Journal of the Pediatric Infectious Diseases Society

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

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

Background: The relationship between recent viral infection and subsequent susceptibility to, or protection against, other viruses remains unclear, particularly across ages and symptom status. Methods: A prospective cohort study enrolled participants aged 6 months to 49 years in Washington and Oregon, USA, 2022-2024. Weekly nasal swabs were tested for SARS-CoV-2, respiratory syncytial virus (RSV), and influenza A/B; additional swabs were collected during symptomatic illness and were also tested for parainfluenza (PIV) 1-4, endemic human coronaviruses (hCOV), adenovirus, human metapneumovirus, human rhinovirus (hRV), and enteroviruses. Proportional hazards regression models were used to characterize associations between incident symptomatic infection (illness) and history of recent illness due to other viruses (within 1-7, 8-14, 15-30, 31-60, 61-90, 91-180 days), adjusted for geographic region, age, sex, daycare/school/work attendance, household size, and number of children in the household. For SARS-CoV-2, influenza, and RSV, these analyses were repeated to study incidence of infection (including asymptomatic cases). Findings: Of 3,560 participants, 2,969 (83%) had [≥]1 illness over 4,299 person-years. Adjusted hazard ratios (aHRs) in the short term ([≤]2 weeks) after an illness were predominantly below 1, indicating that recent viral illness was often associated with lower risk of subsequent illness with other viruses. Across age groups, recent hRV illness was associated with lower risk of hCOV, PIV, and RSV illness (aHRs 0.07-0.27). SARS-CoV-2 illness was associated with a higher short-term risk of adenovirus and PIV illness (aHRs 3.20-3.33). In children aged 6 months-4 years, recent influenza illness was associated with higher short-term risk of SARS-CoV-2 illness. Including asymptomatic infections generally attenuated these associations. Interpretation: Some viral illnesses may alter short-term susceptibility to subsequent viral illnesses. Interactions may differ by age and symptom status. Funding: US Centers for Disease Control and Prevention; Washington State Department of Health.

Background: A large increase in mortality from severe acute respiratory infections (SARI) in Brazil in 2025 was mainly driven by influenza A and respiratory syncytial virus (RSV) among children and the aged, but 2026 data remain largely unpublished. Methods: Secondary data on SARI by age group (<2, 2-4, 5-14, 15-49, 50-64, 65+ years) and virus (Influenza A/B, RSV, SARS-CoV-2, adenovirus, rhinovirus, bocavirus, and metapneumovirus) were retrieved for 35 weeks of 2026. Weekly variations in infection rate (IR) and mortality rate (MR) were described by virus and age group. Case fatality ratio (CFR) and vaccine-preventable deaths from influenza, RSV, and SARS-CoV-2 were analysed by age group. Missing virus classification was estimated by multinomial regression. Poisson-based 95% confidence intervals (CI) were calculated for MR. Results: Influenza A infections quintupled during February and March, with a mortality peak in April, mainly due to H2N3. RSV and rhinovirus caused more deaths than influenza viruses, especially among young children (<2) and the aged (65+). The former were most frequently infected by RSV and the latter by rhinovirus. For those 50 years or older, influenza B reached a CFR of about 20%, compared with 5-15% for influenza A, metapneumovirus, rhinovirus, and other non-subtyped viruses. The highest vaccine-preventable MRs per 100,000 were 17.23 for the oldest and 8.62 for the youngest. Under ideal conditions, 6418 lives could have been saved, about half among children and adolescents <15 years old. Conclusions: Vaccine-preventable SARI in Brazil exerted a high toll in fall and winter 2026, mainly due to influenza A, RSV, and rhinovirus. Better vaccine coverage may significantly reduce this toll.

The longitudinal effects of initial influenza exposure on the magnitude, persistence, and antigen specificity of antibody responses during infancy remain incompletely understood. We investigated humoral antibody responses following primary influenza infection or seasonal vaccination in a prospective US birth cohort with weekly respiratory surveillance for influenza infection. Influenza-specific serum IgG binding to H1 and H3 haemagglutinin (HA) antigens, HA inhibition (HAI), and live-virus neutralizing antibody responses were assessed longitudinally. To minimize influence of maternally derived antibodies, analyses of primary exposure responses were restricted to infants for whom influenza-specific maternal antibodies had declined below the assay detection limit before exposure. Antibody responses were compared following primary infection and vaccination and examined after subsequent annual vaccination. We found that maternal influenza-specific IgG declined rapidly during early infancy. Among infants without detectable pre-exposure influenza-specific antibodies, primary influenza infection was associated with greater post-exposure antibody responses and less measurable decline over follow-up than primary vaccination. These groups differed in age, calendar season, and exposure characteristics, limiting direct attribution of these differences to route of exposure. In infants with previous influenza infection followed by vaccination, responses after subsequent vaccination initially showed greater binding to the previously infecting subtype among the tested HA antigens. With repeated vaccination, responses became more distributed across the tested antigens. Our findings reveal differences in the magnitude, persistence, and antigen specificity of antibody responses according to the nature and sequence of influenza exposure. By prospectively capturing early-life exposures, this study provides longitudinal evidence linking exposure history to subsequent humoral antibody responses.

