Journal of the Pediatric Infectious Diseases Society

Background: Leptospirosis causes around 1 million cases and 60,000 deaths globally annually, predominantly affecting flood-prone tropical regions. Transmitted through contact with water or soil contaminated by animal urine infected with Leptospira spp., this bacterial zoonosis is classified as a high-risk Group B infectious disease in Vietnam. However, epidemiological and clinical data are scarce, particularly in pediatric populations. This study evaluated clinical and laboratory characteristics of leptospirosis cases at the National Children's Hospital, Hanoi, from January 2023 to August 2025. Methodology : All children admitted with probable or confirmed leptospirosis were enrolled. Clinical and laboratory data were analyzed to characterize disease manifestations and identify risk factors for severe leptospirosis. This was defined by the presence of organ dysfunction, including liver or renal failure, hemorrhage (particularly pulmonary), aseptic meningitis, cardiac arrhythmias, pulmonary insufficiency, or hemodynamic collapse. Principal Findings : Of 84 patients (37 confirmed, 47 probable), the mean age was 9.4 years, with 52.4% male and over half aged [≥] 10 years. Fever was the most common presenting symptom (85.7%); gastrointestinal and renal manifestations were frequent, including oliguria in 26.2% of cases. Key laboratory abnormalities included elevated D-dimer (81.8%), elevated C-reactive protein (75.6%), hypoalbuminemia (74.3%), increased liver enzymes (AST 63.3%, ALT 53.2%), and renal impairment ({approx} 46%). Severe disease developed in 48.8% of patients, most frequently as acute kidney injury. Hematuria was independently associated with increased severity (OR = 4.89). Conversely, fever, higher baseline albumin, and longer symptom duration prior to hospitalization were associated with a significantly reduced risk of severe disease. Conclusions : Pediatric leptospirosis in this cohort frequently presented with systemic inflammation and multi-organ involvement, particularly renal impairment. Nearly half the patients developed severe disease. Early recognition of renal signs, especially hematuria, and careful monitoring of albumin levels are critical to identifying children at risk for severe progression and optimizing clinical management.

Background: Neonatal meningitis and pneumonia are important causes of morbidity and mortality among hospitalized newborns in low-resource settings. Numerous single-centre studies have been conducted in Ethiopian public hospitals, yet no quantitative synthesis of neonatal meningitis prevalence previously existed, and the depth of the pneumonia-specific evidence base was undocumented. This review aimed to estimate the pooled prevalence of neonatal meningitis, and to establish the state of the evidence base for neonatal pneumonia, among neonates treated at public hospitals in Ethiopia. Methods: A systematic search of PubMed/MEDLINE, PubMed Central, PLOS, BioMed Central, Frontiers, Taylor & Francis Online, and institutional repositories was conducted without date restriction. Cross-sectional and retrospective studies reporting a standalone prevalence of neonatal meningitis or neonatal pneumonia among neonates treated at Ethiopian public hospitals were eligible. Methodological quality was appraised using the JBI Critical Appraisal Checklist for prevalence studies. A random-effects meta-analysis pooled meningitis prevalence; heterogeneity was quantified with I2 and Cochran's Q. Results: Of 26 full-text articles assessed for eligibility, four studies (N = 3,522 neonates) met inclusion criteria for neonatal meningitis; none met inclusion criteria for a standalone neonatal pneumonia prevalence outcome. The pooled prevalence of neonatal meningitis was 6.26% (95% CI: 2.81-13.35%; I2 = 96.6%), with individual study estimates ranging from 1.73% to 19.30%. A sensitivity analysis restricted to the three studies using a "suspected-meningitis" denominator yielded a pooled prevalence of 4.23% (95% CI: 1.92-9.05%). No eligible primary study reported neonatal pneumonia prevalence as a standalone, separately ascertained outcome across the accessible literature, pneumonia is consistently subsumed within composite "neonatal sepsis" case definitions. Conclusion: An estimated 1 in 16 to 1 in 24 neonates tested for suspected meningitis at Ethiopian public hospitals had a culture-confirmed or clinically diagnosed case, with wide variation across settings and case-ascertainment methods. A previously undocumented evidence gap exists for standalone neonatal pneumonia prevalence in Ethiopia. Future primary studies should report pneumonia as a distinct, separately ascertained neonatal outcome to enable future quantitative synthesis.

