L'impact de la COVID-19 sur la santé des enfants, groupe « protégé ¼ de l'infection.

OBJECTIVE: This article underlines that a viral epidemic and strategies to deal with it 1) have a major impact on groups that are a priori spared by the disease itself, in this case children, and 2) can generate health problems beyond the disease and lead to major social, economic and educational difficulties and an increase of social inequalities in health. METHOD: The observations presented are based on the scientific literature available in the first half of 2020 and on discussions with actors in the field, experts and heads of institutions, conducted by a working group of the Haut Conseil de la Santé Publique reflecting on a global and concerted policy for children's health. RESULTS: The health crisis and its management have had an impact on children's development and their quality of life. They have been more exposed to sedentary lifestyles, screens, accidents, and violence at home. The closure of schools and leisure facilities has led to difficulties in school, socialization, psychological well-being and mental health. Curative or preventive care has been postponed. These effects occurred with significant social and territorial inequalities. CONCLUSION: Any health crisis management requires an assessment of the overall impact of the epidemic and the proposed measures on health, economic, social, and educational indicators. This crisis shows the need for a coordinated children's policy, which is not currently the case in France.

La santé des enfants en France : un enjeu négligé ?

INTRODUCTION: As part of the National Health Strategy, the High Council for Public Health (HCSP) was tasked with leading a reflection on a “comprehensive and concerted child health policy”. Policy-making requires relevant knowledge and statistical benchmarks. It therefore seemed useful to examine the French statistical system and active research topics. This assessment is expected to provide a current portrait of the priorities and implicit health choices for the children. It also aims to reveal insufficiently explored aspects of children’s health. METHODS: The inventory of this system was carried out on the basis of several methods, hearings, work of two documentalists, and analysis of the published and grey literature. RESULTS: The emphasis is on pathologies, medical prevention and behaviors conceived primarily as individual. The idea that the health of tomorrow’s adults is built up behind this apparent good health and its inequalities does not appear, or only marginally. The elements on affective, cognitive or relational development are not sufficiently analyzed, for lack of data. The living conditions of children, especially poverty and violence in all its forms, are not sufficiently considered as health issues. Research is developing today with a hospital-centric vision, without a real strategy of research on children’s health. DISCUSSION: Given the dispersion of data, publishing a summary report on children’s health on a regular basis is essential, as enriching the system with data on the environment, poverty and psychomotor, psychosocial and cognitive development. There is an urgent need to develop research on children’s health and to define a research strategy that does not exist today.

Escherichia Coli Meningitis Features in 325 Children From 2001 to 2013 in France.

BACKGROUND: We aimed to describe features of Escherichia coli meningitis in a large population of children and the molecular characteristics of the involved strains to determine factors associated with severe disease or death. METHODS: Between 2001 and 2013, a prospective national survey collected data for 325 children hospitalized with E. coli meningitis. The national reference center genetically characterized 141 isolates. RESULTS: Among the 325 cases, 65.2% were term, 22.4% late preterm, and 12.5% very/extremely preterm infants. Escherichia coli meningitis was 7-fold more frequent in preterm than term infants. Median age at diagnosis was 14 days; 71.1% of infants were neonates, with 2 peaks of infection at age 0-3 days (mostly preterm neonates) and 11-15 days (mostly term neonates); 8.9% were >89 days old. In total, 51.1% patients were considered to have severe disease, and 9.2% died. B2.1 phylogenetic subgroup (56%) and O1 serogroup (27.7%) were the most frequently identified. On multivariate analysis, death was associated with preterm birth (odds ratio [OR], 3.3 [95% confidence interval {CI}, 1.3-8.4], P = .015 for late preterm infants; OR, 7.3 [95% CI, 2.7-20.9], P < .001 for very/extremely preterm infants) and cerebrospinal fluid (CSF) to blood glucose ratio <0.10 (OR, 15.3 [95% CI, 1.8-128.3], P = .012). Death was associated with uncommon O serogroup strains (P = .014) and severe disease with O7 serogroup (P = .034) and PapGII adhesin (OR, 2.3 [95% CI, 1.2-4.5], P = .015). CONCLUSIONS: In this large study of 325 cases of E. coli meningitis, risk factors of severe disease or death were preterm birth, severe hypoglycorrhachia, CSF/blood glucose ratio <0.10, and molecular characteristics of strains, which should help optimize therapeutic management.

