Publications by authors named "Corinne Levy"

115 Publications

DELAYED BRONCHIOLITIS EPIDEMIC IN FRENCH PRIMARY CARE SETTING DRIVEN BY RESPIRATORY SYNCYTIAL VIRUS: PRELIMINARY DATA FROM THE OURSYN STUDY, MARCH 2021.

Pediatr Infect Dis J 2021 Jul 13. Epub 2021 Jul 13.

From *ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France Assistance Publique - Hôpitaux de Paris, Pediatric Emergency Department, Robert Debré University Hospital, Université de Paris, Paris, France INSERM, ECEVE, UMRS 1123, Université de Paris, Paris, France niversité Paris Est, IMRB-GRC GEMINI Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, France Sanofi Pasteur, Lyon, France.

We report early results from a prospective primary care bronchiolitis surveillance study in France in which a 10-week delayed epidemic was detected from February to March 2021. Among 225 children under 2 years with swab testing for a first bronchiolitis episode, 55% had a positive test for RSV, 0 for influenza, and 1 for severe acute respiratory syndrome coronavirus 2.
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http://dx.doi.org/10.1097/INF.0000000000003270DOI Listing
July 2021

Face Masks in Young Children During the COVID-19 Pandemic: Parents' and Pediatricians' Point of View.

Front Pediatr 2021 23;9:676718. Epub 2021 Jun 23.

Association Clinique et Thérapeutique Infantile du Val de Marne, Créteil, France.

In countries with high SARS-CoV-2 circulation, the pandemic has presented many challenges on different fronts, affecting lives and livelihoods; efforts to keep schools open are among the most important. In France, to keep schools open, wearing a face mask has been mandatory for children from age 6 years since November 2020. To evaluate the acceptability and tolerance of this measure by children as well as both parents and pediatricians. Parents registered on the website of the French Association of Ambulatory Pediatrics and pediatricians members of this association. All parents and pediatricians who agreed to take part in the survey. Among the 2,954 questionnaires for the parents' survey, the reasons for wearing a mask were understood by 54.6% of parents, most of whom (84.6%) explained the reasons to their children. The parents applied this measure because it was mandatory (93.4%) even if they disagreed (63.3%). When interviewed by parents, children said they were usually embarrassed (80.9%) by the mask. The main symptoms or changes of behavior attributed to the mask according to parents were headache (49.0%), speaking difficulties (45%), change in mood (45.2%) and breathing discomfort (28.1%). Among the 663 pediatricians who responded, many agreed with mandatory mask-wearing at age 6 years (67.7%). Overall, 15% of pediatricians systematically asked about the mask tolerance during the consultation. During the medical consultation, when the parents complained about the mask (64.3%), the main drawbacks were related to fog on glasses (reported by 68.2% of pediatricians), breathing discomfort (53.1% of pediatricians), cutaneous disorders (42.4% of pediatricians) and headaches (38.2% of pediatricians). Despite the many inconveniences reported, children agree to wear the mask better than their parents think. Pediatricians should sufficiently take the opportunity during the consultation to further explain the reasons for wearing the mask because their pedagogical role is crucial.
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http://dx.doi.org/10.3389/fped.2021.676718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260829PMC
June 2021

Monitoring outpatient antibiotic utilization using reimbursement and retail sales data: a population-based comparison in France, 2012-17.

J Antimicrob Chemother 2021 Jun 13. Epub 2021 Jun 13.

Université de Paris, Epidemiology and Statistics Research Center-CRESS, INSERM, Obstetrical, Perinatal and Pediatric Epidemiology research team, F-75004, Paris, France.

Objectives: To assess whether a retail sales database could be used to monitor antibiotic utilization in the outpatient setting at the national level.

Methods: We extracted 2012-17 outpatient antibiotic extrapolated retail sales (IQVIA's Xponent) and reimbursement data from the National Health Insurance (SNDS) in metropolitan France. We compared estimates of antibiotic use and consumption [number of antibiotic drug deliveries (DrID) and defined daily doses (DID) per 1000 inhabitants per day]. We relied on relative differences, Pearson's r statistics and time series using autoregressive integrated moving average (ARIMA) modelling to study: (i) differences in point estimates, (ii) correlation, and (iii) consistency in time trends between Xponent and SNDS. The analysis was conducted overall and in subgroups (age groups, therapeutic classes, major antimicrobial agents and regions).

Results: We analysed approximately 377 million antibiotic drug deliveries, comprising nearly 3.4 billion DDDs. Overall, Xponent slightly overestimated SNDS point estimates with yearly relative differences of +3.5% for DrID and +3.3% for DID. Peaks in relative differences were observed for July and August months. Relative differences were <5% in most subgroups, except for fosfomycin and three French regions. Overall and across most subgroups, the correlation between Xponent and SNDS monthly aggregated estimates was almost perfect (r ≥ 0.992 for all subgroups, except for one region). ARIMA modelling showed high consistency between Xponent's and SDNS's DrID time series, but detected timepoints where the series significantly diverged.