Objectives: To compare the effectiveness of povidone-iodine ear wash compared to no ear wash and oral cotrimoxazole compared to placebo given in addition to standard topical antibiotic treatment (ciprofloxacin drops) for chronic suppurative otitis media (CSOM) in Australian Aboriginal children. Methods: A randomised, parallel, 2 x 2 factorial design, assessor-blinded clinical trial in the remote Northern Territory of Australia. Aboriginal children with confirmed CSOM were eligible to be randomised into four treatment groups, allowing two primary treatment comparisons in a 2-in-1 trial approach. Participants received standard treatment (twice daily cleaning and topical ciprofloxacin drops) plus: i) either 16 weeks of pre-treatment povidone-iodine ear wash or no povidone-iodine ear wash; and ii) either 16 weeks of oral cotrimoxazole or placebo. Central randomisation with allocation concealment and triple-blinding of the oral antibiotic treatment arms was used. The relative risk (RR) and risk difference (RD) were estimated after adjustment for age, community, and the other intervention. The primary outcome was the proportion of children with any otorrhoea (clinical failure) after 16 weeks of treatment. Secondary outcomes included size of tympanic membrane (TM) perforation and amount of discharge, time to cessation of discharge, proportion of children with respiratory and other pathogens in ear discharge (at baseline and 16 weeks) and hearing levels (at 12 months). Findings: 280 children with CSOM were randomised and 270 had their primary outcome assessed. Clinical failure (presence of any ear discharge) after 16 weeks of treatment was 66/134 (49%) in the povidone-iodine group versus 69/136 (51%) in the no povidone-iodine group (RD= -1% (-12,11), p= 0.93) and 56/134 (42%) in the cotrimoxazole group versus 79/136 (58%) in the placebo group (RD=-16% (-28,-4), p=0.007). The amount of discharge, TM perforation size, the level of hearing impairment, and serious adverse events were not significantly different in both treatment comparisons. Anaerobic growth (24%), Pseudomonas aeruginosa (21%) and Haemophilus influenzae (17%) were the most common pathogens found in the ear discharge before treatment. Fungi or yeast (24%), Staphylococcus aureus (15%), and anaerobic growth (10%) were the common pathogens after 16 weeks of treatment, with no significant differences between groups. At 12 months post-randomisation, 55-60% of children had at least one discharging ear and there was no difference between treatment groups. Interpretation: Povidone-iodine ear washes did not contribute to better ear outcomes in this study. Cotrimoxazole for 16 weeks resulted in more children with clinical improvement to dry ears. Oral cotrimoxazole may play a role in reducing the burden of CSOM in populations with high rates of persistent disease.

Background Coccidioidomycosis is an emerging fungal disease across the arid Americas and a frequent cause of community-acquired pneumonia. Understanding where Coccidioides populations originate, how they move across space, and whether they are expanding is important for interpreting changing patterns of Valley fever and anticipating future infection risk. Methods We prospectively collected and whole-genome sequenced 186 Coccidioides-positive clinical isolates submitted to a national diagnostic laboratory, and included 126 previously sequenced genomes. We applied genomic clustering, time-calibrated phylogenetic reconstruction, ancestral area reconstruction, mating-type assignment, and demographic inference to identify major populations, infer dispersal patterns, assess evidence for recombination and clonality, and reconstruct historical population dynamics. Findings We analyzed 312 genomes (139 C. immitis; 173 C. posadasii) and identified three major genetic populations within each species. C. immitis included two California-centered populations and one Pacific Northwest population, whereas C. posadasii included two Arizona-centered populations and one Texas-centered population. The most recent common ancestor was estimated at approximately 127,000 years for C. immitis and 234,000 years for C. posadasii. Most populations were not fully monophyletic, consistent with retained ancestral variation and/or ongoing gene flow. Inferred dispersal was largely asymmetric, with most movement originating from California in C. immitis and from Arizona and Texas in C. posadasii. Most populations contained both mating types, but one C. immitis population and a Brazilian subgroup of C. posadasii were clonal. All populations showed recent demographic expansion. Interpretation The evolutionary history of Coccidioides is characterized by strong geographic structure, ongoing gene flow, and recent demographic expansion. These processes are likely to influence future patterns of Valley fever endemicity and supports the use of genomic surveillance to detect shifts in disease risk as environmental conditions change.

