Genetic Susceptibility and Biomarkers in Listeriosis

NCT02924220 | Completed

• 2 other identifiers: 2016-038ID-RCB number : 2016-A00650-51
• Study Type: observational
• Target: 1,080
• Locations: 1 country
• Sites: 1

Brief Summary

Listeriosis is a rare, severe foodborne infection caused by the bacterium Listeria monocytogenes (Lm). It manifests as septicemia, central nervous system (CNS) infection and maternal-fetal (MF) infection. Its associated overall mortality is very high, above of 30%. A better knowledge on the factors involved in its occurrence and in clinical manifestations is therefore needed to improve outcome. A number of frequent acquired risk factors for listeriosis have been identified, such as pregnancy, diabetes, cancer, HIV infection, and immunosuppressive therapies. However, no genetic study on host susceptibility to listeriosis in humans has been performed so far, in the absence of prospective collection of patients' samples. Also, listeriosis diagnosis is based on Lm culture from clinical samples. This method lacks sensitivity, and the contribution of biomarkers to listeriosis diagnosis and prognosis has not been evaluated. The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), is the first national case-control prospective study on listeriosis. It is implemented since 2009 and enrolls all culture-proven cases declared to the NRCL: and collects for each patient clinical and biological data and biological samples. Controls with comparable background and presentation are also included. 818 cases have been included (427 S, 252 CNS and 107 MN) over 3.5 years, along with 456 controls. The aim of the study is to identify human genetic susceptibility factors to listeriosis, biomarkers to improve its diagnosis and prognosis (survival or death), and thereby help improve management of patients with listeriosis. Samples from the completed cohort will be analyzed : SNPs genotyping and exam sequencing; biomarkers a identification in serum and plasma of patients and controls by simultaneous multi-analyte and metabolomic profiling.

Conditions

Listeriosis

Outcome Measures

Primary Outcomes (1)

• Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection

  Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection by whole exome sequencing and whole genome genotyping for all MONALISA cases and controls

  3 years

Secondary Outcomes (2)

• Biomarkers identification in serum and plasma of patients and controls

  3 years

• Biomarkers identification in serum and plasma of patients and controls

  3 years

Study Arms (2)

Case patients

Patients with culture-proven listeriosis. Case patients are classified in 3 groups : * Septicemic infections: isolation of Lm in blood cultures. * CNS infections: isolation of Lm in cerebrospinal fluid, or brain stereotaxic biopsy, or by isolation of Lm in the blood with concomitant meningitis, or radiological encephalitis, rhombencephalitis, brain abscess or meningitis. * MF infections: defined by isolation of Lm in any maternal/fetal/neonatal bacteriological sample. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study.

Control patients

Patients without listeriosis but compatible clinical presentation. Control patients are divided in 3 groups. * Septicemic controls: febrile patient with same co-morbidities as septicemic cases. * CNS controls: patient with any neurological symptom leading to the empiric prescription of amoxicillin at meningeal dosage because of listeriosis presumption. * MF controls: febrile pregnant patient without obvious focal infection. All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses will be included in the MONALISA GENBIO study.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients already recruited in the MONALISA study will be included. The MONALISA study is the first prospective case-control study focused on invasive listeriosis. Cases are patients with culture-proven listeriosis. Controls are patients without listeriosis but compatible clinical presentation.

You may qualify if:

• All patients have given their written consent to participate in the MONALISA cohort and for the collection of a blood sample including DNA samples for DNA analyses.

You may not qualify if:

• Patients included in the MONALISA cohort without biological sample available.

Sponsors & Collaborators

• Institut Pasteur: lead
• Icahn School of Medicine at Mount Sinai: collaborator

Study Sites (1)

Institut Pasteur, Unité de Biologie des Infections

Paris, 75724 Cedex 15, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biological samples (serum, plasma, mononuclear cells and DNA) previously collected from cases patients and control patients included in the MONALISA cohort.

MeSH Terms

Conditions

Listeriosis

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Marc Lecuit

  Institut Pasteur

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2016
• First Posted: October 5, 2016
• Study Start: February 16, 2017
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: October 18, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)