BackgroundPost-acute COVID-19 syndrome (PACS) can cause persistent disability involving fatigue, post-exertional malaise, neurocognitive symptoms, and autonomic manifestations. A clinically overlapping condition has been reported following COVID-19 vaccination and termed post-acute COVID-19 vaccination syndrome (PACVS), but its underlying mechanisms remain poorly understood. We investigated whether immune dysregulation, autoreactivity, antigen persistence, and viral reactivation--mechanisms implicated in PACS--are also present in PACVS. MethodsThis cross-sectional study included 28 PACS patients, 29 PACVS patients, and 16 convalescent controls (CCG). Clinical manifestations were assessed using ME/CFS-related symptom questionnaires and the Bell Score. T-cell phenotypes and T cells reactive to SARS-CoV-2 Spike, {beta}1/{beta}2-adrenergic receptor, and M3/M4 muscarinic receptor antigens were analyzed by multicolor flow cytometry. Circulating Spike protein and GPCR autoantibodies were quantified by ELISA, and EBV load by qPCR. ResultsPACS and PACVS showed substantial clinical overlap, although several symptoms were more severe in PACS. GPCR autoantibody profiles were comparable between patient groups, while {beta}2-adrenergic receptor autoantibodies were increased compared with CCG. Only three of 57 conventional immunophenotyping parameters differed between PACS and PACVS in unadjusted analyses, whereas both groups showed multiple alterations compared with CCG. Circulating Spike protein was detected in both patient groups, with the highest prevalence in PACVS. {beta}1/{beta}2- and M3/M4-reactive CD4+ T cells were increased, whereas Spike-specific CD4+ T cells were reduced compared with CCG. EBV reactivation was rare. ConclusionsPACS and PACVS exhibit substantial clinical and immunological overlap, including GPCR-directed autoreactivity and altered receptor-reactive T-cell responses. These shared immune-mediated features suggest overlapping pathophysiological mechanisms and warrant investigation of whether therapeutic strategies currently explored for PACS may also be relevant to PACVS.

Importance: Antibiotic-resistant infections in neonates often arise from the infant's own colonizing bacteria harboring antibiotic resistance genes (ARG). This study evaluates ARG that impact antibiotic selection and drive resistance-related mortality, termed clinically important antibiotic resistance genes (CI-ARG). Objective: To determine differences in gut CI-ARG abundance in children from birth through 3 years old, stratified by neonatal intensive care unit (NICU) admission and antibiotic (abx) exposure in the first two months Design: Cohort study (sequencing, analysis completed 2025-2026) using shotgun metagenomic sequencing of stool samples from infants in two studies: Neonatal Intestinal Microbiome (+NICU groups, 2015-2022), The First 1000 Days of Life and Beyond (-NICU groups, 2018-2021). Infants grouped into four cohorts: +NICU/+abx, +NICU/-abx, -NICU/-abx, and -NICU/+abx. Prespecified CI-ARG abundance compared longitudinally among groups. Setting: NICU, well-baby nursery, Inova Fairfax Hospital, Virginia Participants: +NICU criteria: admission to the NICU, anticipated length of stay (LOS) of at least five days, maternal age at least 18 years. -NICU: parents with good general health and age at least 18 years enrolled prior to infant birth. Stool samples: adequate stool processing volume, at least one stool sample from before one month and after one year of age, 7-day minimum between serial samples. Exposures: NICU versus well-baby nursery; antibiotics versus none in first two months of corrected age Main Outcomes and Measures: Predefined primary outcome- longitudinal CI-ARG abundance by group, compared using linear mixed effects models with adjustment for multiple comparisons (Benjamini-Hochberg procedure). Predefined secondary outcomes- differences in overall microbiota and resistome composition. Results: 1000 serial stool samples, 179 infants (birth-39 months). Longitudinal abundance significantly differed among cohorts for 11 CI-ARG (p < 0.05); often higher in the +NICU groups in early life, with or without antibiotic exposure. Abundance of ARG conferring resistance to aminoglycosides, macrolides, and fluoroquinolones later decreased below -NICU levels. mecA, which often drives methicillin resistance in Staphylococcus, was detected only in +NICU infants during premature period. Conclusions: This longitudinal study demonstrates significant longitudinal CI-ARG differences in children grouped by early-life NICU status and/or antibiotic exposure. Future studies should explore the mechanisms driving these CI-ARG changes and evaluate their impact on infection risk and community spread.