Conclusions: IQVIA's Xponent and SNDS data were highly consistent. Xponent database seems suitable for monitoring outpatient antibiotic utilization in France.
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http://dx.doi.org/10.1093/jac/dkab185DOI Listing
June 2021

Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap?

Infect Dis Now 2021 May 12. Epub 2021 May 12.

GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Créteil, France; Service de pédiatrie, Centre Hospitalier Armand Trousseau, Paris, France.

Since the beginning of the COVID-19 pandemic, reduced incidence of many viral and bacterial infections has been reported in children: bronchiolitis, varicella, measles, pertussis, pneumococcal and meningococcal invasive diseases. The purpose of this opinion paper is to discuss various situations that could lead to larger epidemics when the non-pharmaceutical interventions (NPI) imposed by the SARS-CoV-2 epidemic will no longer be necessary. While NPIs limited the transmission of SARS-CoV-2, they also reduced the spread of other pathogens during and after lockdown periods, despite the re-opening of schools since June 2020 in France. This positive collateral effect in the short term is welcome as it prevents additional overload of the healthcare system. The lack of immune stimulation due to the reduced circulation of microbial agents and to the related reduced vaccine uptake induced an "immunity debt" which could have negative consequences when the pandemic is under control and NPIs are lifted. The longer these periods of "viral or bacterial low-exposure" are, the greater the likelihood of future epidemics. This is due to a growing proportion of "susceptible" people and a declined herd immunity in the population. The observed delay in vaccination program without effective catch-up and the decrease in viral and bacterial exposures lead to a rebound risk of vaccine-preventable diseases. With a vaccination schedule that does not include vaccines against rotavirus, varicella, and serogroup B and ACYW Neisseria meningitidis, France could become more vulnerable to some of these rebound effects.
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http://dx.doi.org/10.1016/j.idnow.2021.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114587PMC
May 2021

Diagnostic accuracy of rapid nucleic acid tests for group A streptococcal pharyngitis: systematic review and meta-analysis.

Clin Microbiol Infect 2021 May 6. Epub 2021 May 6.

Université de Paris, Centre of Research in Epidemiology and Statistics (CRESS), INSERM, Paris, France; Necker-Enfants malades Hospital, APHP, Université de Paris, Department of General Paediatrics and Paediatric Infectious Diseases, Paris, France. Electronic address:

Background: Acute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.

Objectives: To evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.

Data Sources: MEDLINE, Embase, Web of Science (1990-2020).

Study Eligibility Criteria: Cross-sectional studies and randomized trials.

Participants: Patients with pharyngitis.

Index Test/s And Reference Standards: RNAT commercial kits compared with throat culture.

Methods: We assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.

Results: We included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%-98.3%) and a summary specificity of 95.1% (95% CI 93.6%-96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).

Conclusions: The high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.
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http://dx.doi.org/10.1016/j.cmi.2021.04.021DOI Listing
May 2021

Clinical Prediction of Iron Deficiency at Age 2 Years: A National Cross-sectional Study in France.

J Pediatr 2021 Apr 6. Epub 2021 Apr 6.

Center of Research in Epidemiology and Statistics, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, INSERM UMR 1153, Université de Paris, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker Sick Children Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, Paris, France.

Objective: To assess the diagnostic accuracy of existing clinical criteria and to develop prediction tools for iron deficiency in 2-year-old children.

Study Design: In a national cross-sectional study conducted in primary care pediatricians' practices throughout France, 2-year-old children were consecutively included (2016-2017). Multivariable logistic regression modeling and bootstrapping were used to develop several clinical models to predict iron deficiency (serum ferritin <12 μg/L). These models used the best criteria and combinations among the American Academy of Pediatrics' (AAP) criteria adapted to the European context (n = 10), then all potential predictors (n = 19). One model was then simplified into a simple prediction tool.

Results: Among 568 included infants, 38 had iron deficiency (6.7%). In univariable analyses, no significant association with iron deficiency was observed for 8 of the 10 adapted AAP criteria. Three criteria (both parents born outside the European Union, low weight at 1 year old, and weaning to cow's milk without supplemental iron) were retained in the AAP model, which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.62 (95% CI, 0.58-0.67), 30% (95% CI, 22%-39%), and 95% (95% CI, 92%-97%), respectively. Four criteria were retained in a newly derived simple prediction tool (≥1 criterion among the 3 previous plus duration of iron-rich formula consumption <12 months), which area under the receiver operating characteristic curve, sensitivity, and specificity were 0.72 (95% CI, 0.65-0.79), 63% (95% CI, 47%-80%), and 81% (95% CI, 70%-91%), respectively.

