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1. Antibiotic Resistance of Haemophilus influenzae in Nasopharyngeal Carriage of Children with Acute Otitis Media and in Middle Ear Fluid from Otorrhea

Author

Zein Assad, Robert Cohen, Emmanuelle Varon, Corinne Levy, Stéphane Bechet, François Corrard, Andreas Werner, Naïm Ouldali, Stéphane Bonacorsi, and Alexis Rybak

Subjects
Haemophilus influenzae, nasopharyngeal carriage, acute otitis media, spontaneous perforation of the tympanic membrane, antibiotic resistance, children, Therapeutics. Pharmacology, RM1-950
Abstract

Haemophilus influenzae (Hi) is one of the leading bacteria implicated in childhood acute otitis media (AOM). Recent concerns have been raised about the emergence of Hi-resistant strains. We aimed to analyze the evolution of β-lactam resistance to Hi among strains isolated from nasopharyngeal carriage in children with AOM and in mild ear fluid (MEF) after the spontaneous perforation of the tympanic membrane (SPTM) in France. In this national ambulatory-based cohort study over 16 years, we analyzed the rate of Hi nasopharyngeal carriage and the proportion of β-lactam-resistant Hi strains over time using a segmented linear regression model. Among the 13,865 children (median [IQR] age, 12.7 [9.3–17.3] months; 7400 [53.4%] male) with AOM included from November 2006 to July 2022, Hi was isolated in 7311 (52.7%) children by nasopharyngeal sampling. The proportion of β-lactamase-producing and β-lactamase-negative, ampicillin-resistant (BLNAR) Hi strains in nasopharyngeal carriage remained stable during the study period. Among the 783 children (median [IQR] age, 20 [12.3–37.8] months; 409 [52.2%] male) with SPTM included from October 2015 to July 2022, Hi was isolated in 177 (22.6%) cases by MEF sampling. The proportions of β-lactamase-producing and BLNAR Hi strains did not significantly differ between nasopharyngeal (17.6% and 8.8%, respectively) and MEF (12.6% and 7.4%) samples. Accordingly, amoxicillin remains a valid recommendation as the first-line drug for AOM in France.

Published
2023
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2. Increase of invasive pneumococcal disease in children temporally associated with RSV outbreak in Quebec: a time-series analysisResearch in context

Author

Naïm Ouldali, Geneviève Deceuninck, Brigitte Lefebvre, Rodica Gilca, Caroline Quach, Nicholas Brousseau, Bruce Tapiero, and Philippe De Wals

Subjects
Invasive pneumococcal disease, Pneumococcal conjugate vaccine, Respiratory viral infection, Time series analysis, Child, Respiratory syncytial virus, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Respiratory viruses have been previously suspected to trigger invasive pneumococcal disease (IPD). After progressive non-pharmaceutical interventions (NPI) lifting, an unusual RSV outbreak has been observed in the Fall 2021, raising concerns about the possible consequences on IPD. We aimed to analyse the evolution of IPD incidence across age-groups since NPI lifting, and its temporal association with respiratory viral infections. Methods: We conducted a time-series analysis using 1) population-based IPD surveillance data and 2) statistics from the laboratory surveillance network of respiratory viruses in the province of Quebec, Canada, from January 2013 to January 2022. The monthly IPD incidence was analysed by quasi-Poisson regression models across age-groups. The fraction of IPD incidence change potentially attributable to different viruses in 2021–2022 was estimated. Findings: A total of 7712 IPD cases were included. After a major decrease in IPD incidence from April 2020, IPD rate started to increase in

Published
2023
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3. Early formative objective structured clinical examinations for students in the pre-clinical years of medical education: A non-randomized controlled prospective pilot study.

Author

Naïm Ouldali, Enora Le Roux, Albert Faye, Claire Leblanc, François Angoulvant, Diane Korb, Clémence Delcour, Caroline Caula, Delphine Wohrer, Alexis Rybak, Manon Delafoy, Claire Carrié, Marion Strullu, Mehdi Oualha, Romain Levy, Camille Mimoun, Lucie Griffon, Alexandre Nuzzo, Clara Eyraud, Michael Levy, and Pierre Ellul

Subjects
Medicine, Science
Abstract

BackgroundThe value of formative objective structured clinical examinations (OSCEs) during the pre-clinical years of medical education remains unclear. We aimed to assess the effectiveness of a formative OSCE program for medical students in their pre-clinical years on subsequent performance in summative OSCE.MethodsWe conducted a non-randomized controlled prospective pilot study that included all medical students from the last year of the pre-clinical cycle of the Université Paris-Cité Medical School, France, in 2021. The intervention group received the formative OSCE program, which consisted of four OSCE sessions, followed by debriefing and feedback, whereas the control group received the standard teaching program. The main objective of this formative OSCE program was to develop skills in taking a structured medical history and communication. All participants took a final summative OSCE. The primary endpoint was the summative OSCE mark in each group. A questionnaire was also administered to the intervention-group students to collect their feedback. A qualitative analysis, using a convenience sample, was conducted by gathering data pertaining to the process through on-site participative observation of the formative OSCE program.ResultsTwenty students were included in the intervention group; 776 in the control group. We observed a significant improvement with each successive formative OSCE session in communication skills and in taking a structured medical history (pConclusionOur findings suggest that an early formative OSCE program is suitable for the pre-clinical years of medical education and is associated with improved student performance in domains targeted by the program.

Published
2023
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4. Risk factors for severe COVID-19 in hospitalized children in Canada: A national prospective study from March 2020–May 2021

Author

Daniel S. Farrar, Olivier Drouin, Charlotte Moore Hepburn, Krista Baerg, Kevin Chan, Claude Cyr, Elizabeth J. Donner, Joanne E. Embree, Catherine Farrell, Sarah Forgie, Ryan Giroux, Kristopher T. Kang, Melanie King, Melanie Laffin Thibodeau, Julia Orkin, Naïm Ouldali, Jesse Papenburg, Catherine M. Pound, Victoria E. Price, Jean-Philippe Proulx-Gauthier, Rupeena Purewal, Christina Ricci, Manish Sadarangani, Marina I. Salvadori, Roseline Thibeault, Karina A. Top, Isabelle Viel-Thériault, Fatima Kakkar, and Shaun K. Morris

Subjects
COVID-19, SARS-CoV-2, Hospitalization, Risk factors, Children, Surveillance, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020–May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1–13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.

