Studying Respiratory Infections and Colonisation in Children Using Daily Minimally-invasive Nasal Sampling (SAMSAM)

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 Overview

• Status: Completed
• Conditions: Respiratory Tract; Infection, Upper (Acute); Colonization, Asymptomatic

• Study Type: Observational
• Enrollment (Actual): 46

Contacts and Locations

Study Locations

• Netherlands
  • Hoofddorp, Netherlands
    • Spaarne Gasthuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Children aged 1-6 years old, as these are a main population at risk for severe respiratory tract infections, and a main source of transmission. The study team will recruit families from the area of North/South-Holland as this will facilitate the home visits.

Description

Inclusion Criteria:

• Written informed consent obtained from all legal representatives, for example both parents.
• Child aged 1-5 years of age attending day care, peuterspeelzaal or school at least 2 (half) days a week.
• Parents ability and willingness to adhere to protocol-specified procedures, including availability of a freezer at home to store samples. This does not include donation of saliva by parents themselves, which is related to a secondary endpoint.

Exclusion Criteria:

• History of respiratory tract infections requiring hospitalization
• Current use of antibiotics, or antibiotics use in past four weeks
• Use of immune-altering medication (such as steroids, including inhaled corticosteroid)
• No history of severe concomitant disease (severe congenital heart disease, bronchopulmonary dysplasia, prematurity <32 weeks, cystic fibrosis, sickle cell disease, congenital or acquired immunodeficiency disorders, cardiovascular disease, neuromuscular disorders, oncology patients or major congenital anomalies)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Young children; Children aged 1-5 years old attending school or day care. Follow-up for 28 days using minimally-invasive nasosorption sampling and questionnaires relating to symptoms. No intervention administered
Parents; Parents of enrolled children, if it is a one-child family. Follow-up for 28 days using minimally-invasive saliva sampling. No intervention administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of systemic polysaccharide specific B cells in children that become colonised during the study versus children that do not become colonised	up to study completion, 28 or 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants with pneumococcal colonisation presence over time.	lyta, piab and serotype-specific qPCR	up to study completion, 28 or 29 days
Pneumococcal colonisation density over time.	lyta, piab and serotype-specific qPCR	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.	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.	up to study completion, 28 or 29 days
Local microbiome composition measured by 16S	Relative abundance of ASV	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	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	up to study completion, 28 or 29 days
Symptom questionnaires	Symptoms are scaled on presence/absence	up to study completion, 28 or 29 days
Evaluation/Sample tolerability questionnaires	scale includes completely disagree, disagree, neutral, agree, completely agree for each question	day 28, last visit
Presence of bacteria and viruses in saliva of a subset of parents on a daily interval	Measured using molecular methods	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	up to study completion, 28 or 29 days

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Spaarne Gasthuis
• Investigators: Principal Investigator: Marlies A van Houten, MD, Spaarne Gasthuis

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Actual): November 27, 2023
• Study Completion (Actual): November 27, 2023

Study Registration Dates

• First Submitted: August 31, 2023
• First Submitted That Met QC Criteria: September 15, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 12, 2023
• Last Update Submitted That Met QC Criteria: December 11, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Host-pathogen interactions; Minimally-invasive nasal sampling; Colonization/URT infections in children
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Asymptomatic Diseases; Infections; Communicable Diseases; Respiratory Tract Infections; Asymptomatic Infections
• Other Study ID Numbers: P21.067

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

If any samples or data are shared to perform analyses as described in the study protocol, either inside or outside EU, only pseudonymized material is shared to ensure participant privacy.

This can be done upon request and following the signing of MTA/DTA.

Individual datasets might be placed on repositories with restricted access or fully anonymized (such as Zenodo or flowrepository.org) upon publication.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No