Respiratory syncytial virus (RSV) contributes to substantial morbidity and mortality in young children each year. In 2023, two new prevention products were licensed and recommended in the United States (US), including a prefusion F protein subunit vaccine (RSVpreF) administered during pregnancy and a long-acting monoclonal antibody (mAb) administered in infants. Although post-licensure real-world studies support the effectiveness of RSVpreF vaccine during pregnancy, existing studies have been conducted in settings where only RSVpreF vaccine is available. The real-world effectiveness of RSVpreF vaccine in settings where both RSVpreF vaccine and mAbs are available is not yet well understood. The goal of this study is to estimate the real-world effectiveness of the RSVpreF vaccine against severe infant RSV by applying causal mediation analysis with receipt of mAbs as a mediating variable. Using a national cohort of mother-infant dyads with the Optum Labs Data Warehouse (OLDW), we will model vaccine and mAb effects in a longitudinal cohort spanning the 2023-24, 2024-25, and 2025-26 RSV seasons. Results will be used to better understand the total effect of RSVpreF vaccination when it is used as one component within a hybrid infant RSV prevention program.

Red blood cell (RBC) disorders arose as an advantageous evolutionary response to malaria infections. In a heterozygous condition, such as in Southeast Asian Ovalocytosis (SAO), hosts are protected against severe malaria. In malaria-endemic regions, RBC disorders are presumed to be highly prevalent. Tanjung Leidong, a moderately endemic area in North Sumatra (API 1.13 in 2024), lacks comprehensive data on RBC disorder prevalence beyond G6PD deficiency. Therefore, this study aims to characterize the RBC disorders in this region as well as to characterize the anemia status in children living in Tanjung Leidong. Schoolers attending D. I. Panjaitan elementary to high school were recruited and screened for malaria by microscopy and G6PD deficiency using the STANDARD G6PD Assay. The DNA of the participants was also extracted to be genotyped for SAO, Hemoglobin E (HbE), and -thalassemia. Exclusively, G6PD-deficient DNA samples were genotyped further to determine variants. The proportion of G6PD deficiency, SAO, HbE, -thalassemia one-gene deletion, and two-gene deletion were 0.90%, 0.90%, 2.40%, 6.26%, and 0.30%, respectively. Anemia prevalence was approximately 14%, and RBC disorders were observed across children with normal to obese BMI. No malaria infections were detected by microscopy. The predominance of asymptomatic RBC disorders highlights that they are protective against malaria infection, although their protective role against malaria could not be directly assessed in this study. Both nutritional and genetic factors are found to contribute to anemia in this cohort. These findings underscore the importance of integrated screening strategies for RBC disorders and anemia in malaria-endemic settings.

Background Serosurveillance can estimate the prevalence of antibodies (Ab) acquired through vaccination or current and/or past infection. Multi-pathogen serosurveillance that measures multiple Ab simultaneously, can enable identification of vulnerable sub-populations with immunity gaps to vaccine preventable diseases (VPD) and concurrent burden of neglected tropical disease (NTD), including those nearing elimination (lymphatic filariasis [LF], trachoma) and eradication (yaws). This study aimed to estimate seroprevalence and identify temporal trends of selected VPDs and NTDs in Samoa to inform targeted public health action. Methodology/Principal Findings Dried blood spots were collected from four repeated community-based surveys in eight primary sampling units (PSU) in Samoa in 2018, 2019, 2023 and 2024. Multiplex bead assays were used to detect Abs against antigens (Ag) for diphtheria, measles, rubella, tetanus, LF [Wb123 or Bm14], yaws [both Rp17 and TmpA; <14 years only], and trachoma [Pgp3; <14 years only]. Seroprevalence estimates were adjusted for sampling design and standardised for age and sex. Overall, 2,871 participants were included in this analysis. Seroprevalence of measles increased from 42% in 2018 to 95% in 2024, whereas diphtheria decreased from 79% in 2018 to 65% in 2024. Seroprevalence to yaws remained <1% for all years, whereas trachoma decreased from 21% to 7% (2018-2024). LF seroprevalence decreased between 2018 and 2024 for Bm14 (37% to 9%) and increased for Wb123 (10% to 22%). This study identified 15 (0.5%) individuals who were seronegative to all VPDs (7 in 2018; 8 in 2019); of these, five were seronegative to all VPDs and seropositive to at least one NTD. Conclusions/Significance Identification of sub-populations with concurrent seronegativity to VPDs and seropositivity to NTDs underscores the potential role of multi-pathogen serosurveillance in directing public health interventions to those at greatest risk. Examination of temporal patterns offer a valuable tool for measuring intervention impacts and progress towards elimination goals.