Conclusions: All prediction tools achieved acceptable diagnostic accuracy. The newly derived simple prediction tool offered potential ease of use.

Trial Registration: ClinicalTrials.gov NCT02484274.
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http://dx.doi.org/10.1016/j.jpeds.2021.03.072DOI Listing
April 2021

Shiga toxin-producing carriage in 959 healthy French infants.

Arch Dis Child 2021 Apr 8. Epub 2021 Apr 8.

Service de microbiologie, Centre National de Référence associé Escherichia coli, Hopital Universitaire Robert Debre, Paris, Île-de-France, France

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http://dx.doi.org/10.1136/archdischild-2021-321601DOI Listing
April 2021

French Pediatric Societies Call for School to Stay Open amid the Coronavirus Disease 2019 Pandemic.

J Pediatr 2021 07 3;234:293-295.e2. Epub 2021 Apr 3.

Pediatric Infectious Disease Group (GPIP), Créteil, France; Association of French Primary Care Paediatrians (AFPA), Orleans, France; Association Clinique et Thérapeutique Infantile du Val de Marne, Créteil, France; Paris Est University, IMRB-GRC GEMINI, Créteil, France.

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http://dx.doi.org/10.1016/j.jpeds.2021.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019244PMC
July 2021

Assessment of SARS-CoV-2 infection by Reverse transcription-PCR and serology in the Paris area: a cross-sectional study.

BMJ Paediatr Open 2020 29;4(1):e000887. Epub 2020 Dec 29.

Université Paris Est, IMRB-GRC GEMINI, Créteil, France.

Background: Several studies indicated that children seem to be less frequently infected with SARS-CoV-2 and are potentially less contagious than adults. To examine the spread of SARS-CoV-2, we combined both Reverse transcription-PCR testing and serology in children in the most affected region in France, Paris, during the COVID-19 epidemic.

Methods: From 14 April 2020 to 12 May 2020, we conducted a cross-sectional, prospective, multicentre study. Healthy controls and pauci-symptomatic children from birth to age 15 years were enrolled by 27 ambulatory paediatricians. A nasopharyngeal swab was taken for detection of SARS-CoV-2 by Reverse transcription-PCR and a microsample of blood for micromethod serology.

Results: Among the 605 children, 322 (53.2%) were asymptomatic and 283 (46.8%) were symptomatic. Reverse transcription-PCR and serology results were positive for 11 (1.8%) and 65 (10.7%) children, respectively, with no significant difference between asymptomatic and pauci-symptomatic children. Only three children were Reverse transcription-PCR-positive without any antibody response detected. The frequency of Reverse transcription-PCR SARS-CoV-2 positivity was significantly higher for children with positive than negative serology results (12.3% vs 0.6%, p<0.001). Contact with a person with confirmed COVID-19 increased the odds of Reverse transcription-PCR positivity (OR 7.8, 95% CI 1.5 to 40.7) and serology positivity (OR 15.1, 95% CI 6.6 to 34.6).

Conclusion: In an area heavily affected by COVID-19, after the peak of the first epidemic wave and during the lockdown, the rate of children with Reverse transcription-PCR SARS-CoV-2 positivity was very low (1.8%), but that of serology positivity was higher (10.7%). Most children with positive Reverse transcription-PCR results also had positive serology results.

Trial Registration Number: NCT04318431.
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http://dx.doi.org/10.1136/bmjpo-2020-000887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778737PMC
December 2020

New Approach to the Surveillance of Pediatric Infectious Diseases From Ambulatory Pediatricians in the Digital Era.

Pediatr Infect Dis J 2021 Jul;40(7):674-680

From the AFPA, Association Française de Pédiatrie Ambulatoire, Orléans, France.

Background: Many ambulatory networks in several countries have established syndromic surveillance systems to detect outbreaks of different illnesses. Here, we describe a new Pediatric and Ambulatory Research in Infectious diseases network that combined automated data extraction from the computers of primary care pediatricians.

Methods: Pediatricians who used the same software, AxiSanté 5-Infansoft for electronic medical records were specially trained in infectious diseases, encouraged to comply with French treatments' recommendations, use of point-of-care tests and vaccination guidelines. Infectious disease diagnoses in children <16 years old in the records triggered automatic data extraction of complete records. A quality control process and external validation were developed.

