Journal of the Pediatric Infectious Diseases Society

Importance: Respiratory syncytial virus (RSV) hospitalization rates are highest among children <2 years of age. RSV immunization with infant monoclonal antibody or maternal vaccine is recommended to protect all U.S. infants in their first RSV season. For certain high-risk children aged 8-19 months entering their second RSV season, the monoclonal antibody nirsevimab is recommended. Little is known regarding preexisting health conditions as risk factors for RSV-associated respiratory failure in children during their second season. Objectives: To describe children admitted to the pediatric intensive care unit (PICU) for RSV during their second RSV season by preexisting health conditions, and to compare demographic and clinical characteristics across groups. Design, Setting, and Participants: Surveillance registry of children 8- <24 months old admitted to the PICU in 30 pediatric hospitals in the 2023-2024/2024-2025 RSV seasons. All children had an RSV-positive respiratory sample and received respiratory support with high flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation (IMV). Exposure: Preexisting health conditions potentially increasing risk of severe RSV disease. Main Outcomes and Measures: Patients were classified into four mutually exclusive groups by preexisting health conditions: 1) U.S. nirsevimab eligible criteria, 2) other identified RSV risk conditions (with some evidence of increased risk for severe RSV), 3) other preexisting conditions, and 4) no preexisting conditions. Patient demographic characteristics and level of respiratory support received were compared. Results: Among 574 children: 47 (8.2%) had U.S. nirsevimab eligibility criteria, 76 (13.2%) had other RSV risk conditions, 96 (16.7%) had other preexisting conditions, and 355 (61.8%) had none. A higher proportion of children with nirsevimab eligibility factors (40.4%) than those with other identified RSV risk conditions (17.1%) required IMV, which was higher than other (10.4%) or no (5.9%) preexisting health conditions (ptrend<0.001). Conclusions and Relevance: Approximately 20% of children admitted to the PICU with severe RSV were in the defined groups that met U.S. nirsevimab-eligibility criteria or that had an identified RSV risk condition associated with known risk for severe RSV. A considerable proportion of both groups of children required IMV for respiratory support. These findings may help inform future deliberations regarding U.S. second season nirsevimab-eligibility recommendations.

Zika virus (ZIKV) emerged in Brazil in 2015, causing an unprecedented epidemic of Congenital Zika Syndrome (CZS). A decade later, longitudinal analyses evaluating temporal trends and subnational heterogeneity in CZS burden remain limited. Using publicly available data from SINAN/DATASUS and the RESP-Microcephaly registry (SVS/Ministry of Health, updated July 2024), we conducted a descriptive ecological analysis of ZIKV infection and CZS in Brazil from 2015 to 2023. Of 331,309 notified Zika cases (2015-2023), 213,350 occurred in 2016, followed by an 91.75% decline in 2017 and sustained low-level endemic circulation thereafter. Among 3,751 confirmed microcephaly cases, 1,828 were confirmed with ZIKV etiology. The Northeast region accounted for 75.4% of confirmed cases despite representing approximately 27% of the national population. State-level analyses revealed distinct epidemiological patterns, including persistent microcephaly notifications of non-Zika etiology in Minas Gerais and continued detection of ZIKV-attributed CZS in Amazonas and Goias through 2023. These findings highlight pronounced geographic disparities in congenital Zika burden, reflect significant heterogeneity in diagnostic capacity, and underscore the need for sustained surveillance and systematic etiological investigation of congenital abnormalities in the post-epidemic era.

