peramivir (A-1). 23. Clinicians can consider longer duration of antiviral treatment for patients with a documented or suspected immunocompromising condition or patients requiring hospitalization for severe lower respiratory tract disease (especially pneumonia or acute respiratory distress syndrome ARDS), as influenza viral replication is often protracted (C-III). 24. Clinicians should investigate and empirically treat bacterial coinfection in patients with suspected or laboratory-confirmed influenza who present initially with severe disease (extensive pneumonia, respiratory failure, hypotension, and fever), in addition to antiviral treatment for influenza (A-II). 25. Clinicians should investigate and empirically treat bacterial coinfection in patients who deteriorate after initial improvement, particularly in those treated with antivirals (A-III). 26. Clinicians can consider investigating bacterial coinfection in patients who fail to improve after 3–5 days of antiviral treatment (C-III). 27. Clinicians should investigate other causes besides influenza virus infection in influenza patients who fail to improve or deteriorate despite antiviral treatment (A-III). 28. Influenza NAI resistance testing can be considered for: Patients who develop laboratory-confirmed influenza while on or immediately after NAI chemoprophylaxis (C-III). Patients with an immunocompromising condition and evidence of persistent influenza viral replication (eg, after 7–10 days, demonstrated by persistently positive RT-PCR or viral culture results) and remain ill during or after NAI treatment (B-III). Patients with laboratory-confirmed influenza who inadvertently received subtherapeutic NAI dosing (C-III). Patients with severe influenza who do not improve with NAI treatment and have evidence of persistent influenza viral replication (eg, after 7–10 days) (C-II). 29. Clinicians should remain informed on current CDC and World Health Organization surveillance data on the frequency and geographic distribution of NAI-resistant influenza viruses during influenza season, and with the latest CDC antiviral treatment recommendations (A-III). 30. Clinicians should not administer corticosteroid adjunctive therapy 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 (A-III). 31. Clinicians should not routinely administer immunomodulation using immunoglobulin preparations such as intravenous immunoglobulin for treatment of adults or children with suspected or confirmed seasonal influenza (A-III). Antiviral drugs should not be used for routine or widespread chemoprophylaxis outside of institutional outbreaks; antiviral chemoprophylaxis can be considered in certain situations: 32. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who are at very high risk of developing complications from influenza and for whom influenza vaccination is contraindicated, unavailable, or expected to have low effectiveness (eg, persons who are severely immunocompromised) (C-II). 33. Clinicians can consider antiviral chemoprophylaxis for the duration of the influenza season for adults and children aged ≥3 months who have the highest risk of influenza-associated complications, such as recipients of hematopoietic stem cell transplant in the first 6–12 months posttransplant and lung transplant recipients (B-II). 34. Clinicians can consider short-term antiviral chemoprophylaxis in conjunction with prompt administration of inactivated influenza vaccine for unvaccinated adults and children aged ≥3 months who are at high risk of developing complications from influenza in whom influenza vaccination is expected to be effective (but not yet administered) when influenza activity has been detected in the community (C-II). 35. Clinicians can consider short-term antiviral chemoprophylaxis for unvaccinated adults, including healthcare personnel, and for children aged ≥3 months who are in close contact with persons at high risk of developing influenza complications during periods of influenza activity when influenza vaccination is contraindicated or unavailable and these high-risk persons are to antiviral chemoprophylaxis (C-III). Clinicians can consider patients and of patients to for of antiviral treatment as an alternative to antiviral chemoprophylaxis (C-III). Clinicians should use an NAI oseltamivir or inhaled if preexposure chemoprophylaxis for influenza is than an antiviral (A-II). Clinicians should administer preexposure antiviral chemoprophylaxis for adults and children aged ≥3 months who are at very high risk of developing complications from influenza (eg, severely immunocompromised persons such as hematopoietic stem cell transplant for whom influenza vaccination is contraindicated, unavailable, or expected to have low as soon as influenza activity is detected in the community and for the duration of community influenza activity (A-II). Clinicians should test for influenza and to antiviral treatment dosing in persons receiving preexposure antiviral chemoprophylaxis who preferably with an antiviral with a resistance if not contraindicated (A-II). Clinicians can consider postexposure antiviral chemoprophylaxis for adults and children aged ≥3 months who are at very high risk of developing complications from influenza (eg, severely immunocompromised and for whom influenza vaccination is contraindicated, unavailable, or