Pediatric Infectious Disease Journal

Objective: To describe the clinical characteristics of term neonates with neonatal bacterial meningitis (NBM) and explore the association between different pathogens and imaging complications, providing clinical evidence for early identification and individualized management. Methods: A retrospective study was conducted on 531 term neonates diagnosed with NBM admitted to the Capital Institute of Pediatrics from 2013 to 2025. Demographics, clinical manifestations, laboratory parameters, etiological results, imaging complications and treatment measures were collected. Patients were divided into favorable/adverse discharge outcome groups and pathogen-positive/negative groups. Statistical analyses were performed using appropriate tests, and Cramers V coefficient was used to analyze the association between pathogens and imaging complications. Results: (1) The most common clinical manifestations were abnormal body temperature (79.85%), altered consciousness (55.18%) and jaundice (46.52%). CSF/blood culture was positive in 133 cases (25.05%), with Escherichia coli (27.07%), group B streptococcus (17.29%) and Staphylococcus species (16.54%) as predominant pathogens. The overall incidence of imaging complications was 22.22%, mainly hydrocephalus (5.84%), subdural effusion (4.90%) and encephalomalacia (2.64%). (2) Adverse discharge outcomes occurred in 107 cases (20.15%). Compared with the favorable group, the adverse group had higher incidences of convulsions, altered consciousness, anterior fontanelle bulging, abnormal muscle tone and primitive reflexes (all P<0.001), more obvious laboratory abnormalities (higher CRP, CSF leukocytes and protein, lower CSF glucose, all P<0.05), higher culture positive rates and greater need for adjuvant therapy (all P<0.001). (3) Pathogen-positive patients had higher imaging complication rates. Gram-negative infections were associated with higher hydrocephalus and subdural effusion rates, while Gram-positive infections had higher brain abscess risk. Specifically, Escherichia coli correlated with hydrocephalus and subdural effusion; group B streptococcus with cerebral infarction and encephalomalacia; LM with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). Conclusion: Term NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens are Escherichia coli, group B streptococcus and Staphylococcus species, with hydrocephalus and subdural effusion as common imaging complications. Adverse outcomes are associated with severe symptoms, obvious laboratory abnormalities and higher pathogen positivity. Specific pathogens correlate with distinct imaging complications.

Introduction: Bacterial meningitis (BM) is a common bacterial infection of the central nervous system, and its incidence in children varies by age, with the highest rates observed in infants younger than two months old. Objective: To describe the etiology, epidemiology, and clinical presentation of children under 5 years of age with BM at HOMI between 2016 to 2023. Materials and methods: Descriptive study of children under 5 years of age with suspected BM. Probable cases were those with CSF results consistent with BM. Confirmed cases had a positive CSF culture or blood culture for a bacterial pathogen or a positive molecular test for a bacterium in the CSF. Demographic variables, incidence of BM per year, mortality, and sequelae among survivors were analyzed. Results: A total of 527 suspected cases of BM were evaluated. Of these, 22.8% (120/527) were classified as probable cases and 13.1% (69/527) as confirmed cases. Children under 2 years of age accounted for 37.2% of probable cases and 78.2% of confirmed cases. Among confirmed cases, the most frequent symptoms were fever (98.3%), altered consciousness (39.1%), seizures (36.2%), and lethargy (27.5%). The mortality rate was 11.6% (8/69), and the mean hospital stay among patients with BM was 24.5 days. Streptococcus pneumoniae was identified in 26.1% of confirmed cases, with most isolates belonging to serotypes not included in PCV10. Haemophilus influenzae accounted for 17.4% of cases, of which 77.7% were serotype b. Neisseria meningitidis represented 10.1% of cases, and 60% of these were serogroup C. Other pathogens were identified in 49.1% of patients. Conclusion: Sentinel surveillance makes it possible to measure the impact of public health interventions and evaluate the impact of vaccines already used.