Published
2022
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5. Trends in pediatric ambulatory community acquired infections before and during COVID-19 pandemic: A prospective multicentric surveillance study in France

Author

Pr Robert Cohen, Alexis Rybak, Andreas Werner, Stéphane Béchet, Roxane Desandes, Fréderic Hassid, Jean-Marie André, Nathalie Gelbert, Georges Thiebault, Fabienne Kochert, Fabienne Cahn-Sellem, François Vié Le Sage, Pr François Angoulvant, Naïm Ouldali, Bruno Frandji, and Corinne Levy

Subjects
Ambulatory network, Covid-19 pandemic, Children, Immunity debt, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Covid-19 pandemic control has imposed several non-pharmaceutical interventions (NPIs). Strict application of these measures has had a dramatic reduction on the epidemiology of several infectious diseases. As the pandemic is ongoing for more than 2 years, some of these measures have been removed, mitigated, or less well applied. The aim of this study is to investigate the trends of pediatric ambulatory infectious diseases before and up to two years after the onset of the pandemic. Methods: We conducted a prospective surveillance study in France with 107 pediatricians specifically trained in pediatric infectious diseases. From January 2018 to April 2022, the electronic medical records of children with an infectious disease were automatically extracted. The annual number of infectious diseases in 2020 and 2021 was compared to 2018-2019 and their frequency was compared by logistic regression. Findings: From 2018 to 2021, 185,368 infectious diseases were recorded. Compared to 2018 (n=47,116) and 2019 (n=51,667), the annual number of cases decreased in 2020 (n=35,432) by about a third. Frequency of scarlet fever, tonsillopharyngitis, enteroviral infections, bronchiolitis, and gastroenteritis decreased with OR varying from 0·6 (CI95% [0·5;0·7]) to 0·9 (CI95% [0·8;0·9]), p

Published
2022
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6. Investigation of Concurrent Pneumococcal Meningitis in Two Children Attending the Same Day-Care Center

Author

Alexis Rybak, Emmanuelle Varon, Elodie Masson, Anne Etchevers, Daniel Levy-Brühl, Naïm Ouldali, Corinne Levy, and Robert Cohen

Subjects
invasive pneumococcal disease, cluster, pneumococcal carriage, pneumococcal meningitis, daycare center, Pediatrics, RJ1-570
Abstract

Only a few clusters of invasive pneumococcal disease have been described globally in children, and most of these cases occurred before pneumococcal vaccination implementation. Two unusual cases of pneumococcal meningitis, occurring in the same daycare center over a 3-day period, were reported. Both cerebrospinal fluid (CSF) were sent to the National reference center for pneumococci. In addition, we decided to perform a pneumococcal carriage study on all children and staff of the daycare center to analyze the pneumococcal serotypes circulating in this DCC and to discuss an antibiotic chemoprophylaxis. CSF culture was positive for pneumococcus, and serotype 25A was identified by latex agglutination. The second case had negative CSF culture, but CSF antigen test and gene amplification results were positive for Streptococcus pneumoniae. Serotype 12F was identified by using molecular biology. The absence of correlation between these strains was confirmed by multi-locus sequence typing. In the carriage study, we included 29 children (median age 1.9 years, interquartile range 1.4–2.5) and 10 adults. Among the children, 24 carried Streptococcus pneumoniae (83%). The main serotypes isolated were 23A for 6 children and 25A for 5 children; serotypes were non-typeable for 3 children. Only 1 of 10 adults tested carried Streptococcus pneumoniae (serotype 12F). Despite this temporo-spatial pattern, the cases were unrelated and not due to carriage of a particular serotype. No specific action has been taken for the other children attending this DCC, and no other case of bacterial meningitis occurred.

Published
2022
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7. Dynamics of Antibiotic Resistance of Streptococcus pneumoniae in France: A Pediatric Prospective Nasopharyngeal Carriage Study from 2001 to 2022

Author

Alexis Rybak, Corinne Levy, Naïm Ouldali, Stéphane Bonacorsi, Stéphane Béchet, Jean-François Delobbe, Christophe Batard, Isabelle Donikian, Marie Goldrey, Jessica Assouline, Robert Cohen, and Emmanuelle Varon

Subjects
pneumococcal nasopharyngeal carriage, children, acute otitis media, PCV impact, third-generation pneumococcal conjugate vaccine, next-generation pneumococcal conjugate vaccine, Therapeutics. Pharmacology, RM1-950
Abstract

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for

Published
2023
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8. Shift in Clinical Profile of Hospitalized Pneumonia in Children in the Non-pharmaceutical Interventions Period During the COVID-19 Pandemic: A Prospective Multicenter Study

Author

Alexis Rybak, Naïm Ouldali, François Angoulvant, Philippe Minodier, Sandra Biscardi, Fouad Madhi, Isabelle Hau, Audrey Santos, Emilie Bouvy, François Dubos, Alain Martinot, Marie-Aliette Dommergues, Christèle Gras-Le Guen, Elise Launay, Karine Levieux, Ferielle Zenkhri, Irina Craiu, Mathie Lorrot, Yves Gillet, Ellia Mezgueldi, Albert Faye, Stéphane Béchet, Emmanuelle Varon, Robert Cohen, and Corinne Levy

Subjects
community-acquired pneumonia, COVID-19, children, non-pharmaceutical intervention, time series analysis, Pediatrics, RJ1-570
Abstract

Non-pharmaceutical interventions (NPIs) against coronavirus disease 2019 were implemented in March 2020. These measures were followed by a major impact on viral and non-viral diseases. We aimed to assess the impact of NPI implementation in France on hospitalized community-acquired pneumonia (hCAP) frequency and the clinical and biological characteristics of the remaining cases in children. We performed a quasi-experimental interrupted time-series analysis. Between June 2014 and December 2020, eight pediatric emergency departments throughout France reported prospectively all cases of hCAP in children from age 1 month to 15 years. We estimated the impact on the monthly number of hCAP using segmented linear regression with autoregressive error model. We included 2,972 hCAP cases; 115 occurred during the NPI implementation period. We observed a sharp decrease in the monthly number of hCAP after NPI implementation [−63.0% (95 confidence interval, −86.8 to −39.2%); p < 0.001]. Children with hCAP were significantly older during than before the NPI period (median age, 3.9 vs. 2.3 years; p < 0.0001), and we observed a higher proportion of low inflammatory marker status (43.5 vs. 33.1%; p = 0.02). Furthermore, we observed a trend with a decrease in the proportion of cases with pleural effusion (5.3% during the NPI period vs. 10.9% before the NPI; p = 0.06). NPI implementation during the COVID-19 (coronavirus disease 2019) pandemic led not only to a strong decrease in the number of hCAP cases but also a modification in the clinical profile of children affected, which may reflect a change in pathogens involved.