The evolving epidemiology of COVID-19, driven by successive SARS-CoV-2 variants of concern (VOCs), has prompted ongoing evaluation of their impact on disease severity in children. In low- and middle-income countries (LMICs), children experience a higher burden of severe respiratory illness and pneumonia-related mortality due to factors such as malnutrition, incomplete immunisation, HIV exposure or infection, tuberculosis, and disparities in access to healthcare services. Hospital-based paediatric studies from LMICs are therefore needed to understand how the epidemiology and severity of COVID-19 have changed across pandemic waves. This study examined 354 hospitalised children with SARS-CoV-2 infection during the ancestral, pre-Omicron (Beta and Delta), and Omicron waves at Tygerberg Hospital in Cape Town, South Africa. We analysed data collected over an extended period, from March 2020 to June 2022. Statistical analyses were used to describe clinical characteristics across variant periods, and multivariable logistic regression models were applied to evaluate associations between potential risk factors and disease severity. Paediatric COVID-19 severity varied across VOC periods, with the highest burden observed during the pre-Omicron (Beta and Delta) waves. In multivariable analyses, younger age and circulating variants were associated with disease severity; CRP levels emerged as a marker associated with more severe illness, and corticosteroid treatment, while also associated with disease severity, reflects clinical response to more severe cases. These findings contribute to a better understanding of the epidemiology and clinical impact of COVID-19 in children and highlight the importance of context-specific surveillance and treatment strategies in resource-limited settings.

Background Neural tube defects (NTDs) are preventable congenital malformations that disproportionately affect low and middle income countries and contribute to disability and mortality. Evidence on the long-term outcomes of children and adolescents with NTDs in Eastern Africa has not been comprehensively synthesised. We conducted a systematic review and meta-analysis to assess survival, complications, and functional outcomes among children with NTDs in this region. Methods We searched PubMed, MEDLINE (Ovid), Cochrane Library, Web of Science, and Africa Index Medicus from the earliest records to April 2025. Two reviewers independently screened studies, assessed quality, and extracted data. We included studies reporting outcomes beyond one year of age, except mortality, which was assessed from birth onwards. Random-effects meta-analyses were undertaken when at least two sufficiently studies were available; otherwise, findings were synthesised narratively. Results Of 597 articles screened, 16 studies involving 2,340 children with NTDs met the inclusion criteria. Pooled cumulative mortality was 23% (95% CI: 12 - 36%) in the neonatal period, 9% (95% CI: 2 - 33%) during infancy, 22% (95% CI: 16 - 28%) in toddlers, 37% (95% CI: 30 - 44%) in pre school aged children and 45% (95% CI: 36 - 54%) in school-aged children. The pooled prevalence of hydrocephalus was 41% (95% CI: 34 - 48%) with little variation by age. Neurogenic bladder increased from 53% (95% CI 49 - 81%) in toddlers to 83% (95 % CI 72 - 91%) in adolescents, while impaired mobility affected about 61% (95% CI 48 - 72%) of adolescents. School enrolment was 53% (95% CI: 39 - 67%), with 9% (95% CI: 4% - 19%) in specialized education. Speech, hearing, and bowel dysfunction were understudied (< 2 studies each). Conclusion Many children with NTDs in the Eastern African region survive beyond infancy but frequently experience hydrocephalus, neurogenic bladder and motor impairment. Longitudinal studies, context-specific guidelines, and follow-up systems are urgently needed to improve care and long-term outcomes.

In newborns seen a median of 11 days after birth, 97/1699 (5.7%) had conjunctivitis, including 13/97 (13.4%) with Chlamydia trachomatis or Neisseria gonorrhoeae detected. Among all babies, we estimated that 6.6% (95% confidence interval 3.8-9.9%) would have C. trachomatis or N. gonorrhoeae detected, of which 87.0% (74.8-93.8%) would be asymptomatic.

