Lene Nielsen

Background: The epidemiology of pediatric central nervous system (CNS) infections has shifted over recent decades and remains incompletely described. We aimed to describe the incidence, etiology, age distribution and burden of pediatric CNS infections in a Danish population. Methods: This population-based cohort study included all previously healthy Danish children 0–17 years of age in East Denmark from January 1, 2017, to December 31, 2023, with microbiologically verified CNS infections or cerebral abscess/empyema verified by imaging. Results: Totally 465 patients were included. The total annual incidence per 1,000,000 was 125 (95% confidence interval [CI] 114–137), with 49 (95% CI 42–57) for viral CNS infections, 24 (95% CI 19–29) for bacterial meningitis, 7 (95% CI 5–10) for cerebral abscess/empyema and 44 (95% CI 38–51) for neuroborreliosis. Viral infections dominated in infants under 3 months (88/113, 78%) and adolescents 12–17 years (33/70, 47%), while neuroborreliosis dominated in children 1–11 years (149/255, 58%). Among 44 children 5–17 years old with bacterial infections (except neuroborreliosis), 23 (52%) had abscess/empyema and 21 (48%) bacterial meningitis. Intensive care was required in 1 (<1%) of 166 with viral meningitis/encephalitis, 21 (23%) of 90 with bacterial meningitis and 2 (7%) of 27 with abscess/empyema. Relapse occurred in 6 (7%) with bacterial meningitis and 1 (4%) with abscess/empyema. Death occurred in 5 (6%) children with bacterial meningitis. Conclusions: The pattern of pediatric CNS infections in the 2020 era calls for awareness, as neuroborreliosis was the most common disease, alongside viral infections, while cerebral abscess/empyema occurred as frequently as bacterial meningitis in school-age children. Bacterial meningitis remained associated with high morbidity and mortality.

Background: Adults hospitalized with respiratory syncytial virus (RSV) face mortality risks comparable to or higher than those with influenza A or B. However, studies on the impact of bacterial co-infections on mortality are inconsistent. Methods: This multicenter cohort study included adults hospitalized with RSV, influenza A, or B over 3 years at two tertiary care hospitals. Microbiological testing, bacterial co-infections, antibiotic use, and their association with clinical outcomes were analyzed using adjusted linear and logistic regression models. Results: Of 986 patients, 352 (36%) had RSV, 347 (35%) influenza A, and 287 (29%) influenza B. The median age was 74 years, 54% were women, and 76% had at least one comorbidity. Overall, 32% had pneumonia. The prevalence of bacterial co-infections was comparable across patients with RSV (23%), influenza A (25%), and B (28%). Among patients without bacterial co-infection, antibiotic use within 48 hours remained common across all virus groups (77%, 71%, and 75%, respectively). In adjusted analyses, bacterial co-infection in patients with RSV was not associated with mortality at 14, 30, or 90 days, high-flow oxygen therapy, mechanical ventilation, or length of stay (LOS). Early antibiotic treatment was associated with prolonged LOS but not improved survival. Conclusions: Bacterial co-infections were identified in approximately one-quarter of patients with RSV, influenza A, and B. Among patients with RSV, bacterial co-infection was not associated with adverse clinical outcomes, and early antibiotic treatment did not appear to improve clinical outcomes.

Background: Respiratory viral infections have significant global health impacts. We compared 30‐day intensive care unit (ICU) admission and all‐cause mortality risks in patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta and Omicron variants versus influenza A and B (A/B).Methods: Data from two retrospective inpatient cohorts in Capital Region of Denmark were analyzed. Cohorts included hospitalized influenza A/B patients (2017–2018) and SARS‐CoV‐2 Delta/Omicron patients (2021–2022), aged ≥18 years, admitted within 14 days of a positive real‐time polymerase chain reaction test result. Cumulative ICU admission and mortality rates were estimated using the Aalen–Johansen estimator. Cox regression models calculated hazard ratios (HRs) for ICU admission and mortality.Results: The study encompassed 1459 inpatients (Delta: 49%; Omicron: 26%; influenza A: 6.4%; and influenza B: 18%). Cumulative incidence of ICU admission was 11%, 4.0%, 7.5%, and 4.1%, for Delta, Omicron, influenza A, and B, respectively. For ICU admission, adjusted HRs (aHRs) were 3.1 (p < .001) and 1.5 (p = .34) for Delta and Omicron versus influenza B, and 1.5 (p = .36) and 0.71 (p = .48) versus influenza A. For mortality, aHRs were 3.8 (p < .001) and 3.4 (p < .001) for Delta and Omicron versus influenza B, and 2.1 (p = .04) and 1.9 (p = .11) versus influenza A.Conclusion: Delta but not Omicron inpatients had an increased risk for ICU admission compared to influenza B; however, both variants were associated with higher risks of mortality than influenza B. Only Delta inpatients had a higher risk of mortality than influenza A inpatients.

Different molecular methods for the discrimination of Candida glabrata, C. bracarensis and C. nivariensis were evaluated and the prevalence of these species among Danish blood isolates investigated. Control strains were used to determine fragment length polymorphism in the ITS1, ITS2, ITS1-5.8S-ITS2 regions and in the D1/D2 domain of 26S rDNA using primers designed for this study. A total of 133 blood isolates previously identified as C. glabrata were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the peptide nucleic acid-fluorescent in situ hybridization (PNA-FISH) method. The size of ITS1 allowed differentiation between C. glabrata (483), C. nivariensis (361) and C. bracarensis (385), whereas the ITS2 region was of similar size in C. nivariensis (417) and C. glabrata (418). Sequence analysis of the ITS region suggested that many restriction enzymes were suitable for RFLP differentiation of the species. Enzymatic digestion of the D1/D2 domain with TatI produced unique band sizes for each of the three species. PCR-RFLP and PNA-FISH were in agreement for all of the isolates tested. None of the 133 Danish blood isolates were C. nivariensis or C. bracarensis. Fragment size polymorphism of ITS1 and RFLP of the D1/D2 domain or the ITS region are useful methods for the differentiation of the species within the C. glabrata group. C. bracarensis and C. nivariensis are rare among Danish C. glabrata blood isolates.