Results: From September 2017 to February 2020, 107 pediatricians enrolled 57,806 children (mean age 2.9 ± 2.6 years at diagnosis) with at least one infectious disease diagnosis among those followed by the network. Among the 118,193 diagnoses, the most frequent were acute otitis media (n = 44,924, 38.0%), tonsillopharyngitis (n = 13,334, 11.3%), gastroenteritis (n = 12,367, 10.5%), influenza (n = 11,062, 9.4%), bronchiolitis (n = 10,531, 8.9%), enteroviral infections (n = 8474, 7.2%) and chickenpox (n = 6857, 5.8%). A rapid diagnostic test was performed in 84.7% of cases of tonsillopharyngitis and was positive in 44%. The antibiotic recommendations from French guidelines were strictly followed: amoxicillin was the most prescribed antibiotic and less than 10% of presumed viral infections were treated.

Conclusions: This "tailor-made" network set up with quality controls and external validation represents a new approach to the surveillance of pediatric infectious diseases in the digital era and could highly optimize pediatric practices.
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http://dx.doi.org/10.1097/INF.0000000000003116DOI Listing
July 2021

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

JAMA 2021 03;325(9):855-864

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France.

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown.

Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C.

Design, Setting, And Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021.

Exposures: IVIG and methylprednisolone vs IVIG alone.

Main Outcomes And Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1.

Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]).

Conclusions And Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.
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http://dx.doi.org/10.1001/jama.2021.0694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851757PMC
March 2021

Unexpected lessons from the COVID-19 lockdowns in France: Low impact of school opening on common communicable pediatric airborne diseases.

Clin Infect Dis 2020 Dec 29. Epub 2020 Dec 29.

Assistance Publique - Hôpitaux de Paris, Pediatric Emergency Department, Necker-Enfants Malades University Hospital, Université de Paris, Paris, France.

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http://dx.doi.org/10.1093/cid/ciaa1899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799226PMC
December 2020

Factors Associated With Severe SARS-CoV-2 Infection.

Pediatrics 2021 03 15;147(3). Epub 2020 Dec 15.

Department of Pediatrics, Grand Hôpital de l'Est Francilien, Meaux, France.

Background: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution.

Methods: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement.

Results: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children <90 days old accounted for 37% of cases (145 of 397), but only 4 (3%) had severe disease. Excluding children with multisystem inflammatory syndrome in children ( = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 ( = 62), 23 of 306 (11%) children had severe disease, including 6 deaths. Factors independently associated with severity were age ≥10 years (odds ratio [OR] = 3.4, 95% confidence interval: 1.1-10.3), hypoxemia (OR = 8.9 [2.6-29.7]), C-reactive protein level ≥80 mg/L (OR = 6.6 [1.4-27.5]).

Conclusions: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution. This may help physicians to better identify risk of severe disease progression in children.
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http://dx.doi.org/10.1542/peds.2020-023432DOI Listing
March 2021

Neurodevelopmental Outcomes after Premedication with Atropine/Propofol vs Atropine/Atracurium/Sufentanil for Neonatal Intubation: 2-Year Follow-Up of a Randomized Clinical Trial.

J Pediatr 2021 04 8;231:273-277.e3. Epub 2020 Dec 8.

Neonatal Intensive Care Unit, CHI Créteil, Créteil, France; Université de Paris, CRESS, INSERM, INRA, Paris, France; Université Paris Est Créteil, Faculté de Médecine de Créteil, IMRB, GRC CARMAS, Créteil, France.

This study followed 173 newborn infants in the PREmedication Trial for Tracheal Intubation of the NEOnate multicenter, double-blind, randomized controlled trial of atropine-propofol vs atropine-atracurium-sufentanil for premedication before nonemergency intubation. At 2 years of corrected age, there was no significant difference between the groups in death or risk of neurodevelopmental delay assessed with the Ages and Stages Questionnaire. Trial registration Clinicaltrials.gov: NCT01490580.
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http://dx.doi.org/10.1016/j.jpeds.2020.12.001DOI Listing
April 2021

Association between SARS-CoV-2 infection and Kawasaki-like multisystem inflammatory syndrome: a retrospective matched case-control study, Paris, France, April to May 2020.

Euro Surveill 2020 12;25(48)

Université de Paris, Centre of Research in Epidemiology and Statistics - CRESS, INSERM, F-75004 Paris, France.

We assessed the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and Kawasaki disease (KD)-like multisystem inflammatory syndrome in a retrospective case-control study in France. RT-PCR and serological tests revealed SARS-CoV-2 infection in 17/23 cases vs 11/102 controls (matched odds ratio: 26.4; 95% confidence interval: 6.0-116.9), indicating strong association between SARS-CoV-2 infection and KD-like illness. Clinicians should keep a high level of suspicion for KD-like illness during the COVID-19 pandemic.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.48.2001813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716402PMC
December 2020

Impact of Coronavirus Disease 2019 (COVID-19) Pandemic on Pediatric Infectious Disease Research.

