Pediatric Infectious Disease Journal

Background: Vitamin D modulates innate and adaptive immunity and has been investigated for preventing pediatric respiratory infections. Objective: To assess the effects of vitamin D supplementation on respiratory tract infections (RTIs), including upper RTIs, lower RTIs/recurrent pneumonia, and hospitalization/clinical severity in children and adolescents. Methods: Systematic review and random-effects meta-analysis of 16 publications, of which 13 contributed to quantitative synthesis. Twenty-four effect estimates were pooled, eight per outcome. The odds ratio (OR) was analyzed on its natural logarithmic scale (logOR), using restricted maximum likelihood (REML) estimation and Knapp-Hartung (KH) adjusted inference. Where necessary, risk ratios (RRs), hazard ratios (HRs), and incidence rate ratios (IRRs) were approximated on the logOR scale. Results: For respiratory infection/upper RTI, pooled logOR was -0.284 (KH-adjusted 95% confidence interval [CI]: -0.678 to 0.110; OR 0.753; p = 0.132; I2 = 97.2%). For lower RTI/recurrent pneumonia, logOR was -0.445 (95% CI: -0.987 to 0.097; OR 0.641; p = 0.093; I2 = 89.5%). For hospitalization/clinical severity, logOR was -0.609 (95% CI: -1.134 to -0.083; OR 0.544; p = 0.029; I2 = 78.3%). Conclusions: Pooled estimates favored supplementation in direction for all three groups, although confidence intervals included the null for the first two. Heterogeneity was substantial, and the results are limited by approximations among effect measures, clinically diverse endpoints, and potentially correlated effects from individual studies.

Importance: Nirsevimab, a monoclonal antibody against RSV, was implemented in France in September 2023. Recently, rare resistance-associated substitutions were described in RSV but the effectiveness according to lineages remains unclear. Objective: We aimed to estimate the effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages. Design: We conducted a multicenter test-negative case-control study from October 15, 2023 to March 15, 2025. Setting: This study was based on data from three national multicentric prospective studies. The 12 participating centers were secondary or tertiary hospital with a pediatric department located in France. Participants: We included all children younger than 12 months who were hospitalized for RSV bronchiolitis in one of the participating centers in France during the two first RSV epidemic seasons following the implementation of nirsevimab (from October 15, 2023 to February 29, 2024, and from October 10, 2024 to March 15, 2025). Main outcomes and measures: The main outcome of the study was the RSV test result of bronchiolitis cases. RSV whole-genome sequencing was performed using a tiled amplicon approach covering the complete viral genome, as previously described in the POLYRES studies. We estimated the effectiveness of nirsevimab by a multivariable logistic regression model adjusted for potential confounders. We estimated the adjusted risk of immunization failure for each lineage by calculating relative odds ratio to a reference lineage. A range of sensitivity analyses were conducted. Results: We included 3019 infants with bronchiolitis among which 2273 had a positive RSV test (case patients) and 746 had a negative RSV test (control patients). Overall, 373/2273 (16.4%) case patients were immunized by nirsevimab versus 423/746 (56.7%) control patients. The adjusted effectiveness of nirsevimab against hospitalization for bronchiolitis was 88.4% (95% CI, 84.5-91.4) with RSV-B and 79.4% (95% CI, 73.7-83.8) with RSV-A. The risk of immunization failure was 3.2-fold (95% CI 1.8-5.7) higher for lineages derived from A.D.3 than for lineages derived from B.D.4.1. Conclusion and relevance: In this multicentric case-control study, we observed that nirsevimab effectiveness was variable across RSV lineages, with a lower effectiveness against A.D.3 lineages compare to others. Further surveillance is needed to confirm these findings and assess their implication on RSV lineages epidemiology as nirsevimab use expands.