In 2024, Chicago experienced a measles virus outbreak. Air samples collected as part of routine respiratory virus surveillance from three hospitals that received measles patients were retrospectively analyzed. Measles virus was detected in air samples from one emergency department across five weeks when measles patients were present and another when no known cases were present. Two of three viral sequences derived from air samples were identical to measles patients. The source of one diverging sequence could not be identified and may represent a case not identified by traditional surveillance methods. Air sampling may supplement measles investigation, surveillance and response.

Background: Treponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis. Methods: This Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group. Results: Among 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%--82.9%) in primary and 43.8% (16.7%--69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25--2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis. Conclusions: In primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.

Group A rotavirus G1P[8] strains, which are targeted by the Rotarix vaccine, have persisted in several countries following the introduction of the Rotarix vaccine. However, the evolutionary origins of the persisting strains remain unclear. Here, we leveraged over two decades of rotavirus surveillance data from Malawi to understand the genomic epidemiology of G1P[8] strains in a high-disease-burden sub-Saharan African setting. We observed a reversion of G1P[8] strains to the conventional Wa-like genotype constellation identified pre-vaccination, following transient circulation of DS-1-like G1P[8] strains. Most G1P[8] lineages that re-emerged post-vaccination circulated before vaccine introduction. Furthermore, new strains emerged post-vaccination through re-assortment of pre-existing viruses. The predominant post-vaccination lineage (MW-VP7-L2) contained an N147D substitution at an antigenically important site of the VP7 glycoprotein and showed evidence of episodic diversifying selection. Children infected with the MW-VP7-L2 lineage had a higher severity score of gastroenteritis than infections with other co-circulating lineages. These findings highlight the importance of long-term genomic surveillance to understand rotavirus transmission, evolution, and disease severity, and to guide public health interventions.

Background: Neutrophils migrate to the respiratory epithelium during rhinovirus (RV) infection, but whether RV directly activates neutrophils or whether activation arises from epithelial responses remains unclear. Objective: To determine whether RV directly activates human neutrophils or indirectly activates them through RV infected airway epithelial cells. Methods: Human neutrophils were exposed to purified RV, and activation was assessed by myeloperoxidase activity, CD11b/CD66b expression, and reactive oxygen species (ROS) production. Neutrophils were co-cultured with RV-infected air liquid interface (ALI) bronchial epithelium evaluated for effects on epithelial integrity. At 48 to 72 hours post-infection, we used live-cell imaging to measure ROS responses and neutrophil-tracking assays to measure migration velocity and ROS responses to basolateral supernatants, clarified apical washes, and apical debris from RV-infected epithelial cells. Plaque assays were used to assess for RV infectivity after incubation with apical neutrophils. Results: RV did not directly activate neutrophils. Adding neutrophils to the apical surface of airway epithelial cells increased neutrophil ROS production at 48 to 72 hrs post-infection but did not alter epithelial cytotoxicity. Conversely, basolateral supernatants from infected cells enhanced neutrophil migration but not ROS, consistent with cytokine-mediated priming. Clarified apical washes had no effect on migration or ROS. By contrast, apical debris from infected cultures triggered a robust ROS response. Basolateral fractions from medium control or RV infected cultures did not induce ROS. Infectivity is not impacted by apical neutrophil presence. Conclusion: RV does not directly activate neutrophils. Instead, RV infected epithelial cells release basolateral factors that enhance neutrophil migration, while apical debris from infected cells drives ROS activation. These findings indicate that epithelial injury, not RV itself, is the dominant trigger of neutrophil activation during infection.