Enteric pathogen infections are a major global health challenge, influenced by a variety of host and environmental factors, and their clinical presentation and treatment can be complicated by the presence of co-infections. The prevalence of enteric infections and co-infections tend to vary between rural and urban contexts, likely driven by underlying environmental, geographic, and demographic characteristics. To improve understanding of urbanicity and age on enteric pathogen prevalence and on co-infection risk, we measured 22 enteric pathogens in fecal samples collected from children aged 6, 12, and 18 months across a rural-urban gradient within the ECoMiD birth cohort study (n=473). Enteric pathogen burden was high and increased with age, with at least one pathogen detected in 91% of children at 6 months, 97% at 12 months, and 98% at 18 months. However, prevalence of some pathogens-- notably Salmonella enterica, enterovirus, and rotavirus-- decreased with age. Co-infections were also common (88%), and children were infected with as many as 11 pathogens simultaneously. The most frequently observed co-infection profiles included enteroaggregative E. coli and atypical enteropathogenic E. coli, followed by combinations with diffusely adherent E. coli, enterovirus, enterotoxigenic E. coli, and/or adenovirus. Enteric pathogen detection generally was higher in more rural settings, though patterns varied by pathogen. These results provide useful information for future examination of pathogen dynamics of co-occurrence. Given the ubiquity of enteric infections in high transmission settings, strategies that aim to reduce overall microbial exposure may be needed to supplement interventions targeting control of individual pathogens.

Background Klebsiella pneumoniae is a leading cause of sepsis in young infants. We evaluated the association of invasive K. pneumoniae disease (iKPnD) in relation to antigen-specific immunoglobulin G (IgG) and serum bactericidal activity (SBA) to four polysaccharide capsular (K) serotypes and five lipopolysaccharide (O) serotypes, as well as IgG to MrkA, in infants less than 90 days of age. Methods We conducted a retrospective case-control study in Kenyan and South African infants with blood culture-confirmed iKPnD. Serotype-specific antigen IgG concentrations of cases were compared with hospitalised controls without iKPnD. Geometric mean concentrations (GMCs) were estimated, and scaled covariate-adjusted models were used to estimate risk reduction over a grid of antibody concentrations. Results Transplacental transfer of IgG against various K. pneumoniae antigens increased with advancing gestational age. Serum IgG GMCs (expressed in RLU/mL) to disease-causing homotypic K- or O-serotypes were lower in cases compared with controls for anti-K2 (396 [95%CI: 250-628] vs 660 [95%CI: 562-776]), anti-K25 (396 [95%CI: 251-623 ] vs 1170 [95%CI: 988-1385]), anti-K149 (327 [95%CI: 204-521] vs 492 [95%CI: 435-557]); as well as anti-O1{beta},2 IgG (1282 [95%CI: 782-2101] vs 2250 [95%CI:1904-2658]). Furthermore, overall anti-MrkA IgG was lower in cases (945; 95%CI: 757-1179) compared with controls (1610; 95%CI: 1378-1880). SBA titres (expressed as IC50) did not differ between case and controls by K types, but were lower for O1{beta},2{beta} in cases (27; 95%CI: 12-63 vs. 136; 95% CI: 84-221). Conclusion Our findings provide preliminary evidence that low antibodies against three of four K-antigens, O1{beta},2{beta} and MrkA are inversely associated with iKPnD, and should be explored as potential vaccine antigens.

