Pediatric Infectious Disease Journal

ObjectiveTo 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. MethodsA 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. ResultsO_LIThe 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%). C_LIO_LIAdverse 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). C_LIO_LIPathogen-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; LMs with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). C_LI ConclusionTerm NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens areEscherichia 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.

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

In this large multi-center cohort of children evaluated for Lyme disease in a Lyme-endemic emergency department, we assessed the diagnostic accuracy of clinician suspicion and subsequent clinical decision-making for children presenting with monoarthritis. Among 1,582 children with monoarthritis evaluated for Lyme disease, 623 (39%) had Lyme arthritis and 32 (2%) had septic arthritis. Overall, 313 (20%) had an invasive joint procedure (arthrocentesis or arthroscopy), 194 (12%) received parenteral antibiotics, and 376 (24%) were hospitalized. Clinician suspicion had moderate discriminative ability for Lyme disease (area under the receiver operating characteristics curve: 0.75, 95% confidence interval: 0.72-0.77). Children with higher clinician suspicion were less likely to receive parenteral antibiotics or to be hospitalized, although invasive procedure rates were similar. Our findings highlight the challenge of clinically distinguishing Lyme from septic arthritis. Better diagnostic tools are needed to improve timely diagnosis and minimize invasive testing among children with monoarthritis in Lyme-endemic regions.

Objective: Lyme disease diagnosis in children is challenging due to atypical presentations and testing limitations. We sought to evaluate the association between Lyme disease and socio-geographic risk factors in children. Materials and methods: We enrolled children undergoing evaluation for acute Lyme disease at one of eight Pedi Lyme Net pediatric emergency departments located in high Lyme disease incidence states over a ten-year period (2015-2024). We defined a case of Lyme disease with an erythema migrans (EM) lesion or a positive two-tier serology result in a child with signs and/or symptoms of acute disease. We linked each childs primary residential county to the following factors: urban-rural residence, socioeconomic status, population-level disease incidence, wildland-urban interface, and "Lyme disease" Google searches. We performed a multi-level logistic regression analysis to evaluate associations between Lyme disease and county factors after adjusting for individual demographics. Results: Among 5,529 children enrolled, 1,396 (25.2%) had Lyme disease: 101 (7.2%) with early-localized disease, 584 (41.8%) with early-disseminated disease, and 711 (50.9%) with late-disseminated disease. Rural residence (aOR 1.9, 95% CI 1.3-2.9), higher socioeconomic advantage (aOR 1.3, 95% CI 1.1-1.4), more "Lyme disease" Google searches (aOR 1.1, 95% CI 1.0-1.2), and higher wildland urban interface (aOR 1.2, 95% CI: 1.0-1.4) were independently associated with Lyme disease. Conclusion: Incorporating socio-geographic factors alongside clinical data may augment diagnostic risk assessment in children with suspected Lyme disease. However, these factors should be incorporated carefully to ensure clinical assessments are not based on a childs geographic location alone.

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.

