A recent sharp increase in influenza A(H3N2) activity in the United States has prompted the Centers for Disease Control and Prevention (CDC) to release a health advisory emphasizing the importance of its antiviral treatment recommendations this season.
The Dec. 27, 2017 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 percent 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 percent 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 percent 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.
The CDC is working to improve awareness of the benefits offered by antivirals.
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.
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.