Identification of potential pathogens responsible for influenza-like illness in elderly in The Netherlands. Evaluation of humoral and cellular immunity against identified microorganisms

The public is questioning the effectiveness of seasonal influenza vaccination
in elderly as a result of the general impression that all influenza-like
illness (ILI) is caused by an influenza virus infection. However, several
pathogens, both viral and bacterial, can also cause ILI. A better understanding
of the percentage of ILI caused by an influenza virus infection and the
contribution of other respiratory viruses or involvement of bacteria will allow
a better appreciation of seasonal influenza vaccines. In earlier studies in
this population, the incidences of influenza and other microorganisms were
determined in subjects with ILI, in seasons of varying influenza incidence,
including the humoral response.
In the follow-up study additional information will be collected on the cellular
immune responses induced by the different viruses, bacteria and influenza
vaccination, the severity of respiratory symptoms during ILI, respiratory
symptoms in the absence of ILI, the acceptance of influenza vaccination and the
influence of the intestinal microbiome on the immune responses after infection
or vaccination.

Primary: to determine the percentage of ILI attributable to influenza virus in
elderly individuals * 60 years of age
Secondary: to determine the relative contribution of influenza viral subtypes
Secondary: to determine humoral and cellular immune responses to influenza
virus
Secondary: to identify which microorganisms (viral and bacterial) present in
nasopharynx and oropharynx of elderly suffering from ILI are potential other
causes for ILI
Secondary: to determine humoral and cellular immune responses towards the
potential pathogens identified in PCR/culture data
Secondary: to gain insight in the influence of viral presence on
co-colonization of well-known respiratory bacteria like S. pneumoniae, H.
influenzae, M. catarrhalis, S. aureus in elderly by comparing colonization
during ILI, after recovery and without having had ILI (baseline)
Secondary: to compare the presence of S. pneumoniae in nasopharyngeal swab with
saliva
Exploratory: to evaluate whether differences can be found in incidence of
influenza virus infection between subjects who have, and those who have not,
received the seasonal influenza vaccine in the year of study
Exploratory: to compare the incidences of the detected pathogens with other
available age group cohorts or with other cohorts of the same age group, such
as the previous GRIEP-1/-2 study
Exploratory: to evaluate the immune responses to different herpesviruses in the
context of a possible role in immunosenescence
Exploratory: to analyze the intestinal microbiome in context of influenza
vaccination response and identified microorganisms
Exploratory: to evaluate whether there is a difference in the general physical
and mental health condition as assessed by SF-36 questionnaire and vaccine
acceptance between the subjects that report with ILI and the whole study
population

Observational cross-sectional study without an investigational medicinal
product but with invasive measurements.

The burden associated with participation are reporting of ILI, and collection
of a nasopharyngeal swab, an oropharyngeal swab, 6 tubes of blood (53 ml), some
saliva and a small faecal sample in case a subject reports with ILI. This
sample collection is repeated twice. We expect that at least 200 subjects will
report with ILI during the season. In a subset of 150 subjects who have not
(yet) experienced ILI the same sample sets are collected twice.
The potential risks are considered minimal. There are no benefits for the
individual subjects who participate in this trial. The results may contribute
to a better control of respiratory diseases on a population level in the
future. The study population is the target of the yearly influenza vaccination
campaign.