Infection and Pediatric Arterial Ischemic Stroke Presumably Related to Focal Cerebral Arteriopathy: Data From the COVID-19 Pandemic.

BACKGROUND: Infection may trigger pediatric arterial ischemic stroke (PAIS), notably when related to focal cerebral arteriopathy. Community- and individual-level nonpharmaceutical interventions during the COVID-19 pandemic resulted in a major decrease in pediatric viral infections. We explored the consequences on the incidence of PAIS. METHODS: Using national public health databases, we identified children hospitalized between 2015 and 2022 with PAIS. Using an age proxy (29 days to 7 years) and excluding patients with cardiac and hematologic conditions, we focused on children with PAIS presumably related to focal cerebral arteriopathy or with no definite cause. Considering the delay between infection and PAIS occurrence, we compared a prepandemic reference period, a period with nonpharmaceutical interventions, and a post-nonpharmaceutical intervention period. RESULTS: Interrupted time-series analyses of the monthly incidence of PAIS in this group showed a significant decrease in the nonpharmaceutical intervention period compared with the prepandemic period: -33.5% (95% CI, -55.2%, -1.3%); P=0.043. CONCLUSIONS: These data support the association between infection and PAIS presumably related to focal cerebral arteriopathy.

Age-Specific Resurgence in Invasive Pneumococcal Disease Incidence in the COVID-19 Pandemic Era and Its Association With Respiratory Virus and Pneumococcal Carriage Dynamics: A Time-Series Analysis.

Using multiple national surveillance systems, we found an increase in the incidence of invasive pneumococcal disease during after the relaxation of non-pharmaceutical interventions against COVID-19, which strongly varied by age. Age groups with higher incidence of respiratory syncytial virus and influenza also experienced higher increase in invasive pneumococcal disease incidence, with no change in pneumococcal carriage.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.

Neurological features related to influenza virus in the pediatric population: a 3-year monocentric retrospective study.

Influenza virus is generally characterized by fever, myalgia, and respiratory symptoms. Neurological entities have already been described, such as acute necrotizing encephalitis (ANE). We aimed to highlight the non-exceptional nature and explore the clinical spectrum and evolution of neurological features related to influenza virus in children. This monocentric observational study included patients under 18 years old, positive for influenza virus, between January 2017 and April 2019 in a pediatric university hospital. Patients were classified into two groups: those with or without a previous significant neurological or metabolic disorder. Two hundred eighty-nine children were identified with influenza infection. Thirty seven had a neurological manifestation: 14 patients who had previous significant neurological or metabolic disorder and 23 patients with no medical history. We identified several clinical patterns: 22 patients had seizures, 7 behavior disorders, 5 disturbances of consciousness, and 3 motor deficits. Four were diagnosed with a known influenza-associated neurological syndrome: 1 ANE, 1 cytotoxic lesion of the corpus callosum, 1 hemiconvulsion-hemiplegia-epilepsia syndrome, and 1 recurrent encephalitis in the context of a RANBP2 mutation. The neurological outcome was favorable in most cases. None of the patients with previous significant disorder retained sequalae or had a recurrence. Two patients had a fatal outcome, and both had a predisposing disorder. CONCLUSION: Various neurological manifestations can be associated with influenza virus. Certain entities led to a poor prognosis, but in most cases, symptoms improved within a few days. The severity of the neurological manifestations correlated with previous neurological or metabolic disorders. WHAT IS KNOWN: • Influenza viruses are well known pathogens with a seasonal epidemic evolution, particularly affecting children. These viruses cause acute fever with respiratory symptoms, associated with myalgia and headaches. Neurological presentation in influenza-virus infection is a well-established possibility as influenza virus is considered to be responsible for 27 to 36% of childhood encephalitis. Some specific and severe entity as acute necrotizing encephalitis, cytotoxic lesion of the corpus callosum, or Hemiconvulsion-hemiplegia-epilepsy syndrome are well described. WHAT IS NEW: • In a French monocentric cohort of 37 children with influenza-related neurologic manifestations, the majority of these manifestations, including seizure, drowsiness, motor deficiency, hallucination… are self limiting and do not lead to after-effects. In rare cases (4/37), they may reveal severe encephalitis requiring rapid and appropriate treatment. Otherwise, comparison of a group of 14 children with underlying neurological or metabolic disorder with a group of 23 children free of any significant disorder show that the severity of the neurological manifestations was largely related to previous neurological or metabolic disorders highlighting the importance of vaccination in this population.

