Excrétion du cytomégalovirus (CMV) dans les crèches françaises : une étude nationale sur l'épidémiologie, les facteurs de risque, les pratiques des centres et la sensibilisation des parents au CMV

Abstract Background Congenital cytomegalovirus (CMV) remains an important healthcare burden, resulting from primary or secondary infection in pregnant women. Exposure to young children’s saliva is a major risk factor, as prevalence of CMV shedding can reach 34%. Methods This cross-sectional, multicenter, nationwide study was conducted in randomly selected day care centers (DCCs), and complemented with a survey among parents and DCCs. All children aged >3 months were eligible. The study measured the CMV shedding prevalence in children’s saliva and described CMV genotypes epidemiology. The risk factors for CMV shedding and high viral load were evaluated using multivariable models. Results A total of 93 DCCs participated. Among the 1770 enrolled children with evaluable samples, the CMV shedding prevalence was 40% (713/1770, 95% confidence interval, 34.6–46.1), independently associated with children aged between 12 and 18 months, history of CMV infection in ≥1 parents, a mid-level income. Prevalence increased with DCC staff workload and attending children number. Viral load was ≥5 log-copies CMV/mL in 48% (342/713). Risk factors for higher viral load included children aged between 12 and 18 months, and still being breastfed. The most frequent genotype combinations were gB1-gN4c-gH2 (6.9%), gB1-gN2-gH2 (6.3%), gB4a-gN3a-gH1 (6.3%), and gB1-gN3b-gH2 (5,7%). CMV awareness was low in parents: their serological status was unknown by 72% of mothers and 82% of fathers. Only 41% knew something about CMV. Conclusions CMV shedding was independently associated with risk factors related to the children, family and DCC. Some of these risk factors may influence prevention strategies, including through an improved information provided to parents. Clinical Trials Registration NCT01704222

Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain.

Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm-born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain across models of neuroinflammation-mediated injury (mouse, zebrafish) and primary human and mouse microglia we found using analysis of genes and proteins that a reduction in Wnt/β-catenin signalling is necessary and sufficient to drive a microglial phenotype causing hypomyelination. We validated in a cohort of preterm-born infants that genomic variation in the Wnt pathway is associated with the levels of connectivity found in their brains. Using a Wnt agonist delivered by a blood-brain barrier penetrant microglia-specific targeting nanocarrier we prevented in our animal model the pro-inflammatory microglial activation, white matter injury and behavioural deficits. Collectively, these data validate that the Wnt pathway regulates microglial activation, is critical in the evolution of an important form of human brain injury and is a viable therapeutic target.This study was supported by grants from Inserm, Université Paris Diderot, Université Sorbonne-Paris-Cité, Investissement d'Avenir (ANR-11-INBS-0011, NeurATRIS), ERA-NET Neuron (Micromet), DHU PROTECT, Association Robert Debré, PremUP, Fondation de France, Fondation pour la Recherche sur le Cerveau, Fondation des Gueules Cassées, Roger de Spoelberch Foundation, Grace de Monaco Foundation, Leducq Foundation, Action Medical Research, Cerebral Palsy Alliance Research Foundation Australia, Wellcome Trust (WSCR P32674) and The Swedish Research Council (2015-02493). We wish to acknowledge the support of the Department of Perinatal Imaging and Health, King’s College London. In addition, the authors acknowledge financial support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We also wish to thank Dr Dominique Langui (Institut du Cerveau et de la Moelle épinière, Hôpital Pitié-Salpêtrière, Paris, France) for providing us with access to electron microscopy facilities and Dr Manuela ZinniI INSERM U1141 NeuroDiderot for access to additional molecular biology facilities