Background The 2022-2023 global mpox outbreak highlighted the critical need for robust genomic surveillance capabilities to track mpox virus (MPXV) evolution and transmission dynamics. Methods Building upon our established SARS-CoV-2 sequencing infrastructure, we implemented a Molecular Loop probe-based long-read sequencing approach using Pacific Biosciences Sequel II technology for comprehensive MPXV genomic surveillance across the United States (US). From August 2024 to June 2025, we generated 326 high-quality whole genome sequences from residual mpox-positive clinical specimens collected by Labcorp across all 10 US Department of Health and Human Services regions. Results Our analysis identified two samples containing clade Ib MPXV in January and June 2025 and captured shifting trends in clade IIb diversity, with 13 distinct lineages observed. We also identified multiple instances of large (~1.6-17.6kb) deletions proximal to the inverted terminal repeats in clade IIb genomes. APOBEC3 mutation analysis indicated substantial evidence of human-to-human transmission among both clades. Further, we observed significantly higher APOBEC3-associated SNPs per kilobase (P<0.001) in clade IIb genomic variable regions relative to their central conserved region. Our assay exhibited strong reproducibility across biological replicates from individual patients and accuracy was confirmed via parallel sequencing of select specimens by US Centers for Disease Control and Prevention (CDC) using metagenomic sequencing. We also demonstrated via custom simulation that our assay discriminates all known MPXV clades and lineages, including those we have not observed in the US. Conclusions Our integrated nationwide surveillance system facilitates real-time genomic tracking of outbreak evolution, with demonstrated capacity across SARS-CoV-2 and MPXV, positioning this platform for rapid deployment during future pathogen emergence.

Background: Caregivers of children with retinoblastoma (RB) face substantial psychological and socioeconomic challenges. However, the factors independently associated with caregiver burden and the distribution of risk across caregiver subgroups remain incompletely characterized. We examined psychosocial and socioeconomic correlates of caregiver burden, identified distinct vulnerability profiles, and evaluated factors associated with high-risk profile membership. Methods: This cross-sectional study enrolled 413 primary caregivers of children with RB at a tertiary ophthalmic oncology center. Participants completed validated measures of caregiver burden (ZBI-22), anxiety (GAD-7), perceived social support (PSSS), family functioning (FAD-GF), and mental and physical quality of life (SF-12 MCS and PCS). Multivariable linear regression identified factors independently associated with caregiver burden and mental quality of life. Mediation analysis evaluated the indirect association between social support and burden through family functioning, and moderation analysis assessed whether household income modified the association between family dysfunction and burden. Latent profile analysis (LPA) identified caregiver risk profiles, and multinomial logistic regression examined factors associated with profile membership. Results: Anxiety showed the strongest independent association with greater caregiver burden (standardized coefficient beta = 0.641, 95% CI [1.46, 1.84], P < 0.001) and poorer mental quality of life (beta = -0.483, 95% CI [-0.12, -0.08], P < 0.001). Family debt was independently associated with greater burden (beta = 0.195, P = 0.040). Family functioning accounted for 32.19% of the total association between social support and burden. Household income modified the association between family dysfunction and burden (interaction B = -0.85, P < 0.001), with a steeper gradient in lower-income households. LPA identified three profiles: severe burden-high vulnerability (n = 82, 19.85%), moderate burden (n = 193, 46.73%), and mild burden-high resilience (n = 138, 33.41%). Low-to-moderate household income was associated with higher odds of severe-profile membership (OR = 31.50, 95% CI [6.56, 151.24], P < 0.001). Conclusions: Caregiver burden in pediatric RB was associated more strongly with psychosocial and socioeconomic factors than with the clinical indicators examined. Family functioning partly accounted for the association between social support and burden, while household income modified the association between family dysfunction and burden. These findings support prospective evaluation of family-centered and financial-support interventions and suggest that profile-based screening may help identify caregivers requiring more intensive support.