Background Nirsevimab has been widely administered in the United States since 2023 to protect infants and young children from severe disease caused by respiratory syncytial virus (RSV). Although early post-licensure studies have shown high effectiveness against medically attended RSV infection, uncertainty remains about the durability of protection, effectiveness beyond the first RSV season, and the extent to which changing RSV seasonality influences real-world effectiveness. Objective To estimate the effectiveness of nirsevimab against medically attended RSV infection across three consecutive RSV seasons and to examine how effectiveness varies by season and time since immunization. Methods We conducted a test-negative case-control study utilizing electronic health records of infants and young children tested for RSV by polymerase chain reaction in outpatient and inpatient settings within the Yale New Haven Health System between October 1, 2023, and March 1, 2026. Effectiveness of nirsevimab was estimated using multivariable logistic regression, adjusting for age, weekly RSV activity, pre-existing risk factors, and other potential confounders. Variation in effectiveness was examined by season, encounter setting, and time since immunization up to 24 months. Results Overall, 17,755 infants and young children were tested for RSV infection, of whom 2,388 (13.4%) were cases and 15,367 (86.6%) were controls. The overall effectiveness of nirsevimab was 67.3% (95% confidence interval [CI]: 59.8, 73.3%) against all medically-attended RSV infections, 60.2% (95% CI: 49.6, 68.5%) against RSV-associated outpatient visits, and 88.9% (95% CI: 82.3, 93.0%) against RSV-associated hospitalization. Effectiveness against medically attended RSV infection declined across seasons, from 76.7% (95% CI: 60.5, 86.3%) in 2023/24 to 54.4% (95% CI: 33.0, 68.9%) in 2025/26. Lower season-specific effectiveness in later seasons corresponded with progressively delayed RSV activity over. Protection against RSV-associated hospitalization declined with increasing time since immunization, from 92.5% (95% credible interval [CrI]: 85.9, 96.4%) at 1 month, to 77.2% (95% CrI: 60.4, 87.6%) at 6 months, and 39.9% (95% CrI: 2.4, 63.3%) at 12 months post-immunization, after which effectiveness plateaued. Conclusions Nirsevimab remained effective against RSV-associated hospitalization through 6 to 12 months after immunization. Delayed RSV activity was associated with lower effectiveness, highlighting the importance of aligning administration with local RSV circulation.

Abstract Objectives: Following the COVID-19 pandemic, multiple countries reported a surge in invasive group A streptococcus (iGAS) infections. Posited explanations include reduced population immunity, increased respiratory virus co-infection, and emergence of hypervirulent GAS clones. To assess the relative contribution of these factors, we analyzed the epidemiology and genomics of 3,408 iGAS infections in Scotland. Methods: National surveillance data from 2014-2024 were analyzed to characterize iGAS incidence. Hybrid whole genome sequencing was used to comprehensively genetically characterize 404 emm1 isolates collected from invasive and tonsillitis infections. Results: iGAS incidence markedly increased in late 2022 and early 2023, disproportionately affecting children and older adults. This surge was not associated with a proportional increase in bacteremia but did coincide with increased influenza and respiratory syncytial virus infections. Genomic analyses found that emm1 post-pandemic isolates were not genetically distinct from pre-pandemic isolates in genome-wide polymorphisms, accessory genes including virulence and antimicrobial resistance determinants, mobile genetic elements, or chromosomal structural variants. Conclusions: The post-pandemic iGAS surge in Scotland was not associated with emergence of a novel hypervirulent emm1 clone. Instead, the epidemiologic and population genomic findings are consistent with increased host susceptibility following reduced pathogen exposure during the pandemic and increased respiratory virus co-infection as predominant contributing factors.

Background: Group A streptococcal (GAS) pharyngitis drives substantial antibiotic prescribing in children. The 10-day standard burdens adherence and prolongs exposure, increasing selective pressure for resistance. Yet, whether shorter courses achieve comparable outcomes remains unresolved. Purpose: To address how the duration of oral antibiotics affects clinical outcomes in children and adolescents with suspected or confirmed GAS pharyngitis. Data Sources: MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL from inception to July 2025. Reviewers also searched reference lists of eligible trials and relevant systematic reviews. Study Selection: Randomized trials enrolling children and adolescents [&le;]18 years with suspected or confirmed GAS pharyngitis comparing different durations of oral antibiotics, or oral antibiotics against placebo or no treatment. Data Extraction: Paired reviewers independently screened records, extracted data, and assessed risk of bias. Data Synthesis: We performed random-effects dose-response meta-analyses with restricted cubic splines and rated the certainty of evidence using GRADE. Forty-five trials enrolling 22,636 participants met eligibility criteria. Across outcomes, low to moderate certainty evidence suggests that 3, 5, and 10 days of antibiotic treatment may produce little to no difference. Moderate certainty evidence supports similar effects of 5 and 10 days on clinical cure, relapse, and adverse events. Evidence comparing 3 and 10 days carries lower certainty. Serious adverse events were rare: no deaths, 4 cases of acute rheumatic fever, and 4 cases of post-streptococcal glomerulonephritis among 776, 8,818, and 9,096 participants, respectively, making clinically important differences across treatment durations unlikely. Limitations: Evidence on 3-day courses came almost exclusively from trials of azithromycin, limiting inference about shorter penicillin regimens. Findings apply most directly to high-income settings. Conclusion: These findings challenge the long-standing 10-day standard for pediatric GAS pharyngitis and show that 5 days of oral antibiotics are likely as effective and safe as 10 days.