expected to have low after household to influenza (C-II). Clinicians can consider postexposure antiviral chemoprophylaxis conjunction with influenza for adults and children aged ≥3 months who are unvaccinated and are household contacts of a person at very high risk of complications from influenza (eg, severely immunocompromised after to influenza (C-II). Clinicians can consider patients and for of antiviral treatment as an alternative to postexposure antiviral chemoprophylaxis (C-III). If chemoprophylaxis is clinicians should administer postexposure antiviral chemoprophylaxis as soon as possible after than after (A-III). Clinicians should not administer postexposure antiviral chemoprophylaxis if has antiviral treatment should be as soon as symptoms if treatment is indicated (A-III). Antiviral Clinicians should administer postexposure antiviral chemoprophylaxis in a for days after the most recent to a close contact with influenza (A-III). 46. Clinicians should test for influenza and to antiviral treatment dosing in persons receiving postexposure antiviral chemoprophylaxis who preferably with an antiviral with a resistance if not contraindicated (A-III). Antiviral for Clinicians should administer an NAI or oral if postexposure chemoprophylaxis for influenza is than an antiviral (A-II). surveillance for should be as soon as possible when laboratory-confirmed influenza is in a or of laboratory-confirmed influenza is in a long-term care (A-III). control should be as soon as possible, including antiviral chemoprophylaxis of and surveillance for new when 2 of laboratory-confirmed influenza are within of each other in or patients of the or (A-III). of outbreak control can be considered as soon as possible if or more or patients has suspected influenza and results of influenza molecular testing are not available on the of specimen collection (B-III). an influenza outbreak has been in a long-term care or influenza testing should be for any with or more acute respiratory symptoms, with or without fever, or any of the following without respiratory or or (A-III). antiviral treatment should be as soon as possible to any or with suspected influenza during an influenza outbreak without for the results of influenza diagnostic testing (A-III). Antiviral chemoprophylaxis should be as soon as possible to all or patients who do not have suspected or laboratory-confirmed influenza regardless of influenza vaccination history, in addition to of all other influenza outbreak control measures, when an influenza outbreak has been in a long-term care or (A-III). Antiviral chemoprophylaxis should be to on in addition to surveillance for new influenza the (A-II). Clinicians can consider antiviral chemoprophylaxis for unvaccinated including those for whom chemoprophylaxis may be indicated based upon underlying conditions of the or household (see recommendations 41–43) for the duration of the outbreak (C-III). Clinicians can consider antiviral chemoprophylaxis for who inactivated influenza vaccine during an institutional influenza outbreak for days (C-III). Clinicians can consider antiviral chemoprophylaxis for regardless of influenza vaccination to reduce the risk of in and clinical is and to reduce to care for patients with suspected influenza (C-III). Clinicians should administer antiviral chemoprophylaxis for days and for at days after the onset of symptoms in the during an institutional influenza outbreak (A-III). The panel for of an by and The panel and for and in of the for with systematic and for in and recommendations. IDSA to present and the information in these guidelines is without any of or either or IDSA or will be for any or with to any including or in with these guidelines or on the information The and in are those of the and do not the of the for these guidelines was by the Infectious Diseases Society of of The following is a of has been to the provide the IDSA full of all regardless of to the of such as of is by a process that includes by the and Guidelines the to the development panel and the of to the and if the Task Force of the of for possible will be based on the of the (ie, and the of the (ie, the to an might be by an as to the or of The of these guidelines should be of when the of is from the of Health and from in the of Public and the of is a of the on at is an of the on Infectious Diseases at and is an of the at from and the and from the and outside the from and during the of the and support from and from and the Society of and from the of Health and from the World Health Organization and the University of Antiviral Drug and other from and support and to a and for and for in developing influenza or and from support from and from the the Health and the Centers for and and the of Emergency System outside the from and from and during the of the and for on a data from from and the Canadian of Health and for infection surveillance from the Public Health of outside the and other from and and from and the outside the as a to the and in as a for the of and as a for as a to from the and for and for and and for from the of and Infectious Diseases and the other from and from and outside the other of have the for of of that the consider to the of the have been
Uyeki et al. (Tue,) studied this question.
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