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.

Background. The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. Methods. A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. Results. The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50–400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9–8.2). Conclusions. Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL.

To assess neonatal morbidity in twin pregnancy according to the planned mode of delivery. A retrospective cohort study of 758 consecutive sets of twins born after 35 weeks of gestation with a cephalic-presenting first twin was undertaken in a level III maternity unit in which active management of the second twin delivery is performed routinely. The primary outcome was a composite measure of neonatal mortality and morbidity, including pH less than 7.0, 5-minute Apgar score less than 4, neonatal intensive care unit transfer more than 4 days, pneumothorax, and fracture. Control for potential confounders was performed by excluding from the analysis women who experienced pregnancy complications and by using logistic regression models. Vaginal or cesarean delivery was planned for 657 (86.7%) and 101 (13.3%) women, respectively. Among planned vaginal deliveries, 515 (78.4%) patients delivered both twins vaginally, 139 (21.1%) had a cesarean delivery during labor, and 3 (0.5%) had cesarean delivery for the second twin. After vaginal birth of the first twin, the mean intertwin delivery interval was 4.9+/-3.2 minutes. When patients who experienced pregnancy complications were excluded (n=202), the neonatal composite morbidity for the second twin did not differ between planned cesarean and planned vaginal delivery (5.0% compared with 4.7%, adjusted odds ratio 1.5, 95% confidence interval 0.3-7.4, P=.63). Neonatal composite morbidity of first twins did not differ between groups. For twin gestations with a cephalic-presenting first twin, planned vaginal delivery after 35 weeks of gestation in selected women remains a safe option in centers used to active management of the second twin delivery.

The T cell compartment is considered to be naïve and dedicated to the development of tolerance during fetal development. We have identified and characterized a population of fetally developed CD4 T cells with an effector memory phenotype (T_EM), which are present in cord blood. This population is polyclonal and has phenotypic features similar to those of conventional adult memory T cells, such as CD45RO expression. These cells express low levels of CD25 but are distinct from regulatory T cells because they lack Foxp3 expression. After T cell receptor activation, neonatal T_EM cells readily produced tumor necrosis factor–α (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). We also detected interferon-γ (IFN-γ)–producing T helper 1 (T_H1) cells and interleukin-4 (IL-4)/IL-13–producing T_H2-like cells, but not IL-17–producing cells. We used chemokine receptor expression patterns to divide this T_EM population into different subsets and identified distinct transcriptional programs using whole-genome microarray analysis. IFN-γ was found in CXCR3⁺ T_EM cells, whereas IL-4 was found in both CXCR3⁺ T_EM cells and CCR4⁺ T_EM cells. CCR6⁺ T_EM cells displayed a genetic signature that corresponded to T_H17 cells but failed to produce IL-17A. However, the T_H17 function of T_EM cells was observed in the presence of IL-1β and IL-23. In summary, in the absence of reported pathology or any major infectious history, T cells with a memory-like phenotype develop in an environment thought to be sterile during fetal development and display a large variety of inflammatory effector functions associated with CD4 T_H cells at birth.