Published
2022
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9. Contribution of Serological Rapid Diagnostic Tests to the Strategy of Contact Tracing in Households Following SARS-CoV-2 Infection Diagnosis in Children

Author

Lorelei Charbonnier, Julie Rouprêt-Serzec, Marion Caseris, Marion Danse, Aurélie Cointe, Laure Cohen, Albert Faye, Naïm Ouldali, and Jean Gaschignard

Subjects
SARS-CoV-2, contact-tracing, rapid diagnostic test, children, household, RT-PCR-polymerase chain reaction with reverse transcription, Pediatrics, RJ1-570
Abstract

Background: The contact tracing and isolation of contagious individuals are cornerstones in the control of the COVID-19 pandemic. Strategies to identify household contacts who should be isolated around index children that tested positive for SARS-CoV-2 remain to be clarified. We aimed to compare contact tracing strategies around an index child positive for SARS-CoV-2 using serological rapid diagnostic testing (RDT, chromatography immunoassay).Methods: We conducted a contact tracing study in households of index cases children in the Paris region, France, between May 8 and July 27, 2020. We compared two strategies, one using SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) and one combining RT-PCR and serological RDT, initiated once RDT was available. The contacts RT-PCR–/RDT+ were considered to have been previously infected and not requiring quarantine. The primary outcome was the proportion of contacts that could avoid quarantine with the two screening strategies.Results: We included 34 children as index cases. Median age was 7 years. They generated 184 contacts (111 adults, 73 children) tested by RT-PCR: 24/184 (13%) were positive. The strategy combining RDT and RT-PCR was performed in 120/184 contacts (77 adults, 43 children) of 26 index children: 16/120 (13%) were RT-PCR+ and 47/120 (39%) were RDT+. Among the 16 individuals who were RT-PCR+, 14 (87%) were also RDT+. Among the 104 individuals who were RT-PCR–, 33 were RDT+. Hence 33/120 (27%) individuals were not isolated.Conclusions: Following the diagnosis of SARS-CoV-2 infection in children, a strategy combining serological RDT and nasopharyngeal RT-PCR enabled us to identify around one fourth of contacts with past infection and avoid unnecessary quarantine of these individuals.

Published
2021
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10. Fall of Community-Acquired Pneumonia in Children following COVID-19 Non-Pharmaceutical Interventions: A Time Series Analysis

Author

Alexis Rybak, David Dawei Yang, Cécile Schrimpf, Romain Guedj, Corinne Levy, Robert Cohen, Vincent Gajdos, Julie Tort, David Skurnik, Naïm Ouldali, and François Angoulvant

Subjects
community-acquired pneumonia, children, COVID-19, non-pharmaceutical interventions, mitigation measures, time series analysis, Medicine
Abstract

Non-pharmaceutical interventions (NPIs) were implemented to reduce the spread of coronavirus disease 2019 (COVID-19). A first national lockdown was decided in France on the 17 March 2020. These measures had an impact on other viral and non-viral infectious diseases. We aimed to assess this impact on community-acquired pneumonia (CAP) in children. We performed a quasi-experimental interrupted time series analysis. We used data from a French prospective surveillance system of six pediatric emergency departments (PEDs). All visits from 1 January 2017 to 31 December 2020 were included. Pre-intervention period was before 17 March 2020 and post-intervention period was after 18 March 2020. We estimated the impact on the weekly number of visits for CAP and CAP admission using quasi-Poisson regression modeling. A total of 981,782 PEDs visits were analyzed; among them, 8318 visits were associated with CAP, and 1774 of these were followed by a hospital admission. A major decrease was observed for CAP visits (−79.7% 95% CI [−84.3; −73.8]; p < 0.0001), and CAP admission (−71.3% 95 CI [−78.8; −61.1]; p < 0.0001). We observed a dramatic decrease of CAP in children following NPIs implementation. Further studies are required to assess the long-term impact of these measures.

Published
2021
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11. Dynamics of Antibiotic Resistance of Streptococcus pneumoniae in France: A Pediatric Prospective Nasopharyngeal Carriage Study from 2001 to 2022

Author

Varon, Alexis Rybak, Corinne Levy, Naïm Ouldali, Stéphane Bonacorsi, Stéphane Béchet, Jean-François Delobbe, Christophe Batard, Isabelle Donikian, Marie Goldrey, Jessica Assouline, Robert Cohen, and Emmanuelle

Subjects
pneumococcal nasopharyngeal carriage, children, acute otitis media, PCV impact, third-generation pneumococcal conjugate vaccine, next-generation pneumococcal conjugate vaccine
Abstract

Epidemiological surveillance of nasopharyngeal pneumococcal carriage is important for monitoring serotype distribution and antibiotic resistance, particularly before and after the implementation of pneumococcal conjugate vaccines (PCVs). With a prospective surveillance study in France, we aimed to analyze the dynamics of pneumococcal carriage, antibiotic susceptibility and serotype distribution in children aged 6 to 24 months who had acute otitis media between 2001 and 2022 with a focus on the late PCV13 period from May 2014 to July 2022. Trends were analyzed with segmented linear regression with autoregressive error. For the 17,136 children enrolled, overall pneumococcal carriage was stable during the study. During the late PCV13 period, the five most frequent serotypes were all non-PCV13 serotypes: 15B/C (14.3%), 23B (11.0%), 11A (9.6%), 15A (7.4%) and 35B (6.5%). During the same period, we observed a rebound of penicillin non-susceptibility (+0.15% per month, 95% confidence interval, +0.08 to 0.22, p < 0.001). Five serotypes accounted for 64.4% of the penicillin non-susceptible strains: 11A (17.5%), 35B (14.9%), 15A (13.9%), 15B/C (9.9%) and 19F (8.2%); non-PCV13/PCV15 accounted for

Published
2023
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12. Reassessing the Performance of the 'Step-By-Step' Approach to Febrile Infants 90 Days of Age and Younger in the Context of the COVID-19 Pandemic: A Multicentric Retrospective Study

Author

Alexis, Rybak, Camille, Aupiais, Marie, Cotillon, Romain, Basmaci, Loïc, de Pontual, Stéphane, Bonacorsi, Patricia, Mariani, Luce, Landraud, Ségolène, Brichler, Isabelle, Poilane, Naïm, Ouldali, and Luigi, Titomanlio

Subjects
Microbiology (medical), Fever, COVID-19, Infant, Bacterial Infections, Infectious Diseases, Urinary Tract Infections, Pediatrics, Perinatology and Child Health, Humans, Prospective Studies, Child, Pandemics, Procalcitonin, Retrospective Studies
Abstract

Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants90 days old. The "step-by-step" algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm.We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the "step-by-step" algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL).Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values0.5 ng/mL and only 1 had C-reactive protein level20 mg/L.The "step-by-step" algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants90 days old.

