Transmission Of Respiratory Tract microOrganisms In a School Environment

Respiratory tract infections impose a large burden of disease upon the world.
Pneumonia remains the leading infectious cause of death in children under five
worldwide. Known causative agents of pneumonia include, but are not limited to,
SPn, Haemophilus influenzae (HI), Moraxella catarrhalis (MC) and viruses such
as the Respiratory Syncytial Virus (RSV) and the influenza virus. These
microorganisms are regularly found in the upper respiratory tract (URT) without
causing severe disease. Colonization of the URT is thought to be important both
for immune boosting and to provide competition for other potential harmful
colonizers.

This study aims to provide insights into the processes and key host immune and
microbiota factors that determine the infection kinetics, transmission and
development of immunity during such infections. Furthermore, this study will
enable us to closely study the transmission of commonly found microorganisms in
an environment that is prone to transmission within populations, the close
quarters of school classes in which young children spend a large part of their
time.

Primary Objective:
Describe classroom transmission- and colonization-rate of SPn in young
children. This will be measured at a serotype-level as overall carriage rates
are high.

Secondary Objectives:
a. To study transmission and colonization rates of other URT pathogens in a
classroom setting.
b. To study nasal immune response in response to exposure, infection or
colonization by URT microbes.
c. To describe the relationship between clinical symptoms of RTI*s, host immune
responses, microbiome and URT pathogens.
d. Correlation of medical history with (rate of) transmission and colonization
of respiratory pathogens and immune responses.
e. To measure pollen and bacterial presence (airobiome) in classroom
environment via electrostatic dust fall collector and pollensniffer to
differentiate between RTI and hay fever.
f. To describe the relation of URT pathogen colonization rate in young children
and their teachers.

This is a prospective observational cohort study. Participants, children aged
4-7 years and their teachers, will be recruited from primary schools in
North-Holland and/or South-Holland. Initially contact is made with primary
schools by trained study personnel. If schools are willing to facilitate the
study, contact is made with parents via the teachers, school-newsletters or
directly through an information booth or other contact at the school. Parents
and teachers will be informed about the study by trained study members through
primary schools. Potential participants (or their parents) will have sufficient
time (at least one week) to decide to take part and have the possibility to ask
questions. Throughout the study the researchers will be available via telephone
and e-mail.
Duration of the study for participants will be eight consecutive weeks during
which we collect all samples. This period allows sufficient time to be able to
precisely study transmission episodes and potential development of infection.
Minimally-invasive nasal sampling will take place three times a week at the
participating primary school, yielding 24 samples per participant. We have
previously demonstrated that such minimally-invasive samples are an accurate
tool to measure pneumococcal colonization in children. If participants are sick
and cannot come to school, we will ask permission from them (in case of
teachers) or their parents (in case of children) for a home visit, and will
collect the SAM at home and complete a questionnaire related to the illness and
potential treatment. We will sample in a period between school-holidays to have
an uninterrupted study period. If there are children that join the class during
the course of the study we will inform the parents and ask for informed consent
to include these children as well. The children that start later will finish
the sampling along with the rest of the class, and will thus provide less
samples than the others.
We will also place an EDC in the classroom for the whole study period and
collect weekly air samples by active sampling through a pollensniffer to
measure environment particles. These devices are able to measure environmental
microbes, potential human pathogens along with airborne pollen and give
information on a collective *exposome* for the whole study period as well as
weekly fluctuations based on seasonal differences. By doing so we may
distinguish between hay-fever symptoms and RTIs. Along with the sampling,
clinical symptoms will be observed and recorded by trained study personnel. In
the first weeks of the study a baseline questionnaire will be completed by the
parents.

Data will be collected through digital questionnaires, biological material by
minimally invasive synthetic absorptive matrices (SAMs). Collection will take
place on site (primary schools) by trained members of the study team three
times a week for a period of eight weeks.
To engage children, we will include an educational component where children
will learn from one of the clinical doctors involved in the study about
micro-organisms in relation with health and disease Other than this, there is
no direct benefit for participants, we hope to elucidate the infection kinetics
and transmission of microorganisms in primary school classrooms through this
study, ultimately aiming to identify biomarkers for transmission of and
invasive disease caused by pathogens. This might for example help with
preventing unnecessary school closures in the future during respiratory
infection dynamics. Risks involved for participants are minimal, as SAMs are
minimally-invasive and well-tolerated by young children and adults. We will
study young children because they are a significant risk-group for severe
respiratory infections and spread microorganisms frequently due to close
interaction with peers whilst being a main reservoir for respiratory pathogens.