Rationale: Respiratory tract infections (RTI) are a major cause of morbidity in young children in high- income countries and the major cause of mortality in developing countries. Causative bacteria and viruses are regular residents of the nasopharynx of asymptomatic individuals (colonization) and live there together with other presumed harmless commensals, without causing disease. These non-pathological infections/colonization episodes are important for transmission, intermediate step to disease and boost immune responses. The investigators recently validated the use of minimally-invasive nasal sampling methods that can be done at home for the study of host and microbial parameters in adults and children. In this study the investigators will focus on the daily microbial and immunological composition of the nasopharynx during health in relation to symptoms. Primary objective: Associate acquisition of pneumococcal colonisation with levels of pre-existing polysaccharide specific memory B cells. Secondary objectives include: Validate the use of synthetic absorptive matrices (SAM) for detection of respiratory pathogens versus nasopharyngeal swabs (NPS) and saliva; Assess dynamics of URT infection/colonisation and examine its relationship with symptoms, host responses and microbiota; Measure transmission between children and parents and immune responses in parents. Study design: Prospective community-based cohort study.total of 45 children, aged 1-5 years old attending daycare or (pre-)school, will be included, including a pilot of 10 children to assess tolerability. If there are insufficient pneumococcal acquisitions in the study to assess the primary outcome, additional children can be recruited in groups of 3 or 4 children (up to 10). For a subset of participating children, both parents will be asked to self-collect daily saliva during the study. Primary study parameters: Frequency of systemic polysaccharide specific B cells in children that become colonised during the study versus children that do not become colonised Secondary study parameters: Dynamics of respiratory bacteria and viruses during URT infection/colonisation. Presence and load for bacteria and viruses in children in SAM versus saliva and NPS. Local microbiota and immune profiles and association with infection/colonisation and symptomology. For a subset of parents, daily presence and load of bacteria and viruses as well as host immune factors measured in saliva.
Study Type
OBSERVATIONAL
Enrollment
46
Spaarne Gasthuis
Hoofddorp, Netherlands
Frequency of systemic polysaccharide specific B cells in children that become colonised during the study versus children that do not become colonised
Time frame: up to study completion, 28 or 29 days
The number of participants with pneumococcal colonisation presence over time.
lyta, piab and serotype-specific qPCR
Time frame: up to study completion, 28 or 29 days
Pneumococcal colonisation density over time.
lyta, piab and serotype-specific qPCR
Time frame: up to study completion, 28 or 29 days
The number of participants with presence of other bacteria and viruses
Presence of other respiratory bacteria (such as Haemophilus influenzae and Staphylococcus aureus) and viruses (such as coronaviruses and influenza virus) during URT infection/colonisation, measured by molecular methods.
Time frame: up to study completion, 28 or 29 days
Density of other bacteria and viruses
Density of other respiratory bacteria (such as Haemophilus influenzae and Staphylococcus aureus) and viruses (such as coronaviruses and influenza virus) during URT infection/colonisation, measured by molecular methods.
Time frame: up to study completion, 28 or 29 days
Local microbiome composition measured by 16S
Relative abundance of ASV
Time frame: up to study completion, 28 or 29 days
Nasal and systemic antibodies titres specific for identified pathogens, measured using ELISA or antigen arrays
antigen-specific IgG, IgA and IgM titres
Time frame: up to study completion, 28 or 29 days
Nasal cytokine levels, assessed using multiplex assays such as Luminex
Individual cytokines will be reported in absolute or relative values
Time frame: up to study completion, 28 or 29 days
Symptom questionnaires
Symptoms are scaled on presence/absence
Time frame: up to study completion, 28 or 29 days
Evaluation/Sample tolerability questionnaires
scale includes completely disagree, disagree, neutral, agree, completely agree for each question
Time frame: day 28, last visit
Presence of bacteria and viruses in saliva of a subset of parents on a daily interval
Measured using molecular methods
Time frame: up to study completion, 28 or 29 days
Density of bacteria and viruses in saliva of a subset of parents on a daily interval
Measured using molecular methods
Time frame: up to study completion, 28 or 29 days
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