Objectives: Group B Streptococcus (GBS) is a leading cause of neonatal mortality worldwide. However, the global burden of early-onset GBS disease (EOD-GBS) has not been fully elucidated. We aimed to describe the geographical distribution and epidemiological characteristics of the EOD-GBS burden, and analyze its association with socio-economic development and universal health coverage. Methods: We used data from the Global Burden of Disease Study 2021 and the Universal Health Coverage Service Coverage Index (UHC-SCI) to calculate estimated annual percentage changes (EAPCs) of EOD-GBS mortality. Sex differences were analyzed using the conservative overlap assessment. The geographical distribution of EOD-GBS clinical presentations and mortality was mapped. Health inequality analysis was conducted to evaluate the relationship between the sociodemographic index (SDI), UHC-SCI, and EOD-GBS burden. Results: Global EOD-GBS mortality decreased by nearly 50% from 1990 (693.41 per 100,000) to 2021 (348.80 per 100,000). However, the decline was not uniform: the most significant decrease occurred in high-middle SDI regions (EAPC: -7.17%), and the slowest in low SDI regions (EAPC: -2.23%). Male neonates accounted for the most EOD-GBS deaths, particularly in high SDI regions. Lower respiratory infections were common in Asia and Oceania; meningitis was more prominent in Europe. Inequality analysis revealed a phenomenon of "absolute convergence but relative differentiation": as social development and universal health coverage improves, the absolute mortality gap between countries narrowed, but relative burden concentrated increasingly among the poorest populations. Conclusions: The global burden of EOD-GBS has decreased substantially, but there are marked differences among countries. Continued socioeconomic development and expanded universal health coverage are critical to further reduce neonatal mortality.

BackgroundTo date, accessible diagnostic tools to identify whether a patients pneumonia is a bacterial, or viral infection, are not accurate or timely enough to prevent preemptive antibiotic administration. Relying on single biomarkers or clinical presentations has been insufficient. We aimed to incorporate a wide range of novel biomarkers and clinical presentations in a multivariable model and validate its capacity to differentiate cases of bacterial and viral pneumonia. MethodsData from 457 children aged 2-59 months, admitted to Kilifi County Referral Hospital, Kenya, with bacterial (n = 229) and viral (n = 228) infections, were used to develop and validate a predictive multivariable Poisson regression model to differentiate pneumonia etiology. The Receiver Operating Characteristic curve was used to assess biomarker performance and validate the model internally. ResultsSixty-three percent (63%) of the children presented with severe pneumonia. 72% with viral pneumonia had severe pneumonia, compared to 54% with bacterial pneumonia who had severe pneumonia. In crude analyses, chest-wall indrawing, cough, convulsions, crackles, angiotensinogen, and Serpin Family A Member 1 were significantly associated with pneumonia etiology, controlling for age. However, only chest-wall indrawing remained significant in multivariable analyses after controlling for age. The model demonstrated fair, but inadequate, discrimination, with an Area Under the Curve of 0.61. ConclusionAmong the children admitted to hospital with WHO defined pneumonia, a wide range of biomarkers and clinical presentations still failed to distinguish bacterial from viral pneumonia.

Tuberculosis (TB) is a significant cause of morbidity and mortality in children and adolescents, causing 172,000 deaths in 2024 in children and adolescents worldwide. Diagnostic challenges are pronounced in pediatrics, in which collecting respiratory specimens is challenging and TB is often paucibacillary, leading to delayed diagnosis and increased mortality. We describe the protocol and methodology of the Pediatric TB Diagnostic (PDTBDx) cohort, a study with the primary aim of evaluating non-sputum-based TB diagnostics for diagnosis and treatment response in children. This is a prospective observational cohort study of >400 children recruited from inpatient and outpatient clinical sites in Nairobi, Kenya. Children <15 years presenting to study clinical sites with TB symptoms will be considered for enrollment as symptomatic participants. Enrolled participants will undergo rigorous clinical assessment and longitudinal follow-up to ensure appropriate diagnostic classification by NIH consensus statement guidelines for pediatric TB. Baseline evaluation includes symptom assessment, chest x-ray, HIV testing, respiratory TB culture and GeneXpert Ultra, and urine LAM. Subsequent visits occur at week 2, months 1, 2, 4, 6,12 and 24. Blood and urine specimens will be collected at baseline and at follow-up visits for storage for evaluation of novel diagnostic assays, including exosome-based and CRISPR-based TB biomarkers. This large, prospective cohort of pediatric participants with and without TB follows a consistent and rigorous protocol for diagnosing childhood TB, in concordance with internationally recognized guidelines. Assays evaluated in PDTBDx will guide improved diagnostic strategies for pediatric TB.