Background Quantifying the effect of Shigella diarrhea with and without antibiotic treatment on linear growth faltering is critical to understanding the potential impact of Shigella vaccines. Methods Using individual-level data from five multisite studies, we estimated the effect of Shigella diarrhea on length/height-for-age z-score (HAZ) 60-90 days after the episode compared to diarrhea episodes with no etiology identified and non-diarrheal controls. Effects were estimated under treatment with and without antibiotics using augmented inverse probability weighted estimators with ensemble machine learning. Findings Among 26,752 diarrhea episodes, 5,503 (20.6%) were attributed to Shigella and of those, 2,567 (46.6%) were treated with guideline recommended antibiotics. Compared to other diarrhea episodes, Shigella diarrhea without treatment with guideline recommended antibiotics was associated with small reductions in HAZ (HAZ difference: -0.03, 95% CI: -0.05, -0.01), but not when treated with guideline recommended antibiotics (HAZ difference: -0.01, 95% CI: -0.02, 0.01). Compared to non-diarrheal controls, Shigella diarrhea was associated with decrements in HAZ in the following 60-90 days regardless of antibiotic treatment (HAZ difference overall: -0.08, 95% CI: -0.10, -0.07). A larger impact of Shigella diarrhea was observed among younger children. Interpretation Shigella diarrhea was associated with short-term decrements in height. Treatment with guideline recommended antibiotics prevented the impact of Shigella on linear growth compared to other diarrhea episodes but not compared to non-diarrheal controls. These results suggest that improved recognition and treatment or prevention of Shigella could improve child growth.

Background The outbreak of COVID19 in Greece prompted extensive public health measures, including the first national lockdown and the suspension of in-person schooling. Recognizing the significant role of children in community transmission due to their contacts in schools, school absenteeism data began to be systematically recorded as a potential indicator of outbreak patterns. Objectives This study aims to explore the utility of incorporating school absenteeism data in an early warning surveillance system for respiratory infections, particularly in predicting the onset and spread of diseases such as COVID19 and influenza. Methods We utilized school absenteeism data from primary schools and kindergartens in the Municipality of Larissa for the 2022 2024 school years, alongside health data from the University Hospital of Larissa (UHL). These included incidence rates of respiratory infections, COVID-19, and flu cases, which were cross-referenced with absenteeism patterns. Results The analysis showed that peaks in absenteeism often preceded increases in cases of respiratory infections, COVID19, and flu, suggesting absenteeism as a potential early warning indicator. Notable divergences in patterns were observed during school closures for holidays, which posed challenges in data continuity and surveillance effectiveness. Conclusions School absenteeism data significantly enhances the capability for early detection and monitoring of respiratory disease outbreaks. To improve future surveillance and outbreak prediction, integrating more comprehensive data sources and refining predictive models to accommodate educational calendar variations is recommended.