Published
2022

13. Incidence of Acute Chest Syndrome in Children With Sickle Cell Disease Following Implementation of the 13-Valent Pneumococcal Conjugate Vaccine in France

Author

Zein Assad, Morgane Michel, Zaba Valtuille, Andrea Lazzati, Priscilla Boizeau, Fouad Madhi, Jean Gaschignard, Luu-Ly Pham, Marion Caseris, Robert Cohen, Florentia Kaguelidou, Emmanuelle Varon, Corinne Alberti, Albert Faye, François Angoulvant, Bérengère Koehl, Naïm Ouldali, Angoulvant, François, AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Hôpital Hôtel-Dieu [Paris], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d'Investigation Clinique 1426 (CIC 1426), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHI Créteil, Groupe Hospitalier Nord Essonne [Longjumeau], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Jean Verdier [AP-HP], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Groupe d'Etude des Maladies Infectieuses Néonatales et Infantiles (GEMINI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-MRB-GRC, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Microbiologie Clinique [AP-HP Hôpital européen Georges-Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université des Antilles (UA)-Université Paris Cité (UPCité)

Subjects
Male, Vaccines, Conjugate, [SDV]Life Sciences [q-bio], Incidence, General Medicine, Anemia, Sickle Cell, [SDV] Life Sciences [q-bio], Cohort Studies, Streptococcus pneumoniae, Child, Preschool, Acute Chest Syndrome, Humans, Female, Child
Abstract

International audience; Importance: Acute chest syndrome (ACS) is one of the leading acute severe complications of sickle-cell disease (SCD). Although Streptococcus pneumoniae (S pneumoniae) is highly prevalent in children with SCD, its precise role in ACS is unclear. The efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) implementation on ACS is still unknown.Objective: To assess the association of PCV13 implementation in the general pediatric population with the incidence of ACS in children with SCD.Design, setting, and participants: This cohort study used an interrupted time-series analysis of patient records from a national hospital-based French surveillance system. All children younger than 18 years with SCD (based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision definition) hospitalized in France between January 2007 and December 2019 were included.Exposures: PCV13 implementation.Main outcomes and measures: Monthly incidence of ACS per 1000 children with SCD over time as analyzed by segmented linear regression with autoregressive error; monthly incidence of hospitalization for vaso-occlusive crisis, asthma crisis, and acute pyelonephritis per 1000 children with SCD over the same period as the control outcomes.Results: Among the 107 694 hospitalizations of children with SCD, 4007 episodes of ACS were included (median [IQR] age, 8 [4-12] years; 2228 [55.6%] boys). PCV13 implementation in 2010 was followed by a significant decrease in the incidence of ACS (-0.9% per month; 95% CI, -1.4% to -0.4%; P < .001), with an estimated cumulative change of -41.8% (95% CI, -70.8% to -12.7%) by 2019. Sensitivity analyses yielded the same results, including the incidence of ACS adjusted for that of vaso-occlusive crisis over time. The results were similar among different age groups. By contrast, no change was found for the 3 control outcomes over the study period.Conclusions and relevance: PCV13 implementation was associated with an important reduction in the incidence of ACS in children with SCD. This vaccine benefit provides new evidence of the key role of S pneumoniae in ACS and should be considered when estimating outcomes associated with current PCVs and the potential benefit of next-generation PCVs in children.

Published
2022

14. Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, François Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, Charlène Boulay, Hôpital Robert Debré, CHU Sainte Justine [Montréal], Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, CHU Marseille, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [CHU Necker] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital de la Timone [CHU - APHM] (TIMONE), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Evaluation thérapeutique et pharmacologie périnatale et pédiatrique (EA_7323), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Versailles André Mignot (CHV), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Hôpital Bicêtre, Université Paris-Saclay, CH de Saint-Malo [Broussais], Hôpital Jean Verdier [AP-HP], Institut de rythmologie et modélisation cardiaque [Pessac] (IHU Liryc), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), European Society for Paediatric Infectious Diseases, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPC), CHU Toulouse [Toulouse], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Centre de Référence pour les Maladies Rhumatologiques Auto-Immunes et Systémiques [Paris] (Institut IMAGINE/RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Imagine [Paris Necker] (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE)

Subjects
Oncology, [SDV]Life Sciences [q-bio], Health Policy, Multisystem inflammatory syndrome in children, Internal Medicine, COVID-19 mRNA vaccine, BNT162b2, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, SARS-COV-2, Hyper-inflammatory syndrome, Child
Abstract

International audience; BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is the most severe clinical entity associated with pediatric SARS-CoV-2 infection with a putative role of the spike protein into the immune system activation. Whether COVID-19 mRNA vaccine can induce this complication in children is unknown. We aimed to assess the risk of hyper-inflammatory syndrome following COVID-19 mRNA vaccine in children. METHODS: We conducted a post-authorization national population-based surveillance using the French enhanced pharmacovigilance surveillance system for COVID-19 vaccines. All cases of suspected hyper-inflammatory syndrome following COVID-19 mRNA vaccine in 12-17-year-old children between June 15(th), 2021 and January 1(st), 2022, were reported. Cases were reviewed according to WHO criteria for MIS-C. The reporting rate of this syndrome was compared to the MIS-C rate per 1,000,000 12-17-year-old children infected by SARS-CoV-2. FINDINGS: Up to January 2022, 8,113,058 COVID-19 mRNA vaccine doses were administered to 4,079,234 12-17-year-old children. Among them, 12 presented a hyper-inflammatory syndrome with multisystemic involvement. Main clinical features included male predominance (10/12, 83%), cardiac involvement (10/12, 83%), digestive symptoms (10/12, 83%), coagulopathy (7/12, 58%), cytolytic hepatitis (6/12, 50%), and shock (5/12, 42%). 4/12 (33%) required intensive care unit transfer, and 3/12 (25%) hemodynamic support. All cases recovered. In eight cases, no evidence of previous SARS-CoV-2 infection was found. The reporting rate was 1.5 (95%CI [0.8; 2.6]) per 1,000,000 doses injected, i.e. 2.9 (95%CI [1.5; 5.1]) per 1,000,000 12-17-year-old vaccinated children. As a comparison, 113 MIS-C (95%CI [95; 135]) occurred per 1,000,000 12-17-year-old children infected by SARS-CoV-2. INTERPRETATION: Very few cases of hyper-inflammatory syndrome with multi-organ involvement occurred following COVID-19 mRNA vaccine in 12-17-year-old children. The low reporting rate of this syndrome, compared to the rate of post-SARS-CoV-2 MIS-C in the same age-group, largely supports the vaccination in a context of an important circulation of SARS-CoV-2. FUNDING: ESPID Fellowship Award; Grandir-Fonds de Solidarité Pour L'enfance.

