ATrain Education

 

Continuing Education for Health Professionals

Influenza 2018–2019

Module 8

Diagnosis and Treatment of Influenza

 

Influenza Antiviral Quiz for Clinicians

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The Influenza Antivirals I.Q. is an interactive quiz to test your flu knowledge. http://www.cdc.gov/flu/freeresources/widgets.htm

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, 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 Diseases Society of America (2009, latest available) states that during flu season, consider influenza in the following patients, regardless of vaccination status:

  • Immunocompetent and immunocompromised people
  • People with fever and acute exacerbation of underlying chronic lung disease
  • Infants and young children with fever and no other signs or symptoms
  • Elderly people with new or worsening respiratory symptoms
  • Severely ill people with fever or hypothermia
  • Hospitalized children admitted without fever and acute respiratory symptoms who subsequently develop fever or febrile respiratory illness after hospital admission
  • Hospitalized adults admitted without fever and acute respiratory symptoms who subsequently develop febrile respiratory illness after hospital admission (Harper et al., 2009)

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 (Blanton et al., 2017).

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 (Blanton et al., 2017).

Annual influenza vaccination is recommended for all persons aged ≥6 months and remains the most effective way to prevent influenza illness. Antiviral medications are an important adjunct to vaccination in the treatment and prevention of influenza. Early treatment with neuraminidase-inhibitor antiviral medications is recommended for patients with severe, complicated, or progressive influenza illness and those at higher risk for influenza complications, including adults aged ≥65 years. Antiviral treatment should not be withheld from patients who are at high risk for complications or who are severely ill with suspected influenza infection, even if rapid antigen-detection influenza diagnostic test results are negative (Blanton et al., 2017).

Laboratory Diagnosis

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, 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, 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, 2015PB).

Antiviral Agents

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:

Neuraminidase Inhibitors

  1. Inhaled Zanamivir (trade name Relenza)
  2. Oral oseltamivir (available as a generic version or under the trade name Tamiflu)
  3. Intravenous Peramivir (trade name Rapivab)

Adamantanes

  1. Amantadine
  2. Rimantadine

Influenza virus replication inhibitor

  1. 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, 2015PB).

Neuraminidase Inhibitors

Three influenza antiviral medications approved by the U.S. Food and Drug Administration (FDA) are recommended for use in the United States during the 2017–2018 influenza season: oral oseltamivir (available as a generic version or under the trade name Tamiflu), inhaled zanamivir (trade name Relenza), and intravenous peramivir (trade name Rapivab). These drugs are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses. Generic oseltamivir was approved by the FDA in August 2016 and became available in December of 2016 (CDC, 2018h).

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, 2018h).

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)pdm09 (“2009 H1N1”) viruses. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses (CDC, 2018h).

Xoflusa

The Food and Drug Administration (FDA) approved a new prescription influenza antiviral drug, baloxavir marboxil (trade name Xofluza), on October 24, 2018. Xofluza is administered orally and is indicated for the treatment of acute, uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours (CDC, 2018h).

Baloxavir marboxil is a prodrug that is converted by hydrolysis to baloxavir, the active form that exerts anti-influenza virus activity. Baloxavir inhibits the endonuclease activity of the polymerase acidic (PA) protein, an influenza virus-specific enzyme in the viral RNA polymerase complex required for viral gene transcription, resulting in inhibition of influenza virus replication (CDC, 2018h).

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