Autism development involves multiple genetic and early-life environmental factors. Studying the placenta's gene expression profile may reveal key mechanistic pathways in autism development. Here, using a nested case-cohort design within an Australian population-derived prebirth cohort study (n=1074), we identified 1,644 differentially expressed genes (DEGs; FDR<0.05) in the placenta of children with autism diagnosis (n=43), compared to those without (n=120). The top enriched pathways related to mitochondrial translation, oxidative stress, RNA processing and transcription regulation. CYP1A1, the most important xenobiotic-metabolising enzyme of the placenta, was the top downregulated DEG in the placenta of children with autism, while immuno-regulatory human leukocyte antigen (HLA)-related genes were among the top upregulated DEGs. A machine learning-based approach predicted autism from the transcriptomic data with a median sensitivity of 0.57 (2.5th-97.5th centiles: 0.29, 0.76) and median specificity of 0.92 (2.5th-97.5th centiles: 0.78, 0.98). Weighted Gene Correlation Network Analysis identified eight affected placental gene modules, with the largest five modules being enriched primarily for mitochondrial bioenergetics, oxidative phosphorylation and RNA processing pathways. This placental transcriptomic signature of impaired mitochondrial function and gene transcription regulation among infants subsequently diagnosed with autism has profound implications for understanding both risk factors and prediction, suggesting the possibility of identifying modifiable prenatal pathways to improve autism outcomes.

Aberrant changes in circulating cell-free mitochondrial DNA (ccf-mtDNA) across gestation are associated with adverse pregnancy outcomes. Given the inflammatory properties of ccf-mtDNA via pattern recognition receptors such as Toll-like receptor 9 (TLR9), we hypothesized that extracellular mtDNA induces placental inflammation via TLR9 signaling and that this response differs by fetal sex. Pregnant Sprague-Dawley rats were treated intravenously with purified mtDNA (300 g/kg), nuclear DNA (nDNA), saline, and/or the TLR9 antagonist ODN2088 across five studies. Placental responses were evaluated 4 h (Studies 1-3) and 24 h (Study 4) post-treatment; pregnancy and neonatal outcomes were assessed at delivery (Study 5). Exposure to mtDNA, but not nDNA, increased placental il1{beta}, tnf, and il10 mRNA (p < 0.05), establishing response specificity. mtDNA-induced placental inflammation was fetal sex-dependent: mtDNA increased il6 and il1{beta} mRNA in male placentas (p [&le;] 0.0004) but not female placentas, whereas ifn{gamma} was selectively induced in female placentas (p = 0.0004). TLR9 and MyD88 abundance increased in female but not male placentas, and TLR9 antagonism modified selected inflammatory responses with sex-specific patterns. The 4 h inflammatory transcriptional signature resolved by 24 h, whereas mtDNA exposure was associated with a sex-specific shift in antioxidant enzyme expression persisting to 24 h. Despite no effects on gestational length or neonatal biometrics, mtDNA exposure was associated with a higher estimated stillbirth count per litter (IRR = 4.23, 95% CI [0.89, 20.1], p = 0.069). These findings establish extracellular mtDNA as an acute, sex-differentiated placental inflammatory stimulus with partial TLR9 dependence and a potential impact on fetal viability. New & NoteworthyThis study demonstrates that acute exposure to extracellular mtDNA induces placental inflammatory responses in vivo. This response is specific to mtDNA, fetal-sex dependent, and partially mediated by TLR9, with male and female placentas engaging distinct inflammatory signals within hours of exposure. The biological effects extend beyond the initial inflammatory window, with mtDNA exposure producing lasting, sex-specific changes in antioxidant enzyme expression. mtDNA-exposed dams had higher expected stillbirth counts, suggesting extracellular mtDNA may affect fetal viability.

Abstract Objectives: To estimate surveillance-adjusted county-level residual syphilis risk, quantify posterior support for elevated risk, and identify the geographic distribution of stably high-risk areas across the contiguous United States and the District of Columbia. Methods: County-year primary and secondary syphilis counts from 3,109 counties during 2010-2022 were analyzed using a Bayesian negative-binomial spatial model with county-level covariates capturing social vulnerability and healthcare and surveillance related structure. Residual spatial risk, posterior exceedance probabilities, and stably high-risk counties were estimated. External validation examined whether county-level residual syphilis risk was associated with HIV and gonorrhea burden. Results: A total of 850 stably high-risk counties were identified. These counties were concentrated in the southeastern United States and along the Gulf Coast, with additional clusters in the north-central region and along the Atlantic and Pacific coasts. The social vulnerability index showed the strongest positive association with reported syphilis rates, followed by primary care physician density. External validation and sensitivity analyses showed that higher county-level residual syphilis risk estimates were positively associated with higher HIV diagnosis rates and gonorrhea rates, indicating that these estimates were not merely model-derived numerical outputs but were meaningfully related to the county-level distribution of sexually transmitted infection risk. These findings indicate that surveillance-adjusted residual spatial risk estimates and posterior exceedance probabilities may provide useful county-level evidence for syphilis control prioritization and resource allocation.