Background Neonatal sepsis remains a major cause of neonatal morbidity and mortality, particularly in low- and middle-income countries. Its management is increasingly complicated by antimicrobial resistance (AMR), while limited facility-specific data on causative bacterial pathogens and susceptibility patterns often necessitate empirical antibiotic treatment. This study assessed the prevalence of neonatal sepsis, bacterial pathogens and antimicrobial resistance patterns, and maternal, neonatal and clinical factors associated with neonatal sepsis among neonates admitted to the Neonatal Intensive Care Unit (NICU) at Livingstone University Teaching Hospital (LUTH), Zambia. Methods A retrospective cross-sectional record review was conducted among neonates admitted to the NICU at LUTH from 2020 to 2025. A total of 150 neonatal records were analysed. Neonatal, maternal, clinical, blood culture and antimicrobial susceptibility data were analysed using descriptive statistics, chi-square tests and logistic regression. Missing information was treated as missing and was not imputed; denominators were reported according to the records available for each analysis. Results Neonatal sepsis was identified in 52/150 neonates, giving a prevalence of 34.7% (95% CI: 27.5%-42.6%). Among the 52 sepsis cases, 20 had positive blood cultures, corresponding to a culture positivity rate of 38.5% (95% CI: 26.5%-52.0%); this represented 13.3% of the full study sample. Maternal fever during labour (aOR=6.822; 95% CI: 2.032-22.905; p=0.002) and caesarean delivery (aOR=2.245; 95% CI: 1.050-4.801; p=0.037) were independently associated with neonatal sepsis, while increasing birth weight was protective (aOR=0.891 per 100 g; 95% CI: 0.817-0.973; p=0.010). Escherichia coli was the most frequent isolate (5/20; 25.0%), followed by Klebsiella pneumoniae (4/20; 20.0%) and Staphylococcus aureus (4/20; 20.0%). Resistance was highest to ampicillin (15/19; 78.9%), followed by gentamicin and ceftriaxone (10/19; 52.6% each), while all 19 isolates tested against meropenem were susceptible. Conclusion The findings indicate that empirical management of neonatal sepsis at LUTH should be informed by local microbiological surveillance rather than reliance on historical first-line susceptibility assumptions. Routine blood culture and susceptibility testing, a regularly updated facility antibiogram, strengthened infection prevention and antimicrobial stewardship are required to improve treatment decisions and preserve effective antibiotics. Interpretation should consider the retrospective single-centre design, incomplete routine records and the small number of culture-positive isolates.

Background Despite cerebrospinal fluid (CSF) analysis being the gold standard for definitively diagnosing meningitis, its practical application has presented considerable difficulties, especially in environments with limited resources. Cranial ultrasound (CUS), while not a replacement for CSF analysis, provides rapid imaging to identify meningeal irregularities. Nevertheless, achieving a timely diagnosis of meningitis, particularly in its nascent stages, remains problematic, and healthcare professionals exhibit a notably low awareness of CUS's utility in diagnosing this condition. Methods This was a prospective cohort that recruited 273 term mother-neonate pairs. The neonates were initially divided into those with sepsis-meningitis (exposure group) and those with sepsis (non-exposure group) based on clinical assessment done by the admitting team. The research team further divided the participants into 4 diagnostic subgroups based on CUS findings: positive CUS for meningitis, positive clinical diagnosis for meningitis, positive CUS & clinical diagnosis for meningitis and those with negative CUS & clinical diagnosis for meningitis /sepsis only. Data on socio-demographics, clinical characteristics, blood works and CSF analysis reports, neurologic deficits and mortality outcomes were recorded for each neonate. Descriptive and inferential statistics were performed. Results The 4 diagnostic subgroups based on CUS findings were: positive CUS for meningitis (24.5%), positive clinical diagnosis for meningitis (4.4%), positive CUS & clinical diagnosis for meningitis (6.6%) and those with negative CUS & clinical diagnosis for meningitis /sepsis only (64.5%). Overall, duration of hospitalization was 11 days (range 2-45 days; interquartile range [IQR] 6,16) and the median chronological age of the neonates was 13 days (IQR 7, 21). Meningitis was suspected in 11% of neonates admitted with clinical sepsis. Uptake for lumbar puncture (LP) or ventricular tap (VT) was low at 4.4% (n = 12), underlining barriers to CSF-based diagnosis in this setting. Late-onset sepsis was associated with only 31.9% of NSM. The chronological age of the neonates at admission (p=0.002) and their duration of hospitalization (p=0.042) were significantly different across the 4 categories of neonates. Prominent sulci, hyperechoic brain lesions, ventriculitis, and lateral ventriculomegaly were the most common abnormal findings on CUS. Overall, neonates with meningitis presented later in age and stayed longer on the ward than those with sepsis: clinical meningitis diagnosis was likely to be made in older neonates and was associated with a shorter duration of hospitalization than CUS-diagnosed meningitis. Overall mortality rate was 2.2%. Mortality (16.7%) was highest amongst those with clinical & CUS diagnosed-NSM. Prevalence of Near-Miss cases of NSM was at least 27.6%. A neonate with clinical diagnosis of NSM was 3.94 times (95% CI 1.80, 8.62; p<0.001) more likely to have abnormal CUS at the time of admission. Percent agreement between the clinical and CUS diagnosis for NSM was 71.1%. Nine (75%) out of the 12 CSF reports was positive for meningitis; and the majority 55.6% (5) of the positive CSF report belonged to the category of neonates with sepsis only. Compared to CSF analysis, sensitivity of clinical diagnosis of NSM was 22.2%; specificity was 33.3%; positive predictive value (PPV) was 50%; negative predictive value (NPV) was 12.5% and likelihood ratio (LR) was 0.33. Whereas, sensitivity of CUS was 44.4%; specificity of CUS was 66.7%; PPV was 80%; NPV was 28.6% and LR was 1.33. Conclusion The CUS was only moderately effective at diagnosing meningitis whereas the presence of positive CSF among neonates with sepsis only within this study, further reaffirms the irreplaceability of CSF analysis in the diagnosis of NSM. Nevertheless, the integration of clinical assessment and CUS findings for diagnosing NSM emerged as possessing greater clinical significance in contexts characterized by limited resources. The systematic adoption of CUS for neonates exhibiting features suggestive of sepsis or meningitis (while exploring measures to improve on uptake of CSF analysis) could enhance the promptness of diagnosis, inform the selection of suitable therapeutic interventions, and potentially mitigate mortality rates and the occurrence of long-term neurological impairments, especially within environments facing resource limitations.