J Pediatr 2021 03 30;230:279-281.e2. Epub 2020 Nov 30.

ACTIV, Association Clinique et Thérapeutique Infantile du Val-de-Marne, Créteil, France; GPIP, Groupe de Pathologie Infectieuse Pédiatrique, Paris, France; Université Paris Est, IMRB-GRC GEMINI, Créteil, France; Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, France; AFPA, Association Française de Pédiatrie Ambulatoire, Saint-Germain-en-Laye, France. Electronic address:

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http://dx.doi.org/10.1016/j.jpeds.2020.11.052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834229PMC
March 2021

Changes in Reverse Transcription Polymerase Chain Reaction-positive Severe Acute Respiratory Syndrome Coronavirus 2 Rates in Adults and Children According to the Epidemic Stages.

Pediatr Infect Dis J 2020 11;39(11):e369-e372

From the Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Créteil, France.

From March 2, 2020, to April 26, 2020, 52,588 reverse transcription polymerase chain reaction (RT-PCR) tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were performed in France, 6490 in children and 46,098 in adults. The rate of RT-PCR-positive SARS-CoV-2 tests for children (5.9%) was always less than that for adults (20.3%) but vary according to the epidemic stage. The risk ratio of RT-PCR-positive SARS-CoV-2 tests for adults compared with children was 3.5 (95% confidence interval: 3.2-3.9) for the whole study period.
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http://dx.doi.org/10.1097/INF.0000000000002861DOI Listing
November 2020

Invasive Disease Potential of Pneumococcal Serotypes in Children After PCV13 Implementation.

Clin Infect Dis 2021 04;72(8):1453-1456

Groupe de Pathologie Infectieuse Pédiatrique, Paris, France.

We aimed to assess the invasive disease potential of non-PCV13 serotypes after the implementation of this vaccine. Most non-PCV13 serotypes had low invasive disease potential. Among serotypes with the highest invasive disease potential (12F, 24F, 38, 8, 33F, 22F, and 10A), all but 24F and 38 were included in PCV20.
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http://dx.doi.org/10.1093/cid/ciaa917DOI Listing
April 2021

Invasive pneumococcal disease incidence in children and adults in France during the pneumococcal conjugate vaccine era: an interrupted time-series analysis of data from a 17-year national prospective surveillance study.

Lancet Infect Dis 2021 01 20;21(1):137-147. Epub 2020 Jul 20.

Public health France, the French National Public Health agency, Saint Maurice, France.

Background: The long-term benefits of pneumococcal conjugate vaccines (PCVs) remain unknown because of serotype replacement. We aimed to estimate the effect of PCV implementation on invasive pneumococcal disease incidence in France.

Methods: We did a quasi-experimental interrupted time-series analysis using data from a French national prospective surveillance system. We included all invasive pneumococcal disease cases in children and adults from more than 250 participating hospitals between Jan 1, 2001, and Dec 31, 2017. The primary outcome was incidence of invasive pneumococcal disease (meningitis and non-meningitis) over time, analysed by segmented regression with autoregressive error. Isolates were serotyped by latex agglutination with antiserum samples.

Findings: We included 75 903 patients with invasive pneumococcal disease, including 4302 (5·7%) children younger than 2 years and 37 534 (49·4%) adults aged 65 years or older. Before PCV7 implementation, the estimated monthly incidence of invasive pneumococcal disease was 0·78 cases per 100 000 inhabitants, which did not change significantly up to May, 2010. PCV13 implementation in 2010 was followed by a significant decrease in the incidence of invasive pneumococcal disease (-1·5% per month, 95% CI -2·2 to -0·8), reaching an estimated monthly incidence of 0·52 cases per 100 000 inhabitants in December, 2014. From January, 2015, the incidence rebounded (1·8% per month, 95% CI 1·0 to 2·6), reaching an estimated monthly incidence of 0·73 cases per 100 000 inhabitants in December, 2017. The estimated monthly incidence increased from 0·93 cases per 100 000 in December, 2014, to 1·73 cases per 100 000 in December, 2017, for children younger than 2 years, and from 1·54 cases per 100 000 in December, 2014, to 2·08 cases per 100 000 in December, 2017, for adults aged 65 years or older. The main non-PCV13 serotypes involved in the increase were 24F in young children and 12F, 22F, 9N, and 8 in adults aged 65 years or older.

Interpretation: PCV13 implementation led to a major reduction in the incidence of invasive pneumococcal disease. However, a rebound in cases among children and adults since 2015, driven by several emerging non-PCV13 serotypes, jeopardises the long-term PCV benefits. These findings, if confirmed in the coming years, should be considered in the development of next-generation PCVs and might guide policy makers in the selection of future pneumococcal vaccines.