Background. Persistent SARS-CoV-2 antigen is a leading hypothesis for post-acute sequelae of SARS-CoV-2 infection (PASC), commonly known as Long COVID. Impaired Fc-mediated antiviral antibody function could contribute to inefficient clearance of infected cells and viral antigen despite preserved antibody levels. Therefore, we tested whether PASC is associated with altered Fc{gamma} receptor-mediated antibody function and differences in IgG1 Fc fucosylation, a major regulator of Fc effector function. Methods. Serum samples from RECOVER-Adult participants with prior SARS-CoV-2 infection (99 PASC, 139 non-PASC) were analyzed for anti-SARS-CoV-2 spike receptor-binding domain (RBD) IgG and subclasses, Fc{gamma}RIIIa- and Fc{gamma}RIIa-mediated reporter activity as surrogate measures of antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), anti-RBD IgG1 Fc glycosylation, and circulating fucose-modifying enzymes. Results. Despite higher anti-RBD IgG and IgG1 abundance, PASC sera showed lower ADCC- and ADCP-associated Fc{gamma}R reporter activity, including after normalization for antibody abundance. Anti-RBD IgG1 showed greater fucosylation in PASC samples (30 PASC, 34 non-PASC). Serum FUCA2 was lower in PASC samples (24 PASC, 34 non-PASC), whereas FUCA1 and soluble CD16a levels did not differ between the two groups. Conclusion. PASC is associated with impaired antiviral IgG Fc function, increased IgG1 Fc fucosylation, and reduced circulating FUCA2, identifying a glycoimmune axis that may contribute to impaired Fc-dependent antigen clearance and represents a potentially targetable pathway in Long COVID.

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

Enteric pathogens account for a substantial global disease burden, yet population-based surveillance remains limited by the transient nature of pathogen shedding, which constrains the sensitivity of stool-based molecular testing to a narrow detection window. Detection of IgG responses in serological surveys could enable new insights into enteric pathogen transmission, but benchmarking serological measures relative to stool-based measures of infection remains a critical evidence gap. We compared measures of disease transmission in longitudinal birth cohort samples using multiplex IgG (1,601 dried blood spots, 370 children) and PCR assays (2,231 stool samples, 370 children) that overlapped for nine pathogens (norovirus GI, GII, Shigella/enteroinvasive Escherichia coli (EIEC), Campylobacter spp., enterotoxigenic Escherichia coli (LT-ETEC), Salmonella enterica, Giardia spp., Cryptosporidium spp., Entamoeba histolytica). LT-ETEC and Campylobacter ranked highest while E. histolytica and S. enterica ranked lowest by both IgG and PCR measures of infection. Measures of infection were less aligned for norovirus GI, norovirus GII, Cryptosporidium, Shigella/EIEC, and Giardia. Despite this, for most pathogens, and across both measures, force of infection was lowest in the urban city of Esmeraldas and substantially higher in more rural populations, with relative risks in assay measures (seroconversion rate and PCR detected prevalence) over 2.0 for pathogens with the largest differences (Shigella/EIEC and norovirus GI). Together, our results suggest that although absolute levels of infection differed between assays, IgG and PCR captured consistent relative risk of infection across geographic strata, suggesting either method can identify high- versus low-transmission settings.

Maternal systemic infection during pregnancy is associated with placental dysfunction even when pathogens do not directly invade the placenta, but the cellular pathways linking antecedent infection to persistent placental alterations remain poorly defined. Here we used spatial transcriptomics to resolve trophoblast-, fetal endothelial, and Hofbauer cell-enriched niches in placentas collected at term after clinical recovery from antepartum pyelonephritis. We profiled 168 spatially defined areas from 14 placentas and integrated transcriptional findings with blinded histopathology and quantitative extracellular matrix analysis. Pyelonephritis was associated with strikingly compartment-specific transcriptional responses. Hofbauer cell-enriched niches showed the most extensive alterations, with coordinated enrichment of extracellular matrix remodeling and vascular developmental programs, including increased ELN expression (log2FC = 0.84, FDR = 0.033) and increased expression of genes governing collagen deposition, elastic-fiber assembly, matrix maturation and turnover. Quantitative analysis of 1,790 fetal vessels independently identified altered perivascular matrix composition, with Hofbauer cell-enriched ELN expression correlating with greater perivascular elastin content ({rho} = 0.67, P = 0.008). Fetal endothelial-enriched regions exhibited complementary alterations in vascular remodeling and endothelial identity, including increased PLAC8 (log2FC = 1.36, FDR = 0.047), whereas trophoblast-enriched regions showed little detectable transcriptional response. Histopathology further demonstrated increased lesions associated with maternal vascular malperfusion and perivillous fibrin deposition. Together, these findings identify the villous immune-stromal-vascular microenvironment as a persistent site of placental remodeling following maternal infection and suggest that clinical recovery from maternal illness may not coincide with normalization of placental biology.