Background Otitis media is a leading cause of childhood morbidity and presents a significant healthcare burden worldwide. Streptococcus pneumoniae is a major aetiological agent of OM, and the introduction of pneumococcal conjugate vaccines into the Malaysian National Immunisation Programme in 2020 would have altered pneumococcal carriage and serotype distribution. This study aimed to determine pneumococcal carriage, serotype distribution, and associated risk factors among children with OM in the early post-PCV era in Peninsular Malaysia. Methods and Findings A total of 360 children with OM were recruited from hospitals on the east and west coasts of Peninsular Malaysia between 2023 and 2025. Nasopharyngeal and middle ear fluid samples were collected for Spn isolation by culture, followed by serotyping using multiplex PCR. Sociodemographic, environmental, and medical history data were analysed for associations with pneumococcal carriage using chi-square, Fishers exact tests, and logistic regression. Pneumococcal carriage was detected in 26.7% of children in either NP or MEF samples, with carriage rates of 25.6% and 1.9% in NP and MEF samples, respectively. The most prevalent serotypes were 23A, 15B/15C, non-typable strains, 19F, and 11A/11D. Daycare attendance (p = 0.012, aOR [95% CI]: 2.177 [1.186 - 3.995] and residence in rural areas (p = 0.019, aOR [95% CI]: 2.476 [1.159 - 5.292] were significantly associated with pneumococcal carriage. The main limitation of the study was the reliance on self-reported questionnaire data, which may have introduced recall bias and reporting errors. Conclusions The predominance of non-vaccine serotypes and non-typable Spn indicates ongoing serotype replacement and the emergence of phase-variant strains in the early post-PCV era. Continued surveillance is essential to monitor these changes and inform the development of next-generation pneumococcal vaccines. This study was registered under clinical trial registration number NCT05429541.

Formula-fed infants have altered gut microbiota and immune development relative to breastfed infants. Human milk oligosaccharides (HMOs) and microbes able to ferment these, like Bifidobacterium infantis, promote healthy immune-microbiome interactions in breastfed infants. In this randomized trial, 240 healthy term infants in the Philippines received a synbiotic blend formula (SynF; seven HMOs, bovine milk oligosaccharides, and B. infantis LMG11588) or control formula (CtrlF) for 6 months. SynF supported growth non-inferior to CtrlF and near universal B. infantis colonization (vs <10% in CtrlF). Markers of intestinal inflammation were lower in children fed SynF while secretory IgA was higher. SynF fed infants showed lower markers of systemic inflammation in plasma, slower immune cell maturation, and fewer upper respiratory tract infections (URTI) during their first 6 months of life. These findings suggest that synbiotic formula can dampen inflammatory responses to colonizing microbes and mild infections in fully formula-fed, term infants. Trial registration: NCT06073652.