Funding: Foundation for Medical Research; Pfizer, BioMérieux, Sanofi for the Regional Observatory of Pneumococci.
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http://dx.doi.org/10.1016/S1473-3099(20)30165-1DOI Listing
January 2021

Treatment of Urinary Tract Infections Caused By ESBL-Producing Enterobacteriaceae: Have All Treatment Options Been Considered?

Pediatr Infect Dis J 2020 08;39(8):e216-e217

Université de Paris, IAME, INSERM, F-75018 Paris, France, Service de Microbiologie, Centre National de Référence Escherichia coli, Hôpital Robert-Debré, AP-HP, Paris, France.

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http://dx.doi.org/10.1097/INF.0000000000002654DOI Listing
August 2020

Young children formula consumption and iron deficiency at 24 months in the general population: A national-level study.

Clin Nutr 2021 01 7;40(1):166-173. Epub 2020 May 7.

Centre of Research in Epidemiology and Statistics Sorbonne Paris Cité, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (EPOPé), Inserm UMR 1153, Labex GR-Ex, Paris Descartes University, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants Malades Hospital, AP-HP, Paris Descartes University, Paris, France.

Background & Aims: Iron deficiency (ID) is considered the most frequent micronutrient deficiency in industrialized countries where strategies for its primary prevention vary widely and are insufficiently evaluated. We aimed to study the effectiveness for iron status of a national iron deficiency prevention strategy based on recommendations for young-child formula (YCF) use after age 12 months, taking into consideration other sources of iron and the family's socio-economic status.

Methods: In a cross-sectional observational study conducted in primary care pediatrician offices throughout France from 2016 to 2017, infants aged 24 months were consecutively included for a food survey and blood sampling. Associations between YCF consumption and serum ferritin (SF) level were studied by multivariable regression after adjustment on sociodemographic, perinatal and dietary characteristics, notably other intakes of iron.

Results: Among the 561 infants analyzed, the ID prevalence was 6.6% (37/561; 95% confidence interval [CI] 4.7-9.0). Daily iron intake excluding YCF and total daily iron intake including YCF were below the 5-mg/day recommended average requirements for 63% and 18% of children, respectively. ID frequency was significantly decreased (or SF level was independently higher) with any YCF consumption after age 10 months (odds ratio 0.15, 95% CI 0.07-0.31), current YCF consumption at age 24 months (median SF level 29 vs 21 μg/L if none), prolonged YCF consumption (28 μg/L if >12 months vs 17 μg/L if none), and increasing daily volume of YCF consumed at age 24 months from a small volume (e.g., 29 μg/L if <100 mL/day vs 21 μg/L if none).

Conclusions: Current or past YCF use was independently associated with a better iron status at age 24 months than non-use. The strategy recommending YCF use at weaning after age 12 months seems effective in the general population. CLINICALTRIALS.

Gov Identifier: NCT02484274.
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http://dx.doi.org/10.1016/j.clnu.2020.04.041DOI Listing
January 2021

Community antibiotic prescribing for children in France from 2015 to 2017: a cross-sectional national study.

J Antimicrob Chemother 2020 08;75(8):2344-2352

Université de Paris, Epidemiology and Statistics Research Center - CRESS, INSERM, Obstetrical, Perinatal and Pediatric Epidemiology research team, F-75004 Paris, France.

Objectives: To assess recent community antibiotic prescribing for French children and identify areas of potential improvement.

Methods: We analysed 221 768 paediatric (<15 years) visits in a national sample of 680 French GPs and 70 community paediatricians (IQVIA's EPPM database), from March 2015 to February 2017, excluding well-child visits. We calculated antibiotic prescription rates per 100 visits, separately for GPs and paediatricians. For respiratory tract infections (RTIs), we described broad-spectrum antibiotic use and duration of treatment. We used Poisson regression to identify factors associated with antibiotic prescribing.

Results: GPs prescribed more antibiotics than paediatricians [prescription rate 26.1 (95% CI 25.9-26.3) versus 21.6 (95% CI 21.0-22.2) per 100 visits, respectively; P < 0.0001]. RTIs accounted for more than 80% of antibiotic prescriptions, with presumed viral RTIs being responsible for 40.8% and 23.6% of all antibiotic prescriptions by GPs and paediatricians, respectively. For RTIs, antibiotic prescription rates per 100 visits were: otitis, 68.1 and 79.8; pharyngitis, 67.3 and 53.3; sinusitis, 67.9 and 77.3; pneumonia, 80.0 and 99.2; bronchitis, 65.2 and 47.3; common cold, 21.7 and 11.6; bronchiolitis 31.6 and 20.1; and other presumed viral RTIs, 24.1 and 11.0, for GPs and paediatricians, respectively. For RTIs, GPs prescribed more broad-spectrum antibiotics [49.8% (95% CI 49.3-50.3) versus 35.6% (95% CI 34.1-37.1), P < 0.0001] and antibiotic courses of similar duration (P = 0.21). After adjustment for diagnosis, antibiotic prescription rates were not associated with season and patient age, but were significantly higher among GPs aged ≥50 years.

