Identification of Clinical, Genetic and Immunological Factors Involved in the Development of Severe Bacterial Infections in Pediatrics

Official title

IBSoFACTo : Identification of Clinical, Genetic and Immunological Factors Involved in the Development of Severe Bacterial Infections in Pediatrics

Overview

Severe bacterial infections (SBI) are responsible for significant morbidity and mortality in the paediatric population. There is considerable individual variability in children's susceptibility to developing SBIs. This variability is multifactorial, and the mechanisms at work are not yet fully understood. The investigators of this study therefore propose to study a population of children who had particularly severe bacterial infections requiring hospitalization in a pediatric intensive care unit in France between 2015 and 2018. This study is part of a global approach to understanding the mechanisms favoring the occurrence of IBS in pediatrics. The study will initially focus on analyzing the clinical phenotype of these children in terms of the type of infection presented, as well as immunologically with an immune workup of all these patients. The investigators also plan to contact each family individually to identify other episodes of personal or family IBS or other elements suggestive of immune deficiency (opportunistic infections, autoimmune manifestations, severe atopy). The investigators will also assess the persistent sequelae since their infectious episode, and their quality of life following this IBS. In parallel, the genetic analysis of these patients and their parents will be carried out using whole-exome sequencing. The investigators will compare the results with those obtained in 2 IBS-free control populations (N=70 and N=116). The goal is to identify genetic variants that favor the occurrence of IBS in general, and some that are specific to certain bacteria or clinical presentations.

Interventions

• Other Extended phenotyping
  Extended phenotyping (analysis performed at Nantes University Hospital, MANDATORY DELIVERY WITHIN 24 HOURS) = 1 EDTA 3 mL tube for patients included in Nantes.
• Other Blood sample for WES
  Blood sample for WES : 1 x 3 mL EDTA tube (if not included in DIABACT IV biocollection)
• Other Blood sample for PBMC freezing
  Blood sample for PBMC freezing integrated into the biocollection: 1 EDTA tube = 3 mL
• Other POPC score evaluation
  Assessment of POPC score (Pediatric Overall Performance Category)
• Other Questionnaire completion
  Questionnaires completed by parents or children: * SDQ * PedSQL4.0

Primary outcome measures

• Identification of innate errors of immunity involved in the development of IBS in pediatrics. [Time frame: At the enrollment]

Secondary outcome measures (6)

• Identification of inborn errors of immunity involved in the development of IBS and their association with abnormalities of the immune balance, [Time frame: At the enrollment]
• Identification of rare genetic variants favoring certain clinical types of infection, or certain biological and immunological abnormalities. [Time frame: At the enrollment]
• Identification of immune deficiencies in patients who have developed a severe bacterial infection [Time frame: At the enrollment]
• Assessment of sequelae with the POPC sequelae score (Pediatric Overall Performance Category) at a distance from the IBS episode. [Time frame: At the enrollment]
• Assessment of sequelae at a distance from the IBS episode with the Strengths and Weaknesses Questionnaire (SDQ-Fra). [Time frame: At the enrollment]
• Assessment of quality of life at a distance from the IBS episode. [Time frame: At the enrollment]

Eligibility criteria

Inclusion criteria

For patients:

• Patient included in the DIABACT IV study between 2015 and 2018, following hospitalization in a pediatric intensive care unit in France for a severe bacterial infection.
• Patient affiliated to a social security system
• Patient alive at the time of inclusion.
• Written consent from legal representatives for participation in research. If one of the legal representatives is unable to complete/sign the written consent, it will be sought orally by telephone and recorded in the patient's file. If the patient is over 18, written consent will be obtained. If the patient is a minor, consent will be sought with communication adapted to his/her level of understanding and age.

For parents:

• Patient's biological parents
• Written consent

Exclusion criteria

• Persons under court protection
• Refusal to participate in research

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Other

Study locations

France · 6 centers

• Nantes University Hospital — Nantes
• CHU de Brest — Brest
• Hospices Civils de Lyon — Lyon
• Hôpital Armand Trousseau — Paris
• Hôpital Necker enfants malades — Paris
• CHU de Saint-Étienne — Saint-Etienne

Identifiers

NCT: NCT07111793 · RC25_0061 · 2025-A01367-42

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