BACKGROUND: Adverse consequences of neonatal hyperbilirubinemia disproportionately affect babies in low- and middle-income countries. Laboratory measurement of total serum bilirubin is limited in low-resource settings, necessitating simpler alternatives. Our study aimed to evaluate the diagnostic accuracy of visual inspection of jaundice via the World Health Organization Integrated Management of Childhood Illnesses algorithm compared to transcutaneous bilirubinometry for the identification of hyperbilirubinemia in community settings. METHODS: Hyperbilirubinemia was assessed by visual inspection for jaundice and transcutaneous bilirubinometry at 0-72 hours, 3-5 days, and 5-14 days postnatal in the PRISMA prospective cohort study in six sites in Asia and Africa. We assessed sensitivity, specificity, and positive and negative percent agreement. RESULTS: We analyzed data from 14,331 infants, including 1,852 preterm infants. 15% had hyperbilirubinemia, as defined by transcutaneous bilirubin values and the NICE nomograms, at 3-5 days postnatal. Visual inspection had a sensitivity of 16%, specificity of 96%, positive percent agreement of 56%, and negative percent agreement of 86% at 3-5 days postnatal age, pooled across all sites and gestational ages, versus transcutaneous bilirubin defined by NICE nomograms. CONCLUSION: The poor sensitivity of visual inspection underscores an urgent need for accurate, affordable screening tools to improve screening for hyperbilirubinemia.

BackgroundSevere community-acquired pneumonia (CAP) remains a leading cause of mortality in children under five. The PediCAP trial evaluated oral step-down therapy using dispersible amoxicillin or amoxicillin/clavulanate tablets in African children hospitalised with severe CAP. Dispersible tablet formulations are preferred in children; however, pharmacokinetic data for oral amoxicillin/clavulanate in paediatric populations remain limited. We characterised the pharmacokinetics of 4:1, 7:1, and 14:1 dispersible amoxicillin/clavulanate tablets in children enrolled in the PediCAP trial and predicted target attainment under different dosing schemes. MethodsChildren were randomised within 24 hours of starting intravenous antibiotics to oral step-down therapy with weight-banded dosing of twice-daily amoxicillin/clavulanate (4:1, 7:1, or 14:1). Plasma concentrations were quantified following intensive sampling and analysed using nonlinear mixed-effects modelling with allometric scaling and postmenstrual age-dependent clearance maturation. Pharmacodynamic indices included %fT>MIC for amoxicillin and %fT>Ct for clavulanate. ResultsA total of 157 children (median [range] age, 12 [2-70] months; weight, 8.4 [4.0-22.0] kg) contributed 707 paired concentrations. Amoxicillin was described by a two-compartment model and clavulanate by a one-compartment model, both with sequential zero-and first-order absorption. Typical clearance for an 8-kg individual at full maturation was 11.8L/h for amoxicillin and 6.1L/h for clavulanate. Pharmacokinetics were similar between the formulation ratios. Weight-banded dosing achieved balanced exposures across weight groups. Amoxicillin achieved 40%fT>MIC for MICs[&le;]2mg/L. A proposed clavulanate target of 20%fT>0.5mg/L was achieved in most children even at the lowest amoxicillin/clavulanate ratio. ConclusionWeight-banded dosing using dispersible amoxicillin/clavulanate tablets provide consistent exposure profiles in African children with severe CAP. SUMMARYPopulation pharmacokinetic modelling of dispersible amoxicillin/clavulanate tablets (4:1, 7:1, 14:1) in 157 African children with severe pneumonia showed weight-banded dosing achieved consistent and adequate amoxicillin and clavulanate exposures across formulations.

Background. Obesity has been associated with higher risk of dengue virus (DENV) infection and disease, yet its influence on antibody responses to DENV remains undefined. Methods. We evaluated whether nutritional status -- based on BMI z-score (BMIz) -- or blood markers of body fat -- leptin and adiponectin --are associated with binding and/or neutralizing antibody responses to DENV in 85 children in the Nicaraguan Pediatric Dengue Cohort Study who experienced a primary DENV infection in 2019. Associations were estimated using linear models adjusting for age, sex, and DENV infection outcome. Results. Compared to children with normal weight, those with obesity had higher quantities of DENV binding antibodies (fold-change [FC] 1.89, 95% confidence interval [CI] 1.02, 3.48) but no difference in neutralizing antibodies. Likewise, leptin concentration was associated with higher quantities of binding antibodies (FC 1.22, 95%CI 1.09, 1.37), while adiponectin was associated with lower quantities (FC 0.79, 95%CI 0.67, 0.94), and neither was associated with neutralizing antibodies. Lower neutralizing efficiency (neutralizing/binding antibodies) was observed in children with obesity (FC 0.67, 95%CI 0.48, 0.93). Conclusions. Our results indicate that obesity is associated with higher antibody quantity (binding) but not higher quality (neutralization) post-primary DENV infection -- implying that antibodies generated by children with obesity have lower neutralization efficiency, requiring greater quantities to reach similar levels of neutralization than children with normal weight. Further, the agreement among the three models using distinct proxies of body fat -- BMIz, leptin, and adiponectin -- demonstrates that adipokines are useful in supplementing BMIz analysis or as independent predictors of immune responses.

