French National Reference Center and WHO Collaborating Center for Listeria, Institut Pasteur, Paris, France; Biology of Infection Unit, Institut Pasteur, Paris, France; Inserm U1117, Paris, France; Paris Descartes University, Sorbonne Paris Cité, Necker-Pasteur Infectiology Centre, Necker-Enfants Malades University Hospital, Institut Imagine, Assistance Publique-Hôpitaux de Paris, Paris, France.
Centre of Research in Epidemiology and Statistics Sorbonne Paris Cité, METHODS Team, UMR 1153, INSERM, Paris Descartes University, Sorbonne Paris Cité, Paris, France.
Lancet Infect Dis. 2017 May;17(5):510-519. doi: 10.1016/S1473-3099(16)30521-7. Epub 2017 Jan 28.
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.
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.
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).
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.
Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
李斯特菌病是一种严重的食源性感染，也是法国的一种法定报告疾病。我们进行了一项全国性前瞻性研究，以描述其临床特征和预后因素。
MONALISA 是一项全国性前瞻性观察性队列研究。我们招募了 2009 年 11 月 3 日至 2013 年 7 月 31 日期间向国家李斯特菌参考中心报告的所有微生物学确诊病例（所有病例均强制报告）。主要结局为分析临床特征、鉴定李斯特菌分离株，并采用逻辑回归确定 3 个月死亡率或持续功能障碍的预测因素。还对神经李斯特菌病和菌血症病例进行了主成分分层聚类分析。该研究在 ClinicalTrials.gov 注册，编号为 NCT01520597。
我们从 372 个中心纳入了 818 例病例，包括 107 例母婴感染、427 例菌血症和 252 例神经李斯特菌病。107 例孕妇中仅有 5 例（5%）结局良好。26 例（24%）孕妇出现胎儿丢失，但从未发生在妊娠 29 周以后或入院后 2 天以上。252 例神经李斯特菌病患者中，212 例（84%）表现为脑膜脑炎；仅 42 例（17%）患者出现脑干受累。菌血症患者的 3 个月死亡率高于神经李斯特菌病（风险比[HR]0.54[95%CI 0.41-0.69]，p<0.0001）。对于菌血症和神经李斯特菌病，最强的死亡预测因素均为持续存在的癌症（比值比[OR]5.19[95%CI 3.01-8.95]，p<0.0001）、多器官衰竭（OR 7.98[4.32-14.72]，p<0.0001）、任何预先存在的器官功能障碍恶化（OR 4.35[2.79-6.81]，p<0.0001）和单核细胞减少症（OR 3.70[1.82-7.49]，p=0.0003）。血培养阳性患者（OR 3.67[1.60-8.40]，p=0.002）或接受辅助地塞米松治疗的患者（OR 4.58[1.50-13.98]，p=0.008）的神经李斯特菌病死亡率更高。
李斯特菌病的严重程度比以往报道的更高。我们发现，接受辅助地塞米松治疗的神经李斯特菌病患者的生存率显著降低，并且确定了胎儿丢失的时间窗。MONALISA 提供了重要的新数据，有助于改善李斯特菌病的管理和预测结局。
医院临床研究计划、巴斯德研究所、法国国家健康与医学研究院、法国公共卫生署。
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