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

Severe bacterial infections (SBIs) have become rare in countries with a high economic level but remain severe pathologies responsible for a significant morbidity and mortality in the pediatric population. There is great individual variability in the susceptibility of children to develop IBS. Indeed, when they are infected by bacteria, children will, most of the time, present a mild infection, but some will exceptionally develop an invasive bacterial infection. This variability is multifactorial, and the mechanisms at work are not yet fully understood. It has become clear for several years that genetic factors influence the susceptibility to develop IBS and its evolution. 

The project led by Nicolas Vince aims to identify clinical, immunological and genetic factors involved in the development of SBI. It relies on a nationwide French cohort of 497 children admitted in pediatric intensive care unit in France. They will be followed up 5-10 years post-infection to evaluate their development, sequelae, and immune-related manifestations (e.g. immune deficiency). Our genetic study will utilize a single biological sample collected from each participant at a single time point during the initial inclusion period to perform whole exome sequencing, focusing on protein coding genome region. This to identify genetic variations influencing the susceptibility of developing SBI. We expect to identify rare, potentially pathogenic variants, whether common to SBI in general or specific to certain pathogens (pneumococcus, meningococcus…) or clinical presentations. Finally, all these children will undergo a standardized immunological evaluation to measure their immune system’s performance.

Our IBSoFACTo study aims at preventing SBI consequences by better understanding the mechanisms involved. The integration of clinical, genetic, and immunological data will provide novel insights into pediatric SBI susceptibility. Expected outcomes include therapeutic opportunities targeting dysfunctional proteins, and in the longer term, tailored prevention strategies such as a genetic testing at birth. Ultimately, IBSoFACTo has the potential to  transform early detection, prevention, and management of pediatric sepsis, hence reducing mortality and long-term sequelae.