Published
2022

15. Association of Nonpharmaceutical Interventions During the COVID-19 Pandemic With Invasive Pneumococcal Disease, Pneumococcal Carriage, and Respiratory Viral Infections Among Children in France

Author

Alexis Rybak, Corinne Levy, François Angoulvant, Anne Auvrignon, Piotr Gembara, Kostas Danis, Sophie Vaux, Daniel Levy-Bruhl, Sylvie van der Werf, Stéphane Béchet, Stéphane Bonacorsi, Zein Assad, Andréa Lazzati, Morgane Michel, Florentia Kaguelidou, Albert Faye, Robert Cohen, Emmanuelle Varon, Naïm Ouldali, Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Association Française de Pédiatrie Ambulatoire (AFPA), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Institut Pasteur [Paris] (IP), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire Sainte-Justine and Pediatrics, Université de Montréal (UdeM), and This work was supported by funding from Pfizer (via ACTIV) for the pneumococcal carriage study, funding from the French Institute for Public Health Surveillance (via the National Reference Center for Pneumococci) for the invasive pneumococcal disease study, and a 2021-2023 fellowship award from the European Society of Pediatric Infectious Diseases (Dr Ouldali).

Subjects
Male, MESH: Humans, MESH: Influenza, Human, [SDV]Life Sciences [q-bio], COVID-19, Infant, General Medicine, MESH: Infant, Pneumococcal Infections, MESH: Male, Cohort Studies, MESH: Viruses, MESH: Influenza Vaccines, Streptococcus pneumoniae, Influenza Vaccines, MESH: Child, Influenza, Human, Viruses, Humans, MESH: COVID-19, MESH: Pneumococcal Infections, Child, Pandemics, MESH: Cohort Studies, MESH: Streptococcus pneumoniae
Abstract

International audience; Key PointsQuestion Was the implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic associated with changes in the incidence of invasive pneumococcal disease (IPD) and associated pneumococcal carriage and respiratory viral infections (RSVs) in children in France?Findings In this cohort study using interrupted time series analysis of data from multiple national surveillance systems involving 11 944 children, the incidence of pediatric IPD decreased after implementation of NPIs during the COVID-19 pandemic. This decrease was associated with decreases in influenza and RSV cases, but the pneumococcal carriage rate remained stable.Meaning These results suggest that the established association between pneumococcal carriage and IPD was modified after viral epidemiological changes associated with NPIs, suggesting that interventions targeting respiratory viruses may help prevent a large proportion of pediatric IPD cases.AbstractImportance An association between pneumococcal nasopharyngeal carriage and invasive pneumococcal disease (IPD) has been previously established. However, it is unclear whether the decrease in IPD incidence observed after implementation of nonpharmaceutical interventions (NPIs) during the COVID-19 pandemic was associated with concomitant changes in pneumococcal carriage and respiratory viral infections.Objective To assess changes in IPD incidence after the implementation of NPIs during the COVID-19 pandemic and examine their temporal association with changes in pneumococcal carriage rate and respiratory viral infections (specifically respiratory syncytial virus [RSV] and influenza cases) among children in France.Design, Setting, and Participants This cohort study used interrupted time series analysis of data from ambulatory and hospital-based national continuous surveillance systems of pneumococcal carriage, RSV and influenza-related diseases, and IPD between January 1, 2007, and March 31, 2021. Participants included 11 944 children younger than 15 years in France.Exposures Implementation of NPIs during the COVID-19 pandemic.Main Outcomes and Measures The estimated fraction of IPD change after implementation of NPIs and the association of this change with concomitant changes in pneumococcal carriage rate and RSV and influenza cases among children younger than 15 years. The estimated fraction of change was analyzed using a quasi-Poisson regression model.Results During the study period, 5113 children (median [IQR] age, 1.0 [0.6-4.0] years; 2959 boys [57.9%]) had IPD, and 6831 healthy children (median [IQR] age, 1.5 [0.9-3.9] years; 3534 boys [51.7%]) received a swab test. Data on race and ethnicity were not collected. After NPI implementation, IPD incidence decreased by 63% (95% CI, −82% to −43%; P

Published
2022

16. Reassessing the performance of the 'step-by-step' approach to febrile infants aged 90 days and younger in the context of the COVID-19 pandemic: a multicentric retrospective study

Author

Alexis Rybak, Camille Aupiais, Marie Cotillon, Romain Basmaci, Loïc de Pontual, Stéphane Bonacorsi, Patricia Mariani, Luce Landraud, Ségolène Brichler, Isabelle Poilane, Naïm Ouldali, and Luigi Titomanlio

Abstract

BackgroundInfants with COVID-19 can often present with fever without source which is a challenging situation in infants < 90 days old. The “step-by-step” algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm.MethodsWe performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the “step-by-step” algorithm to four clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk.ResultsAmong the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but one infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill appearance (72%), an age ≤ 21 days (27%) and/or leukocyturia (19%). All these infants had procalcitonin values < 0.5 ng/mL and only one had C-reactive protein level > 20 mg/L.ConclusionsThe “step-by-step” algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants < 90 days old.

Published
2022

17. [Multisystemic inflammatory syndrome in children (MIS-C) associated with Covid]

Author

Jean-Christophe, Mercier, Naïm, Ouldali, and Romain, Basmaci

Subjects
SARS-CoV-2, COVID-19, Humans, Mucocutaneous Lymph Node Syndrome, Child, Systemic Inflammatory Response Syndrome
Abstract

Multisystemic inflammatory syndrome in children (mis-c) Asociated with covid Although children are less susceptible to sars-cov-2 and less symptomatic than adults with low mortality, clusters of Septic shock associated with elevated cardiac biomarkers and unusual vasoplegia have been recently described and Treated by inotropes, vasopressors, and fluid loading. Both clinical symptoms (i.e., high and persistent fever, gastrointestinal Disorders, skin rash, conjunctivitis and dry cracked lips) and biological signs (e.g., elevated crp/procalcitonin, high Levels of ferritinemia) resembled kawasaki disease. In most instances, intravenous immunoglobin therapy with glucosteroids Improved the cardiac function and led to full recovery within a few days. However, adjunctive biotherapy (e.g., Anti-il-1ra, anti-il-6 monoclonal antibodies) was sometimes necessary. Although almost all children fully recovered Within a few days, some of them developed late coronary artery dilation or aneurysm. Thus, a new "multisystem inflammatory Syndrome in children" (mis-c) associated with sars-cov-2 has been identified, and its pathophysiology better Understood.Syndrome inflammatoire multisystémique associé au covid Chez l’enfant Si les enfants apparaissent moins susceptibles au sars-cov-2 et sont moins symptomatiques que les adultes, avec Une faible mortalité, des états de choc associés à une élévation des biomarqueurs cardiaques et à une vasoplégie Inhabituelle, nécessitant un traitement par inotropes, vasopresseurs et un remplissage vasculaire ont été décrits. Les Symptômes cliniques observés (fièvre élevée et durable, troubles digestifs, rash cutané, injection conjonctivale, chéilite) Et le profil biologique (crp/procalcitonine élevées, hyperferritinémie) peuvent parfois mimer un syndrome de kawasaki Atypique. Cette nouvelle entité répond le plus souvent à la perfusion intraveineuse d’immunoglobulines associée à Une corticothérapie, et nécessite parfois une biothérapie anti-il-1ra ou anti-il-6. La majorité des enfants guérit en Quelques jours, avec cependant une possible dilatation des artères coronaires. Ainsi, un nouveau syndrome inflammatoire Multisystémique associé au sars-cov-2 mimant un syndrome de kawasaki a récemment été identifié chez L’enfant et sa physiopathologie est mieux comprise.