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

BackgroundCOVID-19 pandemic modified trends of infant bronchiolitis, leading cause of emergency room (ER) attendance in infants in high income countries, primarily due to Respiratory Syncytial Virus. Understanding recent pandemic-related epidemiological shifts could inform affordable prevention efforts to improve sustainability and coverage of prophylactic treatments beyond maternal vaccines and infant monoclonal antibodies. MethodsWe estimated incidence rates (IR) of bronchiolitis ER presentations in 0-6month olds in 2012-2023 in a region-wide cohort of almost 1 million births using administrative health data from Lombardy, Italy. To assess potential contributors, we investigated direct and indirect COVID-19-related factors, including disease severity, shape of the epidemic peak, parental health seeking behaviour and vaccine coverage. We estimated COVID-19 maternal vaccination associations using mothers-infants data linkages and multivariable-adjusted logistic regression. FindingsCompared to pre-pandemic levels, IRs doubled in 2021-2023 (from 2 to [&ge;] 4/100 person-time). The surge could not be explained by changes in infant age at ER visit, clinical severity or in the shape of the epidemic peak. Adjusted models showed little support for a role of infant routine or maternal COVID-19 vaccination on bronchiolitis episodes (respectively hazard ratio 1.09, 95%CI: 0.98-1.22 and odds ratio 0.91, 95%CI: 0.76-1.09). InterpretationThe post-pandemic increase in infant bronchiolitis is likely driven by multiple epidemiological changes rather than a single factor. As maternal RSV vaccination and infant RSV monoclonal antibodies are introduced and scale up, identifying these mechanisms will be critical to maximise their public health impact, inform complementary prevention strategies, and improve preparedness for future RSV epidemics.

Background: Risk adjustment for disease severity in pediatric intensive care research commonly relies on clinical organ dysfunction scores requiring detailed clinical and laboratory information, which is often unavailable in administrative healthcare datasets. We therefore evaluated the feasibility of a coding-based Pediatric Organ Dysfunction Index (PODI) derived from International Classification of Diseases (ICD-10) and Operation and Procedure System (OPS) codes, for approximating sepsis-related organ dysfunction and adjusting for disease severity, using the pediatric Sequential Organ Failure Assessment (pSOFA) score as a reference standard. Methods: In this retrospective single-center cohort study, pediatric sepsis episodes treated between November 2011 and November 2021 were identified. Discrimination for in-hospital mortality and calibration were assessed. Agreement between PODI and pSOFA was quantified using Spearman's rank correlation, and organ-specific agreement using sensitivity, specificity, and predictive values. An expanded PODI incorporating additional ICD-10 and OPS codes was evaluated in sensitivity analyses. Results: A total of 488 pediatric sepsis episodes were included, with an in-hospital mortality of 14.1%. The PODI showed good discrimination for in-hospital mortality (AUC 0.85, 95% CI 0.80-0.89), comparable to the maximum pSOFA (pSOFAmax) (AUC 0.78, 95% CI 0.72-0.83) and superior to pSOFA at sepsis onset (pSOFAonset) (AUC 0.73, 95% CI 0.67-0.80). Agreement between PODI and pSOFA organ-specific components varied considerably across organ systems, with the highest sensitivity to detect pulmonary dysfunction. Correlation between both scores was moderate (0.54 for pSOFAonset and 0.60 for pSOFAmax), indicating that comparable predictive performance does not render the scores interchangeable. The expanded PODI improved organ-level sensitivity for selected components but did not meaningfully improve mortality discrimination. Conclusions: The standard PODI may represent a practical approach to adjust for organ dysfunction and therapy intensity in administrative datasets with ICD-10 coding where clinical and laboratory information is unavailable. Given only moderate agreement with the pSOFA, the PODI should be understood as a covariate for risk adjustment at the group level rather than as a substitute for clinical organ dysfunction scores in individual patients. Further validation and refinement in non-sepsis cohorts are required before broader implementation in large-scale administrative research can be recommended.

