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Aim: Continuous monitoring of blood culture (BC) systems allows rapid detection of microbial growth. We aimed to determine differences in time to positivity (TTP) in BACTEC BC between organisms and whether a 36-h period was sufficient to detect all relevant pathogenic bacteria for children admitted to a tertiary care paediatric hospital., Methods: This was a retrospective audit of positive aerobic (AE) and anaerobic (AN) BC from paediatric inpatients with available TTP from 1 August 2016 to 2 January 2019. First positive BC per bacteraemia episode was analysed., Results: Overall, 649 BC were positive, of which 480 first positive BC were analysed: 246 AE (51.3%) only, 216 paired (45%) (108 AE and 108 AN) and 18 AN (3.8%) only. There were 372 episodes of bacteraemia in 340 patients. Median age was 19 months (interquartile range (IQR): 1.25-60). Median TTP for AE and AN cultures was 13.20 (IQR: 9.84-18.48) and 13.92 h (IQR: 10.32-17.04), respectively. Organisms were GNR 49.7%, GPC 29.6%, contaminants 14.5%, mixed 3.0%, other 2.4% and yeast 0.8%. Streptococcus agalactiae had the fastest median TTP in AE and AN cultures, followed by Escherichia coli (AE 8.88 vs. 10.20 h). For paired AE and AN cultures, TTP was faster for AE versus AN cultures (13.36 vs. 14.52 h, P = 0.001). A 36-h cut-off time captured 97.7% AE BC and 99.1% AN BC with pathogens, and 86.5% AE BC and 91.7% AN BC with contaminants, respectively., Conclusions: GNR were the commonest pathogens in paediatric BC and faster growth was detected in AE versus AN cultures. By 36 h, >97.7% of BC were positive for pathogens versus 86.5% for contaminants., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children., Methods: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining., Findings: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens., Interpretation: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19., Funding: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002)., Competing Interests: Declaration of interests MQ: none; SH: none; SKH: none; JZ: none; CWT: none; CYC: none; JGL: none; LW: none; AB and NLB: report a pending patent for a method to monitor virus-specific T cells in biological samples and are co-founders of T Cell Diagnostic (TCD) Ltd., a biotech company developing T cell diagnostic for viral infections. CFY: reports honoraria and funding to attend conferences from Sanofi, Pfizer and Takeda., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In studies of infectious disease prevention, the level of protective efficacy of medicinal products such as vaccines and prophylactic drugs tends to vary over time. Many products require administration of multiple doses at scheduled times, as opposed to one-off or continual intervention. Accurate information on the trajectory of the level of protective efficacy over time facilitates informed clinical recommendations and implementation strategies, for example, with respect to the timing of administration of the doses. Based on concepts from pharmacokinetic and pharmacodynamic modeling, we propose a non-linear function for modeling the trajectory after each dose. The cumulative effect of multiple doses of the products is captured by an additive series of the function. The model has the advantages of parsimony and interpretability, while remaining flexible in capturing features of the trajectories. We incorporate this series into the Andersen-Gill model for analysis of recurrent event time data and compare it with alternative parametric and non-parametric functions. We use data on clinical malaria disease episodes from a trial of four doses of an anti-malarial drug combination for chemoprevention to illustrate, and evaluate the performance of the methods using simulation. The proposed method out-performed the alternatives in the analysis of real data in terms of Akaike and Bayesian Information Criterion. It also accurately captured the features of the protective efficacy trajectory such as the area under curve in simulations. The proposed method has strong potential to enhance the evaluation of disease prevention measures and improve their implementation strategies., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Chia-Yin CHong reports financial support was provided by Government of Singapore Ministry of Health. Chee-Fu Yung reports financial support was provided by National Medical Research Council.]., (Copyright © 2024. Published by Elsevier India Pvt Ltd.)