Severe neonatal hyperbilirubinaemia represents a considerable cause of mortality and long term-morbidity in neonates born in low resource settings. Early identification of risk factors, such as glucose-6-phosphate dehydrogenase (G6PD) status, has the potential to prevent severe hyperbilirubinaemia and improve the clinical outcomes. The primary aim of the study was to assess equivalency of cord blood and neonatal capillary blood for diagnosis of G6PD deficiency using the quantitative point-of-care "STANDARD G6PDTM" test (SD Biosensor, Korea). Additional secondary aims were to compare the "STANDARD G6PDTM" with gold standard spectrophotometry and to analyse changes in G6PD activity in the first 4 months of life. A total of 75 neonates born in Shoklo Malaria Research Unit (SMRU) clinics were selected based on their G6PD status assessed through routine cord blood screening using the "STANDARD G6PDTM" test. Using activity thresholds established before in this setting, 25 G6PD deficient, 25 G6PD intermediate and 25 G6PD normal neonates were identified and re-tested on capillary blood collected within 24 hours of life and at day 7. They were also followed-up at 1 and 4 months of age to study haematologic and G6PD activity changes over time. The results showed that the "STANDARD G6PDTM" can be used reliably up to one week of life for testing neonates using the same thresholds established in cord blood. Performance of the point-of-care test as compared to the gold standard spectrophotometry remained excellent at all sampling time-points. Nevertheless, G6PD activity assessed longitudinally in the same participants decreased over time, both at 1 month of age and at 4 months of age, and interpretation of results in female infants with intermediate activity might require different thresholds. The study demonstrated that the "STANDARD G6PDTM" can effectively support clinical care in neonates and infants in populations with prevalent G6PD deficiency at the primary care level and especially in low-resource settings.

Background: Extrauterine growth restriction (EUGR) is a common and clinically significant complication among preterm infants, contributing to adverse neurodevelopmental and metabolic outcomes. Early and individualized risk prediction remains challenging. This study aimed to develop and validate an interpretable machine learning model for early prediction of EUGR using routinely available clinical variables, and to implement a user-friendly web-based calculator for clinical use. Methods: We retrospectively analyzed 1,431 preterm infants admitted within 24 hours after birth to our hospital between May 2020 and March 2025. Infants from the Yangpu campus (n=863) formed the training set, and those from the Huangpu campus (n=568) formed the validation set. Early clinical variables available within 48-72 hours were screened using the Boruta algorithm. Logistic regression, XGBoost, random forest, decision tree, and support vector machine models were developed and compared. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Brier score. SHapley Additive exPlanations (SHAP) were applied to assess global and individual feature contributions, nonlinear effects, and interactions. A web-based calculator was constructed based on the optimal model. Results: Nine variables were identified as important predictors: birth weight, small for gestational age status, gestational age, breastfeeding, multiple gestation, neonatal respiratory distress syndrome, patent ductus arteriosus, maternal hypertension, and maternal group B Streptococcus infection. Among the five models, XGBoost achieved the best performance in the validation set (AUC 0.922, accuracy 0.849, Brier score 0.108). SHAP analysis showed that low birth weight, small for gestational age, maternal group B Streptococcus infection, and patent ductus arteriosus were major risk factors, while breastfeeding was protective. Notable nonlinear and interactive effects were observed, particularly between birth weight and gestational age and between breastfeeding and patent ductus arteriosus. The web-based calculator provides real-time individualized risk estimation and visualized interpretation. Conclusions: An interpretable XGBoost-based model and web calculator were successfully developed and validated for early prediction of EUGR in preterm infants. This tool may support clinicians in identifying high-risk infants and guiding individualized nutritional and clinical management.

