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Prompt Use of Antivirals is Key this Flu Season

Doctor talking with patient

A recent sharp increase in influenza A(H3N2) activity in the United States has prompted the CDC to release a health advisory emphasizing the importance of its antiviral treatment recommendations this season. Read more about what clinicians can do.

The December 27 health advisory published via CDC’s Health Alert Network (HAN) highlights the potential for influenza A(H3N2) virus-predominant seasons to be associated with more hospitalizations and deaths in persons aged 65 years and older and young children compared with other age groups.

In addition, the HAN also discusses that influenza (flu) vaccines are generally less effective against influenza A(H3N2) viruses than against influenza A(H1N1)pdm09 or influenza B viruses. Last season, flu vaccine effectiveness (VE) against circulating influenza A(H3N2) viruses was estimated to be 32% in the United States. While CDC’s preliminary VE estimates for the 2017-2018 season will not be available until later in the season, CDC expects that U.S. VE estimates against circulating A(H3N2) viruses will be similar to last season, assuming the same A(H3N2) viruses continue to predominate. This underscores the need for clinicians to step up influenza treatment efforts this season with the appropriate use of antiviral medications.

Treatment with neuraminidase inhibitor (NAI) antiviral medications has been shown to have clinical and public health benefit in reducing illness and severe outcomes of influenza based on evidence from randomized controlled trials, meta-analyses of randomized controlled trials, and observational studies during past influenza seasons and during the 2009 H1N1 pandemic. The NAI antivirals recommended for use in the United States this season are oseltamivir, zanamivir and peramivir. Influenza antiviral medications are most effective in treating influenza and reducing complications when started early. CDC recommends that influenza antivirals be administered within 48 hours of illness onset. However, antiviral treatment initiated later than 48 hours after illness onset can still be beneficial for some patients.

Unfortunately, evidence from previous flu seasons suggest that flu antiviral drugs are underutilized. A 2014 study by Havers et al, reported that only 19% of outpatients who were at high risk for complications from influenza and who presented early with acute respiratory illness were treated with antiviral medications. A more recent 2017 study by Schicker et al, reported that of high-risk outpatients with acute respiratory illness and laboratory-confirmed influenza who sought care early, only 37% were prescribed antivirals. A list of people at high risk of developing flu-related complications is available online. CDC encourages patients at high risk of complications to contact their provider without delay if they have flu symptoms, and CDC recommends that high-risk patients receive prompt antiviral treatment. All hospitalized, severely ill, and high-risk patients with suspected or confirmed influenza should be treated with an NAI antiviral medication as soon as possible.

CDC has done limited qualitative research into clinician knowledge, attitudes and practices related to influenza antiviral medications. The findings suggest that there are probably a number of factors involved in under-prescribing. These include:

  • low clinician awareness of CDC’s antiviral recommendations;
  • a wide range in perception about how well these medications work;
  • some clinicians may require a positive flu test before prescribing antivirals (even though the results of rapid influenza diagnostic tests, if ordered, may not be accurate);
  • and lastly, some clinicians may not prescribe antivirals after the two-day window during which benefit is optimal.

CDC is working to improve awareness of the benefits offered by antivirals.

Background on Flu Vaccine Effectiveness Against Influenza A(H3N2) Viruses

There are a number of reasons why flu vaccine effectiveness against influenza A(H3N2) viruses may be lower compared to other influenza viruses. One reason is how quickly A(H3N2) viruses tend to change compared to influenza A(H1N1)pdm09 and influenza B viruses. While all influenza viruses undergo frequent genetic changes, the changes that have occurred in influenza A(H3N2) viruses have more frequently resulted in differences between the virus components of the flu vaccine and circulating influenza viruses (i.e., antigenic change) compared with influenza A(H1N1)pdm09 and influenza B viruses. That means that between the time when the composition of the flu vaccine is recommended and the flu vaccine is delivered, A(H3N2) viruses are more likely than A(H1N1)pdm09 or influenza B viruses to have changed in ways that could impact how well the flu vaccine works.

