Systematic Severe Acute Respiratory Syndrome Coronavirus 2 Screening at Hospital Admission in Children: A French Prospective Multicenter Study.

To assess the relevance of systematic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening of all children admitted to hospital, we conducted a prospective multicenter study including 438 consecutive hospitalized children. A symptom-based SARS-CoV-2 testing strategy failed to identify 45% (95% confidence interval, 24%-68%) of hospitalized children infected by SARS-CoV-2. To limit intrahospital transmission, a systematic screening of children admitted to hospital should be considered.

[Medication and children: Practical situations to address the risks]. / Médicaments et enfants : approche des risques par des mises en situation pratiques.

Medications are an important source of intoxication or misuse in the pediatric population. It is therefore important to raise parents' awareness on this point. To do so, a team of professionals has set up an e-learning, presented in the form of a slide show. Nineteen cases were selected, then divided into three themes (administration error, danger and storage error) and in four rooms of the home (living room, bathroom, child's room and parent's room).

Implementation of a large-scale simulation-based cardiovascular clinical examination course for undergraduate medical students - a pilot study.

BACKGROUND: We report the implementation of a large-scale simulation-based cardiovascular diagnostics course for undergraduate medical students. METHODS: A simulation-based course was integrated into the curriculum of second-year medical students (> 400 students/year). The first session aimed at teaching cardiac auscultation skills on mannequins and the second at teaching blood pressure measurement, peripheral arterial examination, and the clinical examination of heart failure in a technical skill-based manner and in a scenario. RESULTS: A total of 414 (99.8%) and 402 (98.5%) students, as well as 102 and 104 educators, participated during the 2016-2017 and 2017-2018 academic years across both types of sessions. The number of positive appreciations by students was high and improved from the first to the second year (session 1: 77% vs. 98%, session 2: 89% vs. 98%; p < 0.0001). Similar results were observed for educators (session 1: 84% vs. 98%, p = 0.007; session 2: 82% vs. 98%, p = 0.01). Feedbacks by students were positive regarding the usefulness of the course, fulfillment of pedagogical objectives, quality of the teaching method, time management, and educator-student interactivity. In contrast, 95% of students criticized the quality of the mannequins during the first year leading to the replacement of the simulation material the following year. Students most appreciated the auscultation workshop (25%), the practical aspect of the course (22%), and the availability of educators (21%). CONCLUSIONS: Despite the need to commit significant human and material resources, the implementation of this large-scale program involving > 400 students/year was feasible, and students and educators reacted favorably.

Invasive pneumococcal disease in children can reveal a primary immunodeficiency.

BACKGROUND: About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. METHODS: We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. RESULTS: We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). CONCLUSIONS: Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.

CUBN and NEBL common variants in the chromosome 10p13 linkage region are associated with multibacillary leprosy in Vietnam.

Leprosy is caused by infection with Mycobacterium leprae and is classified clinically into paucibacillary (PB) or multibacillary (MB) subtypes based on the number of skin lesions and the bacillary index detected in skin smears. We previously identified a major PB susceptibility locus on chromosome region 10p13 in Vietnamese families by linkage analysis. In the current study, we conducted high-density association mapping of the 9.5 Mb linkage peak on chromosome region 10p13 covering 39 genes. Using leprosy per se and leprosy subtypes as phenotypes, we employed 294 nuclear families (303 leprosy cases, 63 % MB, 37 % PB) as a discovery sample and 192 nuclear families (192 cases, 55 % MB, 45 % PB) as a replication sample. Replicated significant association signals were revealed in the genes for cubilin (CUBN) and nebulette (NEBL). In the combined sample, the C allele (frequency 0.26) at CUBN SNP rs10904831 showed association [p = 1 × 10(-5); OR 0.52 (0.38-0.7)] with MB leprosy only. Likewise, allele T (frequency 0.42) at NEBL SNP rs11012461 showed association [p = 4.2 × 10(-5); OR 2.51 (1.6-4)] with MB leprosy only. These associations remained valid for the CUBN signal when taking into account the effective number of tests performed (type I error significance threshold = 2.4 × 10(-5)). We used the results of our analyses to propose a new model for the genetic control of polarization of clinical leprosy.

Assessment of adherence to the 2020 Surviving Sepsis Campaign guidelines for fluid resuscitation in children with suspected septic shock in paediatric emergency departments: a prospective multicentre study.