Escherichia coli bacteremia in children: age and portal of entry are the main predictors of severity.

BACKGROUND: Escherichia coli bacteremia is a major cause of severe sepsis in children. Little is known about predictors of severity. METHODS: We analyzed 84 children ≤ 18 years of age with E. coli bacteremia from the prospective COLIBAFI study performed during 2005-2007. The severity of bacteremia was defined as occurrence of death or transfer to intensive care unit. Studied characteristics included age, gender, birth weight, history of prematurity, immunodepression, nosocomial infection, portal of entry, phylogenetic group and subgroup belonging, O-type, virulence gene content and antimicrobial susceptibility. We compared bacterial characteristics in urinary- versus digestive-source bacteremia, in children ≤ 3 versus >3 month of age, and in children versus adults. We also searched for risk factors of severity. RESULTS: Median age was 2.4 months, 57% males. Most frequent portals of entry were urinary (66.2%) and digestive (19.5%) tracts. Most isolates (63.1%) belonged to B2 phylogroup. Strains in children ≤ 3 months of age exhibited more virulence genes, especially neuC and fyuA/irp2, and were less resistant to antibiotics than in children >3 months of age. Comparing community-acquired urinary-source bacteremia between children and adults, we found that bacteremia were less severe in children, whose strains exhibited a specific virulence gene repertoire and had a higher resistance score than in adults. Seventeen children (20.2%) had a severe bacteremia and 8 died. Non-urinary portal of entry and age ≤ 3 months of age were the only risk factors associated with severity. CONCLUSIONS: E. coli strains responsible for bacteremia exhibit specific characteristics according to age of children. However, host characteristics and portal of entry are the main determinants of severity of E. coli bacteremia in children, as observed in adults.

Fluoroquinolones in pediatrics: review of hospital prescription use over 2 years.

OBJECTIVE: Numerous studies have shown that the tolerance of children to fluoroquinolones (FQs) is satisfactory, and some indications have been recently agreed upon. However, vigilance is required when prescribing FQ to children. The aim of our study was to describe the prescription of FQs to children hospitalized in our hospital. MATERIALS AND METHODS: This is a chart retrospective observational study at the Robert-Debré teaching Hospital between January 2009 and December 2010. Data was collected about patients (name, sex, weight, age) and prescribed treatments (indication, international nonproprietary names, dose, number of doses per day, administration route). Quality of collected data was assessed by analyzing the clinical files of 32 randomly selected patients. RESULTS: We analyzed data for 397 patients (3 days - 18 years old and 640 g - 115 kg). Ciprofloxacin was prescribed for 382 patients (96%), ofloxacin for 10 patients (3%), and levofloxacin for 5 patients (1%). Febrile neutropenia was the most common indication (108 patients, i.e., 27%), followed by inflammatory bowel disease (50 patients, 13%). Doses conformed to recommendations for 88% of the patients. Analysis of the 32 cases indicated an overall compliance percentage of 94.4%. CONCLUSION: This is the first study to collect so much data on FQ prescriptions for hospitalized children. Use in practice went beyond the licensed indication. Doses were consistent with those for recommended indications.

Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants.

