Juvenile neuropsychiatric systemic lupus erythematosus: identification of novel central neuroinflammation biomarkers

International audienceIntroduction Juvenile systemic lupus erythematosus (j-SLE) is a rare chronic autoimmune disease affecting multiple organs. Ranging from minor features, such as headache or mild cognitive impairment, to serious and life-threatening presentations, j-neuropsychiatric SLE (j-NPSLE) is a therapeutic challenge. Thus, the diagnosis of NPSLE remains difficult, especially in pediatrics, with no specific biomarker of the disease yet validated. Objectives To identify central nervous system (CNS) disease biomarkers of j-NPSLE. Methods A 5-year retrospective tertiary reference monocentric j-SLE study. A combination of standardized diagnostic criteria and multidisciplinary pediatric clinical expertise was combined to attribute NP involvement in the context of j-SLE. Neopterin and interferon-alpha (IFN-α) protein levels in cerebrospinal fluid (CSF) were assessed, together with routine biological and radiological investigations. Results Among 51 patients with j-SLE included, 39% presented with j-NPSLE. J-NPSLE was diagnosed at onset of j-SLE in 65% of patients. No specific routine biological or radiological marker of j-NPSLE was identified. However, CSF neopterin levels were significantly higher in active j-NPSLE with CNS involvement than in j-SLE alone ( p = 0.0008). Neopterin and IFN-α protein levels in CSF were significantly higher at diagnosis of j-NPSLE with CNS involvement than after resolution of NP features (respectively p = 0.0015 and p = 0.0010) upon immunosuppressive treatment in all patients tested ( n = 10). Both biomarkers correlated strongly with each other ( R s = 0.832, p < 0.0001, n = 23 paired samples). Conclusion CSF IFN-α and neopterin constitute promising biomarkers useful in the diagnosis and monitoring of activity in j-NPSLE

Immune debt: Recrudescence of disease and confirmation of a contested concept

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Factors associated with death in children with purpura fulminans: a French national prospective cohort study

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Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey

Summary Background Successive implementation of seven-valent then 13-valent pneumococcal conjugate vaccines (PCVs) led to a marked decrease in pneumococcal disease burden, including pneumococcal meningitis. We assessed the long-term effect of implementation of PCVs on incidence of pneumococcal meningitis in children in France over a 16-year period. Methods We did a quasi-experimental, population-based interrupted time-series analysis with a nationwide prospective survey over 16 years in France, recruiting children aged younger than 15 years from 227 paediatric wards from January, 2001, to December, 2016. The main outcome by the time-series model was the estimated incidence of pneumococcal meningitis per 100?000 children (of a population of 12·6 million children in 2017) before and after PCV7 and PCV13 implementation. The time-series model was based on segmented regression with autoregressive error. Findings We enrolled 1778 children with pneumococcal meningitis. PCV13 implementation led to a significant reduction in monthly incidence of pneumococcal meningitis from 0·12 per 100?000 children before PCV13 to a nadir of 0·07 in December, 2014 (?38%, 95% CI ?56·1 to ?20·4;

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

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<0.001). Among children with isolated bacterial otopathogens (n = 219), non-typable Haemophilus influenzae (NTHi) was the most frequent otopathogen isolated (n = 106, 48.4% [95% CI 41.6%;55.2%]), followed by Streptoccocus pyogenes (group A streptococcus [GAS]) (n = 76, 34.7% [95% CI 28.4%;41.4%]) and Streptococcus pneumoniae (Sp) (n = 61, 27.9% [95% Ci 22.0%;34.3%]). NTHi was frequently isolated in infants and toddlers (53.1%), whereas the main otopathogen in older children was GAS (52.3%). In cases of co-infection with at least two otopathogens (16.9%, n = 37/219), NTHi was frequently involved (78.4%, n = 29/37). When Sp was isolated, PCV13 serotypes accounted for 32.1% of cases, with serotype 3 the main serotype (16.1%). Among Sp strains, 29.5% were penicillin-intermediate and among NTHi strains, 16.0% were β-lactamase-producers. More than 5 years after PCV13 implementation, the leading bacterial species recovered from AOM with SPTM was NTHi for infants and toddlers and GAS for older children. In both age groups, Sp was the third most frequent pathogen and vaccine serotypes still played an important role. No resistant Sp strains were isolated, and the frequency of β-lactamase-producing NTHi did not exceed 16%

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

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

Unique Changes in the Incidence of Acute Chest Syndrome in Children with Sickle-Cell Disease Unravel the Role of Respiratory Pathogens: A Time-Series Analysis

International audienceBackground: Acute chest syndrome (ACS) is a life-threatening complication of sickle-cell disease (SCD). Although respiratory pathogens are frequently detected in children with ACS, their respective role in triggering the disease is still unclear. We hypothesized that ACS incidence followed the unprecedented population-level changes in respiratory pathogens dynamics following the COVID-19-related non-pharmaceutical interventions (NPIs).Research question: What is the respective role of respiratory pathogens in ACS epidemiology?Study design: AND METHODS. We performed an interrupted time-series analysis of patient records from a national hospital-based surveillance system. All children < 18 years of age with SCD hospitalized for ACS in France between January 2015 and May 2022 were included. The monthly incidence of ACS per 1000 children with SCD over time was analyzed using a quasi-Poisson regression model. The circulation of 12 respiratory pathogens in the general pediatric population over the same period was included in the model to assess the fraction of ACS potentially attributable to each respiratory pathogen.Results: Among the 55,941 hospitalizations of children with SCD, 2306 episodes of ACS were included (median [IQR] age, 9 [5-13] years). We observed a significant decrease in ACS incidence after NPI implementation in March 2020 (-29.5%; 95% CI, -46.8% to -12.2%; P = .001) and a significant increase after lifting of the NPIs in April 2021 (24.4%; 95% CI, 7.2% to 41.6%; P = .007). Using population-level incidence of several respiratory pathogens, we found that Streptococcus pneumoniae accounted for 30.9% (95% CI, 4.9% to 56.9%; P = .02) of ACS incidence over the study period and influenza 6.8% (95% CI, 2.3% to 11.3%; P = .004), whereas other respiratory pathogens had only a minor role.Interpretation: NPIs were associated with significant changes in ACS incidence concomitantly with major changes in the circulation of several respiratory pathogens in the general population. This unique epidemiological situation allowed to unravel the contribution of these respiratory pathogens, in particular S. pneumoniae and influenza, to the burden of childhood ACS, highlighting the potential benefit of vaccine prevention in this vulnerable population