Genetic Susceptibility and Biomarkers in Listeriosis (MONALISA-GENBIO)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,080
- 试验地点
- 1
- 主要终点
- Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection
研究概览
简要总结
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.
详细描述
Context :
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. Surveillance of human listeriosis in France relies on the mandatory reporting of cases and the submission of the corresponding Lm strains to the National Reference Centre for Listeria (NRCL).
A number of acquired risk factors for listeriosis have been identified, such as pregnancy, age, cirrhosis, renal insufficiency, diabetes, cancer, HIV infection, transplantation and immunosuppressive therapies. If listeriosis is rare, the exposure to Lm is universal. The high prevalence of known risk factors in the general population and the low occurrence of the disease suggest that unknown parameters, such as host genetic factors, contribute to the susceptibility to listeriosis. This is supported by animal studies, which have shown that genes involved in innate and cell-based immunity are critical to control listeriosis. 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.
Listeriosis diagnosis is based on Lm culture from clinical samples. This specific method lacks sensitivity, and the usefulness of PCR or serological assays have not been assessed in prospective case-control studies. Biomarkers are useful tools to diagnose infections and assess their severity, but their contribution to listeriosis diagnosis and prognosis has not been evaluated.
The Multicentric Observational NAtional Analysis of Listeriosis and Listeria (MONALISA), a national case-control prospective study on listeriosis, was launched in 2009. It enrolls all culture-proven cases declared to the NRCL: clinical and biological data and biological samples (plasma, serum, PBMC) are collected at inclusion for each patient. 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •Patients included in the MONALISA cohort without biological sample available.
结局指标
主要结局
Characterisation of genetic susceptibility markers for infection as a whole and for each form and/or for the severity of infection
时间窗: 3 years
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
次要结局
- Biomarkers identification in serum and plasma of patients and controls(3 years)
