Influenza-like Illness Incidence Is Not Reduced by Influenza Vaccination in a Cohort of Older Adults, Despite Effectively Reducing Laboratory-Confirmed Influenza Virus Infections

Abstract

Background: Data on the relative contribution of influenza virus and other respiratory pathogens to respiratory infections in community-dwelling older adults (≥60 years) are needed.

Methods: A prospective observational cohort study was performed in the Netherlands during 2 winters. Nasopharyngeal and oropharyngeal swabs were collected during influenza-like illness (ILI) episodes and from controls. Viruses and bacteria were identified by multiplex ligation-dependent probe amplification assay and conventional bacterial culture.

Results: The ILI incidence in the consecutive seasons was 7.2% and 11.6%, and influenza virus caused 18.9% and 34.2% of ILI episodes. Potential pathogen were detected in 80% of the ILI events with influenza virus, coronaviruses, rhinoviruses, human metapneumovirus, respiratory syncytial virus, parainfluenza viruses, and Haemophilus influenzae being the most common. Influenza vaccination reduced influenza virus infection by 73% (95% confidence interval [CI], 26%-90%) and 51% (95% CI, 7%-74%) in ILI patients. However, ILI incidence was similar between vaccinated (7.6% and 10.8%) and nonvaccinated (4.2% and 11.4%) participants in 2011-2012 and 2012-2013, respectively (P > .05).

Conclusions: Influenza virus is a frequent pathogen in older adults with ILI. Vaccination reduces the number of influenza virus infections but not the overall number of ILI episodes: other pathogens fill the gap. We suggest the existence of a pool of individuals with high susceptibility to respiratory infections.

Clinical trials registration: NTR3386.

Keywords: influenza virus; influenza virus infection; influenza-like illness; older adults; vaccination.

Figure 1.

Flow diagram of enrollments and influenza-like illness (ILI) cases (2011–2012 and 2012–2013) (A) and the subgroup of asymptomatic controls (2012–2013) (B). A subject could have multiple ILI episodes per season. An ILI visit (V1) was considered “out of window” if the sample was taken >72 hours after start of fever. For the recovery visit (V2), the window was 7–9 weeks after ILI onset. Subjects were considered lost to follow-up if they did not respond to the end of study mailing and had no ILI visit (A). After the baseline visit had been performed, a subject could have an ILI event. Subjects were considered lost to follow-up if they did not respond to the end of study mailing and had no ILI visit (B).

Figure 2.

Distribution of detected viruses and bacteria per influenza-like illness (ILI) event. The incidence of virus or bacterium, or combination of both (“any pathogen”) detected in the swab is depicted per ILI events in 2011–2012 (n = 143) (A), 2012–2013 (n = 275) (B), and asymptomatic controls (n = 340) (C). If a sample set was not complete, the event was excluded.

Figure 3.

Viruses and bacteria detected in swabs of influenza-like illness (ILI) cases and samples of asymptomatic controls. Incidence per virus or bacterium detected in naso- and oropharyngeal swabs in 2011–2012 (n = 143) (A), 2012–2013 (n = 275) (B), and asymptomatic controls (n = 340) (C). The percentages were calculated per ILI event. Multiple pathogens could be detected in a single event and therefore contribute to the incidence for multiple pathogens. Abbreviations: hMPV, human metapneumovirus; ILI, influenza-like illness; RSV, respiratory syncytial virus.