OBJECTIVE: To determine whether neonatal infections are associated with a higher risk of adverse neurodevelopment at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all live births between 22 and 32 weeks of gestation, from 9 regions in France, in 1997 (EPIPAGE study). Of the 2665 live births, 2277 were eligible for a follow-up evaluation at 5 years of age: 1769 had a medical examination and 1495 underwent cognitive assessment. Cerebral palsy and cognitive impairment were studied as a function of early-onset sepsis (EOS) and late-onset sepsis (LOS), after adjustment for potential confounding factors, in multivariate logistic regression models. RESULTS: A total of 139 (5%) of the 2665 live births included in the study presented with EOS alone (without associated LOS), 752 (28%) had LOS alone (without associated EOS), and 64 (2%) displayed both EOS and LOS. At 5 years of age, the frequency of cerebral palsy was 9% (157 of 1769) and that of cognitive impairment was 12% (177 of 1495). The frequency of cerebral palsy was higher in infants with isolated EOS (odds ratio [OR]: 1.70 [95% confidence interval (CI): 0.84-3.45]) or isolated LOS (OR: 1.71 [95% CI: 1.14-2.56]) than in uninfected infants, and this risk was even higher in cases of combined EOS and LOS (OR: 2.33 [95% CI: 1.02-5.33]). There was no association between neonatal infection and cognitive impairment. CONCLUSIONS: Neonatal infections in these very preterm infants were associated with a higher risk of cerebral palsy at the age of 5 years, particularly in infants presenting with both EOS and LOS.

Neonatal bacterial meningitis.

Neonatal meningitis contributes substantially to neurological disability worldwide. Its incidence remains low but is significantly higher in neonates with documented sepsis, preterm infants, and when meningitis is nosocomial. Neonates are at higher risk of meningitis because of immaturity in humoral and cellular immunity, and the absence of specific clinical signs makes diagnosis of meningitis more difficult in neonates than in older children. Neonatal meningitis remains, therefore, a public health challenge for pediatricians. Mortality and long-term complications in survivors are observed in 10-15% and 20-50%, respectively, depending on term at diagnosis, type of identified organisms, and delay before treatment. Neurological deficits range from moderate-to-severe disabilities to more subtle problems including visual deficits, middle-ear disease, and cognitive and behavioral impairments. Intracerebral complications should be documented using magnetic resonance imaging. Treatment should be initiated once the diagnosis is suspected using a parenteral combination of bactericidal antibiotics adapted to pathogen sensitivity.

Escherichia coli isolates causing bacteremia via gut translocation and urinary tract infection in young infants exhibit different virulence genotypes.

Escherichia coli bacteremia in young infants may arise via either urinary tract infection or gut translocation (GT). E. coli GT isolates have rarely been investigated. Molecular analysis of 100 E. coli isolates recovered from bacteremic infants revealed that GT isolates had multilocus sequence types similar to those of urosepsis isolates but different prevalences of PapGII adhesin, TcpC protectin, and ibeA invasin. Compared with late-onset GT isolates, early-onset isolates were associated with significantly different rates of the conserved virulence plasmidic region common to human and avian pathogenic strains and α-hemolysin. We identified genetic determinants potentially involved in specific pathophysiological steps preceding E. coli bloodstream invasion.

Neonatal Bacterial Meningitis: 444 Cases in 7 Years.

BACKGROUND: Neonatal bacterial meningitis remains a severe infectious disease with mortality rates varying between 10% and 15%. The clinical and bacteriologic features of neonatal meningitis collected from January 2001 to December 2007 in a French national survey are presented here. METHODS: Cases of neonatal meningitis were prospectively collected by a network of 252 pediatric wards covering 61% of French pediatric wards, associated with 168 microbiology laboratories. Neonatal meningitis was classified as early-onset (d0-d4) and late-onset (d5-d28). Statistical analyses were performed according to gestational age and weight at birth. RESULTS: A total of 444 cases of neonatal bacterial meningitis were reported by 114 pediatric wards. Five cases were excluded from analysis. Group B streptococci (GBS) and Escherichia coli accounted respectively for 59% and 28% of the cases, followed by Gram-negative bacilli other than E. coli (4%), other streptococci (4%), Neisseria meningitidis (3%), and Listeria monocytogenes (1.5%). GBS was the most common pathogen both in early-onset (77% vs. 18% for E. coli) and in late-onset meningitis (50% vs. 33% for E. coli). Among preterm infants, E. coli was more commonly isolated (45% vs. 32% for GBS), especially in very preterm infants (54%). GBS was more often involved in seizures than E. coli (41% vs. 25%). The overall mortality rate was 13% but reached 25% in preterm or small for gestational age infants, regardless of the etiology. CONCLUSIONS: GBS was the dominant cause of neonatal bacterial meningitis, with 77% of early-onset and 50% of late-onset cases. E. coli was the most common bacteria in preterm infants.