Bangladesh reported a nationwide measles outbreak in April 2026 involving over 19,000 suspected cases, despite high reported first-dose vaccine coverage ([&ge;]95%). We assessed whether publicly available molecular data could support epidemiologic interpretation of this resurgence and evaluated broader sequence sharing practices across South Asia. We analyzed public outbreak reports, WHO/UNICEF Estimates of National Immunization Coverage (WUENIC), PubMed indexed literature, and NCBI GenBank records from nine regional countries. Public sequence visibility across the region was highly uneven. While India and Pakistan associated records dominated the public dataset, only 32 Bangladesh origin records were retrieved, and notably, none were collected after 2019. The sole 2026 Bangladesh linked molecular record was a travel associated genotype B3 genome isolated in Australia (PZ189094.1). Its closest public N450 relative was a contemporaneous Pakistan sequence (2-nucleotide difference). The historical Bangladesh sequences were more distant, precluding robust phylogenetic inference regarding local viral persistence, cross-border importation, or transmission direction. Immunization data revealed a high regional baseline but highlighted subnational vulnerability and a significant pandemic era coverage collapse in neighboring Myanmar. The absence of timely, publicly available genomic data during the critical early months of the outbreak highlights a severe genomic surveillance gap. Public molecular records were historically sparse and insufficient to reconstruct outbreak transmission dynamics. To support elimination goals, establishing targeted sequencing pipelines, enforcing minimum metadata standards, and ensuring rapid public data deposition are urgently needed. Keywords: measles; Bangladesh; South Asia; genomic surveillance; molecular epidemiology; immunization coverage

Background Klebsiella pneumoniae (Kpn) is a major cause of neonatal sepsis in Africa. 3rd generation cephalosporin and gentamicin resistant Kpn is the norm in many sites, rendering WHO recommended first- and second-line antimicrobials ineffective. An understanding of which neonates and infants are most at risk of sepsis caused by Kpn would support the case for improved access to WHO watch and reserve antimicrobials (i.e. carbapenems) for patients most likely to benefit from them. Methods A prospective case-control study was conducted at Queen Elizabeth Central Hospital, Malawi. Cases were infants <3 months of age with blood or CSF culture confirmed Kpn infection. Controls were healthy infants from the same wards and were matched 2:1. Univariate and multivariate logistic regression were performed on mean-centred data to determine risk factors for infection with Kpn. Results We analysed data from 38 cases and 76 controls between August 2021 and April 2023. Mortality at 3 months of age was 21/38 (29%) for cases, with 14/38 (37%) identified postmortem and 6/76 (7.9%) for controls (OR 14.0 (95% CI 4.59, 49.2, p>0.001). Cases were more likely to be born out of QECH than controls (42% vs. 24%, p = 0.043), and cases had lower birthweights (median 2200g vs. 2850g, p = 0.005). Multivariate logistic regression analysis revealed that increasing birthweight was protective against Kpn infection (OR: 0.858 [95% CI: 0.745, 0.987] per 100g increase), while longer hospital stay was associated with increased odds of infection (OR: 1.148 [95% CI: 1.012, 1.1.303] per additional day). Most infecting isolates (34/38 [89%]) were resistant to first- and second-line antimicrobial agents, but all were sensitive to meropenem and 33/36 [92%] to amikacin. Conclusion Low birthweight infants with prolonged hospital stay were at greatest risk of Kpn infections that were typically resistant to WHO first- and second-line antimicrobial therapy. These infants should be prioritised for antibiotics that have the potential to be life-saving. The overlapping and evolving nature of these risk factors makes it difficult to design a simple tool to support empiric initiation of meropenem. Neonates critically ill with Kpn sepsis cannot, however, afford to wait for blood culture confirmation before receiving effective treatment. This highlights the need for empiric decision making frameworks that allow rapid initiation of effective therapy in high-risk neonates.