A second factor has to do with what is known as “egg-adapted changes,” which refers to differences that occur in the A(H3N2) virus component of the flu vaccine (which is grown in eggs) and the A(H3N2) viruses that circulate among people. Growth in eggs is part of the production process for most seasonal flu vaccines. While all influenza viruses undergo changes when they are grown in eggs, changes in influenza A(H3N2) viruses tend to be more likely to result in antigenic changes compared with changes in other influenza viruses. These so-called “egg-adapted changes” are present in vaccine viruses recommended for use in vaccine production and may reduce their potential effectiveness against circulating influenza viruses. Other vaccine production technologies, e.g., cell-based vaccine production or recombinant flu vaccines, could circumvent this shortcoming associated with the use of egg-based candidate vaccine viruses in egg-based production technology, but CDC also is using advanced molecular techniques to try to get around this short-coming.

Despite the lower effectiveness of A(H3N2) virus strains compared to other vaccine components, influenza vaccination during predominantly influenza A(H3N2) virus seasons prevents a large burden of illness, including hospitalizations and deaths. For more information, see Estimated influenza illnesses, medical visits, hospitalizations and deaths averted by vaccination in the United States.

Messages to Clinicians

CDC’s antiviral recommendations are summarized in Influenza Antiviral Medications: Summary for Clinicians, and are also available in the HAN Advisory: Seasonal Influenza A(H3N2) Activity and Antiviral Treatment of Patients with Influenza.

Note the following important messages:

  1. Influenza activity has increased significantly over recent weeks, so influenza should be high on the list of possible diagnoses for ill patients.
  2. CDC recommends NAI antiviral medications (oseltamivir, zanamivir and peramivir) for treatment of influenza as an important adjunct to annual influenza vaccination. Treatment with antivirals has been shown to have clinical and public health benefit in reducing illness and severe outcomes of influenza, as evidenced from randomized controlled trials, meta-analyses of randomized controlled trials, and observational studies conducted during past influenza seasons and during the 2009 H1N1 pandemic.
  3. All hospitalized patients with suspected or confirmed influenza should be treated with oseltamivir as soon as possible.
  4. All high-risk outpatients and those with progressive illness not requiring hospitalization with suspected or confirmed influenza should be treated as soon as possible with one of three available and recommended influenza NAI antiviral medications.
  5. Antiviral treatment of a patient with suspected influenza should commence regardless of a patient’s influenza vaccination status, and without waiting for confirmatory influenza laboratory testing.
  6. While antiviral drugs work best when given early after illness onset, therapeutic benefit has been observed even when treatment is initiated later for some patients.
Girl in hospital

Antiviral drugs work best for flu treatment when they are started within 2 days of getting sick. However, starting antivirals later can still be helpful for some people.

Resources for Patient Education

Results from unpublished CDC qualitative research shows that most people interviewed were not aware that drugs to treat influenza illness are available. Patients being provided a prescription for an influenza antiviral drug may have questions. A fact sheet for patients is available.

Note the following important background information for patients:

  • If you get sick with flu, antiviral drugs can be used to treat your illness.
  • It is very important that antiviral drugs are used early to treat hospitalized patients, people with severe flu illness, and people who are at high risk of serious flu complications based on their age or health.
  • If you have severe illness or are at high risk of serious flu complications, you may be treated with flu antiviral drugs if you get sick with flu.
  • For people with a high-risk condition, treatment with an antiviral drug can mean the difference between having milder illness instead of very serious illness that could result in a hospital stay.
  • Other people also may be treated with antiviral drugs by their doctor this season, based on the clinical judgment of their doctor.
  • Antiviral drugs work best when started within two days of symptoms first appearing, but there are data to suggest they can still be beneficial in very ill patients even up to five days after getting sick. This would be especially important for a person who is at high risk of serious flu complications and who is very sick.
  • If your health care provider thinks you have the flu, your health care provider may prescribe antiviral drugs. Your provider may sometimes order a test for flu, but this is not necessary for treatment to begin.
  • Antibiotics don’t work on viruses like those such as those that cause flu. It is important to remember that anytime you take antibiotics it can lead to antibiotic resistance and cause side effects. Antibiotics can be effective against bacterial co-infection with flu virus infection, but are not needed if bacterial infection is not suspected.
  • Other practices that may help decrease the spread of influenza include respiratory hygiene, social distancing (e.g., staying home from work and school when ill, staying away from people who are sick) and hand washing.
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