Published
2022

18. Analysis of COVID-19 Vaccination Status Among Parents of Hospitalized Children Younger Than 5 Years With SARS-CoV-2 Infection During the Delta and Omicron Waves

Author

Florie Solignac, Naïm Ouldali, Camille Aupiais, Paul Casha, Robert Cohen, Corinne Levy, and François Angoulvant

Subjects
Parents, COVID-19 Vaccines, SARS-CoV-2, Vaccination, Humans, COVID-19, General Medicine, Child, Child, Hospitalized
Abstract

This cohort study uses COVID-19 Pediatric Observatory study data to analyze the vaccination status of parents with young children hospitalized for SARS-CoV-2 variants Delta and Omicron.

Published
2022

19. Correction to 'Hyper inflammatory syndrome following COVID-19 mRNA vaccine in children: A national post-authorization pharmacovigilance study'

Author

Naïm Ouldali, Haleh Bagheri, Francesco Salvo, Denise Antona, Antoine Pariente, Claire Leblanc, Martine Tebacher, Joëlle Micallef, Corinne Levy, Robert Cohen, Etienne Javouhey, Brigitte Bader-Meunier, Caroline Ovaert, Sylvain Renolleau, Veronique Hentgen, Isabelle Kone-Paut, Nina Deschamps, Loïc De Pontual, Xavier Iriart, Christelle Gras-Le Guen, Francois Angoulvant, Alexandre Belot, Aurelie Donzeau, Layal El Aridi, Sophie Lety, Bertrand Leboucher, Agnes Baur, Lucas Jeusset, Maelle Selegny, Cristian Fedorczuk, Marion Lajus, Philippe Bensaid, Yacine Laoudi, Charlotte Pons, Anne-Cécile Robert, Camille Beaucourt, Muriel Richard, Etienne Goisque, Olivier Brissaud, Pierre Segretin, Julie Molimard, Marie-Clothilde Orecel, Gregoire Benoit, Lucille Bongiovanni, Margaux Guerder, Robin Pouyau, Jean-Marie De Guillebon De Resnes, Ellia Mezgueldi, Fleur Cour-Andlauer, Come Horvat, Pierre Poinsot, Cecile Frachette, Antoine Ouziel, Yves Gillet, Catherine Barrey, Jacques Brouard, Florence Villedieu, Vathanaksambath Ro, Narcisse Elanga, Vincent Gajdos, Romain Basmaci, Hadile Mutar, Sébastien Rouget, Elodie Nattes, Isabelle Hau, Sandra Biscardi, Houmam El Jurdi, Camille Jung, Denis Semama, Frederic Huet, Anne-Marie Zoccarato, Mayssa Sarakbi, Guillaume Mortamet, Cécile Bost-Bru, Joachim Bassil, Caroline Vinit, Véronique Hentgen, Pascal Leroux, Valérie Bertrand, Caroline Parrod, Irina Craiu, Philippe Durand, Pierre Tissiere, Caroline Claude, Guillaume Morelle, Tamazoust Guiddir, Charlotte Borocco, Frédérique Delion, Camille Guillot, Stéphane Leteurtre, François Dubos, Mylene Jouancastay, Alain Martinot, Valentine Voeusler, Jeanne Languepin, Nathalie Garrec, Arnaud Chalvon Demersay, Aurélie Morand, Emmanuelle Bosdure, Noémie Vanel, Fabrice Ughetto, Fabrice Michel, Marie Caujolle, Renaud Blonde, Jacqueline Nguyen, Olivier Vignaud, Caroline Masserot-Lureau, François Gouraud, Carine Araujo, Tara Ingrao, Sanaa Naji, Mohammed Sehaba, Christine Roche, Aurelia Carbasse, Christophe Milesi, Mustapha Mazeghrane, Sandrine Haupt, Cyril Schweitzer, Benedicte Romefort, Elise Launay, Christèle Gras-Le Guen, Ahmed Ali, Nathalie Blot, Antoine Tran, Anne Rancurel, Mickael Afanetti, Sophie Odorico, Deborah Talmud, Anais Chosidow, Anne-Sophie Romain, Emmanuel Grimprel, Marie Pouletty, Jean Gaschignard, Olivier Corseri, Albert Faye, Isabelle Melki, Camille Ducrocq, Cherine Benzoïd, Johanna Lokmer, Stéphane Dauger, Maryline Chomton, Anna Deho, Fleur Lebourgeois, Fabrice Lesage, Florence Moulin, Laurent Dupic, Yael Pinhas, Agathe Debray, Martin Chalumeau, Véronique Abadie, Pierre Frange, Jeremie F Cohen, Slimane Allali, William Curtis, Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Lucile Houyel, Damien Bonnet, Christophe Delacourt, Brigitte Bader Meunier, Pierre Quartier, Youssef Shaim, Laurence Baril, Samuel Crommelynck, Baptiste Jacquot, Philippe Blanc, Natacha Maledon, Blandine Robert, Camille Loeile, Clémence Cazau, Gauthier Loron, Simona Gaga, Cécile Vittot, Loubna El Nabhani, François Buisson, Muriel Prudent, Hugues Flodrops, Fadhila Mokraoui, Simon Escoda, Laurent Bonnemains, Sarah-Louisa Mahi, Clara Mertes, Joelle Terzic, Julie Helms, Charlotte Idier, Soraya Chenichene, Nicoleta Magdolena Ursulescu, Gladys Beaujour, Abdelhak Hakim, Alice Miquel, Agnès Rey, Arnaud Wiedermann, Anne Charbonneau, Agnès Veauvy-Juven, Alexandrine Ferry, Alexis Mandelcwajg, Alix Rousseau, Amandine Prenant, Anne-Laure Bourneuf, Anne Filleron, Audrey Robine, Arthur Félix, Aude Parizel, Aurélie Labarre, Aymeric Cantais, Barbara Ros, Basile Coulon, Blandine Biot, Bérengère Dalichoux, Benjamin Fournier, Benoit Cagnard, Blandine Vanel, David Brossier, Bruno Ménager, Bruno Ozanne, Carole Marie-Jeanne, Camille Bergerot, Camille Chavy, Camille Guidon, Candice Fabre, Caroline Galeotti, Catherine Baker, Claire Ballot-Schmit, Céline Belleau, Céline Charasse, Caroline Favel, Chadia Toumi, Charlène Ferrandiz, Charlotte Couturier, Charlotte Pouchoux, Maryline Chomton-Cailliez, Charlotte Kevorkian-Verguet, Clément Brunet, Céline Manteau, Clémence Mougey, Coline Santy, Coralie Fitament, Charlotte Petriat, Charlotte Rebelle, Cyril Charron, Maxime Dartus, David Toulorge, Cécile Guillou-Debuisson, Dorann Bartebin, Valérie Klein, E Broustal, E. Desselas, Elodie Marteau, Emmanuelle Bouvrot, Elise Delacroix, Edeline Coinde, Loubna Elnabhani, Elsa Amouyal, Emilie Chaillou, Emeline Gabilly-Bernard, Emilie Ruiz, Emilie Thibault, Emilie Robin, Etienne Darrieux, Eva Blondel, Floriane Socchi, François Cazassus, Fanny Bajolle, Fatma Lacin, Fouad Madhi, Franck Zekre, François Guerin, Gerald Boussicault, Henri Ginies, Gnansounou Magloire, Guilhem Arnold, Ines Coulognon, Iona Sicard-Cras, Jean-Emmanuel Kahn, Jeanne Bordet, Jeanne-Lise Fausser, Jean-François Baleine, Josephine Brice, Julie Gendras, Kaan Pekin, Karine Norbert, Clément Karsenty, Léa Savary, Laurence Martinat, Léa Lesniewski, Lorelei Charbonnier, Louise Alexandre, Lucas Percheron, Marie Vincenti, Manon Lanzini, Margot Grisval, Marianne Mercy, Marie-Emilie Lampin, Marie Desgranges, Marie Duperril, Marie-Clothilde Orcel, Marion Audier, Marion Favier, Mathieu Carpentier, Mathilde Balcean, Mathilde Bonnet, Maurine Jouret, Marie Delattre, Michael Levy, Michael Valensi, Mickael Shum, Morgane Dumortier, Morgane Gelin, Morgane Nemmouchi, Morgane Williaume, M. Sebaha, Nicoleta Genetay-Stanescu, Nathan Giroux, Nicolas Crassard, Neil Derridj, Noemie Lachaume, Oscar Werner, Olivier Guilluy, Olivier Richer, Olivier Tirel, Aurianne Pauvert, Paul Casha, Noémie Perez, Pauline Gras, Pierre-Louis Leger, Marion Pinchou, Pierre Mornand, Prisca Largo, Ramona-Christina Ibanez, Charlotte Roulland, Salam Hadah Albarazi, Said Bichali, Sarah Faton, Amandine Schott, Sébastien Walser, Severine Guillaume, Solene Vincent, Sophie Galene-Gromez, Stanislas Kozisek, Thierry Maugard, Thierry Blanc, Thierry Navarro, Thomas Lauvray, Tamas Kovacs, Valérie Launay, Véronique Despert, Victoria Lhostis, Virginie Gall, Xavier Micaelli, Yasmine Benadjaoud, Zied Matoussi, Hélène Géniaux, Anthony Facile, Tessa Pietri, Pascale Palassin, Sylvine Pinel, Laurent Chouchana, Delphine Callot, and Charlène Boulay