What are the clues for an inherited metabolic disorder in Reye syndrome? A single Centre study of 58 children.

OBJECTIVES: Reye Syndrome is an acute encephalopathy with increased liver enzymes and blood ammonia, without jaundice. The prevalence of an underlying inherited metabolic disorder (IMD) is unclear, nor the clinical or biological factors directing toward this diagnosis. Our aims were to define these clues in a large series of patients. PATIENTS AND METHODS: We retrospectively studied all patients with Reye admitted in our institution from 1995. We defined 3 groups: Group 1 with a confirmed IMD, Group 2 considered as free of IMD, Group 3 unclassified. Statistical analysis compared patients in Groups 1 and 2, to find criteria for a diagnosis of IMD. RESULTS: Fifty-eight children were included; 41 (71%) had a confirmed IMD, 12 (20%) were free of IMD, and 5 remained unclassified. IMDs included Urea Cycle Disorders (51%), Fatty-Acid Oxidation Disorders (24%), ketogenesis defects (5%), other mitochondrial energy metabolism defects (10%), NBAS mutation (7%), Glycosylation Disorders (2%). In Group 2, the trigger was a viral infection, or a drug, deferasirox in three children. Univariate analysis showed that onset before 2 years-old, recurrent Reye and the association with rhabdomyolysis were significantly associated with IMD. Blood ammonia was a poor discriminating marker. All children were admitted into the intensive care unit, 23% needed continuous venovenous hemodialysis and one died from brain oedema. CONCLUSION: Metabolic tests should be performed early in all cases of Reye, regardless of triggers. As they can be inconclusive, we suggest to systematically go to Next-Generation Sequencing study. These children should be transferred early to a specialized unit.

Neuroinflammatory Disease following Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children.

OBJECTIVE: To describe neurologic, radiologic and laboratory features in children with central nervous system (CNS) inflammatory disease complicating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: We focused on CNS inflammatory diseases in children referred from 12 hospitals in the Paris area to Necker-Sick Children Reference Centre. RESULTS: We identified 19 children who had a history of SARS-CoV-2 infection and manifest a variety of CNS inflammatory diseases: encephalopathy, cerebellar ataxia, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, or optic neuritis. All patients had a history of SARS-CoV-2 exposure, and all tested positive for circulating antibodies against SARS-CoV-2. At the onset of the neurologic disease, SARS-CoV-2 PCR results (nasopharyngeal swabs) were positive in 8 children. Cerebrospinal fluid was abnormal in 58% (11/19) and magnetic resonance imaging was abnormal in 74% (14/19). We identified an autoantibody co-trigger in 4 children (myelin-oligodendrocyte and aquaporin 4 antibodies), representing 21% of the cases. No autoantibody was found in the 6 children whose CNS inflammation was accompanied by a multisystem inflammatory syndrome in children. Overall, 89% of patients (17/19) received anti-inflammatory treatment, primarily high-pulse methylprednisolone. All patients had a complete long-term recovery and, to date, no patient with autoantibodies presented with a relapse. CONCLUSIONS: SARS2-CoV-2 represents a new trigger of postinfectious CNS inflammatory diseases in children.

Coronavirus Disease 2019 Pandemic: Impact Caused by School Closure and National Lockdown on Pediatric Visits and Admissions for Viral and Nonviral Infections-a Time Series Analysis.

A time series analysis of 871 543 pediatric emergency visits revealed that the coronavirus disease 2019 (COVID-19) lockdown and school closures were associated with a significant decrease in infectious diseases disseminated through airborne or fecal-oral transmission: common cold, gastroenteritis, bronchiolitis, and acute otitis. No change was found for urinary tract infections.

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

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

Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P = .008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P = .004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design.

Predictors of clinically urgent intracranial pathology at neuroimaging in children with complex febrile seizures: a retrospective cross-sectional study.