Conclusions: Future antibiotic stewardship campaigns should target presumed viral RTIs, broad-spectrum antibiotic use and GPs aged ≥50 years.
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http://dx.doi.org/10.1093/jac/dkaa162DOI Listing
August 2020

Epidemiology of Community-Onset Severe Bacterial Infections in Children and Its Evolution: A Population-Based Study in France.

Pediatr Crit Care Med 2020 06;21(6):e325-e332

Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team (Epopé), Centre of Research in Epidemiology and StatisticS (CRESS), Université de Paris, Paris, France.

Objectives: To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution.

Design: Prospective, observational, population-based study from 2009 to 2014.

Setting: An administrative area accounting for 13% of the French pediatric population.

Patients: All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection.

Interventions: None.

Measurements And Main Results: The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period.

Conclusions: The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.
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http://dx.doi.org/10.1097/PCC.0000000000002300DOI Listing
June 2020

Group A Streptococcal Paronychia and Blistering Distal Dactylitis in Children: Diagnostic Accuracy of a Rapid Diagnostic Test and Efficacy of Antibiotic Treatment.

J Pediatric Infect Dis Soc 2020 Dec;9(6):756-759

Association Clinique et thérapeutique Infantile du Val de Marne, Saint-Maur des Fossés, France.

Among 174 children with blistering distal dactylitis or paronychia, 36.2% had a positive group A Streptococcus (GAS) rapid detection antigen. For GAS, the outcome for patients who received amoxicillin was favorable in all cases without any surgical procedures; 44.6% of cases due to Staphylococcus aureus infection (38.7%) required surgery.
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http://dx.doi.org/10.1093/jpids/piz079DOI Listing
December 2020

Escherichia coli O80 hybrid pathotype strains producing Shiga toxin and ESBL: molecular characterization and potential therapeutic options.

J Antimicrob Chemother 2020 03;75(3):537-542

Université de Paris, IAME, INSERM, F-75018 Paris, France.

Objectives: Enterohaemorrhagic Escherichia coli (EHEC) infections may be complicated by haemolytic uraemic syndrome (HUS). The emerging worldwide EHEC serogroup O80 has acquired a mosaic plasmid combining extraintestinal virulence and antibiotic resistance. This hybrid pathotype is associated with invasive infections that require antibiotic therapy, classically not recommended in EHEC infections, increasing the risk of HUS. We characterized two ESBL-producing O80 EHEC strains, which is an unusual resistance mechanism among EHECs, and determined the safest therapy to be used for invasive infections.

Methods: WGS of two strains isolated from the stools of an asymptomatic carrier and a patient with HUS was performed using Illumina and Nanopore technologies. Generated reads were combined to assemble genomes. We determined the safest therapy by comparing Shiga toxin (Stx) production by the two strains in the presence of several antibiotics.

Results: The strains were genetically close to the O80 EHEC clone, belonging to ST301 and harbouring stx2d, eae-ξ, ehxA and genes characteristic of the extraintestinal virulence plasmid pS88. Long-read sequencing identified the acquisition of an additional plasmid harbouring CTX-M-type genes (blaCTX-M-14 and blaCTX-M-1). Azithromycin decreased Stx production at subinhibitory concentrations, ciprofloxacin increased it and imipenem had no major effect. The combination of azithromycin and imipenem overall reduced Stx production.

Conclusions: Acquisition of an additional plasmid harbouring ESBL genes is a step towards increasing the risk of O80 EHEC dissemination and represents a serious public health concern. The combination of azithromycin and imipenem reduced Stx production and suggests that this combination could be tested in clinical trials.
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http://dx.doi.org/10.1093/jac/dkz484DOI Listing
March 2020

Diversity and trends in population structure of ESBL-producing Enterobacteriaceae in febrile urinary tract infections in children in France from 2014 to 2017.

J Antimicrob Chemother 2020 01;75(1):96-105

Université de Paris, IAME, INSERM, F-75018, Paris, France.

Background: The population structure of extraintestinal pathogenic Escherichia coli evolves over time, notably due to the emergence of antibiotic-resistant clones such as ESBL-producing Enterobacteriaceae (ESBL-E).

Objectives: To analyse by WGS the genetic diversity of a large number of ESBL-E isolated from urinary tract infections in children from paediatric centres across France between 2014 and 2017 and collected by the National Observatory of febrile urinary tract infection (FUTI) caused by ESBL-E.