ABSTRACT Breast milk is essential for optimal neonatal nutrition and survival, particularly among preterm and low-birth-weight infants. When a mothers own milk is unavailable, donor breast milk is the recommended alternative. However, Rwanda currently lacks accredited breast milk donation systems and milk banks, and little is known about healthcare providers perspectives on their potential implementation. The main objective of the study was to assess the acceptability of breast milk donation and explore the potential factors that could influence its adoption among healthcare providers in two Rwandan district hospitals. A convergent parallel design with a qualitative-dominant approach was conducted in the neonatology units of Kirehe District Hospital and Ruhengeri Level-II Teaching Hospital, Rwanda. Quantitative data were collected from 41 healthcare providers using structured questionnaires, including a six-item Likert scale (0=strongly disagree to4=strongly agree) to measure acceptability. Scores[&ge;]2.4 were interpreted as indicating high acceptability. Qualitative data were obtained through in-depth interviews with 10 healthcare providers and analyzed using inductive thematic analysis. Quantitative data were analyzed using descriptive statistics and non-parametric tests. The overall acceptability of breast milk donation was high, with 82.9% of healthcare providers expressing agreement (mean score: 2.83{+/-}1.10). Most participants (97.6%) perceived donor breast milk as beneficial for neonatal health. Key barriers included cultural resistance, limited maternal awareness, and inadequate infrastructure, while facilitators were staff training, institutional policies, and community engagement. Qualitative findings highlighted that providers were generally familiar with the concept of breast milk donation but noted the absence of formal programs in Rwanda. They emphasized that cultural concerns often stem from limited knowledge rather than entrenched opposition and strongly endorsed the benefits for infant health and maternal wellbeing. Providers stressed that successful implementation would depend on awareness-raising, trust in safety procedures, and institutional support through training and clear guidelines. Breast milk donation is highly acceptable among healthcare providers in Rwanda, with a mean score of 2.83{+/-}1.10 on the 0-4 Likert scale. Providers strongly recognized its benefits for vulnerable infants. Addressing gaps in awareness, infrastructure, and policy frameworks, alongside culturally sensitive community education, will be critical for successful implementation. These findings support the feasibility of introducing breast milk banking in Rwanda and provide evidence to guide policy and program development.

Background: Pertussis has resurged in the post-COVID-19 era, yet diagnostic delay remains a barrier to timely treatment and transmission interruption, particularly among adults. Methods: Retrospective observational cohort study of 787 patients with confirmed pertussis from January 2016 through March 2026 across two South Carolina health systems. Electronic health record data from the 60 days preceding confirmation were used to characterize diagnostic timing (same-day vs. delayed), delay duration, and respiratory pathogen testing patterns including pertussis test modality. Results: Adults accounted for 48.4% of cases (median age 16 years [IQR 4-52]; 61.6% female). Same-day diagnosis was highest among children aged 1-4 years (75.4%) and lowest among adults aged 50 and older (approximately 50%). Among the 305 patients (38.8%) with delayed diagnosis, median delay ranged from 7-12 days in children to 22.5-26.5 days in adults aged 50 and older. Delay did not vary significantly by COVID-19 period, race, ethnicity, or insurance type. Testing breadth was greater in inpatient and emergency settings than outpatient. Pertussis testing was predominantly PCR-based in children but serologic in adults, potentially reflecting later clinical presentation relative to illness onset; however, the near-absence of PCR testing in older adults may contribute to missed diagnoses during the early illness window when PCR sensitivity is highest. Conclusions: Older adults experienced markedly delayed pertussis diagnoses compared with children. Earlier consideration of pertussis in adults with prolonged cough, including PCR testing early in illness before serologic conversion, may reduce diagnostic delay and facilitate timelier treatment and contact tracing.

Background: Refractory and macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) has emerged as a major challenge in pediatric respiratory medicine, amplified by the post-2023 resurgence. However, a systematic overview of the research landscape specific to treatment-refractory and drugresistant disease in children remains lacking. Methods: Research articles and reviews on pediatric refractory or macrolide-resistant MPP published between 2000 and 2025 were retrieved from OpenAlex using Boolean searches. After screening, 2,286 records were quantitatively analyzed for annual output, contributing countries/institutions, thematic clusters, and citation-burst dynamics using Python. Results: Annual publications grew exponentially, with a pronounced surge after 2023 (n=378 in 2025). China produced the highest volume (45.1%) but recorded fewer citations per publication than the US, Japan, and Canada. The literature resolved into four clusters: macrolide resistance/molecular basis, epidemiology, etiology/co-infection, and refractory disease management. Burst analysis showed an evolution from earlier fronts like 23S rRNA mutations and azithromycin to recent emerging trends like pandemic-related co-circulation, genotype surveillance, and co-infection. Conclusions: Research on pediatric refractory and resistant MPP is expanding rapidly, shifting in emphasis from etiologic descriptions toward resistance mechanisms and clinical management. Standardizing the treatment of macrolide-unresponsive disease and post-pandemic epidemiological surveillance represent the principal directions for future work. Keywords: Mycoplasma pneumoniae; children; macrolide resistance; refractory pneumonia; bibliometric analysis; research trends