BackgroundRespiratory tract infections range from asymptomatic colonisation to an invasive disease. Recent studies suggest that nasopharyngeal microbiota may influence this variability. Emerging evidence points to Dolosigranulum pigrum, a nasopharyngeal commensal, as a potentially protective bacterium. This study aimed to identify variables associated with the presence of D. pigrum in the nasopharynx of children with varying respiratory health statuses. MethodsNasopharyngeal aspirates were collected from children <18 years who were asymptomatic (n=65), had banal viral infection (n=48), or Invasive Pneumococcal Disease (IPD) (n=27). The presence of D. pigrum was defined as >0.1% of total sequences obtained by 16S rRNA gene sequencing. Variables included sex, breastfeeding, delivery mode, S. pneumoniae carriage, respiratory viruses and clinical features. ResultsAmong 140 children (73 males, 67 females), D. pigrum was detected in 79 (56.4%): 44/65 in the healthy group; 26/48 of viral and 9/27 IPD cases. Multivariate analysis revealed significant associations with health status and sex. Healthy children were more likely to carry D. pigrum than IPD cases (44/79 vs. 26/79; p= 0.028). Males were more frequently D. pigrum carriers than females (48/79 vs. 31/79; p= 0.033). ConclusionD. Pigrum was associated with respiratory health, being more prevalent in healthy children, and showed potential sex-related differences.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition associated with pediatric SARS-CoV-2 infection. While COVID-19 vaccines prevent infection and reduce severity, less conclusive evidence exists regarding their role in preventing MIS-C during breakthrough infections. This systematic review assessed the impact of SARS-CoV-2 vaccination on MIS-C risk during breakthrough infection. Cross-sectional studies, surveillance studies, and cohort studies were included. Of the 944 studies identified, 6 were included. A significant protective effect was seen in patients who received two doses of SARS-CoV-2 vaccination after exclusion of a biased sample (d= 0.71 [95% CI 0.07 to 1.35; p=0.03]). A trend towards a protective effect was seen after one dose of vaccination, but this effect was not statistically significant. Current literature supports a protective effect of two doses of SARS-CoV-2 vaccination against development of MIS-C in breakthrough COVID-19. The evidence supports clinician advocacy for continued vaccination of children against SARS-CoV-2.

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.

BackgroundEvidence to guide the choice of injectable antibiotics and supportive care for children with severe pneumonia is limited and may not reflect changes in epidemiology associated with vaccination and antimicrobial resistance. MethodsIn this pragmatic, open-label, factorial, randomized trial conducted in 16 hospitals in Kenya, children aged 2-59 months with World Health Organization-defined severe pneumonia were assigned to receive one of three injectable antibiotic regimens: benzylpenicillin plus gentamicin (standard care), ceftriaxone, or amoxicillin-clavulanic acid. Eligible children were also randomly assigned to receive nasogastric tube feeding or intravenous fluids. The primary outcome was death from any cause by day 5 after enrollment. ResultsA total of 4393 children underwent randomization to the antibiotic groups, and 1064 to the supportive care groups. By day 5, deaths occurred in 87/1463 children (6.0%) receiving benzylpenicillin plus gentamicin, 82/1458 (5.6%) receiving amoxicillin-clavulanic acid (adjusted risk ratio [aRR], 0.94; 97.5% confidence interval [CI], 0.67 to 1.31), and 81/1462 (5.5%) receiving ceftriaxone (aRR vs. benzylpenicillin plus gentamicin, 0.95; 97.5% CI, 0.68 to 1.33). Death by day 5 occurred in 30/531 children (5.7%) receiving nasogastric tube feeding and 35/532 (6.7%) receiving intravenous fluids (aRR, 1.13; 97.5% CI, 0.71 to 1.79). Secondary outcomes were similar across groups. ConclusionsAmong children hospitalized with severe pneumonia, outcomes with benzylpenicillin plus gentamicin were similar to those with ceftriaxone or amoxicillin-clavulanic acid, and nasogastric tube feeding was similar to intravenous fluids with respect to mortality and safety.

Background: Diarrheal illness in children leads to 3.5 million care visits and 200,000 hospitalizations annually in the US. Viruses are responsible for most pediatric diarrheal cases, yet limited guidance on distinguishing viral from bacterial etiologies complicates clinical decision-making, especially regarding empiric antibiotic use. Methods: We used clinical and qualitative molecular etiologic data from the Implementation of Molecular Diagnostics for Pediatric Acute Gastroenteritis (IMPACT) study to develop prediction models for viral etiology of diarrhea. We used conditional random forests to identify informative clinical and environmental predictors and evaluated model performance using logistic regression and random forests within a 5-fold cross-validation framework. We conducted external validation using the Alberta Provincial Pediatric Enteric Infection Team (APPETITE) dataset. Results: Variables predictive of viral etiology included younger age, non-bloody diarrhea, winter season, and presence of vomiting. External validation showed that an AUC of 0.82 can be achieved with a parsimonious 5-variable model, yielding a sensitivity of 0.92 and specificity of 0.55 Conclusion: Our results suggest that in North American healthcare settings, clinical prediction models can inform decision-making by identifying children with a high probability of viral diarrhea, improving diagnostic clarity, and reducing unnecessary testing and treatment.

