Charting the impact of maternal antibodies and repeat exposures on sapovirus immunity in early childhood from a Nicaraguan birth cohort.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis in childhood. While vaccines against sapovirus may reduce gastroenteritis burden, a major challenge to their development is a lack of information about natural immunity. METHODS: We measured sapovirus-specific IgG in serum collected, between 2017 and 2020, of mothers soon after delivery and at 6 time points in Nicaraguan children until 3 years of age (n=112 dyads) using virus-like particles representing three sapovirus genotypes (GI.1, GI.2, GV.1). RESULTS: Sixteen (14.3%) of the 112 children experienced at least one sapovirus gastroenteritis episode, of which GI.1 was the most common genotype. Seroconversion to GI.1 and GI.2 was most common between 5 and 12 months of age, while seroconversion to GV.1 peaked at 18 to 24 months of age. All children who experienced sapovirus GI.1 gastroenteritis seroconverted and developed genotype-specific IgG. The impact of sapovirus exposure on population immunity was determined using antigenic cartography: newborns share their mothers' broadly binding IgG responses, which declined at 5 months of age and then increased as infants experienced natural sapovirus infections. CONCLUSION: By tracking humoral immunity to sapovirus over the first 3 years of life, this study provides important insights for the design and timing of future pediatric sapovirus vaccines.

Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity.

There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life.

Practice Patterns and Adverse Events of Nitrous Oxide Sedation and Analgesia: A Report from the Pediatric Sedation Research Consortium.

OBJECTIVES: To describe practice patterns and adverse events associated with nitrous oxide (N2O) administration as the primary sedative outside the operating room in varied settings by a diverse range of providers, and to identify patient and sedation characteristics associated with adverse events. STUDY DESIGN: Data prospectively collected by the Pediatric Sedation Research Consortium, which is comprised of 40 children's and general/community hospitals, was retrospectively analyzed for children who received N2O as the primary sedative. Descriptive measures of patient and sedation characteristics and adverse events were reported. A multivariable regression model was used to assess potential associations between patient and sedation characteristics and adverse events. RESULTS: A total of 1634 N2O administrations were identified. The majority was performed in sedation units, and most by advanced practice nurses or physician assistants. The most common adjunct medication was midazolam. There was a low prevalence of adverse events (6.5%), with vomiting as the most common (2.4%) and only 3 (0.2%) serious adverse events reported. The odds of vomiting increased when concomitant opioids were administered (OR 2.89, 95% CI 1.14, 7.32) and when nil per os (NPO) clear fluids <2 hours (OR 4.16, 95% CI 1.61, 10.76). NPO full meal <6 hours did not change the odds of vomiting (OR 1.42, 95% CI 0.57, 3.57). There were no aspiration events. CONCLUSIONS: There was a very low prevalence of serious adverse events during N2O administration in children outside of the operating room and by nonanesthesiologists. The odds of vomiting increased when concomitant opioids were administered and NPO clear fluids <2 hours.