Streptococcus pneumoniae is the leading cause of empyema and pneumonia in children, and monitoring of effectiveness of polyvalent pneumococcal vaccines has been essential for controlling invasive pneumococcal disease (IPD) in children and elderly adults. Conventional serotyping of pneumococci has relied on Quellung reaction following laboratory culture, however more recently whole genome sequencing (WGS) has been implemented in many reference laboratories to enhance traditional typing. Pleural fluid samples from cases with empyema are often culture negative, limiting the utility of WGS and requiring polymerase chain reaction (PCR) or 16S rRNA sequencing to detect S. pneumoniae. These molecular methods have limited sensitivity and capacity to characterise pneumococcus in clinical samples, especially in specimens with a low pathogen abundance. This study applied capture-based enrichment (tNGS) to identify and characterise S. pneumoniae directly from pleural fluid samples. A total of 51 pleural fluid samples were subjected to tNGS with a custom probe panel, for 39 known positive fluids collected from IPD cases between 2018-2025 in New South Wales, Australia. tNGS results were benchmarked against molecular-based serotyping. Our tNGS achieved 100% sensitivity and specificity in detecting S. pneumoniae. Serotyping results were concordant with PCR and 95% (37/39) of S. pneumoniae PCR positive pleural fluid cases could be serotyped using tNGS. Standard molecular methods however could only determine serotype in 56% (22/39) of samples. This tNGS enabled 39% improvement in ability to directly identify and serotype IPD-associated serotypes of S. pneumoniae in difficult-to-culture pleural fluids can significantly enhance laboratory surveillance of IPD as well as our understanding of vaccine effectiveness.

Background: Preterm births contribute to approximately 35% of neonatal deaths globally, with an estimated 13.4 million infants born prematurely each year. Despite this substantial burden, limited evidence exists on time to discharge and its determinants among preterm neonates admitted to Neonatal Intensive Care Units (NICUs), particularly in rural Ugandan settings. This study aimed to investigate time to discharge and associated factors among preterm neonates admitted to Kiwoko Hospital in Nakaseke District, Uganda. Methods: A retrospective cohort study was conducted using secondary data from Kiwoko Hospital on preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) between 2020 and 2021 (n = 847). The cumulative incidence function was used to estimate the probability of discharge within 28 days of admission, accounting for competing events. A Fine and Gray sub-distribution hazard regression model was fitted to identify factors associated with time to discharge. Results: Of the 847 preterm admissions, 70.1% were discharged alive within 28 days. The median time to discharge was 14 days. The cumulative incidence of discharge by 28 days was 68%, accounting for competing events. During follow-up, 165 neonates did not complete the 28-day period, including 88 deaths. Factors significantly associated with time to discharge included place of delivery (SHR: 0.62; 95% CI: 0.53-0.73; p<0.001), maternal residence in other districts (SHR: 0.69; 95% CI: 0.48-0.99; p=0.044), extreme preterm (SHR: 0.05; 95% CI: 0.03-0.09; p<0.001), very preterm (SHR: 0.18; 95% CI: 0.14-0.25; p<0.001), moderate preterm (SHR: 0.59; 95% CI: 0.46-0.76; p<0.001), triplet births (SHR: 0.40; 95% CI: 0.23-0.68; p=0.001), 2-4 ANC visits (SHR: 0.70; 95% CI: 0.56-0.87; p=0.002), <=1 ANC visit (SHR: 0.64; 95% CI: 0.49-0.85; p=0.002), respiratory distress syndrome (SHR: 0.64; 95% CI: 0.48-0.74; p<0.001), and birth trauma (SHR: 2.62; 95% CI: 1.60-4.29; p<0.001). Conclusions: Respiratory distress syndrome, fewer antenatal care visits, out-of-district residence, and higher degrees of prematurity were associated with prolonged time to discharge among preterm neonates. Strengthening antenatal care utilization and improving access to quality neonatal care in underserved areas may enhance discharge outcomes.

Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

Recognizing the challenges faced by primary caregivers regarding the health of children with congenital craniofacial anomalies (CCAs) contributes to strengthening healthcare programs according to patient[s] and families differential needs. This qualitative study presents the experiences of 25 caregivers of children with CCAs from Bogota and Cali, Colombia, identified from care registries and consultation statistics provideed from public high-complexity healthcare institutions. Grounded in Giorgis descriptive phenomenology and employing thematic analysis, this research utilized semi-structured interviews and focus groups to explore the diagnostic process and its impact, experiences with healthcare services, and the caregivers role and daily care activities. Data were analyzed using MAXQDA(R) qualitative software. Findings highlighted the emotional complexity of caring for childre[n]s health. Challenges included late diagnoses, pessimistic views of the children with CCAs condition by healthcare team members; lack of effective support, information, and guidance from health staff; absence of clear care and referral protocols, and limited access to specific adaptations and timely specialized care for children with CCAs. There were also reduced therapeutic services, and a pronounced gendered caregiving burden when responsibilities fall almost exclusively on mothers. System fragmentation, reflected in deficiencies in communication and a lack of clear, coordinated, and timely pathways of care, as well as the absence of adequate psychosocial support for families, emerged as common structural problems in healthcare services in both geographic settings where this research has been conducted. Gender-sensitive strategies focused on alleviating emotional concerns and the burden of caregiving from diagnosis onward within a patient and family-centered care model are decisive. Improving comprehensive CCAs training for healthcare personnel and making adjustments to care pathways are suggested to contribute to the implementation of inclusive health programs that address the diverse needs of children and their families.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

Abstract Introduction: Streptococcus is the second genus involved in bone and joint infections (BJIs) after Staphylococcus. Streptococcus agalactiae is the predominant Streptococcus species implicated in BJIs. However, unlike Staphylococcus-related BJIs, data on S. agalactiae infections remain scarce. Methods: We conducted a retrospective cohort study from the West Region cohort of the CRIOAc registry among six university hospitals including all microbiologically confirmed streptococcal BJI in adults between 2014 and 2023. Results: 1454 patients were included, with a median age of 67 years and 65% male. S. agalactiae was the predominant streptococcal species involved 423/1454(29%). The most prevalent comorbidities identified were obesity (378/1454;26%) and diabetes mellitus (343/1454;24%). Prosthetic joint infections (PJIs) were the most common (653/1454;45%), although diabetic foot osteitis was less prevalent overall, it was significantly more associated with S. agalactiae infections (48/423;11% versus 70/1031;7%, p=0.05). S. agalactiae BJIs were more frequently lower-limb infections and chronic infections (240/423;57% versus 502/1031;49%, p=0.04). Half of the cohort had a polymicrobial infection and were slightly more frequent with S. agalactiae BJIs (235/423;56% versus 498/1031;48%, p=0.1). These results were consistent with a sensitivity analysis excluding diabetic foot related osteitis. Logistic regression analysis identified arteriopathy (OR: 4.16; IC95:1.64-11.24, p=0.003), and obesity (OR: 2.57; IC95: 1.41-4.78, p=0.002) as specific risk factors for S. agalactiae BJIs. Conclusion: S. agalactiae emerges as a prominent and distinct pathogen in complex streptococcal BJIs, with specific risk factors such as arteriopathy, obesity and diabetes mellitus, and more chronic infections.