Importance Pharmacogenomic (PGx) guidelines can improve medication efficacy and reduce toxicity, but their application in pediatric intensive care units (PICUs) remains largely unexplored. Objective To determine the frequency of medications with established PGx guidelines administered in the PICU and assess the capacity of exome sequencing to capture PGx phenotypes for these medications. Design Retrospective cohort study integrating electronic medical record and exome sequencing data. Setting Morgan Stanley Children's Hospital of NewYork-Presbyterian, a single center tertiary care children's hospital. Participants A total of 4,939 children admitted to the PICU (2020 - 2024), and 192 children admitted to the PICU who underwent exome sequencing for research purposes (2015 - 2023). Exposure Critical illness requiring PICU admission. Main Outcomes and Measures Frequencies of administration of medications with established PGx guidelines in the PICU and the proportion of individuals with exome sequencing with identifiable PGx phenotypes. Results Among 4,939 PICU patients, 37.2% (n=1,837) received at least one medication with established PGx guidelines and 14.4% (n=712) received two or more such medications. Twenty PGx genes were implicated; CYP2C9 was most common (17.3%, n=853). An estimated 8.2% of patients received medications for which PGx-guided recommendations would have altered clinical management. Among 192 patients who underwent exome sequencing, at least one metabolizer phenotype was identified in 62% (n=119). Conclusions and Relevance Many critically ill children receive medications with established PGx guidelines. This study highlights an opportunity for more personalized medicine for critically ill children admitted to a tertiary care hospital and assesses the strengths and weaknesses of exome sequencing to uncover pertinent PGx phenotypes.

Objectives To assess the feasibility of using clinical data automatically extracted via the Swiss Personalized Health Network (SPHN) to complement or replace manually abstracted clinical data in the Swiss Paediatric Airway Cohort (SPAC). Materials and Methods We studied 1,075 SPAC participants enrolled between 2017-2023 at two Swiss children's hospitals. Clinical data were extracted from electronic health records via SPHN in Resource Description Framework format, transformed into visit-centered datasets, and compared with manually abstracted SPAC clinical data and parent-reported emergency department (ED) visits and hospitalizations from follow-up questionnaires. We assessed feasibility by identifying challenges in acquiring data and evaluated data quantity, completeness, and agreement between datasets. Results We obtained analysis-ready SPHN-derived datasets from two hospitals after 24 months. SPHN-derived data captured more pneumology outpatient visits than manual abstraction (Hospital A: 1,963 vs 1,049; Hospital B: 2,343 vs 1,010) and identified clinical events among children without follow-up questionnaires. Completeness of variables varied across hospitals and encounters, reflecting differences in local clinical documentation practices. SPHN-derived and manually abstracted data showed high agreement for structured clinical variables, including spirometry measurements (concordance correlation coefficient >0.99). Self-reported and SPHN-derived ED visits and hospitalizations showed high absolute agreement but moderate concordance. Discussion and Conclusion Automated extraction of routine clinical data increased the completeness of longitudinal information compared with manual abstraction, suggesting that SPHN-derived data can complement manual data collection in cohort studies. Broader use remains limited by heterogeneous clinical documentation practices and the substantial effort required to harmonize and transform extracted data into analysis-ready research datasets.

During the 2025-26 respiratory virus season, changes to COVID-19 vaccine eligibility, recommendations, and communication may have made vaccination follow-through especially challenging. Under-vaccination may reflect not only lack of willingness, but also breakdowns between willingness and uptake. We analyzed data from 3,390 adults in the CHASING COVID Cohort who completed assessments in August 2025 and March 2026 to examine gaps between vaccine willingness and subsequent influenza and COVID-19 vaccination. Vaccine willingness was defined using prior-season vaccination and stated intention to vaccinate during the 2025-26 respiratory virus season. In August 2025, 73% of participants were influenza vaccine willing and 68% were COVID-19 vaccine willing. Among vaccine-willing participants, 17% and 39% were unvaccinated for influenza and COVID-19, respectively, by March 2026. Absence of prior-season vaccination was the strongest predictor of not vaccinating for influenza and COVID-19, respectively (aRR [95% CI]: 4.04 [3.44-4.74]; 3.01 [2.72-3.34]). Non-vaccination was also associated with food insecurity (1.99 [1.66-2.37]; 1.47 [1.33-1.63]), any healthcare barrier (1.89 [1.57-2.28]; 1.51 [1.36-1.67]), and being not at all confident in vaccine safety (2.95 [2.15-4.05]; 2.21 [1.88-2.59]). Trajectory analyses suggested willingness-uptake gaps reflected incomplete follow-through on intentions and discontinuation among some prior vaccinators. Commonly reported reasons among vaccine-willing non-vaccinators included difficulty finding a convenient time, place, or appointment and, for COVID-19, lack of healthcare provider recommendation. Findings among non-vaccinated adults with prior or stated openness to vaccinate highlight missed opportunities and suggest avenues to improve coverage through strategies that reinforce vaccine confidence, reduce access and logistical barriers, and make vaccination easier to complete.

