Vaccine reduces influenza infections, but not influenza-like illnesses

Although vaccination reduced the incidence of influenza virus infections among older adults, it did not reduce the number of influenza-like illnesses, according to researchers in the Netherlands.

“Vaccine effectiveness varies per season and depends on age and health of the recipients, and the antigenic match of vaccine strains with circulating strains,” Josine van Beek, of the Centre for Infectious Diseases Control at the National Institute for Public Health and the Environment, Bilthoven, Netherlands, and colleagues wrote. “Furthermore, there is scientific debate about the methodology of determining [vaccine efficacy].”

The researchers noted that members of the general public tend not to distinguish between influenza and influenza-like illnesses, creating a perception that vaccination is ineffective and reducing uptake.

“To counter this trend, data on the relative contribution of influenza virus and other respiratory infections to [influenza-like illnesses] in older community-dwelling adults are lacking and needed,” the researchers wrote.

Van Beek and colleagues performed a prospective observational cohort study over the course of two winters — 2011 to 2012 (n = 1,992) and 2012 to 2013 (n = 2,368). All participants were aged 60 years or older, and were recruited either through the Netherlands Civil Registry or their general practitioners. The researchers collected nasopharyngeal and oropharyngeal swabs both from patients experiencing influenza-like illnesses and controls, then identified viruses and bacteria with conventional bacterial cultures and multiplex ligation-dependent probe amplification assays.

The winter of 2011 to 2012 had an influenza-like illness incidence of 7.2%, compared with 11.6% in 2012 to 2013, the researchers wrote. Influenza virus caused 18.9% of episodes in the first winter and 34.2% in the second. Most cases (80%) of influenza-like illnesses demonstrated potential pathogens, with the most common being influenza, coronavirus, rhinovirus, human metapneumovirus, respiratory syncytial virus, parainfluenza virus and Haemophilus influenzae, van Beek and colleagues wrote.

Vaccination reduced infection with influenza virus by 73% (95% CI, 26%-90%) in the first winter and 51% in the second (95% CI, 7%-74%); however, the incidence of influenza-like illnesses was similar in both vaccinated (7.6% in 2011 to 2012 and 10.8% in 2012 to 2013) and nonvaccinated patients (4.2% in 2011 to 2012 and 11.4% in 2012 to 2013; P > .05 for all).

Van Beek and colleagues acknowledged that the study was limited in that it did not monitor severity or duration of disease. These details, they wrote, would allow specialists to evaluate relative risk posed by a variety of pathogens.

“In combination with other medical information, it may then be possible to assemble a profile of individuals potentially at risk for influenza-like illness or worse,” the researchers wrote.

In an accompanying editorial, Janet E. McElhaney, M.D., FRCPC, FACP,  of the Health Science North Research Institute, Sudbury, Canada, and Shelly A. McNeil, MD, FRCPC, of the Canadian Center for Vaccinology, wrote that observational studies of community-dwelling adults tend to be limited by “healthy-vaccinee bias,” in which healthier patients who are at lower risk for “severe outcomes” are more likely to be vaccinated than those who are frailer, producing an overestimate of vaccine effectiveness.

Another study centered on influenza A (H3N2), the predominant influenza strain examined in van Beek and colleague’s paper, included a large number of frail adults and “demonstrates that frailty is a significant confounder in the analysis, leading to underestimates of vaccine efficacy,” McElhaney and McNeil wrote.
“Taken together, these studies highlight the importance of test-negative case-control study designs with prospective measures of frailty in older adults and support including influenza seasons in which A(H3N2) is the predominant circulating strain to assess the effectiveness of influenza vaccine in adults.” – by Andy Polhamus

Disclosure: McElhaney reports honoraria from GSK, Merck, Sanofi and Pfizer outside of the submitted work. McNeil reports grants from GSK, Sanofi and Pfizer, as well as honoraria from GSK, Merck and Pfizer. Van Beek reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.