Genetic Susceptibility to Listeriosis (Listeria-GEN)

Genetic Susceptibility to Listeriosis - Listeria-GEN

Listeriosis is a rare, severe foodborne infection, responsible for severe invasive infections. It occurs in the great majority of cases in elderly patients and / or patients with comorbidities, with a deficit of innate or cellular immunity. Pregnancy is also a risk factor.

The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA) is an ongoing national case-control prospective study on listeriosis implemented since 2009 to study risk and prognosis factors for listeriosis. In this cohort, which enrolled 902 patients on 1 August 2014, 7% of patients with neurolisteriosis are under 40 years of age and have no identified risk factor. Genetic susceptibility is suspected in these patients. Genetic susceptibility could also explain the inconstant development of a neurolisteriosis or fetal infection, as well as the particular severity of some infections (death, foetal loss, neurological sequelae).

The aim of the study is to identify genetic susceptibility to Listeriosis.

Study Overview

• Status: Recruiting
• Conditions: Listeriosis
• Intervention / Treatment: Procedure: Human biological samples

Detailed Description

Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm), responsible for severe invasive infections. It occurs in the great majority of cases in elderly patients and / or patients with comorbidities, with a deficit of innate or cellular immunity. Pregnancy is also a risk factor.

The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA) is an ongoing national case-control prospective study on listeriosis implemented since 2009 to study risk and prognosis factors for listeriosis. In this cohort, which enrolled 902 patients on 1 August 2014, 7% of patients with neurolisteriosis are under 40 years of age and have no identified risk factor. Genetic susceptibility is suspected in these patients. Genetic susceptibility could also explain the inconstant development of a neurolisteriosis or fetal infection, as well as the particular severity of some infections (death, foetal loss, neurological sequelae).

The analysis of the genetically transmitted vulnerability of Lm has not yet been studied, because of the lack of accessibility to prospective cohorts (and their DNA) for this rare and severe infection.

The aim of the study is to identify genetic susceptibility to Listeriosis that will optimize the patient care in terms of treatment and prevention.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marc Lecuit; Phone Number: +33 1 40 61 34 20; Email: marc.lecuit@pasteur.fr
• Study Contact Backup: Name: Caroline Charlier-Woerther; Phone Number: +33 1 40 31 30 10; Email: caroline.charlier@pasteur.fr

Study Locations

• France
  • Paris, France, 75015
    • Recruiting
    • Centre Médical de l'Institut Pasteur
    • Contact: Caroline Charlier-Woerther, MD; Phone Number: +33 1 40 61 30 10; Email: caroline.charlier@pasteur.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for patients with Listeriosis :

• Microbiologically documented Listeriosis (either a severe form of listeriosis, or an atypical form of listeriosis, or less than 40 years old and without any co-morbidity identified)
• Affiliated or beneficiary of a social security system
• Informed and written consent

Inclusion Criteria for volunteers related to patients with Listeriosis (after identifying a genetic susceptibility in the patient with Listeriosis) :

• defined as father, mother, brother (s), sister (s), child (ren), grandparent (s), uncle (s), aunt (s), cousin (s), nephew (s), niece (s).
• Affiliated or beneficiary of a social security system
• Informed and written consent

Exclusion Criteria for volunteers related to patients with Listeriosis:

• Inability to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with Listeriosis; Patients with Listeriosis. Human biological samples : Blood sample; Skin biopsy; Saliva	Procedure: Human biological samples; Blood sample; Skin biopsy; Saliva
Experimental: Volunteers related with patients with Listeriosis; Volunteers related with patients with Listeriosis. Human biological samples : Blood sample; Skin biopsy; Saliva	Procedure: Human biological samples; Blood sample; Skin biopsy; Saliva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of a susceptibility factor associated with Listeriosis infection	In patients with Listeriosis, the hypothesis that the identified genetic variation is the mutation responsible for the infection will be verified : by verifying that it is not a listed polymorphism by sequencing genomic DNA controls; by verifiyng that family genetic segregation is compatible with clinical segregation; by verifying the function of the mutated protein in the patient's cell lines and / or fresh cells; by performing complementation experiments by transfecting the wild-type allele into the patient's cells	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of a susceptibility factor associated with the most severe or atypical forms	In patients with Listeriosis, the susceptibility factor associated with the most severe or atypical forms will be characterized : By testing the response and production of cytokines involved in infection control.; By identifying chromosomal regions associated with the disease by a homozygosity mapping genetic study on multiplex and / or inbred families.; By sequencing the identified candidate genes.	10 years

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: Icahn School of Medicine at Mount Sinai
• Investigators: Study Director: Marc Lecuit, Institut Pasteur

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: November 24, 2017
• First Submitted That Met QC Criteria: November 24, 2017
• First Posted (Actual): November 30, 2017

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 18, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Listeriosis
• Other Study ID Numbers: 2014-31; ID-RCB number : 2015-A01386-43 (Other Identifier: French national registration number of the study)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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