Discussion

Interim influenza vaccine effectiveness estimates for the 2016–17 season indicate that vaccination reduced the risk for influenza-associated medical visits by approximately half. Influenza activity is likely to continue for several more weeks in the United States, and vaccination efforts should continue as long as influenza viruses are circulating. Persons aged ≥6 months who have not yet received the 2016–17 influenza vaccine should be vaccinated as soon as possible.§ As of February 3, 2017, approximately 145 million doses of influenza vaccine had been distributed in the United States for the 2016–17 season.

Interim VE estimates indicate improved protection during the 2016–17 influenza season against the predominant influenza A (H3N2) virus belonging to genetic group 3C.2a, which emerged in early 2014 and was predominant during the 2014–15 influenza season in the United States. During 2014–15, these influenza A (H3N2) 3C.2a viruses were antigenically different from the recommended A (H3N2) vaccine component, and this resulted in low (1%) vaccine effectiveness against illness caused by influenza A (H3N2) 3C.2a viruses (4). Low effectiveness of the 2014–15 vaccines likely contributed to high rates of influenza-associated hospitalizations that season, especially among adults aged ≥65 years. In contrast, rates of influenza-associated hospitalizations observed to date have been substantially lower during the 2016–17 season (2). Virologic surveillance indicates that the majority of influenza A (H3N2) viruses collected by U.S. laboratories during the 2016–17 season remain antigenically similar to the A/Hong Kong/4801/2014–like cell propagated reference virus belonging to genetic group 3C.2a, which is the recommended influenza A (H3N2) component of the 2016–17 Northern Hemisphere vaccine.

Since the 2009 influenza A (H1N1) pandemic, VE estimates for A (H3N2) viruses have been lower than VE estimates against A (H1N1) and influenza B viruses. Interim VE estimates against illness caused by influenza A (H3N2) viruses during the 2016–17 influenza season are similar to U.S. VE estimates against A (H3N2)-related illness during the 2011–12 and 2012–13 seasons (VE = 39%) (5,6). Also, a meta-analysis of VE studies using the test-negative design conducted from the 2007–08 through the 2014–15 influenza seasons reported a pooled VE estimate against A (H3N2)-related illness of 33% (CI = 26%–39%), compared with 61% (CI = 57%–65%) against influenza A (H1N1)pdm09 and 54% (CI = 46%–61%) against influenza B virus–related illness (7). These results reflect properties unique to A (H3N2) viruses that pose special challenges. Influenza A (H3N2) viruses undergo more frequent and extensive genetic changes than do influenza A (H1N1) and influenza B viruses, and require more frequent updates to the A (H3N2) vaccine virus components to maintain activity against evolving circulating strains. In addition, A (H3N2) viruses continue to undergo changes in their receptor-binding specificity, which might result in genetic changes during growth in eggs. Most influenza vaccines are manufactured using egg-based production processes. These genetic changes (referred to as egg-adapted changes) alter the antigenic properties of candidate vaccine viruses (CVVs) as they are grown in eggs and potentially during the vaccine production process (8). The egg-adapted changes might contribute to the lower vaccine effectiveness seen with A (H3N2) viruses compared with A (H1N1) and B viruses. Efforts are ongoing to improve influenza vaccine effectiveness against A (H3N2) viruses in CVV development and in manufacturing.

As of February 10, 2017, influenza activity remained elevated nationally and was widespread across most of the United States. During recent A (H3N2) virus predominant–seasons, persons aged ≥65 years and young children experienced higher rates of severe illness and influenza-associated hospitalization compared with other age groups. With vaccine effectiveness of 48%, some vaccinated persons will become infected with influenza. Clinicians should maintain a high index of suspicion for influenza infection among persons with acute respiratory illness while influenza activity is ongoing, especially among older adults. Early antiviral treatment can reduce severity and complications of influenza-associated illness (9). Early antiviral treatment is recommended for persons with suspected influenza with severe or progressive illness (e.g., hospitalized persons) and persons at high risk for complications from influenza, such as children aged <2 years, adults aged ≥65 years and persons with underlying health conditions,¶ even if illness is less severe. Antiviral medications should be used as recommended for treatment in patients with suspected influenza, regardless of vaccination status. The decision to initiate antiviral treatment should not be delayed while waiting for laboratory confirmation of influenza and should not be dependent on insensitive assays, such as rapid influenza diagnostic tests.

The findings in this report are subject to at least four limitations. First, vaccination status included self-report at four of five sites. End-of-season VE estimates based on updated documentation of vaccination status might differ from interim estimates. Second, information from medical records and immunization registries is needed to evaluate VE by vaccine type and for fully vaccinated compared with partially vaccinated children (children aged <9 years require 2 vaccine doses during their first vaccination season), as well as to evaluate the effects of prior season vaccination and timing of vaccination; end-of-season analysis of VE by vaccine type and effects of partial or prior season vaccination is planned. Third, an observational study design has greater potential for confounding and bias relative to randomized clinical trials. However, the test-negative design is widely used in VE studies and has been used by the U.S. Flu VE Network to estimate VE for the past several influenza seasons. Finally, small sample sizes in some age groups resulted in wide confidence intervals, and end-of-season VE estimates could change as additional patient data become available or if there is a change in circulating viruses late in the season. It is also important to note that the VE estimates in this report are limited to the prevention of outpatient medical visits, rather than more severe illness outcomes, such as hospitalization or death; data from studies measuring VE against more severe outcomes will be available at a later date.

Annual vaccination against circulating influenza viruses remains the best strategy for preventing illness from influenza. As of early November 2016, only 37% of children aged 6 months–17 years, 37% of adults aged 18–64 years, and 57% of adults aged ≥65 years had received influenza vaccine this season (10). Among pregnant women, early estimates for 2016–17 indicated that only 47% had been vaccinated by early November 2016 (10). In addition to ongoing vaccination efforts, antiviral medications continue to be an important adjunct to the treatment and control of influenza and should be used as recommended, regardless of patient vaccination status.