AIM: To assess the prevalence of clinically urgent intracranial pathology (CUIP) in children visiting the emergency department with a complex febrile seizure (CFS). METHODS: Retrospective cohort review. We analysed the visits of patients for a CFS from January 2007 to December 2011 in seven paediatric emergency departments. Our main outcomes were the proportions of CUIP diagnosed between day 0 and 1 and within 30 days after the index visit. RESULTS: From 1 183 487 visits, 839 were for a CFS and 130 (15.5%) of these had a neuroimaging performed within 30 days (CT scan for 75 visits [8.9%], MRI for 30 visits [3.6%] and both for 25 visits [3.0%]). Three CUIP were diagnosed between day 0 and 1 (0.4% [CI-95%: 0.1-1.3]), 5 within 30 days after the index visit (0.7% [CI-95%: 0.2-1.7]) but none among the 630 visits of children presenting with a normal neurological clinical examination (0% [95% CI: 0.0-0.7]), nor among the 468 presenting only with multiple seizure (0% [95% CI: 0.0-1.0]). CONCLUSION: In children with a CFS, CUIP is rare event in the subgroup of children with a normal neurological clinical examination and in those with brief generalised multiple seizures.

SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020.

End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Pneumococcal susceptibility to antibiotics in carriage: a 17 year time series analysis of the adaptive evolution of non-vaccine emerging serotypes to a new selective pressure environment.

BACKGROUND: Pneumococcal conjugate vaccine (PCV) implementations led to major changes in serotype distribution and antibiotic resistance in carriage, accompanied by changes in antibiotic consumption. OBJECTIVES: To assess the dynamic patterns of antimicrobial non-susceptibility across non-PCV13 serotypes following PCV implementations. METHODS: We conducted a quasi-experimental interrupted time series analysis based on a 17 year French nationwide prospective cohort. From 2001 to 2018, 121 paediatricians obtained nasopharyngeal swabs from children with acute otitis media who were aged 6 months to 2 years. The main outcome was the rate of penicillin-non-susceptible pneumococci (PNSP), analysed by segmented regression. RESULTS: We enrolled 10 204 children. After PCV13 implementation, the PNSP rate decreased (-0.5% per month; 95% CI -0.9 to -0.1), then, after 2014, the rate slightly increased (+0.7% per month; 95% CI +0.2 to +1.2). Global antibiotic use within the previous 3 months decreased over the study period (-22.2%; 95% CI -33.0 to -11.3), but aminopenicillin use remained high. Among the main non-PCV13 serotypes, four dynamic patterns of penicillin susceptibility evolution were observed, including unexpected patterns of serotypes emerging while remaining or even becoming penicillin susceptible. In contrast to PNSP strains, for these latter patterns, the rate of co-colonization with Haemophilus influenzae increased concomitant with their emergence. CONCLUSIONS: In a context of continuing high antibiotic selective pressure, a progressive increase in PNSP rate was observed after 2014. However, we highlighted an unexpected variability in dynamic patterns of penicillin susceptibility among emerging non-PCV13 serotypes. Antibiotic resistance may not be the only adaptive mechanism to antimicrobial selective pressure, and co-colonization with H. influenzae may be involved.

Hemodynamic Shock Caused by Tension Pneumoperitoneum in a 5-Year-Old Girl.

Tension pneumoperitoneum is a relatively rare occurrence in the pediatric population. However, tension pneumoperitoneum is associated with significant morbidity and mortality if it is not promptly diagnosed and treated. A 5-year-old girl was admitted to emergency department with abdominal pain. She was in shock, and the radiograph film of the abdomen revealed a voluminous tension pneumoperitoneum. Aggressive fluid challenges were performed in intensive care followed by urgent laparotomy. Primary abdominal compartment due to trapped gas caused a decreased venous return and visceral perfusion. In the absence of hemodynamic improvement after vascular filling, needle decompression was performed before surgery.

Impact of Implementing National Guidelines on Antibiotic Prescriptions for Acute Respiratory Tract Infections in Pediatric Emergency Departments: An Interrupted Time Series Analysis.