Diarrheal disease remains a leading cause of morbidity and mortality among children under five globally, with poor sanitation and hygiene accounting for over 88% of diarrhea and malnutrition burden. In Kenya, diarrhea ranks third in under-five mortality, particularly affecting arid and semi-arid regions. School-Led Total Sanitation (SLTS), adapted from Community-Led Total Sanitation (CLTS), uses pupils as change agents for household hygiene knowledge transfer. However, SLTS effectiveness in addressing diarrhea and malnutrition has not been evaluated in Kenya. This study assessed SLTS effects on diarrheal disease and nutritional outcomes among children aged 5-59 months in Baringo County. A pre- and post-test quasi-experimental design with nonequivalent control groups was employed in Mogotio (intervention) and Baringo South (control) sub-counties. Using multistage sampling, 440 children aged 6-59 months were enrolled. The six-month SLTS intervention included capacity building, school health club formation, triggering activities using Participatory Rural Appraisal tools, Information, Education, and Communication materials distribution, continuous sensitization, and household monitoring. Data were collected at baseline and three months post-intervention using electronic questionnaires and anthropometric measurements. Nutritional status was assessed using WHO Anthro software z-scores for length/height-for-weight (HWZ), and weight-for-age (WAZ) to determine wasting, and underweight prevalence. Chi-square analysis assessed intervention-control differences. Baseline and endline socio-demographic characteristics were comparable between groups. At endline, no significant nutritional outcome differences were observed: wasting prevalence was at 15.0% versus 16.4% ({chi}{superscript 2}=0.155, df=1, p=0.694) while underweight was 12.3% versus 13.6% ({chi}{superscript 2}=0.181, df=1, p=0.670). However, diarrheal disease prevalence significantly reduced in intervention versus control groups: 5.9% versus 13.2% ({chi}{superscript 2}=6.738, df=1, p=0.009), representing a 53% reduction. SLTS intervention showed no significant effect on nutritional outcomes but demonstrated a significant reduction in diarrheal disease among children aged 6-59 months. These findings provide strong evidence for integrating school-based sanitation and hygiene approaches into broader public health strategies addressing diarrheal diseases.

Background Pneumococcal disease is a leading cause of paediatric pneumonia and meningitis. Pneumococcal colonisation is the fundamental step to pneumococcal disease causation. We aimed to identify genetic loci associated with pneumococcal colonisation amongst children. Methods We conducted a genome-wide association study on 2111 Nepalese children, comprising 1346 cases carrying pneumococcus and 765 controls. We tested 8.1 million imputed variants using logistic regression and ten principal components as covariates. Fine mapping and functional evidence were used to identify suspected causal variants and related genes of interest. Findings A cluster of 22 variants of genome-wide significance (p<5x10-8) were identified on chromosome 12q21.31, eight of which were within PPFIA2. Fine mapping of this region identified 5 variants within 0.1 Mb of the 5-prime region of PPFIA2 all of which are significant eQTLs for PPFIA2. We further describe three loci (10q23.31, 12q23.1, and 20p11.21) which had variants with highly suggestive associations (p<5x10-7)with pneumococcal carriage. Interpretation Our study demonstrate human susceptibility to pneumococcal carriage to be polygenic with genetic variations which regulate PPFIA2 expression playing a key role in the ability for pneumococcus to colonise children. Targeting these genetic factors and the associated pathways are a means for preventing pneumococcal disease. Funding This study was supported by funding from Gavi - the vaccine alliance, the European Unions Horizon 2020 research and innovation program under grant agreement number 668303 (PERFORM), and a Robert Austrian Research Award.

