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Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

https://doi.org/10.1016/S1473-3099(16)30521-7Get rights and content

Summary

Background

Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors.

Methods

MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597.

Findings

We enrolled 818 cases from 372 centres, including 107 maternal–neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41–0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01–8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32–14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79–6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82–7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60–8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50–13·98], p=0·008).

Interpretation

The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis.

Funding

Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.

Introduction

Listeria monocytogenes causes listeriosis, a severe foodborne bacterial infection. L monocytogenes is the foodborne pathogen associated with the highest case-fatality rate in the western hemisphere, where its incidence is estimated at around three to six cases per 1 million population per year.1, 2 Invasive listeriosis is classified in three forms: bacteraemia, neurolisteriosis, and maternal–neonatal infection; localised forms are also reported.3, 4, 5 Epidemiological studies have identified host risk factors for bacteraemia and neurolisteriosis, including older age, innate and cellular immune defects, malignancies, HIV infection, cirrhosis, diabetes mellitus, alcoholism, and immunosuppressive therapies.6 However, all clinical and most epidemiological studies have been retrospective and have compiled data from heterogeneous timeframes and geographical areas.3, 4, 5, 6, 7, 8, 9, 10 Thus, a precise analysis of disease presentation based on homogeneous and prospectively acquired data is lacking. Furthermore, because listeriosis cases are relatively rare and scattered, no clinical trial has been done, and therapeutic guidelines are not evidence based. The prognosis for listeriosis has not improved over the past decades.3, 7

Listeriosis has been a notifiable disease in France since 1999, with mandatory notification of culture-confirmed cases and submission of isolates to the National Reference Center for Listeria (NRCL). A recent capture–recapture study estimated at 85–87% the exhaustiveness of the national surveillance system for the 2008–13 period, and since 2000, an average 98% of nationally reported cases have isolates submitted to the NRCL.11 Taking advantage of the quasi-exhaustiveness of this surveillance system, we implemented the prospective Multicentric Observational NAtional Study on LISteriosis and ListeriA (MONALISA), a nationwide cohort, to precisely characterise the clinical patterns and identify prognostic factors for invasive listeriosis.

Section snippets

Study design and patients

MONALISA is a national prospective observational cohort study. We enrolled eligible cases declared to the NRCL (all microbiologically proven), in the context of mandatory reporting. We report the study in accordance with the STROBE reporting guidelines for observational studies.12

Research in context

Evidence before this study

We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords

Results

Of the 1063 cases notified to the NRCL between Nov 9, 2009, and July 31, 2013, 869 patients gave informed consent, of whom 818 (94%) were included in the study (figure 1): 427 patients with bacteraemia, 252 patients with neurolisteriosis, 107 patients with maternal–neonatal infection (table 1), and 32 patients with other forms. Follow-up was available for 99% of patients (median follow-up period 5 months [IQR 3–10]). Comparison between cases included and not included is shown in the appendix (p

Discussion

The quasi-exhaustiveness of the National Surveillance System for listeriosis in France made it possible to do the first prospective clinical study on listeriosis. We found that more than 80% of infected mothers experienced major fetal or neonatal complications and only 39% of patients with neurolisteriosis survived and fully recovered. Fetal losses occurred at less than 29 weeks of gestation and within 2 days of hospital admission and new factors independently associated with mortality were

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