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.

Bubble continuous positive airway pressure (bCPAP) is a low-cost respiratory support device that has demonstrated different outcomes for children with severe pneumonia in different settings. Some differences in outcomes may be attributable to implementation factors (e.g., patient monitoring and feeding practices). We aimed to characterize bCPAP reach, implementation fidelity, and safety outcomes for children with severe pneumonia in Pakistan. We conducted a prospective cohort study at Aga Khan University Hospital and Abbasi Shaheed Hospital from February through May 2025. We enrolled children 1-59 months who met WHO criteria for severe pneumonia within 24 hours of presentation to the emergency department. Participants were followed daily via chart review, caregiver survey, and physical exam through discharge, transfer, or death. We reported the proportion of children receiving bCPAP ("reach") and constructed a mixed-effects, multinomial logistic regression model with robust standard errors to report: fidelity (child location in a highly monitored area, continuous monitoring, avoidance of unplanned disruptions to bCPAP, and avoidance of oral feeding); safety (aspiration events and pneumothorax); bCPAP failure (death, respiratory support escalation, or leaving against medical advice); and in-hospital mortality. Of 165 children with severe pneumonia, 88 (53%) received bCPAP over 141 bCPAP days. The average predicted probabilities (95% CI) of our fidelity measures were: 85% (78-92%) for location in a highly monitored area; 56% (51-60%) for continuous monitoring; 66% (57-75%) for continuous bCPAP without disruptions; 46% (36-55%) for avoidance of oral feeding while on bCPAP. Among children receiving bCPAP, 9 (10%) experienced an aspiration event, 1 (2.2%) experienced a pneumothorax; 19 (22%) experienced bCPAP treatment failure. One child (1.1%) died; 6 (6.8%) required respiratory support escalation; 14 (16%) left against medical advice. We identified several gaps in bCPAP reach and fidelity. These may be modifiable by individual-and team-targeted strategies to reduce bCPAP-related complications and pneumonia-related child deaths.

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.

Background Diarrhea remains a leading cause of child morbidity and mortality worldwide. Improved and ongoing estimates of the etiologies of severe diarrhea, particularly in low- and middle-income countries (LMICs), are crucial to inform the use of current vaccines and other interventions and to help prioritize the development of new vaccines. Producing rigorous longitudinal data on the global burden and etiology of pediatric diarrhea requires a geographically broad surveillance network with standardized epidemiologic, laboratory, and analytic protocols. Methods We describe the rationale and methods of the Global Pediatric Diarrhea Surveillance (GPDS) network, a World Health Organization (WHO)-coordinated public health surveillance network investigating the etiology of hospitalized diarrhea among children aged <5 years in LMICs. The GPDS network enrolls children hospitalized with diarrhea at 38 sentinel surveillance sites in 31 LMICs across all 6 WHO Regions. Randomly selected stool specimens were tested by TaqMan Array Card quantitative polymerase chain reaction for 16 enteric pathogens previously associated with pediatric diarrhea. GPDS produces estimates of pathogen-specific attributable fractions and incidence of diarrheal hospitalizations at the global, regional, and country levels. Conclusions As a WHO-coordinated global surveillance network, GPDS evaluates pathogens associated with hospitalized pediatric diarrhea. The network monitors the changing burden of pathogens over time, monitors circulating strains, and generates data to inform decision-making around public health interventions. GPDS also improves global, regional, and country diarrheal disease burden estimates, informs new enteric vaccine development, and potentially provides a platform for future enteric vaccine evaluation.

