Genetic Susceptibility and Biomarkers in Listeriosis (MONALISA-GENBIO)

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.