Clinical trial NCT01520597: National Study on Listeriosis and Listeria
Official title: Multicentric Observational NAtional Study on LISteriosis and ListeriA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Listeriosis
Pregnancy Complications
Infectious
Central Nervous System Infections
Septicemia
Sepsis; Listeria Monocytogenes
Keywords: Multicentric
National
Prospective on
Listeriosis
Listeria
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut Pasteur
name: French National sanitory
First posted: 2012-01-30
Enrollment: 2132
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Case: patient with culture-proven listeriosis (blood CSF, fetal/placental sample, other...).

Controls: patient above the age of 18 years with medical background and clinical features compatible with one of the 3 forms of systemic listeriosis: febrile pregnant women (temp \> 38°C), febrile patient with co-morbidity for septicaemic listeriosis, and any febrile symptom leading to empiric amoxicillin prescription.

Brief summary: Listeriosis is a foodborne infection responsible for severe disease. Three main forms are described: septicaemia, central nervous system infections and maternal-fetal infections. Available data on the disease, are mostly retrospective and do not provide an accurate picture of the clinical / biological / genetic risk factors for the disease, nor identify any element to determine which patients are at higher risk of death, severe neurological impairment or fetal loss.

The primary purpose of the study is to identify clinical, biological and genetic risk factors for systemic listeriosis and the determinants of listeriosis-associated mortality in the setting of a large prospective nation-wide study.

Detailed description: Context: Listeriosis is a foodborne infection responsible for severe disease. Surveillance of human listeriosis in France is based on both mandatory reporting of cases and voluntary submission of L. monocytogenes strains to the National Reference Center for Listeria (NRC) since 1999. The exhaustiveness of this reporting estimated by capture-recapture is of at least 87%. A recent and consistent increase of sporadic and cluster-associated systemic listeriosis cases has been reported in Europe since several years (since 2006 in France), but remains poorly understood in the absence of any new environmental risk factor(s). A total of 322 cases have been reported in 2009 in France. Three main clinical forms are identified: septicemia, central nervous system and maternal-fetal infection. They have been characterized only through retrospective studies and pooling of heterogeneous patients. Such studies do not provide an accurate picture of the disease and fail to identify precise biological / genetic risk factors for the disease. Prognostic factors associated with higher risk of death, of severe neurological impairment or of fetal loss also remain to be determined.

Main purpose:

- to study clinical, biological and genetic risk factors for systemic listeriosis and identify determinants of listeriosis-associated mortality in the setting of a large prospective nation-wide study

Secondary purposes:

* to determine the clinical/biological and radiological presentation of listeriosis
* to describe and further study current therapeutic practices in the 3 forms of the disease (namely, septicaemic, neurologic and maternal-fetal)
* to identify inherited risk factors for listeriosis

Ancillary studies:

- to evaluate serologic/PCR diagnostic tools

Study design:

National prospective multicenter study with nested case control study. Clinical, biological and radiological data are collected. Additionally a questionnaire focusing on dietary habits is proposed. A bank of biological samples is performed. For each patient, 25ml of heparinized blood / and 2ml of serum are collected per patient

Eligibility criteria: Inclusion Criteria:

Case:

* Patient with culture-proven listeriosis (blood, CSF, fetal/placental sample, other...).

Control:

* Patient above the age of 18 years with medical background and clinical features compatible with one of the 3 forms of systemic listeriosis: febrile pregnant women (temp \> 38°C), febrile patient with co-morbidity for septicaemic listeriosis, and any febrile symptom leading to empiric amoxicillin prescription.
* For feasibility reasons, controls are included in Paris (France) emergency wards.