BACKGROUND: Many antibiotics are prescribed inappropriately in pediatric emergency departments (PEDs), but little data are available in these settings about effective interventions based on guidelines that follow the antimicrobial stewardship principle. Our aim was to assess the impact of implementing the 2011 national guidelines on antibiotic prescriptions for acute respiratory tract infection (ARTI) in PEDs. METHOD: We conducted a multicentric, quasiexperimental, interrupted time series analysis of prospectively collected electronic data from 7 French PEDs. We included all pediatric patients who visited a participating PED during the study period from November 2009 to October 2014 and were diagnosed with an ARTI. The intervention consisted of local protocol implementation, education sessions, and feedback. The main outcome was the antibiotic prescription rate of discharge prescriptions for ARTI per 1000 PED visits before and after implementation, analyzed using the segmented regression model. RESULTS: We included 242534 patients with an ARTI. The intervention was associated with a significant change in slope for the antibiotic prescription rate per 1000 PED visits (-0.4% per 15-day period, P = .04), and the cumulative effect at the end of the study was estimated to be -30.9%, (95% CI [-45.2 to -20.1]), representing 13136 avoided antibiotic prescriptions. The broad-spectrum antibiotic prescription relative percentage decreased dramatically (-62.7%, 95% CI [-92.8; -32.7]) and was replaced by amoxicillin. CONCLUSION: Implementation of the 2011 national French guidelines led to a significant decrease in the antibiotic prescription rate for ARTI and a dramatic drop in broad-spectrum antibiotic prescriptions, in favor of amoxicillin.

Do All Children Who Present With a Complex Febrile Seizure Need a Lumbar Puncture?

STUDY OBJECTIVE: We assess the prevalences of bacterial meningitis and herpes simplex virus meningoencephalitis (HSV-ME) in children with a complex febrile seizure and determine these prevalences in the subgroup of children with a clinical examination result not suggestive of meningitis or encephalitis. METHODS: This multicenter retrospective study was conducted in 7 pediatric emergency departments (EDs) in the region of Paris, France. Visits of patients aged 6 months to 5 years for a complex febrile seizure from January 2007 to December 2011 were analyzed. We defined a subgroup of patients whose clinical examination result was not suggestive of meningitis or encephalitis. Bacterial meningitis and HSV-ME were sequentially sought for by analyzing bacteriologic and viral data at the visit, looking for data from a second visit to the hospital after the index visit, and telephoning the child's parents. RESULTS: From a total of 1,183,487 visits in the 7 pediatric EDs, 839 patients presented for a complex febrile seizure, of whom 260 (31.0%) had a lumbar puncture. The outcomes bacterial meningitis and HSV-ME were ascertainable for 715 (85%) and 657 (78.3%) visits, respectively, and we found 5 cases of bacterial meningitis (0.7% [95% confidence interval [CI] 0.2% to 1.6%]) and no HSV-ME (0% [95% CI 0% to 0.6%]). Among the 630 visits of children with a clinical examination result not suggesting meningitis or encephalitis, we found no bacterial meningitis (0% [95% CI 0% to 0.7%]) and no HSV-ME (0% [95% CI 0% to 0.8%]). CONCLUSION: In children with a complex febrile seizure, bacterial meningitis and HSV-ME are unexpected events when the clinical examination after complex febrile seizure is not suggestive of meningitis or encephalitis.

Extended-spectrum ß-lactamase-producing bacteria caused less than 5% of urinary tract infections in a paediatric emergency centre.

AIM: The last decade has seen a significant increase in extended-spectrum ß-lactamase (ESBL) secreting organisms responsible for paediatric urinary tract infections (UTIs), particularly in community-acquired infections. These expose patients to the risks of antibiotic treatment failure and renal scarring. This prospective study examined the prevalence and risk factors of febrile ESBL UTIs and their treatment in the paediatric emergency department of a university hospital. METHODS: In this prospective observational study, all children from 0 to 16 years of age with febrile UTIs were included from May 2012 to April 2013. Cases with and without ESBL involvement were compared. RESULTS: Of the 474 diagnosed febrile UTIs, 22 (4.6%) with a 95% confidence interval (95% CI) of 2.9-6.9 were due to an ESBL-producing organism. Escherichia coli was found in 85% of cases. Significant odds ratios (OR) for ESBL urinary tract infections were prior hospitalisation (OR 4.1, 95% CI 1.6-10.8), urinary tract abnormalities (OR 3.9, 95% CI 1.5-10.2) and previous antibiotic treatment (OR 3.1, 95% CI 1.2-8.8). All ESBL urinary tract infections had positive outcomes. CONCLUSION: The prevalence of febrile ESBL urinary tract infections was less than 5% in a paediatric emergency department. This low rate was not high enough to justify changing our guidelines.