Nasopharyngeal (NP) swabs remain the dominant gold standard for respiratory infection diagnostics. While there has been increased use of alternative sample types since the COVID-19 pandemic, guidance on their use for detecting respiratory viruses is not yet definitive, especially for children. In this systematic review and meta-analysis, we aimed to compare the diagnostic accuracy and tolerability of multiple respiratory specimen types for detecting respiratory viruses in pediatric populations. Searches were conducted on July 17, 2025 in MEDLINE, Embase, Web of Science, and Scopus, with screening and data extraction performed in Covidence. English-language primary research articles published since 2000 comparing respiratory virus detection rates in children, using nucleic acid amplification tests between paired respiratory specimens, were included. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies criteria. We calculated pooled sensitivities and specificities of index specimens: nasopharyngeal aspirates (NPA), mid-turbinate swabs (MT), anterior nasal swabs (ANS), oropharyngeal swabs (OP), and bronchoalveolar lavage fluid (BAL), as compared to the reference, NP swabs, using random-effects modeling, firstly without discrimination by virus. Index specimens were then grouped by sample collection site as nasal, oral, and lower respiratory tract (LRT) specimens for virus-specific analyses. Overall performance and statistical validity were evaluated by hierarchical summary receiver operating characteristic (HSROC) analysis. Data regarding sampling tolerability was also assessed. We screened 2,448 studies and identified 36 publications (total N participants = 10,687) that reported diagnostic test accuracy using paired index-reference data in children. Of these, 18 (total N participants = 4,310) used NP specimens as the reference and were included in the diagnostic test accuracy analysis. Virus-agnostic pooled sensitivity estimates indicated that MT (0.92%) performed most similarly to NP, though sensitivities of ANS (0.79%) and OP (0.70%) were also moderately high for detection of any respiratory virus. BAL sensitivity was the lowest (0.37%). All sample types demonstrated high specificity (0.98%-0.99%). Group estimates and HSROC statistics found that nasal specimens, when grouped, had the highest sensitivity and accuracy for all examined viruses, including for influenza (92%) and RSV (90%). By comparison, oral and LRT specimens performed less well, with more variability, though both showed moderately high sensitivities for RSV (78%, 76%, respectively) and influenza (82%, 80%, respectively), and LRT samples showed high sensitivity for HMPV (82%). Analysis of sample tolerability found that NP swabs consistently ranked as the least comfortable and least preferred, while nasal swabs and saliva both performed well. Datasets for LRT and oral specimens were sparser than for nasal, and this contributed to greater variability, underscoring the need for further diagnostic accuracy studies on alternatives to NP sampling. These data support the viability of nasal and oral alternatives to NP swabs and affirm their application in pediatric care, particularly in outpatient settings. Such alternatives could greatly improve sampling tolerability and increase global access, including in resource-limited settings, to accurate diagnostic methods for respiratory infections.