Exclusion Criteria:

Case:

* Patient who would refuse to sign informed consent agreement

Control:

* Patient who would refuse to sign informed consent agreement, or whose samples would evidence L. monocytogenes

Primary outcomes:
measure: Clinical, biological and genetic risk factors for systemic listeriosis
timeFrame: At Day 1 (case and control)
measure: Clinical, biological and genetic risk factors for systemic listeriosis
timeFrame: At Day 90 (case)
Secondary outcomes:
measure: Clinical/biological and radiological presentation of listeriosis
timeFrame: At Day 1 and Day 90 (case), at Day 1 (control)
measure: Current therapeutic practices
timeFrame: At Day 1 and Day 90 (case), at Day 1 (control)
Other outcomes:
Locations:
city: Paris
country: France
facility: Centre National de Reference et Centre Collaborateur OMS Listeria, Institut Pasteur
Study officials:
affiliation: Institut Pasteur
name: Caroline Charlier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Pasteur
name: Lecuit Marc, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore). 1998 Sep;77(5):313-36. doi: 10.1097/00005792-199809000-00002.
citation: Mylonakis E, Paliou M, Hohmann EL, Calderwood SB, Wing EJ. Listeriosis during pregnancy: a case series and review of 222 cases. Medicine (Baltimore). 2002 Jul;81(4):260-9. doi: 10.1097/00005792-200207000-00002. No abstract available.
citation: Lecuit M, Vandormael-Pournin S, Lefort J, Huerre M, Gounon P, Dupuy C, Babinet C, Cossart P. A transgenic model for listeriosis: role of internalin in crossing the intestinal barrier. Science. 2001 Jun 1;292(5522):1722-5. doi: 10.1126/science.1059852.
citation: Disson O, Grayo S, Huillet E, Nikitas G, Langa-Vives F, Dussurget O, Ragon M, Le Monnier A, Babinet C, Cossart P, Lecuit M. Conjugated action of two species-specific invasion proteins for fetoplacental listeriosis. Nature. 2008 Oct 23;455(7216):1114-8. doi: 10.1038/nature07303. Epub 2008 Sep 17.
citation: Charlier C, Leclercq A, Cazenave B, Desplaces N, Travier L, Cantinelli T, Lortholary O, Goulet V, Le Monnier A, Lecuit M; L monocytogenes Joint and Bone Infections Study Group. Listeria monocytogenes-associated joint and bone infections: a study of 43 consecutive cases. Clin Infect Dis. 2012 Jan 15;54(2):240-8. doi: 10.1093/cid/cir803. Epub 2011 Nov 18.
citation: Charlier C, Perrodeau E, Leclercq A, Cazenave B, Pilmis B, Henry B, Lopes A, Maury MM, Moura A, Goffinet F, Dieye HB, Thouvenot P, Ungeheuer MN, Tourdjman M, Goulet V, de Valk H, Lortholary O, Ravaud P, Lecuit M; MONALISA study group. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis. 2017 May;17(5):510-519. doi: 10.1016/S1473-3099(16)30521-7. Epub 2017 Jan 28.
citation: Charlier C, Barrault Z, Rousseau J, Kermorvant-Duchemin E, Meyzer C, Semeraro M, Fall M, Coulpier G, Leclercq A, Charles MA, Ancel PY, Lecuit M. Long-term neurological and neurodevelopmental outcome of neonatal listeriosis in France: a prospective, matched, observational cohort study. Lancet Child Adolesc Health. 2023 Dec;7(12):875-885. doi: 10.1016/S2352-4642(23)00195-5. Epub 2023 Oct 20.
citation: Charlier C, Poiree S, Delavaud C, Khoury G, Richaud C, Leclercq A, Helenon O, Lecuit M; MONALISA Study Group. Imaging of Human Neurolisteriosis: A Prospective Study of 71 Cases. Clin Infect Dis. 2018 Oct 15;67(9):1419-1426. doi: 10.1093/cid/ciy449.
citation: Charlier C, Kermorvant-Duchemin E, Perrodeau E, Moura A, Maury MM, Bracq-Dieye H, Thouvenot P, Vales G, Leclercq A, Ravaud P, Lecuit M. Neonatal Listeriosis Presentation and Outcome: A Prospective Study of 189 Cases. Clin Infect Dis. 2022 Jan 7;74(1):8-16. doi: 10.1093/cid/ciab337.
citation: Charlier C, Perrodeau E, Levallois C, Cachina T, Dommergues M, Salomon LJ, Azria E, Goffinet F, Ravaud P, Lecuit M. Causes of fever in pregnant women with acute undifferentiated fever: a prospective multicentric study. Eur J Clin Microbiol Infect Dis. 2020 May;39(5):999-1002. doi: 10.1007/s10096-019-03809-3. Epub 2020 Jan 18.