Methods: A total of 40 905 Enterobacteriaceae-positive urine cultures were identified. ESBL-E were found in 1983 samples (4.85%). WGS was performed on 251 ESBL-E causing FUTI. STs, core genome MLST (cgMLST), serotype, fimH allele, ESBL genes and presence of papGII key virulence factor were determined.

Results: E. coli and Klebsiella pneumoniae were found in 86.9% (218/251) and 11.2% (28/251) of cases, respectively. Several STs predominate among E. coli such as ST131, ST38, ST69, ST73, ST95, ST405, ST12 and ST1193, while no ST emerged in K. pneumoniae. E. coli ST131, ST38 and ST1193 increased during the study period, with a heterogeneity in papGII prevalence (64.5%, 35% and 20% respectively). Most isolates harboured the CTX-M type (97%) with a predominance of blaCTX-M-15. blaCTX-M-27, an emerging variant in E. coli, is found in various STs. cgMLST enabled discrimination of clusters within the main STs.

Conclusions: The predominance of ST131, and the emergence of other STs such as ST38 and ST1193 combined with ESBL genes deserves close epidemiological surveillance considering their high threat in infectious disease. cgMLST could be a discriminant complementary tool for the analyses.
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http://dx.doi.org/10.1093/jac/dkz423DOI Listing
January 2020

Association between National Treatment Guidelines for Upper Respiratory Tract Infections and Outpatient Pediatric Antibiotic Use in France: An Interrupted Time-Series Analysis.

J Pediatr 2020 01 11;216:88-94.e4. Epub 2019 Oct 11.

Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Biostatistics Sorbonne Paris Cité (CRESS), Paris Descartes University, Paris, France; Department of General Pediatrics and Pediatric Infectious Diseases, Necker - Enfants malades Hospital, Assistance Publique - Hôpitaux de Paris, Paris Descartes University, Paris, France.

Objective: To test whether updated clinical practice guidelines for managing upper respiratory tract infections released in France in November 2011 were associated with changes in national outpatient pediatric antibiotic use.

Study Design: We performed an interrupted time-series analysis using national antibiotic dispensation data in French children from January 2009 to December 2017 (IQVIA Suivi de la Dispensation Médicale database). We described the overall evolution of antibiotic prescription rates and modeled the changes in the proportion of amoxicillin and the proportion of broad-spectrum antibiotics following the guidelines in 2 age groups (0-5 and 6-14 years old).

Results: We analyzed 123 million pediatric antibiotic prescriptions. The most commonly prescribed individual antibiotic agent was amoxicillin (37.7%). Over the study period, the annual antibiotic prescription rate decreased by 33.1% (from 1387 to 928 per 1000 pediatric inhabitants per year), consistently across age groups and major antibiotic agents except for amoxicillin (+14.4%). After the release of the guidelines, we observed a gradual increase in the proportion of amoxicillin (relative change 5 years postintervention of +64.3% [95% CI 51.6-80.1] and +28.4% [21.1-36.2] for children 0-5 and 6-14 years, respectively) concomitantly with a gradual decrease in the proportion of broad-spectrum antibiotics (relative change 5 years postintervention of -26.1% [-29.3, -23.7] and -19.8% [-22.1, -16.0] for children 0-5 and 6-14 years old, respectively).

Conclusions: The 2011 guidelines for upper respiratory tract infections preceded changes in outpatient pediatric antibiotic use at the national level, with a replacement of broad-spectrum antibiotics by amoxicillin.
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http://dx.doi.org/10.1016/j.jpeds.2019.09.017DOI Listing
January 2020

Diversity of Serotype Replacement After Pneumococcal Conjugate Vaccine Implementation in Europe.

J Pediatr 2019 10;213:252-253.e3

Université Paris Est, Mondor Institute of Biomedical Research-Groupement de Recherche Clinique (IMRB-GRC) Groupe d'étude de Maladies Infectieuses Néonatales et Infantiles (GEMINI), Créteil, France; Association Clinique Thérapeutique Infantile du Val de Marne (ACTIV), Pediatric Clinical and Therapeutical Association of the Val de Marne, Saint-Maur des Fossés, France; Clinical Research Center (CRC), Centre Hospitalier Intercommunal de Créteil, Créteil, France; Association Française de Pédiatrie Ambulatoire (GPIP), Pediatric Infectious Disease Group, France; AFPA, French Association of Ambulatory Pediatricians, Saint-Germain-en-Laye, France; Unité Court Séjour, Petits Nourrissons, Service de Néonatologie, Centre Hospitalier Intercommunal de Créteil, France.

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http://dx.doi.org/10.1016/j.jpeds.2019.07.057DOI Listing
October 2019