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

Introduction: RSV vaccines reduce the risk of severe outcomes such as hospitalization and emergency department (ED) visits for at least 2 RSV seasons following vaccination. No data have been published on real-world RSV vaccine effectiveness (VE) beyond the second season after vaccination. This study evaluates bivalent RSVpreF VE against RSV-related lower respiratory tract disease (LRTD) hospitalizations/ED visits throughout 3 seasons after vaccination. Methods: This retrospective test-negative case-control evaluates bivalent RSVpreF VE among adults aged >/= 60 years at Kaiser Permanente Southern California with LRTD over 3 RSV seasons (11/24/20230-4/18/2026). Cases were RSV-positive without coinfection. Controls were negative for RSV, hMPV, influenza, SARS-CoV-2, and positive for a non-vaccine preventable disease pathogen. Exposure was bivalent RSVpreF (Abrysvo) receipt >/= 21 days before LRTD. Adjusted VE was estimated using odds ratios from multivariable logistic regression or generalized estimating equations. Results: Overall, adjusted VE against RSV-related LRTD hospitalization/ED visits was 80% (95% CI:68-87), 70% (95% CI:53-81), and 51% (95% CI:-12-78) in the first, second, and third season after vaccination, respectively. Among non-immunocompromised individuals, adjusted VE against RSV-related LRTD was 87% (95% CI:75-94), 76% (95% CI:55-87), and 58% (95% CI:-21-86) in the first, second, and third season after vaccination, respectively. Adjusted VE across the 3 combined seasons was 73% (95% CI: 64-80) overall and 80% (95% CI: 69-87) among non-immunocompromised individuals. Conclusion: These results suggest Bivalent RSVpreF provides protection against RSV-related LRTD outcomes for at least three seasons after vaccination in this population of older adults with a prevalence of comorbidities. This suggests RSV vaccination results in substantial individual and public health benefit.

Background Severe Clostridioides difficile infection (CDI) morbidity and mortality disproportionately affect Black and Hispanic patients in the United States. Antibiotic exposure is the primary modifiable risk factor for CDI, and clindamycin is among the agents most strongly associated with related harm. Characterizing inequities in prescribing is critical. Dentistry is a major source of clindamycin prescriptions. Academic dental clinics serve diverse patient populations and provide an ideal setting to evaluate prescribing across racial and ethnic groups. We therefore examined antibiotic use and cumulative clindamycin exposure as measures of CDI-associated risk. Methods We conducted a retrospective study of electronic health records from 5 US academic dental institutions from 2021 through 2023. We analyzed 552,428 encounters among 132,770 patients with documented race/ethnicity to estimate adjusted odds of receiving any oral antibiotic and clindamycin by race/ethnicity. Secondary outcomes evaluated total antibiotic exposure among dental provider-prescribed antibiotics, focusing on higher-than-standard cumulative dosing of clindamycin (>8400 mg) and amoxicillin (>10,500 mg). Results Oral antibiotic prescribing occurred in 1.9% of encounters. Compared with White patients, Black, Hispanic, and Other race patients had slightly lower adjusted odds of receiving any oral antibiotic, while Black patients had greater odds of receiving a higher-than-standard cumulative clindamycin dose when clindamycin was prescribed (adjusted odds ratio, 2.19; 95% confidence interval, 1.25-3.82). Conclusion Racial and ethnic inequities in dental antibiotic prescribing extended beyond antibiotic receipt to cumulative clindamycin exposure. Although CDI outcomes were not directly measured, these prescribing differences may have implications for disparities in CDI-associated harm and warrant further investigation.