BACKGROUND: Paediatric sepsis is the leading cause of death in children under 5 years. No studies have evaluated the application of the Surviving Sepsis Campaign 2020 (SSC-2020) guidelines in paediatric emergency departments (PEDs). OBJECTIVE: To assess physician adherence to the SSC-2020 fluid resuscitation guidelines in children with suspected septic shock in PEDs. METHODS: This was a prospective multicentre observational study conducted in 21 French hospitals over 5 sequential weeks, between November 2021 and March 2022. Children with suspected septic shock and who received antimicrobial therapy within 72 hours were included. Primary outcome was SSC-2020 fluid resuscitation guidelines adherence (low 0-24%; moderate 25-74%; high 75-100%) according to: bolus volume of 10-20 mL/kg each, exclusive administration of balanced crystalloids at 1 and 24 hours of management, and initiation of fluid resuscitation within 1 hour of septic shock recognition. RESULTS: 63 children were included. 10 (16%) children had severe sepsis and 2 (3%) met the definition of septic shock. Compared with the SSC-2020 guidelines, 43 (68%) patients received boluses of 10-20 mL/kg; fluid resuscitation was initiated within 1 hour of septic shock recognition in 42 (76%) cases; balanced crystalloids were the only fluids administrated in 35 (56%) and 34 (55%) children at 1 and 24 hours of management, respectively. Main barriers reported by physicians were difficult intravenous access (43%), lack of team training (29%), workload constraints (28%), and absence or out-of-date protocols (24%). CONCLUSIONS: This study found high adherence for fluid resuscitation initiation but moderate adherence for bolus volume and fluid choice. TRIAL REGISTRATION NUMBER: NCT05066464.

Detection of enterovirus in cerebrospinal fluids without pleocytosis in febrile infants under 3 months old reduces antibiotherapy duration.

Background: Infants under 3 months old with fever often receive empirical antibiotic treatment. Enterovirus is one of the leading causes of infection and aseptic meningitis but is not systematically screened. We aimed to evaluate enterovirus positive RT-PCR proportion in cerebrospinal fluid (CSF) with no pleocytosis and its impact on antibiotic treatment duration. Methods: During the enterovirus endemic season, from 2015 to 2018, we retrospectively studied infants under 3 months old, consulting for fever without cause, with normal CSF analysis, and receiving empirical antibiotic treatment. Clinical and biological data were analyzed, notably enterovirus RT-PCR results. The primary outcome was the duration of antibiotic therapy. Results: 92 patients were recruited. When tested, 41% of infants were positive for enterovirus, median antibiotic duration was reduced in enterovirus positive in comparison to negative patients with respectively 1.9 [interquartile range (IQR), 1.7-2] vs. 4.1 [IQR, 2-6], p < 0.001. No clinical nor biological features differed according to the enterovirus status. Conclusion: In this population, enterovirus positive CSF are frequent despite the absence of pleocytosis. However, its research was not guided by clinical or biological presentations. Systematic and routine use of enterovirus RT-PCR during enterovirus season, regardless of CSF cell count, could reduce the prescription of antibiotics in febrile infants under 3 months old without clinical orientation.

Invasive Bacterial Infections in Children With Sickle Cell Disease: 2014-2019.

BACKGROUND: Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. METHODS: Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. RESULTS: We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). CONCLUSIONS: In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.

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

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.

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

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.

Factors Associated With Severe SARS-CoV-2 Infection.

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 (n = 29) and hospitalized for a diagnosis not related to SARS-CoV-2 (n = 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.

Management of Febrile Urinary Tract Infection With or Without Bacteraemia in Children: A French Case-Control Retrospective Study.

Background: Febrile urinary tract infections (FUTIs) are common among children, and are associated with a bacteraemia between 4 and 7% of cases. No data is available concerning the management of children with a bacteraemic FUTI. Objectives: To compare the antibiotic treatment (parenteral and total duration) among children with bacteraemic and non-bacteraemic FUTIs, and the mean hospital length of stay (LOS); to describe clinical, microbiological and imaging features of children with bacteraemic and non-bacteraemic FUTIs and observed management modifications when the blood culture was positive. Methods: A retrospective case-control study between 2009 and 2015 at Robert Debré's Pediatric Emergency Department (Paris, France). Children with a bacteraemic FUTI were included and matched for age and sex with two children with a non-bacteraemic FUTI. Results: We included 50 children with a bacteraemic FUTI matched to 100 children with a non-bacterameic FUTI. The mean duration of parenteral antibiotics was longer for bacteraemic children (6.7 vs. 4.0 days, p < 0.001) but this difference was only significant in children > 28 days-old. The mean total duration of antibiotic was similar (11.3 vs. 11.6 days, p = 0.61). The mean LOS was longer for bacteraemic children (5.1 vs. 2.0 days, p < 0.001) but this difference was only significant in children > 28 days-old. A positive blood culture changed the management in 66% of patients. Clinical features at presentation were comparable. Bacteraemic patients had a higher procalcitonin (p = 0.006) and C-reactive protein (p = 0.01), lower mean lymphocyte count (p < 0.001). Conclusions: A bacteraemic FUTI in children induced a longer duration of parenteral antibiotic treatment, a longer hospitalization in children > 28 days-old, and a modification of management for 66% of patients.

Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation.