Subjects
Oncology, Health Policy, Internal Medicine
Published
2022

21. Baisse des infections virales et viro-induites pédiatriques pendant les confinements en 2020.

Author

Dawei Yang, Naïm Ouldali, Alexis Rybak, Vincent Gajdos, Romain Guedj, Soussan-Banini, Valérie, Basmaci, Romain, Lefevre-Utile, Alain, Schrimpf, Cécile, Vasante, Loganayagi, Tort, Julie, Skurnik, David, and Angoulvant, François

Subjects
*VIRAL diseases in children, *COMMUNICABLE diseases in children, *COVID-19 pandemic, *STAY-at-home orders, *COMMUNICABLE disease control, *PUBLIC health
Abstract

Background: The COVID-19 pandemic had led to several national lockdown in France such as many other countries. We hypothesized that these measures would be associated with a decrease in pediatric viral and virus-induced infections that usually disseminate through social contacts. [ABSTRACT FROM AUTHOR]

Published
2021
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22. Calculating the fraction of Kawasaki disease potentially attributable to seasonal pathogens: a time series analysisResearch in context

Author

Zaba Valtuille, Alain Lefevre-Utile, Naim Ouldali, Constance Beyler, Priscilla Boizeau, Cécile Dumaine, Arthur Felix, Zein Assad, Albert Faye, Isabelle Melki, Florentia Kaguelidou, and Ulrich Meinzer

Subjects
Kawasaki disease, Virus, Covid 19, Sars-Cov-2, Inflammation, Medicine (General), R5-920
Abstract

Summary: Background: Kawasaki disease is an acute, febrile, systemic vasculitis of children that primarily affects medium-sized blood vessels with a tropism for the coronary arteries. Although the etiological factors remain unknown, infections have been suggested as the trigger of Kawasaki disease. We sought to calculate the fraction of Kawasaki disease potentially attributable to seasonal infections. Methods: This cohort study used a population-based time series analysis from the French hospitalisation database (Programme de Médicalisation des Systèmes d’Information), which includes all inpatients admitted to any public or private hospital in France. We included all children aged 0–17 years hospitalised for Kawasaki disease in France over 13 years. The monthly incidence of Kawasaki disease per 10,000 children over time was analysed by a quasi-Poisson regression model. The model accounted for seasonality by using harmonic terms (a pair of sines and cosines with 12-month periods). The circulation of eight common seasonal pathogens (adenovirus, influenza, metapneumovirus, Mycoplasma pneumoniae, norovirus, rhinovirus, rotavirus, respiratory syncytial virus, and Streptococcus pneumonia) over the same period was included in the model to analyse the fraction of Kawasaki disease potentially attributable to each pathogen. Infections were identified on the basis of polymerase chain reaction or rapid antigen testing in hospital laboratories. Findings: Between Jan 1, 2007, and Dec 31, 2019, we included 10,337 children with Kawasaki disease and 442,762 children with the selected infectious diseases. In the Kawasaki disease cohort, the median age [IQR] was 2 [0–4] years, 6164 [59.6%] were boys. Adenovirus infection was potentially responsible for 24.4% [21.5–27.8] (p

Published
2023
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23. Development of a score for early identification of children with Kawasaki disease requiring second-line treatment in multi-ethnic populations in Europe: A multicentre retrospective cohort study

Author

Naim Ouldali, Rosa Maria Dellepiane, Sofia Torreggiani, Lucia Mauri, Gladys Beaujour, Constance Beyler, Martina Cucchetti, Cécile Dumaine, Adriano La Vecchia, Isabelle Melki, Rita Stracquadaino, Caroline Vinit, Rolando Cimaz, and Ulrich Meinzer

