Loïc de Pontual

Streptococcus pneumoniae is a colonizer of the child s nasopharynx and a leading cause of invasive pneumococcal disease (IPD). Despite widespread use of pneumococcal conjugate vaccines, recent rebounds in IPD incidence have coincided with serotype replacement. Whether this phenomenon is driven by the replacement of serotypes within lineages or the replacement of the lineages themselves is unclear. Here, we quantified the relative contribution of these two mechanisms to serotype replacement in carriage and their consequences for IPD. We combined nationwide longitudinal surveillance of carriage and IPD in children from 2002 to 2023 with whole-genome sequencing. Observed lineage-specific carriage rates across PCV-related periods were fitted with polynomial logistic regression and compared with two counterfactual scenarios, each isolating one mechanism with: (i) fixed serotype composition within varying lineages and (ii) serotype shifts within fixed lineage carriage rates over time. Carriage dynamics were consistent with an 82% contribution of serotype shifts within persistent lineages. Estimates of serotype-specific IPD incidence derived from this predominant scenario correlated with observed IPD trends. These findings quantify the dominant role of serotype replacement within persistent lineages, disentangling the vaccine-driven adaptive history of S. pneumoniae.

Introduction Bronchiolitis is the leading cause of hospitalization for infants but its economic burden is not well documented. Our objective was to describe the clinical evolution and to assess the 1-month cost of a first episode of acute bronchiolitis presenting to the emergency department (ED). Methods Our study was an epidemiologic analysis and a cost study of the cohort drawn from the clinical trial GUERANDE, conducted in 24 French pediatric EDs. Infants of 6 weeks to 12 months of age presenting at pediatric EDs with a first episode of bronchiolitis were eligible. The costs considered were collected from a societal viewpoint, according to the recommendations of the French National Health Authority. Results A total of 777 infants were included with a median age of 4 months. A total of 57% were hospitalized during the month following the first consultation in the ED, including 28 (3.6%) in an intensive care unit. The mean length of stay was 4.2 days (SD = 3.7). The average time to relief of all symptoms was 13 days (SD = 7). Average total cost per patient was €1919 (95% confidence interval: 1756–2138) from a societal perspective, mostly due to hospitalization cost. The estimated annual cost of bronchiolitis in infants was evaluated to be between €160 and €273 million in France. Discussion Bronchiolitis represent a high cost for the health care system and broadly for society, with hospitalizations costs being the main cost driver. Thus significant investments should be made to develop innovative therapies, to reduce the number of hospitalizations and length of stay.

The burden of bronchiolitis has remained high for the past 20 years. Each year, 1 in 5 infants has a respiratory infection caused by respiratory syncytial virus (RSV).¹ In the United States, an estimated 280 000 visits to emergency departments (EDs) for bronchiolitis occur annually.^2,3 Each year, 150 000 infants are hospitalized, with an estimated cost of more than $1.7 billion in 2009.^4,5 Bronchiolitis is the first cause of hospitalization among infants younger than 1 year.⁵

Rationale, Aims and Objectives: Errors in hospitals during the preparation and administration of intravenous drugs to infants and children have been reported to a rate of 13% to 84%. This study aimed to investigate the potential for hazardous events that may lead to an accident for preparation and administration of drug injection in a pediatric department and to describe a reduction plan of risks.Methods: The preliminary hazard analysis (PHA) method was implemented by a multidisciplinary working group over a period of 5 months (April‐August 2014) in infants aged from 28 days to 2 years. The group identified required hazard controls and follow‐up actions to reduce the error risk. To analyze the results, the STATCART APR software was used.Results: During the analysis, 34 hazardous situations were identified, among 17 were quoted very critical and drawn 69 risk scenarios. After follow‐up actions, the scenarios with unacceptable risk declined from 17.4% to 0%, and these with acceptable under control from 46.4% to 43.5%.Conclusion: The PHA can be used as an aid in the prioritization of corrective actions and the implementation of control measures to reduce risk. The PHA is a complement of the a posteriori risk management already exists.

Auriculocondylar syndrome and isolated question mark ear result from dysregulation of the endothelin 1‐endothelin receptor type A signaling pathway. Animal models have highlighted the role of the transcription factor MEF2C as an effector of this pathway. We report heterozygous MEF2C loss‐of‐function as a possible cause of question mark ear associated with intellectual deficiency.

Patients with terminal complement pathway deficiency (TPD) are susceptible to recurrent invasive meningococcal disease (IMD). Neisseria meningitidis (Nm) strains infecting these patients are poorly documented in the literature. We identified patients with TPD and available Nm strains isolated during IMD. We investigated the genetic basis of the different TPDs and the characteristics of the Nm strains. We included 56 patients with C5 (n = 8), C6 (n = 20), C7 (n = 18), C8 (n = 9), or C9 (n = 1) deficiency. Genetic study was performed in 47 patients and 30 pathogenic variants were identified in the genes coding for C5 (n = 4), C6 (n = 5), C7 (n = 12), C8 (n = 7), and C9 (n = 2). We characterized 61 Nm strains responsible for IMD in the 56 patients with TPD. The most frequent strains belonged to groups Y (n = 27 [44%]), B (n = 18 [30%]), and W (n = 8 [13%]). Hyperinvasive clonal complexes (CC11, CC32, CC41/44, and CC269) were responsible for 21% of IMD cases. The CC23 predominates and represented 26% of all invasive isolates. Eleven of the 15 clonal complexes identified fit to 12 different clonal complexes belonging to carriage strains. Unusual meningococcal strains with low level of virulence similar to carriage strains are most frequently responsible for IMD in patients with TPD.

Background The etiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been reported to be associated with INS onset and relapse. The aim of this study was to describe the epidemiology of a population-based cohort of children with INS and propose a spatiotemporal analysis. Methods All children aged 6 months to 15 years with INS onset between December 2007 and May 2010 and living in the Paris area were included in a prospective multicenter study. Demographic and clinical features at diagnosis and 2 years were collected. Results INS was diagnosed in 188 children, 93 % of whom were steroid sensitive. Annual incidence was 3.35/100,000 children. Standardized incidence ratio (SIR) was higher in one of the eight counties: Seine-Saint-Denis, with SIR 1.43 [95 % confidence interval (CI) 1.02–1.95]. A spatial cluster was further identified with higher SIR 1.36 (95 % CI 1.09–1.67). Temporal analysis within this overincidence area showed seasonal variation, with a peak during the winter period (p p <0.0001). Conclusion The clustering of cases, the seasonal variation within this particular area, and the progression over the Paris area altogether suggest that INS may occur on an epidemic mode.