Nitrous oxide (N2O) is widely used as an anesthetic or an analgesic. N2O prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to N2O. This was an incentive to prospectively investigate functional vitamin B12 deficiency in patients affected by sickle cell disease regularly exposed to N2O. We measured plasma concentrations of vitamin B12, total homocysteine, methionine and methylmalonic acid in 39 patients with sickle cell disease between 2015 and 2016. No patients developed neurological symptoms related to N2O administration but 19 patients (49%) had biochemical abnormalities suggesting mildly disturbed vitamin B12 metabolism e.g. decreased B12 vitamin, hypomethioninemia, or slightly increased methylmalonic acid or homocysteine. The clinical case highlight the potential severe deleterious effects of N2O over exposure on B12 vitamin metabolism in particular in patients affected with sickle cell disease. Conversely, when used without excess even repeatedly, there seem to be no overt clinically relevant abnormalities in vitamin B12 metabolism as observed on the cohort of 39 sickle cell disease affected patients.

Respiratory pathogens and acute chest syndrome in children with sickle cell disease.

BACKGROUND: Acute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS. MATERIALS AND METHODS: An observational, prospective, single-centre cohort study with nested case-control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray). RESULTS: We included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4-8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case-control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS. CONCLUSIONS: Viral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.

Emergence of Kawasaki disease related to SARS-CoV-2 infection in an epicentre of the French COVID-19 epidemic: a time-series analysis.

BACKGROUND: Kawasaki disease is an acute febrile systemic childhood vasculitis, which is suspected to be triggered by respiratory viral infections. We aimed to examine whether the ongoing COVID-19 epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with an increase in the incidence of Kawasaki disease. METHODS: We did a quasi-experimental interrupted time series analysis over the past 15 years in a tertiary paediatric centre in the Paris region, a French epicentre of the COVID-19 outbreak. The main outcome was the number of Kawasaki disease cases over time, estimated by quasi-Poisson regression. In the same centre, we recorded the number of hospital admissions from the emergency department (2005-2020) and the results of nasopharyngeal multiplex PCR to identify respiratory pathogens (2017-2020). These data were compared with daily hospital admissions due to confirmed COVID-19 in the same region, recorded by Public Health France. FINDINGS: Between Dec 1, 2005, and May 20, 2020, we included 230 patients with Kawasaki disease. The median number of Kawasaki disease hospitalisations estimated by the quasi-Poisson model was 1·2 per month (IQR 1·1-1·3). In April, 2020, we identified a rapid increase of Kawasaki disease that was related to SARS-CoV-2 (six cases per month; 497% increase [95% CI 72-1082]; p=0·0011), starting 2 weeks after the peak of the COVID-19 epidemic. SARS-CoV-2 was the only virus circulating intensely during this period, and was found in eight (80%) of ten patients with Kawasaki disease since April 15 (SARS-CoV-2-positive PCR or serology). A second peak of hospital admissions due to Kawasaki disease was observed in December, 2009 (six cases per month; 365% increase ([31-719]; p=0.0053), concomitant with the influenza A H1N1 pandemic. INTERPRETATION: Our study further suggests that viral respiratory infections, including SAR-CoV-2, could be triggers for Kawasaki disease and indicates the potential timing of an increase in incidence of the disease in COVID-19 epidemics. Health-care providers should be prepared to manage an influx of patients with severe Kawasaki disease, particularly in countries where the peak of COVID-19 has recently been reached. FUNDING: French National Research Agency.

Kawasaki disease: abnormal initial echocardiogram is associated with resistance to IV Ig and development of coronary artery lesions.

BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis that affects small and medium blood vessels. Intensified treatments for the most severely affected patients have been proposed recently, and the early identification of KD patients at high risk for coronary artery aneurysms (CAA) is crucial. However, the risk scoring systems developed in Japan have not been validated in European populations, and little data is available concerning the link between initial echocardiogram findings other than high z-scores and cardiac prognosis. METHODS: In order to investigate whether the presence of any abnormalities, other than high z-scores in first echocardiogram, are associated with resistance to IV immunoglobulins and/or subsequent development of CAA, we retrospectively analyzed data from children diagnosed with KD between 2006 and 2016 at a tertiary Hospital in Paris, France. RESULTS: A total of 157 children were included. The initial echocardiogram was performed after a median of 7 days of fever and was abnormal in 48 cases (31%). The initial presence of any echocardiographic abnormality (coronary artery dilatation, CAA, pericardial effusion, perivascular brightness of the coronary arteries, left-ventricular dysfunction and mitral insufficiency) was strongly associated with resistance to intravenous immunoglobulin (p = 0.005) and development of coronary artery lesions within the first 6 weeks of disease (p = 0.01). All patients (n = 7) with persistent coronary abnormalities at 1 year already had an abnormal initial echocardiogram. Severity scoring systems from Japan had low sensitivity (0-33%) and low specificity (71-82%) for predicting immunoglobulin resistance or cardiac involvement. CONCLUSIONS: In European populations with mixed ethnic backgrounds, the presence of any abnormalities at the initial echocardiogram may contribute to early identification of patients with severe disease.