BACKGROUND: Half of positive blood cultures in pediatric emergency departments (PEDs) represent contaminants, driving unnecessary hospitalization, antibiotic exposure, and repeat visits. A clinical decision rule derived at CHU Sainte-Justine showed 99% sensitivity and 60% specificity for distinguishing bacteremia from contaminants but had not been externally validated. We sought to validate this rule in an independent pediatric cohort. METHODS: This retrospective diagnostic study spanned from January 2015 to May 2025 at a tertiary PED in Switzerland, using positive blood cultures from patients younger than 16 years. The four predictors (Gram-negative organisms or Gram-positive cocci in pairs or chains; time to positivity <17 hours; indwelling device; suspected osteoarticular infection) classified each case as low, moderate, or high risk. The primary outcome was bacteremia, adjudicated by two independent reviewers, based on organism identity and infectious disease specialist's assessment. Diagnostic accuracy was assessed with 95% CIs. RESULTS: Of 130 children enrolled (median age 3.8 years [IQR 0.9-9.9]; 61.5% male), 78 (60.0%) had true bacteremia. The rule yielded a sensitivity of 97.4% (95% CI, 91.0-99.7), specificity of 69.2% (95% CI, 54.9-81.3), positive predictive value of 82.6% (95% CI, 73.3-89.7), and negative predictive value of 94.7% (95% CI, 82.3-99.4). Both false-negatives were immunocompetent children with methicillin-susceptible Staphylococcus aureus bacteremia without indwelling devices. Among contaminants, 71% received antibiotics under usual care versus 31% classified as moderate or high risk by the rule. CONCLUSIONS: This first external validation supports the Sainte-Justine rule in a distinct pediatric population, preserving sensitivity with higher specificity. Multicenter validation is warranted before adoption.

Background Nipah virus (NiV) is a priority zoonotic pathogen causing high-fatality outbreaks. Early NiV outbreaks in Malaysia and Singapore had limited transmission beyond spillover events. However, since 2001, NiV outbreaks with person-to-person transmission have occurred in Bangladesh and India, driven by the NiV-Bangladesh genotype and NiV-India genotype. Our study aims to estimate the reproduction number, offspring dispersion, and serial interval governing NiV transmission in Bangladesh and India during 2001-2026. Methods We conducted a systematic review of NiV outbreak investigations in Bangladesh and India, searching PubMed, Embase, Web of Science, and grey literature through 28 February 2026. Case-level offspring counts from 27 eligible sources (323 cases across 67 outbreaks) were used as input to a hierarchical Bayesian negative binomial offspring distribution model. The serial interval was estimated by parametric distribution fitting to 137 transmission pairs. Country-stratified and sensitivity analyses were performed to evaluate the robustness of estimates. Results Pooling across 67 outbreaks, we estimated a median reproduction number of 0.46 (95% CrI: 0.28-0.73), an offspring dispersion parameter of 0.07 (0.05-0.10), and a serial interval of 13.3 days (95% CI: 12.8-13.8). Country-stratified median reproduction numbers were 0.48 (0.23-0.97) for India and 0.35 (0.19-0.59) for Bangladesh, and dispersion parameters were 0.04 (0.02-0.07) and 0.11 (0.06-0.18), respectively, indicating marked overdispersion in both settings. Conclusion NiV transmission is self-limiting on average and highly overdispersed, suggesting that a disproportionate share of onward transmission arises from a small number of cases. This epidemiological profile supports targeted containment measures, including contact tracing and quarantine, for effective NiV outbreak control.

Background. Post acute sequelae of COVID 19 (PASC) is clinically heterogeneous and mechanistically unresolved, and single-analyte studies have struggled to explain it. Methods. We profiled matched plasma proteomics, metabolomics and whole-blood transcriptomics at acute infection and convalescence (mean 86 days later) in a Belgian cohort, using linear mixed models, multiomic gene-set enrichment, and a degree-matched differential-correlation approach to quantify how each node's interactions were rewired between patients who developed PASC and those who recovered; seven axis proteins were additionally quantified by multiplex immunoassay as orthogonal validation. Findings. Single omic testing yielded few FDR significant features, yet multi-omic enrichment showed sustained complement cascade involvement from acute illness to follow-up in PASC. Correlation networks re-organised topologically toward C3 and lost the immunoglobulin V gene coexpression seen in recovery. The most rewired nodes, heparin cofactor II (SERPIND1), alpha 1 antitrypsin (SERPINA1), complement factor H related 5 (CFHR5), prothrombin/thrombin (F2) and immunoglobulin V gene transcripts (notably IGLV3 21), changed in their co-expression structure rather than in abundance. In multiplex validation, acute CRP was elevated in patients who developed PASC (FDR = 0.012), whereas the directly measured abundances of the network-nominated proteins were unchanged. Interpretation. These trajectory aware, cross omic networks nominate a thrombo inflammatory axis in which complement and coagulation regulation remain dysregulated in PASC at the level of wiring rather than abundance, providing a systems framework for validation and for exploring interventions at the complement coagulation platelet interface.