Abstract Objective Infant skin is highly susceptible to dermatitis, barrier dysfunction, and infections, necessitating safe and evidence-based skincare. This study assessed perspectives of Indian healthcare professionals (HCP) on infant skincare practices, product recommendations, prescribing behavior, and unmet needs in sensitive skin and atopic dermatitis management. Methods An online multicentric 4 independent cross-sectional survey was conducted involving 358 healthcare professionals across India, including pediatricians, dermatologists, and other clinicians, using structured questionnaires. The survey assessed prescribing behaviors, awareness of parents of the available products, and unmet needs in sensitive skin and atopic dermatitis management. Results The survey findings identified sensitive skin as the most frequently encountered infant skincare concern (91%), followed by eczema/atopic dermatitis (89%), and diaper rash (83%). Emollients were the most preferred first-line management strategy for mild-to-moderate sensitive infant skin (69%), followed by natural skincare products (63%), reflecting a strong preference for barrier-supportive and moisturizing therapies. Most HCPs preferred baby skincare products free from harsh chemicals (92.9%), while more than 90% routinely recommended natural/ayurvedic formulations. Additionally, Most HCPs were aware of cow ghee-based baby skincare products (93.8%) and considered barrier-focused early skincare important in preventing atopic dermatitis and the atopic march (81-87%), with 89% strongly endorsed consistent daily skincare as a key strategy for preventing flares and maintaining long-term control in infant atopic dermatitis. Conclusion Indian healthcare professionals favor preventive, barrier-focused infant skincare, with strong preference for natural and dermatologically safe formulations, while emphasizing the need for stronger clinical evidence in sensitive skin and atopic dermatitis management.

Background: Preventive chemotherapy via single-dose benzimidazoles remains the core strategy for soil-transmitted helminth (STH) control. However, single-dose regimens often yield sub-optimal clearance against species such as Trichuris trichiura and hookworm. This systematic review and meta-analysis evaluated the comparative efficacy of repeated-dose versus standard single-dose albendazole or mebendazole regimens in paediatric populations. Methods: Registered prospectively on PROSPERO (CRD420261491616), a comprehensive search of PubMed, Embase, Cochrane Library, and Google Scholar identified clinical trials comparing repeated-dose against single-dose albendazole or mebendazole in paediatric STH infections. Primary outcomes were cure rate (CR) and egg reduction rate (ERR). Random-effects models synthesized pooled odds ratios (OR) and mean differences (MD). Risk of bias was assessed using the Cochrane RoB 2 tool. Results: Five randomized clinical trials (N = 1,718 participants) met the inclusion criteria. Overall, repeated dosing demonstrated significant superiority in cure rate (pooled OR = 4.47, 95% CI: 1.58-12.67; I{superscript 2} = 92%) and egg reduction rate (pooled MD = 0.17, 95% CI: 0.01-0.32; I{superscript 2} = 87%). Discussion: Repeated-dose benzimidazole regimens offer superior overall therapeutic efficacy compared to standard single-dose administration in children. However, this therapeutic advantage is drug-specific: multi-dose albendazole consistently enhances parasite clearance across trial settings, whereas multi-dose mebendazole exhibits variable performance and lacks conclusive superiority over single dosing. Conclusion: Transitioning to targeted, multi-dose albendazole protocols--rather than mebendazole--may serve as an effective public health intervention to eliminate residual parasite reservoirs in high-transmission endemic regions.

