BackgroundThe cost-effectiveness of universal rotavirus (RV) vaccination is controversial in developed countries. As a result, RV vaccination programs do not currently exist in most European countries. Hospitalization is the main driver of RV disease costs, and prematurity, low birth weight (LBW) and underlying medical conditions have been associated with RV hospitalization and complications. We investigated the cost-effectiveness of targeted RV vaccination of high-risk infants and universal RV vaccination versus no vaccination.MethodsDisease burden, mortality and healthcare costs of RV hospitalization for children with and without prematurity, LBW and congenital pathology were quantified in two hospital-based observational studies in the Netherlands. Cost-effectiveness analysis was based on an age-structured stochastic multi-cohort model of the Dutch population comparing universal RV vaccination and targeted vaccination of high-risk infants to no vaccination. The primary endpoint was the incremental cost-effectiveness ratio (ICER), with a threshold of €35,000/quality-adjusted life year (QALY) from the healthcare provider perspective. Sensitivity analyses included vaccine price and coverage, herd-immunity and QALY losses.ResultsA total of 936 children with RV infection were included. Prematurity, LBW and congenital pathology were associated with increased risks of RV hospitalization (relative risks (RR) ranging from 1.6 to 4.4), ICU admission (RR ranging from 4.2 to 7.9), prolonged hospital stay (1.5 to 3.0 excess days) and higher healthcare costs (€648 to €1,533 excess costs). Seven children succumbed due to RV complications, all belonging to the high-risk population. Targeted RV vaccination was highly cost-effective and potentially cost-saving from the healthcare provider perspective with ICERs below €20,000/QALY in all scenarios with total (undiscounted) annual healthcare costs between -€0.1 and €0.5 million/year. Results were most sensitive to mortality rates, but targeted vaccination remained highly cost-effective up to reductions of 90% compared to observed mortality. Universal RV vaccination was not considered cost-effective (mean ICER: €60,200/QALY) unless herd-immunity and caretaker QALY losses were included and vaccine prices were €60 at most (mean ICER: €21,309/QALY).ConclusionWe recommend targeted RV vaccination for high-risk infants in developed countries.

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Comprehending humoral immunity to SARS-CoV-2, including in children, is crucial for future public health and vaccine strategies. Others have suggested that mucosal antibody measurement could be an important and more convenient tool to evaluate humoral immunity compared to circulating antibodies.

BackgroundAs SARS-CoV-2 will likely continue to circulate, low-impact methods become more relevant to monitor antibody-mediated immunity. Saliva sampling could provide a non-invasive method with reduced impact on children. Studies reporting on the differences between systemic and mucosal humoral immunity to SARS-CoV-2 are inconsistent in adults and scarce in children. These differences may be further unraveled by exploring associations to demographic and clinical variables.MethodsTo evaluate the use of saliva antibody assays, we performed a cross-sectional cohort study by collecting serum and saliva of 223 children attending medical services in the Netherlands (irrespective of SARS-CoV-2 exposure, symptoms or vaccination) from May to October 2021. With a Luminex and a Wantai assay, we measured prevalence of SARS-CoV-2 spike (S), receptor binding domain (RBD) and nucleocapsid-specific IgG and IgA in serum and saliva and explored associations with demographic variables.FindingsThe S-specific IgG prevalence was higher in serum 39% (95% CI 32 – 45%) than in saliva 30% (95% CI 24 – 36%) (P ≤ 0.003). Twenty-seven percent (55/205) of children were S-specific IgG positive in serum and saliva, 12% (25/205) were only positive in serum and 3% (6/205) only in saliva. Vaccinated children showed a higher concordance between serum and saliva than infected children. Odds for saliva S-specific IgG positivity were higher in girls compared to boys (aOR 2.63, P = 0.012). Moreover, immunocompromised children showed lower odds for S- and RBD-specific IgG in both serum and saliva compared to healthy children (aOR 0.23 – 0.25, P ≤ 0.050).ConclusionsWe showed that saliva-based antibody assays can be useful for identifying SARS-CoV-2 humoral immunity in a non-invasive manner, and that IgG prevalence may be affected by sex and immunocompromisation. Differences between infection and vaccination, between sexes and between immunocompromised and healthy children should be further investigated and considered when choosing systemic or mucosal antibody measurement.

The difficulty in recognizing early-onset neonatal sepsis (EONS) in a timely manner due to non-specific symptoms and the limitations of diagnostic tests, combined with the risk of serious consequences if EONS is not treated in a timely manner, has resulted in a low threshold for starting empirical antibiotic treatment. New guideline strategies, such as the neonatal sepsis calculator, have been proven to reduce the antibiotic burden related to EONS, but lack sensitivity for detecting EONS. In this review, the potential of novel, targeted preventive and diagnostic methods for EONS is discussed from three different perspectives: maternal, umbilical cord and newborn perspectives. Promising strategies from the maternal perspective include Group B Streptococcus (GBS) prevention, exploring the virulence factors of GBS, maternal immunization and antepartum biomarkers. The diagnostic methods obtained from the umbilical cord are preliminary but promising. Finally, promising fields from the newborn perspective include biomarkers, new microbiological techniques and clinical prediction and monitoring strategies. Consensus on the definition of EONS and the standardization of research on novel diagnostic biomarkers are crucial for future implementation and to reduce current antibiotic overexposure in newborns.