Background Dengue is intensifying globally due to climate change, urbanization, and land use changes. In Nepal, dengue has expanded from lowland regions to higher altitudes, with record outbreaks in 2022 and 2023. However, reliance on passive surveillance and hospital-based studies may underestimate community level infection burden. Methods We conducted a population-based serologic cohort study in Kathmandu and Kavrepalanchok districts, Nepal, enrolling a geographically representative, age stratified random sample of residents aged 0 to 25 years from pre-defined hospital catchment areas. Enrollment occurred in two phases: Phase I (February 2019 to April 2021) with follow-up visits at approximately 3, 6, and 12 months, and Phase II (February to June 2023) revisiting the original cohort. At each household visit, we collected capillary blood samples by finger-prick onto filter paper and tested the samples for IgG responses against dengue-derived recombinant antigen using InBios DENV DetectTM ELISA. Serostatus was classified using the manufacturer's recommended immune status ratio (ISR) cutoffs. We calculated seroprevalence at each time point and estimated seroincidence rates by identifying seroconversion events per 1,000 person-years. We assessed risk factors using multivariable regression models. Results Between 2019 and 2023, we enrolled 840 participants and collected 2,082 blood samples. The overall seroincidence rate was 33.8 per 1,000 person-years (95% CI [24.9 to 45.0]), with the highest rates in urban Kathmandu ([105.7], 95% CI [75.1 to 144.4]). Seroincidence increased with age and over time from 46.1 in 2019 to 51.0 in 2023. Participants living with a dengue-positive individual in the same household (adjusted RR [4.65], 95% CI [2.72 to 8.0]) and households with water-filled flower basins (adjusted RR [2.53], 95% CI [1.28 to 5.74]) had significantly higher risk of seroconversion. Conclusions This study reveals a significant and increasing burden of dengue infection in the Kathmandu Valley between 2019 and 2023. highlighting an urgent need for immediate public health interventions to mitigate dengue's rise in Nepal's higher-altitude regions.

Dengue is a mosquito-borne, viral disease of increasing public health significance. Currently, most public health interventions target the vector, with efficacy dependent on timing within the season. Whilst seasonal profiles have been characterised in some endemic settings a global assessment is lacking. Here, we develop and apply a proportion-based measure of dengue seasonality to reported case time series from 1990 to 2024 across 106 countries and territories, the largest assessment of this phenomenon to date. We identify regional differences in seasonality such that every month of the year saw cases peak in at least one country or territory. Latitude was identified as influencing seasonality, with cases peaking between March and April in the southern hemisphere and July and October in the northern hemisphere. Equatorial locations displayed flat seasonality, and amplitude increased with distance from the equator. K-means clustering identified three seasonal profile types: two with pronounced seasonal outbreaks (with distinct peak timing and shape) and one with flatter, more endemic transmission. Peak month timing covaried among locations within the same seasonality cluster, with phase differences meaning that information on shifts in peak timing may be available several months in advance in some settings, of potential significance for prediction and intervention planning. Beyond aiding public health planning, identification of seasonal clusters suggests that information on dynamics in one location could be leveraged to improve forecasting power in others with similar seasonal dynamics.

Aims To develop the Bowel Irrigation Questionnaire (BIQ), a patient-reported experience measure (PREM) designed to assess the user experience of transanal irrigation (TAI). Methods Statements were generated through literature review and qualitative interviews with healthcare professionals (HCPs) and product users. Statements were rated on a 6-point content validity index scale through an international three-round online Delphi survey by 20 expert panel members. Consensus attainment was defined based on percentage agreement, statements which did not meet consensus were discussed at a final international online consensus meeting. The content validity of the PREM was evaluated through cognitive interviews and the Questionnaire on Questionnaires (QQ-10). Reliability was assessed using a test-retest design, where users completed the BIQ on two occasions one week apart. Results 215 statements were generated from 9 multi-disciplinary qualitative interviews and literature review. Statements were refined to reduce repetition and ensure clarity. 73 statements grouped into 11 domains were reviewed through the Delphi survey. Following the Delphi survey and clinical consensus meeting, the preliminary BIQ consisted of 15 items. Six cognitive interviews were conducted, resulting in a finalised BIQ of 16 items. 32 product users completed both the QQ-10 and test-retest study, the results of which demonstrated good content validity and temporal stability respectively. Conclusions The Bowel Irrigation Questionnaire is a novel PREM designed to assess the user experience of TAI in both clinical and research settings. The instrument demonstrates good validity, acceptability and temporal stability, supporting its use as a reliable measure of patient experience.