Best Practice Recommendations for the Diagnosis and Management of Children With Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS; Multisystem Inflammatory Syndrome in Children, MIS-C) in Switzerland.

Background: Following the spread of the coronavirus disease 2019 (COVID-19) pandemic a new disease entity emerged, defined as Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C). In the absence of trials, evidence for treatment remains scarce. Purpose: To develop best practice recommendations for the diagnosis and treatment of children with PIMS-TS in Switzerland. It is acknowledged that the field is changing rapidly, and regular revisions in the coming months are pre-planned as evidence is increasing. Methods: Consensus guidelines for best practice were established by a multidisciplinary group of Swiss pediatric clinicians with expertise in intensive care, immunology/rheumatology, infectious diseases, hematology, and cardiology. Subsequent to literature review, four working groups established draft recommendations which were subsequently adapted in a modified Delphi process. Recommendations had to reach >80% agreement for acceptance. Results: The group achieved agreement on 26 recommendations, which specify diagnostic approaches and interventions across anti-inflammatory, anti-infectious, and support therapies, and follow-up for children with suspected PIMS-TS. A management algorithm was derived to guide treatment depending on the phenotype of presentation, categorized into PIMS-TS with (a) shock, (b) Kawasaki-disease like, and (c) undifferentiated inflammatory presentation. Conclusion: Available literature on PIMS-TS is limited to retrospective or prospective observational studies. Informed by these cohort studies and indirect evidence from other inflammatory conditions in children and adults, as well as guidelines from international health authorities, the Swiss PIMS-TS recommendations represent best practice guidelines based on currently available knowledge to standardize treatment of children with suspected PIMS-TS. Given the absence of high-grade evidence, regular updates of the recommendations will be warranted, and participation of patients in trials should be encouraged

Human germline heterozygous gain-of-function STAT6 variants cause severe allergic disease

STAT6 (signal transducer and activator of transcription 6) is a transcription factor that plays a central role in the pathophysiology of allergic inflammation. We have identified 16 patients from 10 families spanning three continents with a profound phenotype of early-life onset allergic immune dysregulation, widespread treatment-resistant atopic dermatitis, hypereosinophilia with esosinophilic gastrointestinal disease, asthma, elevated serum IgE, IgE-mediated food allergies, and anaphylaxis. The cases were either sporadic (seven kindreds) or followed an autosomal dominant inheritance pattern (three kindreds). All patients carried monoallelic rare variants in STAT6 and functional studies established their gain-of-function (GOF) phenotype with sustained STAT6 phosphorylation, increased STAT6 target gene expression, and TH2 skewing. Precision treatment with the anti-IL-4Rα antibody, dupilumab, was highly effective improving both clinical manifestations and immunological biomarkers. This study identifies heterozygous GOF variants in STAT6 as a novel autosomal dominant allergic disorder. We anticipate that our discovery of multiple kindreds with germline STAT6 GOF variants will facilitate the recognition of more affected individuals and the full definition of this new primary atopic disorder

Vaccination in immunosuppressed children: a comprehensive review and practical guide

Immunosuppressed children are particularly at risk of vaccine preventable diseases, however, vaccine coverage in this population remains too low. This is explained by a fear of possible adverse effects of vaccines under immunosuppression, but also lack of data and clear recommendations in particular regarding vaccination with live vaccines in this population. In this review, the latest literature and various recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to give practical guidelines on vaccination to specialists caring for children suffering from different dysimmune disorders and treated with various immunosuppressive regimens

Une étude de la réponse des cellules B mémoires au vaccin polysaccharidique conjugué contre le méningocoque du sérogroupe C

"Neisseraia meningitidis" est une cause importante de maladies invasives chez les enfants. En Angleterre, le vaccin polysaccharidique conjugué contre le sérogroupe C fait partie du plan de vaccination de routine. Chez les enfants de moins d'une année, 3 doses de vaccin induisent une montée importante des anticorps bactéricides, mais qui ne persistent pas au-delà d'une année. Les cellules B mémoires, semblent essentielles pour protéger les jeunes enfants primo-immunisés comme nourrissons. Dans cette étude, j'ai évalué la persistance dans le sang des plasmocytes producteurs d'anticorps et des cellules mémoires spécifiques chez des enfants de 12 mois primo-immunisés à 2,3, et 4 mois. Les résultats montrent que ces cellules, généralement non détectables, réapparaissent à jour 6 (plasmocytes) ou 8 (cellules B mémoire) après une dose de rappel de vaccin conjugué. Ces données permettent de mieux comprendre la participation de l'immunité mémoire à la protection contre les infections invasives à "N. meningitidis"

