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During the influenza season, when flu is circulating within the community, most people who get the flu will experience self-limiting symptoms. However, severe disease can occur in older adults, in those with underlying medical conditions, and in the very young.
Appropriate treatment of patients with respiratory illness depends on accurate and timely diagnosis. The diagnosis of influenza is usually suspected on the basis of characteristic clinical findings, particularly if influenza has been reported in the community (CDC, 2019, 2015PB).
Early diagnosis of influenza can reduce the inappropriate use of antibiotics and provide the option of using antiviral therapy. However, because certain bacterial infections can produce symptoms similar to influenza, bacterial infections should be considered and appropriately treated, if suspected. In addition, bacterial infections can occur as a complication of influenza.
The Infectious Disease Society of America states that antiviral treatment should start as soon as possible for adults and children with documented or suspected influenza, irrespective of influenza vaccination history, who meet the following criteria (Uyeki et al., 2018):
- Persons of any age who are hospitalized with influenza, regardless of duration of illness.
- Outpatients of any age with severe or progressive illness, regardless of the duration of illness.
- Outpatients with chronic medical conditions and immunocompromised patients.
- Children younger than 2 years and adults ≥65 years.
- Pregnant women and those within 2 weeks postpartum.
Antiviral treatment should be considered 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
- Outpatients with up to 2 days illness onset before presentation.
- Symptomatic household contacts of persons at high risk of developing complications from influenza, especially those who are severely immunocompromised.
- Symptomatic healthcare providers of patients at high risk of developing complications from influenza, especially those who are severely immunocompromised (Uyeki et al., 2018)
Although summer influenza activity in the United States typically is low, influenza cases and outbreaks can occur during summer months. Clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses. Testing for seasonal influenza viruses and monitoring for novel influenza A virus infections should continue year-round (Xu et al., 2019).
Healthcare providers also are reminded to consider novel influenza virus infections in persons with influenza-like illness and swine or poultry exposure or with severe acute respiratory infection after travel to areas where avian influenza viruses have been detected. Providers should alert the local public health department if novel influenza virus infection is suspected.
Influenza should be suspected in ill travelers returning from countries with ongoing influenza activity. Suspected variant influenza infections should be referred to state public health departments for testing (Xu et al., 2019).
Annual influenza vaccination is recommended for all persons aged ≥6 months and remains the most effective way to prevent influenza illness. Treatment as soon as possible with influenza antiviral medications is recommended for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at high risk for influenza-associated complications, including adults ≥65 years. Providers should not rely on less sensitive assays such as rapid antigen detection influenza diagnostic tests to inform treatment decisions. (Xu et al., 2019).
The diagnosis of influenza is usually suspected on the basis of characteristic clinical findings, particularly if influenza has been reported in the community. Virus can be isolated from throat and nasopharyngeal swabs obtained within 3 days of onset of illness. Culture is performed by inoculation of chick embryos or certain cell cultures that support viral replication. A minimum of 48 hours is required to demonstrate virus, and 1 to 2 additional days to identify the virus type. Culture is helpful in defining the etiology of local epidemics, but not in individual case management (CDC, 2019, 2015PB).
Serologic confirmation of influenza requires demonstration of a significant rise in influenza immunoglobulin G (IgG). The acute-phase specimen should be taken less than 5 days from onset, and a convalescent specimen taken 10 to 21 days (preferably 21 days) following onset. Complement fixation (CF) and hemagglutination inhibition (HI) are the serologic tests most commonly used. The key test is HI, which depends on the ability of the virus to agglutinate erythrocytes and inhibition of this process by specific antibody. Diagnosis requires at least a fourfold rise in antibody titer (CDC, 2019, 2015PB).
Rapid diagnostic testing for influenza antigen is available, but because these tests fail to detect many patients with influenza, CDC recommends antiviral treatment with oseltamivir or zanamivir as early as possible for patients with confirmed or suspected influenza who have severe, complicated, or progressive illness; who require hospitalization; or who are at greater risk for serious influenza-related complications (CDC, 2019PB).
Influenza antiviral prescription drugs can be used to treat influenza or to prevent influenza. In the United States, five antiviral agents are licensed for preventing or treating influenza. A sixth “prodrug” (Xoflusa) was approved by the FDA on October 24, 2018:
- Inhaled Zanamivir (trade name Relenza)
- Oral oseltamivir (available as a generic version or under the trade name Tamiflu)
- Intravenous Peramivir (trade name Rapivab)
Influenza virus replication inhibitor
- Baloxavir marboxil (trade name Xofluza) (CDC, 2018h)
Antiviral agents for influenza are an adjunct to vaccine and are not a substitute for vaccine. Vaccination remains the principal means for preventing influenza-related morbidity and mortality (CDC, 2019, 2015PB).
During periods of community co-circulation of influenza viruses and SARS-CoV-2, empiric antiviral treatment of influenza is recommended as soon as possible for the following priority groups: a) hospitalized patients with respiratory illness; b) outpatients with severe, complicated, or progressive respiratory illness; and c) outpatients at higher risk for influenza complications who present with any acute respiratory illness symptoms (with or without fever) (CDC, 2020 August 31).
Three chemically-related antiviral medications known as neuraminidase inhibitors block the viral neuraminidase enzyme and have activity against both influenza A and B viruses: oral oseltamivir phosphate (available as a generic version or under the trade name Tamiflu), inhaled zanamivir (trade name Relenza), and intravenous peramivir (trade name Rapivab). (CDC, 2019r).
Adamantanes (Amantadine and Rimantadine)
Amantadine and rimantadine are antiviral drugs in a class of medications known as adamantanes. These medications are active against influenza A viruses, but not influenza B viruses (CDC, 2019a).
As in recent past seasons, there continues to be high levels of resistance (>99%) to adamantanes among circulating influenza A(H3N2) and influenza A(H1N1) viruses. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses (CDC, 2019a).
The newest antiviral is oral baloxavir marboxil (trade name Xoflusa), which is active against both influenza A and B viruses, but has a different mechanism of action than neuraminidase inhibitors. Baloxavir is an endonuclease inhibitor that interferes with viral RNA transcription and blocks virus replication (CDC, 2019r).
Baloxavir was approved by the FDA in October of 2018. It is not recommended for pregnant women, breastfeeding mothers, outpatients with complicated or progressive illness, or hospitalized patients, because there is no information about its use in these patients (CDC, 2019a).
FDA Approved Antivirals for 2020–2021
There are four influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) for use in the United States during the (2020–2021) influenza season:
- Oseltamivir phosphate (available as a generic version or under the trade name Tamiflu, is available as a pill or liquid suspension. Both are FDA approved for early treatment of flu in people 14 days and older.
- Zanamivir (trade name Relenza) is a powder that is inhaled and approved for early treatment of flu in people 7 years and older. It is not recommended for people with breathing problems like asthma or COPD.
- Peramivir (trade name Rapivab) is given intravenously by a health care provider and approved for early treatment of flu in people 2 years and older.
- Baloxavir marboxil (trade name Xoflusa) is a pill given as a single dose by mouth that is approved for early treatment of flu in people 12 years and older (CDC, 2019r).
Duration of treatment with antiviral drugs varies depending on the antiviral drug prescribed. Oseltamivir and zanamivir are usually prescribed to be taken twice daily for 5 days, although people hospitalized with flu may need antiviral treatment for longer than 5 days. Peramivir is given one time intravenously over a period of 15 to 30 minutes. Baloxavir is given as a single oral dose (CDC, 2019a).