Introduction Cesarean delivery accounts for nearly one-third of U.S. births and is associated with substantial maternal morbidity and health care costs. Persistent racial disparities have been documented, yet the structural factors contributing to these differences remain incompletely understood. The extent to which insurance coverage shapes racial disparities in cesarean delivery remains unclear. Objective To evaluate the independent and interactive associations of race/ethnicity and insurance coverage with cesarean delivery in the United States. Methods Population-based retrospective cohort study using singleton live births recorded in the United States Vital Statistics Natality files from 2014 to 2024. Multivariable logistic regression was used to estimate the independent effects of race/ethnicity and insurance status on cesarean delivery, including interaction terms to test effect modification, using national birth certificate data. Models were adjusted for maternal demographics, clinical factors, and temporal covariates. Adjusted odds ratios, predicted probabilities, and absolute risk differences were derived from post-estimation marginal effects. The main outcome measure was cesarean delivery (yes vs no). Results Among 41,543,568 deliveries from 2014 to 2024, 13,312,221 (32.0%) were cesarean deliveries. After adjustment, both race and ethnicity and insurance status were independently associated with cesarean delivery. Compared with non-Hispanic White women, non-Hispanic Black women had higher odds of cesarean delivery (odds ratio [OR], 1.22; 95% CI, 1.22-1.23). Relative to uninsured women, those with private insurance had 59% higher odds of cesarean delivery (OR, 1.59; 95% CI, 1.58-1.60). Significant interaction effects were observed, indicating that insurance coverage modified racial and ethnic differences in cesarean delivery. Non-Hispanic Black women had the highest predicted probabilities across all insurance categories, with the largest absolute disparities observed among uninsured women. Conclusion Racial and ethnic differences in cesarean delivery persist in the United States and are modified by insurance coverage, suggesting that coverage-related differences may contribute to inequities in obstetric care.

Globally, respiratory tract infections (RTI) are the main cause of morbidity, and in Low-middle-income countries (LMICs) RTI including pneumonia are a leading cause of morbidity and mortality in children <5 years. Diarrheal illness increases RTI risk in young children through micronutrient depletion, and immune stress, yet data on post-diarrhea RTI burden in LMICs are limited. We determined the prevalence and risk factors of RTI within three months following medically-attended diarrhea (MAD) in children aged 6-35 months enrolled in seven EFGH country sites in Asia, Africa and South America. The EFGH study prospectively enrolled children aged 6-35 months with MAD in selected health facilities during a 24-month period from 2022 to 2024 and followed them for three months. RTI was defined as cough or difficulty breathing and the presence of one of the following symptoms at any scheduled or unscheduled visit during follow-up: stridor; fast-breathing; oxygen saturation <90%; or chest indrawing. The period prevalence and 95% confidence intervals of RTI were calculated, and correlates of RTI were assessed using modified-Poisson regression. From June 2022 to August 2024, 9,476 children aged 6-35 months presenting with MAD in the EFGH study sites were screened: 9,116 (96.2%) included in the current study. Nearly half were female (46.7%), and median age was 15 months. Overall, 48.5% received all age-appropriate vaccines, and 87.6% received the pneumococcal vaccine, with significant variation across countries. Nearly one-quarter of children were stunted, 17.2% wasted, and 21.9% underweight. RTI occurred in 3.8% of children during the three-month follow-up, mostly within the first month. Higher prevalence of RTI occurred among children aged 12-23 months (8.7%), those undernourished (16.1%), unvaccinated (4.0%) or living in poor sanitation settings (4.1%). While children who received all age-appropriate or pneumococcal vaccinations had a lower crude prevalence of RTI, these associations were not statistically significant after adjusting for age, sex and study site. RTI was infrequently observed in the three months following MAD presentation, with significant variability by site and with the highest prevalence in Malawi. RTI risk was highest in 12-23-month-olds and among children with undernutrition, and those living in poor sanitation conditions.