Background: Infections of the central nervous system (CNS) in children remain a major cause of mortality and long-term disability globally, particularly in low- and middle-income countries (LMICs), where a high proportion of cases lack an identified pathogen. Sporadically, human parvovirus 4 (PARV4) has been detected in a small number of cerebrospinal fluid (CSF) from children with CNS infections, but its pathogenic role is unclear. We investigated the prevalence, clinical impact, and genomic characteristics of PARV4 in children with suspected meningitis. Methods: We retrospectively analyzed CSF samples collected from children with WHO-defined suspected meningitis at the largest pediatric hospital in Bangladesh between 2015-2022. All samples underwent routine diagnostics, including bacterial culture and serological testing. Additional testing for PARV4 and parvovirus B19 was performed using qPCR of samples with >9 white blood cell (WBC)/ul followed by metagenomic sequencing of a subset. Clinical and laboratory data were extracted from patient records. Associations between PARV4 detection and mortality were assessed using logistic regression, adjusting for age, WBC count, and co-infections. Genomic and phylogenetic analyses were conducted on PARV4-positive samples. Findings: Among 2,793 CSF samples with >9 WBC/ul, 526 (18.8%) were PARV4-positive. The median age of PARV4-positive cases was lower than that of PARV4-negative cases (4 vs 7 months, p<0.001). Co-infections were more common among PARV4-positive cases (49.6%) than PARV4-negative cases (16.4%). PARV4 positivity was independently associated with increased in-hospital mortality (adjusted odds ratio 2.09, 95%CI:1.46-2.96; p<0.001). Phylogenetic analysis indicated most strains belonged to genotype 2, with two sequences forming a distinct clade. Interpretation: PARV4 is frequently detected in the CSF of children with suspected meningitis and is associated with increased in-hospital mortality. Its high prevalence, detection early in life, and frequent co-infection with other pathogens highlight the need to investigate PARV4 as an emerging CNS pathogen in LMICs. Funding: Gates Foundation

Background: 48,XXYY syndrome is a rare sex chromosome aneuploidy (SCA) characterized by neurodevelopmental deficits and medical comorbidities. The limited information available in the literature is almost exclusively limited to postnatally diagnosed cases. This study aims to describe the early medical and developmental features of prenatally identified 48,XXYY infants, with comparisons to 47,XYY, 47,XXY cohorts, and typical populations, as well as previously reported postnatally diagnosed 48,XXYY cases. Methods: The eXtraordinarY Babies Study prospectively follows children prenatally identified to be at high risk for SCA with annual medical and neurodevelopmental evaluations. Data presented herein include the prevalence of medical conditions, developmental milestones, developmental and adaptive functioning assessment scores, and therapy utilization in participants confirmed to have 48,XXYY. Comparisons were made between this cohort and the typical population, infants with 47,XYY and 47,XXY also enrolled in the eXtraordinarY Babies Study, and a 2008 cohort of individuals postnatally identified 48,XXYY. Results: Infants with 48,XXYY exhibited a range of early medical features, including high rates of feeding and GI disorders (breastfeeding difficulties, gastroesophageal reflux, and eosinophilic esophagitis), allergic disorders (food allergies and environmental allergies), and hypotonia. Developmental and adaptive functioning scores indicated delays in motor, communication, and social domains, with nearly all infants receiving speech therapy, physical and/or occupational therapy. Comparisons with the 47,XYY and 47,XXY cohorts revealed more medical and developmental challenges in the 48,XXYY group, however there was variability and some overlap with both the general population and sex chromosome trisomy conditions. Additionally, comparison to the 2008 postnatally identified 48,XXYY cohort indicated that while prenatal diagnosis allowed for earlier intervention, developmental outcomes in the first years of life were similar between the two groups. Conclusions: 48,XXYY diagnosed prenatally facilitates early monitoring, anticipatory guidance, and proactive referrals for medical evaluations and intervention, given developmental delays and medical challenges are more common in infancy and early childhood compared to the general population and trisomy SCAs. These findings provide valuable insights for genetic counselors and healthcare providers, emphasizing the spectrum of medical and developmental findings and importance of early and proactive care to support individual outcomes. Prospective study of this prenatally identified cohort will provide important natural history and phenotypic variability in XXYY, as well as identification of predictors of health and developmental outcomes.

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.