Are cytochrome P450 CYP2C8 and CYP2C9 polymorphisms associated with ibuprofen response in very preterm infants?

BACKGROUND: Patent ductus arteriosus (PDA) in extremely preterm infants remains a challenging condition with conflicting treatment strategies. Ibuprofen is currently used to treat PDA with ductal closure failure rate up to 40%. We test the hypothesis that cytochrome P450 CYP2C8/2C9 polymorphisms may predict ibuprofen response. METHODOLOGY/PRINCIPAL FINDINGS: We studied extremely preterm neonates with haemodynamically significant PDA and treated with ibuprofen. One or two variant CYP2C8 and/or 2C9 alleles were found in 17% of the population, most of them were from Caucasian ethnicity (67-74%). Response to ibuprofen and clinical course of infants carrying variants CYP2C8 and CYP2C9 were similar. Comparing infants with wild type or variant CYP2C8 and CYP2C9 genotypes, response rate to ibuprofen was significantly higher in wild type than in mutated carriers in univariate analysis (73% versus 52%, p = 0.04). Comparing responders (ductus closure; n = 75) and non-responders (surgical ligation; n = 36), the only two factors significantly associated with the response to ibuprofen using multivariate analysis were higher gestational age and non Caucasian ethnicity but not CYP2C polymorphism. CONCLUSIONS: CYP2C polymorphism was not associated with PDA response to ibuprofen and this factor appears not appropriate to optimize the ductal closure rate by modulating ibuprofen dosing strategy. This study points out the role for ethnicity in the interindividual variability of response to ibuprofen in extremely preterm infants.

Association of meningococcal phenotypes and genotypes with clinical characteristics and mortality of meningitis in children.

BACKGROUND: Neisseria meningitidis meningitis represents approximately one-half of the meningococcal cases in French children. To explore the contribution of bacterial typing in improving the management of cases, we aimed to describe clinical characteristics and mortality of meningococcal meningitis in children reported to the multicenter survey system, GPIP/ACTIV, in association with phenotypes/genotypes of bacterial isolates. METHODS: From 2001 to 2005, 259 pediatric wards and 168 microbiology laboratories enrolled all children with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded. RESULTS: A total of 962 cases of Neisseria meningitidis meningitis among a total of 2131 bacterial meningitis (45%) were recorded (mean age, 4.5 +/- 4.7 years). Serogroup distribution of the isolates was 62.3%, 33.7%, 2.9%, 0.6%, and 0.6% for serogroups B, C, W135, A and Y, respectively. The major clonal complexes were ST-41/44 (32.2%), ST-11 (21.9%), ST-32 (20.8%), ST-8 (8.2%), and ST-269 (4.9%). Despite global heterogeneity of the isolates, 2 phenotypes/genotypes were of interest. Isolates of the phenotype/genotype B:14:P1.7,16/ST-32 (56% clustered in the region of Haute Normandie) were observed in older children (8.6 years) and were associated with a higher case fatality rate (12%) than were other phenotypes of serogroup B. The phenotype/genotype C:2a:P1.5/ST-11 was found in 26.3% of serogroup C cases and was possibly associated with a higher mortality among serogroup C (9.9% for C and 5.9% for B, P = 0.04). CONCLUSIONS: This large survey provides data that could be important for implementation of future vaccines. Typing of meningococcal isolates could contribute to an understanding of prognosis in meningococcal meningitis.

Congenital malaria in neonates: two case reports and review of the literature.