Objectives. To compare the efficacy and safety of invasive sacral neuromodulation (SNM) and noninvasive enteral neuromodulation (ENM) in children with refractory gastrointestinal motility disorders (GMD). Materials and Methods. This prospective interventional trial enrolled pediatric patients with GMD between 2019 and 2024 at a single tertiary referral center. Children with inflammatory bowel disease or mechanical causes of GMD were excluded. Participants received either SNM via an implanted device or ENM via surface electrodes. Stimulation was delivered at 14 Hz, 210 s pulse width, with individualized intensity (median 1.0 mA for SNM; 6.0 mA for ENM). Primary outcomes were abdominal pain, fecal incontinence, defecation frequency, and stool consistency. Treatment success was defined as clinically significant improvement in at least two of these four domains. Quality of life was assessed at baseline and 12 weeks. Safety outcomes were monitored over a 12-month follow-up. Results. Of 70 eligible patients, 48 completed the study (18 SNM; 30 ENM). Diagnoses included Hirschsprung disease, functional constipation, and congenital neuronal malformations. Severe comorbidities were more frequent in the SNM group (45%) than the ENM group (3%; P = .0018). Treatment success was observed in 80% of ENM and 83% of SNM patients (P = 1.00). No significant differences were found between groups for individual outcomes. No major complications occurred. Minor adverse events were comparable (ENM 27% vs SNM 17%; P = .50). Conclusions. Both SNM and ENM are effective and safe options for treating pediatric GMD and may be considered within a multimodal therapeutic approach.

We aimed to evaluate disparities in perinatal ICU admissions at an urban medical center and to contextualize these findings relative to national U.S. data provided by the Centers for Disease Control and Prevention (CDC). To do so, we performed a retrospective review of all pregnant and < 6-week postpartum patients admitted to the ICU between October 2023 and June 2025. The cohort included 58 patients: 81% were non-Hispanic Black, and 91% were publicly insured. These local data can be compared to national data, which demonstrate higher rates of severe maternal morbidity (SMM) and ICU admission among Black patients and those insured by Medicaid. In 2023, the U.S. maternal mortality rate was 18.6 per 100,000 live births, down from 22.3 in 2022. However, significant disparities persist, with mortality rates of 50.3 per 100,000 among Black women compared with 14.5 per 100,000 among White women. The most frequently reported indications for obstetric ICU admission include hypertensive disorders of pregnancy, obstetric hemorrhage, and severe underlying medical comorbidities.

Background: Sub-Saharan Africa (SSA) still experiences a high burden of micronutrient deficiencies. For monitoring of micronutrient status among young children in SSA, non-invasive alternatives to blood-based biomarkers are desirable. Handheld Raman spectrophotometry appears to offer this alternative to quantify intracellular stores of micronutrients. In rural Burkina Faso and Kenya, we validated the Cell-/SO-Check device (ZellCheck(R)) against conventional laboratory-based methods. Methods: For this validation study, we recruited children aged [&ge;]24 months attending routine clinics within the Health and Demographic Surveillance Systems (HDSS) in Siaya and Nouna. Anthropometric measurements and venous blood samples were taken. Plasma ferritin, soluble transferrin receptor (sTfR) and C-reactive protein (CRP) were measured by ELISA, and plasma zinc by atom absorption. The spectrometer was used to quantify zinc and iron. For continuous outcomes, we generated Bland Altman plots and calculated bias and limits of agreement (LoA). For binary outcomes, we produced Receiver Operator Characteristic (ROC) areas under the curve (AUC), and estimated sensitivity, specificity and predictive values. Results: We analysed data of 48 children from Burkina Faso and 54 children from Kenya (male: 53%; age range: 24-66 months). According to spectrophotometry, the proportions of iron deficiency and zinc deficiency were 16.7% and 25.5%, respectively. The median concentrations were for ferritin 24.0 {micro}g/L (range: 2.0-330.0), for sTfR 5.7 mg/L (2.8-51.0), and for zinc 9.9 {micro}mol/L (5.2-25.0). The corresponding bias for iron levels by spectrophotometry was 42.4 with LoA: -18.7, 103.6. The bias for zinc levels was 7.5 with LoA: -49.3, 64.2. For the classification of deficiency, the ROC-AUC, sensitivity, and specificity for spectrophotometry vs. biomarker-based diagnosis were for iron deficiency 0.62, 68% and 55%, respectively, and for zinc deficiency 0.55, 33% and 91%, respectively. Conclusions: The Cell-/SO-Check device may be used to rank children in population-based studies in SSA according to their zinc status, but not iron status. The method should not replace the standard laboratory measurements for clinical diagnoses of zinc and iron deficiencies.

