Abstract Background The declining uptake of SARS-CoV-2 vaccines, combined with evolving schedules and recurrent infections, underscores the need to monitor the durability of hybrid immunity in children. The objective of this study was to assess children’s SARS-CoV-2-specific immune responses post-second vaccine dose and to compare immune responses between unvaccinated children and children vaccinated with two or three vaccine doses. Methods Three observational cohorts of children aged 3–14 years were followed longitudinally from December 2021 to October 2023 in Montreal, Canada. Two had scheduled serology assessments before their second dose and at one, six and twelve months post-second dose. The other cohort included unvaccinated and vaccinated children, with 2-4 serology assessments, every 2-3 months. Linear mixed models adjusting for infection history were used to assess immune waning post-second dose and differences over time by vaccine status. Results Controlling for recent infection, anti-spike IgG, anti-receptor binding domain (RBD) IgG, and neutralizing titers against wild-type SARS-CoV-2 declined by six months post-vaccination. For example, average IgG anti-RBD was 1 374.1 BAU/mL one month after dose two, with an estimated decline of −856.1 BAU/mL at six months (95% CI, −1 303.5 to −596.0; p<0.0001). T cell responses showed little evidence of decline over 12 months across all groups with a history of infection. Comparing children by vaccine status, the highest humoral responses were associated with three doses whereas the lowest with unvaccinated status (e.g., crude average two-dose IgG anti-RBD: 920.0 BAU/ml; unvaccinated estimated difference −515.1 BAU/mL; 95% CI, −698.0 to −444.7; p<0.0001). Spike-specific CD4+ T cell responses were lower among the unvaccinated. Conclusions Humoral responses declined significantly within six months of vaccination. Cellular responses were comparable across vaccine status groups, yet vaccinated children tended to maintain higher levels for more than one-year post-vaccination. Hybrid immunity could contribute to a more robust and durable cellular response.
ABSTRACT Background The current epidemiology of carbapenem-resistant Enterobacterales (CRE) among pediatric patients in the United States is poorly described. We assessed trends in pediatric CRE and carbapenemase-producing-CRE (CP-CRE) incidence in the U.S. and characterized recent pediatric CP-CRE cases. Methods We analyzed CRE clinical isolates from patients <18 years submitted to CDC’s Antimicrobial Resistance Laboratory Network from January 2019 through December 2024. Annual unadjusted incidence rates for CRE and CP-CRE were estimated overall and by age group for a national convenience sample and an open cohort of 29 states with required CRE isolate submission. Trends were assessed using Poisson regression. For pediatric patients with incident CP-CRE identified from January 2023 through March 2024, medical chart reviews were performed. Results From 2019–2024, the estimated national pediatric CRE and CP-CRE incidence increased 51% (IRR:1.51; 95% CI:1.22, 1.88) and 92% (IRR:1.92; 95% CI:1.25, 2.99), respectively; increases were similar in the open cohort. Infants had the highest incidence rates. Overall, NDM-CRE incidence increased (IRR: 4.24; 95% CI: 2.07, 9.16), surpassing KPC-CRE as the most prominent carbapenemase. Chart reviews were completed for 109 of 129 pediatric patients with CP-CRE; 14% were in patients without healthcare risk factors. Among patients with healthcare risk factors, 75% had an underlying medical condition; the most common underlying condition among infants and toddlers was cardiovascular disease (64%) and among older children was neurocognitive conditions (49%) and malignancies (41%). Common exposures across all age groups included intensive care unit hospitalization (40%) and healthcare outside the United States (37%). Conclusions Pediatric CP-CRE incidence is increasing, driven by NDM-CRE for which there are few treatment options. Most cases occurred among children with serious underlying conditions receiving high-acuity care. Prevention opportunities may include admission screening for patients with prior healthcare exposure outside the United States and strengthening infection prevention practices.
Background Primary ciliary dyskinesia (PCD) is a rare congenital disorder marked by impaired motile ciliary function, resulting in chronic oto-sino-pulmonary infections, including Pseudomonas aeruginosa. While enhanced infection prevention and control (IPC) practices have successfully reduced P. aeruginosa prevalence and transmission in cystic fibrosis (CF), comparable IPC strategies have not been evaluated in PCD. This study aimed to characterize bacterial epidemiology across PCD Clinical Centers, hypothesizing that P. aeruginosa prevalence would be higher at centers lacking enhanced IPC measures. Methods We performed a retrospective observational study assessing the period prevalence and chronic infection rates of P. aeruginosa and other respiratory microorganisms at 3 pediatric PCD Centers and 1 adult Center. Between-center comparisons of patients ever infected status used Fisher's exact test, with age-adjusted repeated-measures analyses conducted via Bayesian mixed-effects logistic regression. Results The cohort included 41 pediatric patients from Center A (Standard Precautions), 25 from Center B (clinic cohorting), and 30 from Center C (enhanced IPC based on CF Foundation Guidelines, CF-IPC). An additional 13 adult patients from Center A were included for descriptive analysis only. Pseudomonas aeruginosa period prevalence at pediatric Centers A, B, and C was 37%, 32%, and 47%, respectively (P = .55). In contrast, pediatric Haemophilus influenzae prevalence (P = .001) and chronic H. influenzae infection rates (P < .0001) were significantly higher at Center A compared with Centers B and C. Age-stratified analysis across all pediatric Centers demonstrated increasing P. aeruginosa prevalence beginning around age 10, while H. influenzae prevalence declined with age. Nearly 85% of adults had a history of P. aeruginosa infection. Conclusions Our findings suggest that CF-IPC protocols may not exert the same influence on bacterial epidemiology in PCD as they do in CF. Pseudomonas aeruginosa may be more prevalent in PCD than previously recognized, and variations in IPC strategies were not significantly associated with differences in P. aeruginosa rates across pediatric PCD Centers.