Background Obtaining uncontaminated urine samples from children can be difficult. Clean catch urine (CCU) is non-invasive but may be slow and lead to a contaminated sample, whereas transurethral bladder catheterisation (TUBC) and suprapubic aspiration (SPA) are invasive. We assessed the feasibility of randomising children to a definitive trial. Methods FROG was a multicentre, randomised feasibility trial with a mixed-methods perspectives study, health-economic analysis and stakeholder consensus meeting. Children under 16 years requiring urine testing for suspected urinary tract infection (UTI) who could not provide a midstream sample were eligible for the feasibility trial. Parents, children and healthcare professionals were eligible for the perspectives study and consensus meeting. Results Of 703 children screened, 170 were offered the study and 99 were recruited. Overall, 64/170 (37.6%) consented to randomisation, exceeding the feasibility threshold (33%); 32 were allocated to CCU and 32 to TUBC. The allocated method was received by 46/64 (71.9%); delays, unsuccessful collection and distress contributed to non-receipt. Among participants with available cultures, contamination occurred in 2/12 (16.7%) allocated CCU and 0/6 allocated TUBC. No participants consented to randomisation involving SPA. The perspectives study included 14 parent interviews, 89 parent questionnaires and 28 staff across 5 focus groups and 1 interview. CCU and TUBC were considered acceptable, although participants balanced speed and accuracy against pain and distress. SPA availability and acceptability were limited. A total of 19 stakeholders attended the consensus meeting; 94% supported recruiting children aged under 18 months and 100% supported comparing CCU with TUBC, without SPA. Accuracy was the highest-ranked outcome. Conclusions A definitive trial comparing CCU-first with TUBC-first in children aged under 18 months is feasible. Its primary outcomes should reflect diagnostic accuracy and clinical consequences of contamination, with successful collection, collection time, pain and distress assessed as key secondary outcomes.

Incidence of ventilator-associated pneumonia (VAP) is increased in patients admitted for brain injury. Staphylococcus aureus appears to be a particularly common pathogen in these respiratory infections. Our aim was to confirm the extent of S. aureus involvement in VAP among patients with neurological injuries. We conducted a retrospective, multicenter study including patients with and without neurological injuries who developed VAP during their ICU stay. Among 15 702 patients admitted in the participant centers during the study period. 407 were finally included in the study. S. aureus was involved in 122 (61.6%) VAP in brain-injured patients and 63 (30.1%) of non-brain-injured patients. In brain-injured patients, multivariate analysis identified age (0.97 [0.95; 0.98]), antibioprophylaxis (0.31 [0.18; 0.53]; p < 0.0001), subarachnoid hemorrhage (2.18 [1.01; 4.68]; p=0.0461), lower Glasgow coma score (0.92 [0.87; 0.97]; p= 0.004) and SAPS II (0.98 [0.97; 1]; p=0.0174) as critical factors associated with the risk of S. aureus in VAP. In the non-brain-injured population, multivariate analysis identified antibioprophylaxis (0.38 [0.22; 0.65]; p=0.0006), age (0.96 [0.95; 0.98]; p<0.0001), SAPS II (0.98 [0.97; 1]; p=0.0265), thoracic surgery (0.21 [0.09; 0.48]; p=0.0002) and peripheral neurosurgery (1.95 [1.2; 3.19]; p=0.0076) as critical factors. A total of 172 patients (42.3%) died during their ICU stay and 90-days mortality was 194 (47.7%). No difference of mortality was noticed function of VAP-associated pathogen.

Background: Infants <30 weeks gestational age (very preterm (VPT)), are at risk of experiencing multiple serious neonatal morbidities. These morbidities impart serious biological stress, which may be reflected in dysregulated protein expression even after the morbidities have resolved. Recent studies suggest that DNA methylation-based predictors of circulating proteins may reflect the molecular effects of neonatal adversity. The objective of this study is to examine associations between DNA methylation-derived EpiScores, which are externally trained methylation signatures that proxy circulating protein levels, and neonatal morbidity burden in children born VPT. Buccal DNA methylation was obtained at NICU discharge in 537 infants from the NOVI cohort. A total of 111 EpiScores were calculated and tested for association with multimorbidity (0-1 vs. [&ge;] 2 morbidities) using adjusted linear regression models. Cross-tissue analyses in an external paired blood-buccal dataset (n=21) were used to identify EpiScores with moderate-to-strong correlations across tissues. Results: Eighteen EpiScores were nominally associated with multimorbidity (p < 0.05), with Melanoma-derived growth regulatory protein (MIA) with FDR < 0.05 (beta = 0.0023, p = 0.0004). In cross-tissue analyses, 35 EpiScores yielded r > 0.50 (p<0.05), 11 of which showed nominal associations with multimorbidity, including MIA. Overall, the morbidity-associated EpiScores reflected immune, inflammatory, metabolic, and growth-related pathways. Conclusions: Buccal DNA methylation-derived EpiScores capture biological signatures associated with neonatal morbidity burden in very preterm infants.