BackgroundThe Toto Bora trial tested whether a course of azithromycin reduced rates of re-hospitalization or death in the 6 months following hospitalization among Kenyan children. We hypothesized that azithromycin would reduce enteric bacteria and increase carriage of macrolide resistance in the subsequent 3 months. MethodsKenyan children (1-59 months) hospitalized and subsequently discharged for non-traumatic conditions provided fecal samples before and 3 months after randomization to a 5-day course of azithromycin or placebo. Quantitative PCR identified enteropathogens and AMR-conferring genes in fecal samples. Generalized estimating equations assessed the impact of the randomization arm on pathogen and resistance gene detection, accounting for baseline presence and site. ResultsAmong 1,393 baseline stools, 12.4% had at least one bacterial enteropathogen, 94.7% had at least one macrolide-resistance gene, and 92.6% had at least one beta-lactamase-resistance gene identified. At month 3, children randomized to azithromycin had a 6.1% higher likelihood of carrying a macrolide resistance gene compared to placebo (adjusted prevalence ratio [aPR], 1.06; 95% CI, 1.04-1.08; P<0.001). Specifically, azithromycin randomization was associated with a higher relative prevalence of erm(B) (aPR, 1.09 [95% CI, 1.04-1.15]; P=0.001), erm(C) (aPR, 1.23 [95% CI, 1.14-1.31]; P<0.001), msr(A) (aPR, 1.14 [95% CI, 1.04-1.25]; P=0.007), and msr(D) (aPR, 1.07 [95% CI, 1.03-1.11]; P=0.001). There was no difference in overall bacterial pathogen prevalence (18.9% vs 17.3%) between randomization arms, but a slightly lower proportion of children had Shigella after randomization in the azithromycin arm (3% vs. 5%, aPR, 0.79 [95% CI, 0.62, 1.01]; P=0.063). InterpretationAzithromycin at hospital discharge was associated with higher carriage of macrolide-resistance-conferring genes in the post-discharge period compared with placebo, without significant declines in enteric pathogen carriage other than modest changes to Shigella. The potential benefits and risks of empiric azithromycin need to be considered, as children are increasingly exposed to this broad-spectrum antibiotic.

Background To anticipate the impact of new pneumococcal vaccines and guide future updates, accurate forecasts of changes in non-vaccine serotypes (NVTs) are needed. We developed and evaluated three models that incorporated different assumptions about the way in which NVTs will increase and generated ensemble predictions for the frequency of NVTs in different post- pneumococcal conjugate vaccines (PCV) periods. Methods We analyzed age- and serotype-specific invasive pneumococcal disease (IPD) cases from the United States CDCs Active Bacterial Core surveillance during the pre-PCV (1998-1999), early post-PCV7 (2000-2004), late post-PCV7/pre-PCV13 (2005-2009), early post-PCV13 (2010-2014), and late post-PCV13 (2015-2019) periods. These data were augmented with IPD cases from several countries and combined with serotype-specific invasiveness to infer serotype-specific carriage prevalence. Three models (Ranking, Proportionate, NFDS-lite) generated independent predictions of post-PCV IPD frequencies, which were integrated using an accuracy-weighted ensemble. Model performance was evaluated using the normalized root mean square error (NRMSE). Results A total of 23,959 non-PCV7 and 15,580 non-PCV13 cases were analyzed. NVT cases increased from the pre-PCV7 to the late post-PCV7 and post-PCV13 periods. The accuracy of predictions across age groups and models was consistent and high during the post-PCV13 periods but varied during the post-PCV7 periods. The Proportionate model (NRMSE=0.70-3.95) outperformed the NFDS-lite (NRMSE=0.93-8.91) and Ranking (NRMSE=1.51-5.37) models during the early-post-PCV7 period, whereas the NFDS-lite model (NRMSE=1.55-9.82) was superior to the Proportionate (NRMSE=1.45-10.22) and Ranking (NRMSE=1.86-11.35) models during the late post-PCV7 period. The Ensemble model improved on these individual models. Conclusions The Ensemble model offers a tool for forecasting serotype patterns to inform pneumococcal vaccines impact and future pneumococcal vaccine formulation.