Shigella is a major cause of childhood diarrhea in sub-Saharan Africa. Current World Health Organization (WHO) guidelines recommend empiric antibiotics only for dysentery, yet non-dysenteric presentations account for 40-89% of Shigellainfections. We quantified the performance of existing guidelines to identify Shigella infection and evaluated enhanced syndromic criteria for improved management of Shigella cases. We leveraged data from the Enteric for Global Health (EFGH) Kenyan site, which enrolled children aged 6-35 months with medically attended diarrhea, collected rectal swabs at enrolment, and tested these for Shigella using both the culture and TaqMan-array cards (TAC). Shigella positivity was defined as either a culture-confirmed Shigella or a TAC-attributable result (CT <29.5). We compared categorical variables using the {chi}{superscript 2} test or Fishers exact as appropriate while continuous variables were compared between groups using the Wilcoxon rank-sum test. A logistic regression model was fitted to identify a parsimonious set of predictors. Out of the enrolled 1400 MAD cases, of whom 175 (12.5%) were Shigella positive, of which 134 (76.5%) being non-dysenteric. Among all enrolled children, 148 (10.6%) were dysenteric and 1,252 (89.4%) were non-dysenteric. Of the non-dysenteric cases, 57/1,252 (4.6%) and 129/1,251 (10.3%) of children were Shigella attributable by culture and TAC, respectively. Compared to Shigella negative cases, positive cases were older (Median age in months [Q1-Q3]: 20 [14-24] vs 13 [8-19], p<0.001), had higher stool frequency (5 [3-6] vs 4 [3-5], p<0.049) and were more likely to be dysenteric (42 [24%] vs 106 [8.7%], p<0.001). Contrarily, Shigella positive cases were less likely to present with vomiting (66 [37.7%] vs 587 [47.9%], p=0.014) and difficulty in breathing (0 (0%) vs 27 [2.2%], p<0.040). Dysentery alone had minimal predictive power to identify Shigella (area under the ROC curve (AUC) [95% CI]: 0.58 [0.54-0.61]), while Dysentery and Age binary (<17 months) (0.70 [0.66-0.74]), and Dysentery, Vomiting, Difficult breathing, and Age binary (0.72 [0.68-0.76]) had acceptable predictive performance. Our data shows that current guidelines miss up to 76.5% of Shigella-positive cases which are non-dysenteric. This suggests that dysentery alone has limited predictive power, but incorporating additional symptoms increases discriminatory ability by up to 14%, with age alone improving it by 12%. These findings support the need to re-evaluate the current syndromic based guidelines to better detect Shigellosis and strengthen antibiotic stewardship.

Kawasaki disease (KD) is a systemic vasculitis in young children, and early diagnosis remains challenging when clinical features are incomplete or overlap with those of other febrile illnesses. Because electrocardiography (ECG) is noninvasive and widely available, we investigated whether ECG-derived features could help distinguish complete KD from pediatric patients with fevers. We conducted a single-center retrospective study of hospitalized febrile children aged 1-8 years who underwent digital 12-lead ECG recording during the initial evaluation. Five amplitude features and six timing features extracted from the ECG were used to develop a logistic regression model to distinguish between complete KD and other febrile illnesses. The model discriminated between the KD and non-KD groups in the validation dataset. The prediction score was not significantly correlated with the age and body temperature. S-wave amplitude, the RR interval, and P-and Q-wave amplitudes were suggested to contribute to discrimination. These findings suggest that ECG-derived features may provide adjunctive information for distinguishing complete KD from other febrile illnesses. Author SummaryKawasaki disease is an inflammatory illness in young children that can lead to coronary artery complications if treatment is delayed. Early diagnosis is often difficult because its initial symptoms overlap with those of many common febrile illnesses. We investigated whether a routine 12-lead electrocardiogram (ECG), which is noninvasive, rapid, and widely available, contains information that can help distinguish complete Kawasaki disease from other febrile conditions. We retrospectively analyzed digital ECGs from hospitalized febrile children and extracted waveform amplitude and timing features. Using these features, we built a logistic regression model and evaluated it in a temporally separate validation cohort. The model distinguished patients with Kawasaki disease from patients with fever. P-, Q-, and S-wave amplitudes and the RR interval were repeatedly selected as important contributors, suggesting that both waveform morphology and heart-rate-related information may be relevant. These findings indicate that ECG-derived features may provide useful adjunctive information during the clinical assessment of complete Kawasaki disease.