UNLABELLED: Congenital malaria is uncommon in nonendemic countries. We describe two cases involving neonates hospitalized with fever, anaemia and thrombocytopaenia. Thick and thin blood smears were positive for Plasmodium vivax (P. vivax) and P. ovale, respectively. These two cases were discussed regarding the literature and potential implications of HIV coinfection in the mother. CONCLUSION: Consistent data in the literature suggest that peripheral blood films should be performed in HIV-positive women who travelled to an endemic area or with a history of malaria prior to gestation. With today's travelling patterns, congenital malaria should be considered as an important differential diagnosis of neonatal sepsis.

Sensitivity of the bacterial meningitis score in 889 children with bacterial meningitis.

OBJECTIVE: To validate sensitivity of the bacterial meningitis score (BMS) in a large population of children with bacterial meningitis (BM). STUDY DESIGN: Secondary analysis of prospective data for children presenting with BM to a hospital emergency department between January 2001 and February 2005. The BMS was applied to all children with acute BM using the same inclusion criteria proposed by the authors of the rule. The sensitivity of the rule was calculated. RESULTS: Of the 900 children aged 29 days to 18 years with acute BM who met all inclusion criteria, 889 had enough data for assigning the BMS. Use of the BMS correctly identified 884 children with BM, for 99.6% sensitivity (95% confidence interval: 98.9% to 99.8%). CONCLUSIONS: The sensitivity of the BMS to detect disease was very high, but a few cases of BM were missed. Further refinements of the BMS may be warranted to lower the false-negative rate.

Comparison of CD8+ T Cell responses to cytomegalovirus between human fetuses and their transmitter mothers.

BACKGROUND: The mechanisms responsible for the increased susceptibility of fetuses to cytomegalovirus (CMV) were studied by comparing CD8(+) T cell responses to the virus in susceptible fetuses to those in their comparatively more resistant mothers. METHODS: Included in the study were 16 transmitter mothers who underwent seroconversion during the first trimester of pregnancy as well as their fetuses, who were positive for CMV in amniotic fluid by polymerase chain reaction at 17-19 weeks of gestation. Fetal and maternal blood samples were collected between the 22nd and 39th week of gestation. Cytotoxic T lymphocytes (CTLs) that had activated (HLA-DR(+)), effector/memory (CD28(-)), and memory (CD18(high)) phenotypes; that stained with the HLA-A2/pp65 or the HLA-B7/pp65 multimer; and that secreted interferon (IFN)- gamma were enumerated by flow cytometry. Viral loads were determined simultaneously. RESULTS: The results showed (1) similar levels of activated, effector/memory, and memory CTLs in fetuses and mothers but a smaller pp65-specific CTL pool in fetuses (median, 0.015% vs. 0.99%; P=.003); (2) similar percentages of CTLs secreting IFN- gamma after stimulation with ionomycin/phorbol myristate acetate in fetuses and mothers but lower percentages of CTLs secreting IFN- gamma after stimulation with a CD3 monoclonal antibody in fetuses (median, 1% vs. 14%; P=.01); and (3) higher viral loads (mean, 17,290 vs. <250 genome equivalents/mL) in fetuses. CONCLUSION: Impaired viral clearance might be related to a defective expansion of the pp65-specific CTL pool and/or to the immaturity of IFN- gamma -secreting cells in fetuses.

Combined multilocus sequence typing and O serogrouping distinguishes Escherichia coli subtypes associated with infant urosepsis and/or meningitis.

The genetic relatedness of 223 invasive Escherichia coli strains that cause either meningitis or urosepsis without meningitis in young infants was determined by multilocus sequence typing (MLST), ribotyping, and phylogenetic polymerase chain reaction grouping. We also determined the serotypes and virulence genotypes (on the basis of 11 virulence genes). The strains belonged to 29 sequence type complexes (STc), 20 ribotypes, 26 O serogroups, and 39 virulence genotypes. MLST combined with O serogrouping identified 49 subtypes, or "sequence O types." Some sequence O types were almost exclusively associated with either urosepsis (STc27(O2), STc27(O6), and STc29(O2)) or meningitis (STc29(O18)). In contrast, STc29(O45) was equally frequent in these 2 infection sites. Similarly, several virulence genotypes were specifically associated with one of these syndromes. These results point to the existence of specialized invasive subtypes that cause urosepsis or meningitis in infants and identify a new dually virulent invasive clone.