Subjects
Kawasaki disease, Vasculitis, Pediatric rheumatology, Coronary artery, Echocardiography, Severity score, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Early identification of high-risk patients is essential to stratify treatment algorithms of Kawasaki disease (KD) and to appropriately select patients at risk for complicated disease who would benefit from intensified first-line treatment. Several scores have been developed and validated in Asian populations but have shown low sensitivity in predicting intravenous immunoglobulin (IVIG) resistance in non-Asian populations. We sought methods to predict the need for secondary treatment after initial IVIG in non-Asian populations. Methods: We conducted a retrospective, multicenter study including consecutive patients with KD admitted to two tertiary pediatric hospitals in France and Italy from 2005 to 2019. We evaluated the performance of the Kawanet-score and compared it with the performances of initial echocardiography findings, and of a newly proposed score combining the Kawanet-score and initial echocardiography findings. For each score, we assessed the AUC, sensitivity and specificity for predicting the need for second-line treatment. Findings: We included 363 children with KD, 186 from France and 177 from Italy, of whom 57 (16%) required second-line therapy after the first IVIG dose. The Kawanet score, coronary artery dilation or aneurysm with maximal Z-score ≥2.0 at baseline, and abnormal initial echocardiography had a sensitivity of 43%, 55% and 65% and a specificity of 73%, 78%, 73%, respectively, for predicting the need for second-line treatment. The Kawanet-score was significantly improved by combining it with initial echocardiography findings. The best predictive performance (Sensitivity 76%, Specificity 54%) was obtained by combining the Kawanet-score with abnormal initial echocardiography, defined by the presence of either coronary artery maximal Z-score ≥2.0, pericarditis, myocarditis and/or ventricular dysfunction. This score predicted the need for second-line treatment in European, African/Afro-Caribbean and Asian ethnicity with a sensitivity of 80%, 65% and 100%, respectively, and a specificity of 56%, 51% and 61%, respectively. Interpretation: Our study proposes a score that we named the Kawanet-echo score, which allows early identification of children with KD who require a second-line treatment in multi-ethnic populations in Europe. Funding: None.

Published
2022
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25. Diagnostic Accuracy of Routinely Available Biomarkers to Predict Bacteremia in Children With Community-Acquired Pneumonia: A Secondary Analysis of the GPIP/ACTIV Pneumonia Study in France, 2009–2018

Author

Danaé Dudognon, Corinne Levy, Martin Chalumeau, Sandra Biscardi, Marie-Aliette Dommergues, François Dubos, Karine Levieux, Marie Aurel, Philippe Minodier, Ferielle Zenkhri, Ellia Mezgueldi, Irina Craiu, Laurence Morin, Stéphane Béchet, Emmanuelle Varon, Robert Cohen, Jérémie F. Cohen, The Pneumonia Study Group, François Angoulvant, Yves Gillet, Christèle Gras-Le Guen, Isabelle Hau, Laure Hees, Elise Launay, Mathie Lorrot, Fouad Madhi, Alain Martinot, and Naim Ouldali

Subjects
pneumonia, bacteremia, biomarkers, procalcitonin (PCT), pneumococcus (Streptococcus pneumoniae), diagnostic test, Pediatrics, RJ1-570
Abstract

Objective(s): Blood cultures (BC), when performed in children seen in the emergency department with community-acquired pneumonia (CAP), are most of the time sterile. We described the diagnostic accuracy of white blood cells (WBC), absolute neutrophils count (ANC), C-reactive protein (CRP), and procalcitonin (PCT) to predict blood culture (BC) result in childhood CAP.Study Design: Secondary analysis of a prospective study carried out in eight pediatric emergency departments (France, 2009–2018), including children (≤15 years) with CAP. Analyses involved univariate comparisons and ROC curves.Results: We included 13,752 children with CAP. BC was positive in 137 (3.6%) of the 3,829 children (mean age 3.7 years) in whom it was performed, mostly with Streptococcus pneumoniae (n = 107). In children with bacteremia, ANC, CRP and PCT levels were higher (median 12,256 vs. 9,251/mm3, 223 vs. 72 mg/L and 8.6 vs. 1.0 ng/mL, respectively; p ≤ 0.002), but WBC levels were not. The area under the ROC curve of PCT (0.73 [95%CI 0.64–0.82]) was significantly higher (p ≤ 0.01) than that of WBC (0.51 [0.43–0.60]) and of ANC (0.55 [0.46–0.64]), but not than that of CRP (0.66 [0.56–0.76]; p = 0.21). CRP and PCT thresholds that provided a sensitivity of at least 90% were 30 mg/L and 0.25 ng/mL, respectively, for a specificity of 25.4 and 23.4%, respectively. CRP and PCT thresholds that provided a specificity of at least 90% were 300 mg/L and 20 ng/mL, respectively, for a sensitivity of 31.3 and 28.9%, respectively.Conclusions: PCT and CRP are the best routinely available predictive biomarkers of bacteremia in childhood CAP.

Published
2021
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27. Assessment of SARS-CoV-2 infection by Reverse transcription-PCR and serology in the Paris area: a cross-sectional study

Author

Naim Ouldali, Odile Launay, Aurelie Sellam, Christophe Batard, Fabienne Cahn-Sellem, Annie Elbez, Alain Wollner, Olivier Romain, François Corrard, Said Aberrane, Nathalie Soismier, Rita Creidy, and Mounira Smati-Lafarge

Subjects
Pediatrics, RJ1-570
Abstract

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

Published
2020
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28. Bacterial causes of otitis media with spontaneous perforation of the tympanic membrane in the era of 13 valent pneumococcal conjugate vaccine.

Author

Corinne Levy, Emmanuelle Varon, Naim Ouldali, Alain Wollner, Franck Thollot, François Corrard, Andreas Werner, Stéphane Béchet, Stéphane Bonacorsi, and Robert Cohen

Subjects
Medicine, Science
Abstract

After pneumococcal conjugate vaccine (PCV) implementation, the number of acute otitis media (AOM) episodes has decreased, but AOM still remains among the most common diagnoses in childhood. From 2% to 17% of cases of AOM feature spontaneous perforation of the tympanic membrane (SPTM). The aim of this study was to describe the bacteriological causes of SPTM 5 to 8 years years after PCV13 implementation, in 2010. From 2015 to 2018, children with SPTM were prospectively enrolled by 41 pediatricians. Middle ear fluid was obtained by sampling spontaneous discharge. Among the 470 children with SPTM (median age 20.8 months), no otopathogen was isolated for 251 (53.4% [95% CI 48.8%;58.0%]): 47.1% of infants and toddlers, 68.3% older children (p

Published
2019
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