Persistence of protection against invasive bacteria-memory b cell response in infants after immunisation

Rapid waning of antibody and vaccine effectiveness is observed following infant immunisation with protein-polysaccharide conjugate vaccines. This is despite the demonstrable presence of immunological memory. However, disease can develop within a few days of carriage acquisition of encapsulated bacteria. Persistence of functional antibody, therefore, appears to be the key determinant of long-term protection against invasive bacterial diseases. Antibody persistence is thought to depend on the survival of long-lived plasma cells and memory B cells generated in germinal centres (GC). Using the ELISpot method, the kinetics of the B cell response following a booster dose of MenC conjugate vaccine (MenCV) at one year of age, and following a 2 dose-primary course of a new tetravalent meningococcal vaccine (MenACWY-CRM197) given at 2 and 4 months of age, were determined. It was found that priming with these vaccines induced protective antibody levels in the majority of children but detectable memory B cells only in a subset of children. A strong association was found between the level of polysaccharide-specific antibody and memory B cells produced after priming, and the persistence of functional antibody at one year of age

Novel approaches to reactivate pertussis immunity

Introduction: Whole cell and acellular pertussis vaccines have been very effective in decreasing the deaths of neonates and infants from Bordetella pertussis. Despite high vaccine coverage worldwide, pertussis remains one of the most common vaccine-preventable diseases, thus suggesting that new pertussis vaccination strategies are needed. Several candidates are currently under development, such as acellular pertussis vaccines that use genetically detoxified pertussis toxin, acellular pertussis vaccines delivered with new adjuvants or new delivery systems, or an intranasally delivered, live attenuated vaccine. Areas covered: This review discusses the different possibilities for improving current pertussis vaccines and the present state of knowledge on the pertussis vaccine candidates under development. Expert opinion: Until there is a safe, effective, and affordable alternative to the two types of existing vaccines, we should maintain sufficient childhood coverage and increase the vaccination of pregnant women, adolescents, and young adults.</p

Vaccination in Children With Autoimmune Disorders and Treated With Various Immunosuppressive Regimens: A Comprehensive Review and Practical Guide

Children with autoimmune disorders are especially at risk of vaccine-preventable diseases due to their underlying disease and the immunosuppressive treatment often required for a long period. In addition, vaccine coverage remains too low in this vulnerable population. This can be explained by a fear of possible adverse effects of vaccines under immunosuppression, but also a lack of data and clear recommendations, particularly with regard to vaccination with live vaccines. In this review, the latest literature and recommendations on vaccination in immunosuppressed children are discussed in detail, with the aim to provide a set of practical guidelines on vaccination for specialists caring for children suffering from different autoimmune disorders and treated with various immunosuppressive regimens

Impact de la vaccination sur les otites moyennes aiguës

Acute otitis media (AOM) is an important reason for medical visits and antibiotic use in children, with possible complications. Pneumococcal conjugate vaccines (PCV) have been developed from 2000, with first the apparition of the 7-valent PCV (PCV7), and from 2013, of the 13-valent PCV (PCV13). First developed to prevent invasive pneumococcal infections, they have been shown to reduce the number of AOM as well. PC13 has allowed to reduce the nasopharyngeal carriage of the majority of pneumococcal serotypes found in AOM, with a reduction of 77% of pneumococcal AOM, according to one study

Review of maternal immunisation during pregnancy: focus on pertussis and influenza

Seasonal influenza and pertussis infections are known to be significant causes of morbidity and mortality in neonates and infants worldwide. Influenza has also been associated with severe complications in pregnant women and after delivery. The most efficient and safe strategy to protect mothers and their offspring is maternal immunisation during pregnancy. The maternal antibodies thus acquired are transferred to the fetus as of the second trimester and confer passive immunity until the first infant immunisations. Therefore, it is strongly advised to administer booster doses of seasonal influenza and pertussis vaccines specifically during pregnancy. Influenza vaccines can be given at any time-point during pregnancy and pertussis vaccines after the first trimester. Both need a minimum interval of 14 days between immunisation and delivery and, especially for pertussis, early immunisation has been shown to increase neonatal antibody titres. Healthcare workers play a crucial role in vaccine uptake. This article aims to review the recommendations for maternal influenza and pertussis immunisation, and their physiological rationale, safety and benefit