Multidrug-resistant bacteria in hospitalized children: a 5-year multicenter study.

OBJECTIVE: The objective of this study was to determine the incidence of multidrug-resistant bacteria in hospitalized children. METHODS: This multicenter study was conducted in 5 hospitals in the Paris area from 1999 to 2003. We recorded all isolations of multidrug-resistant bacteria from clinical samples that were obtained from hospitalized children. Strains that were isolated during systematic screening for carriers were excluded. RESULTS: The mean incidences were 0.9 per 1000 hospitalization-days for methicillin-resistant Staphylococcus aureus, 0.45 for extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, 0.32 for extended-spectrum beta-lactamase-producing Enterobacteriaceae other than Klebsiella pneumoniae, 0.40 for Enterobacter species with derepressed cephalosporinase, and 0.01 for vancomycin-resistant Enterococcus. The incidences per 1000 hospitalization-days of methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, extended-spectrum beta-lactamase-producing Enterobacteriaceae other than Klebsiella pneumoniae, and Enterobacter species with derepressed cephalosporinase decreased significantly from 1999 to 2003, whereas the incidence of vancomycin-resistant Enterococcus remained very low. The proportion of resistant strains within the species did not vary significantly for methicillin-resistant Staphylococcus aureus (11% to 9.6%), extended-spectrum beta-lactamase-producing Enterobacteriaceae other than Klebsiella pneumoniae (1.1%), and vancomycin-resistant Enterococcus (0.03% to 0.023%). In contrast, the frequency of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae decreased from 31.6% to 7.4%, and that of Enterobacter species with derepressed cephalosporinase decreased from 38.8% to 18.5%. CONCLUSIONS: We report significant decreases in the incidence of methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, extended-spectrum beta-lactamase-producing Enterobacteriaceae other than Klebsiella pneumoniae, and Enterobacter species with derepressed cephalosporinase in hospitalized children during a 5-year period.

Detection and identification by PCR of a highly virulent phylogenetic subgroup among extraintestinal pathogenic Escherichia coli B2 strains.

Closely related Escherichia coli B2 strains O1:K1, O2:K1, O18:K1, and O45:K1 constitute a major subgroup causing extraintestinal infections. A DNA pathoarray analysis was used to develop a PCR specific for this subgroup that was included in the multiplex phylogenetic-grouping PCR method. Our PCR may serve to identify this virulent subgroup among different ecological niches.

Treatment failure of nosocomial pertussis infection in a very-low-birth-weight neonate.

We describe a case of nosocomial maternal transmission of Bordetella pertussis to a very-low-birth-weight (VLBW) neonate in whom treatment was unsuccessful. This case underscores the need for rapid and sensitive PCR diagnosis in VLBW neonates and in parents with clinical signs of pertussis and suggests that standard treatment may not be appropriate for VLBW neonates.

Bacterial meningitis in children: a French prospective study.

From January 2001 through December 2003, a total of 1084 children with bacterial meningitis were enrolled in a prospective French nationwide survey. The most frequent pathogens found in children older than 28 days were Neisseria meningitis (55.3%) and Streptococcus pneumoniae (33.4%). S. pneumoniae was the most frequent pathogen found among infants aged 2-12 months (49.5%), whereas N. meningitidis was the most frequent pathogen among children >12 months old (69.7%). Approximately one-half of S. pneumoniae isolates had diminished susceptibility to penicillin. The case-fatality rates were 7.6% for children with N. meningitidis meningitis and 10.8% for children with S. pneumoniae infection.