Typhoid intestinal perforation (TIP) is a late complication of Salmonella enterica serovar Typhi infection, and blood cultures, if available, are often negative at this stage, making etiologic confirmation challenging. In areas without access to blood culture diagnostics, TIP incidence can serve as a proxy for enteric fever burden. Antibodies against hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS) are promising serologic markers for typhoid, but their diagnostic utility for TIP remains unclear. In this study, we assessed the diagnostic accuracy of anti-HlyE and anti-LPS IgG and IgA antibodies measured by kinetic enzyme immunoassay in children undergoing emergency laparotomy for acute abdomen in Niger. Dried blood spots (DBS) were collected pre-operatively (baseline) and within 30 days post-hospital discharge (convalescence). Patients classified intraoperatively as TIP (n = 341) or as confirmed non-typhoid-related alternative etiology (i.e., controls, n = 48) were included in this serologic analysis. The primary analyses were conducted in a longitudinal sub-cohort of 122 TIP cases and 33 controls in whom all four anti-HlyE and anti-LPS IgA and IgG responses were measured at baseline and at convalescence. Anti-HlyE IgA and anti-LPS IgA were additionally measured at baseline in the full analytic cohort. In the primary analysis, all antigen-antibody isotype combinations distinguished TIP cases from controls with high accuracy: anti-HlyE IgA (AUC 0.94), anti-HlyE IgG (AUC 0.94), anti-LPS IgA (AUC 0.96), and anti-LPS IgG (AUC 0.96). Anti-HlyE IgA and anti-LPS IgA performed similarly in the full cohort (AUC 0.93 and 0.93, respectively), supporting the representativeness of the sub-cohort. Anti-LPS IgG showed the best overall performance (99% sensitivity, 94% specificity), exceeding that of all other individual markers, and combining markers did not improve diagnostic accuracy. Diagnostic performance at convalescence was similar to or lower than that observed at presentation. Overall, anti-HlyE and anti-LPS antibodies showed high diagnostic accuracy for TIP at presentation, extending the potential utility of these serologic markers for supporting the diagnosis of typhoid-associated intestinal perforation and improving surveillance of severe typhoid disease when patients present with late-stage complications. Our findings show that serologic testing could improve case detection and burden estimation of enteric fever and its complications in resource-limited settings.

The emergence of a dominant poultry-associated strain of Campylobacter jejuni in New Zealand coincided with a multi-year epidemic of human campylobacteriosis. This was characterised by an increase in cases to 2006, when one of the highest national case-rates in the world was recorded, followed by a rapid decline attributed to interventions in the poultry industry. The strain belonged to an internationally rare multilocus sequence type, ST474 - a member of Clonal Complex (CC) 48 - that was highly prevalent in both poultry and human cases in New Zealand but was also identified in other samples. ST474 isolates from humans, animal reservoirs and environmental water samples were collected between 2005 and 2019 and whole genome sequenced (N=443). Isolates from a 2018/9 case-control study of campylobacteriosis in New Zealand were included for genomic comparisons with other sequence types and CCs. This presented an opportunity to examine the genomic epidemiology of a single, relatively recently emerged lineage of C. jejuni, and improve our understanding of drivers of emergence and persistence in a relatively isolated ecosystem. Six subpopulations (clades) of ST474 were identified and these varied in terms of their host association, persistence, patterns of homologous recombination, and complement of mobile genetic elements, including plasmids and chromosomally integrated elements. Clade E was associated with a single poultry supplier in the initial epidemic phase and accounted for 34.5% of human cases. Clade F emerged from a declining Clade E after the peak in human cases and was also associated with poultry. The emergence of Clade F was accompanied by the loss of integrated element CJIE5 and the acquisition of multiple blocks of recombination, likely from diverse ancestral C. jejuni lineages, and the loss of the methionine biosynthesis operon metAB. In contrast, Clades A-D were detected at low frequencies in human cases over the 14-year period of surveillance and were associated with multiple hosts. This longitudinal study sheds light on the evolutionary processes that result in strain emergence and differentiation, highlighting the role of horizontal gene transfer in the evolution and adaptation of this pathogen to new niches, and the subsequent impact on public health.

Encephalopathy is a lethal manifestation of global cerebral dysfunction spanning hypoxic, metabolic, toxic, and vascular etiologies, yet its population burden is difficult to quantify because it predominantly appears as a contributing rather than underlying cause of death. Here, we analyzed US multiple-cause death records from 1999 through 2024 using harmonized CDC WONDER datasets. A longitudinally consistent core definition of 10 ICD-10 codes identified 953,846 encephalopathy-associated deaths. The national age-adjusted mortality rate increased 28.4%, from 9.143 per 100,000 in 1999 to 11.738 in 2024, after peaking at 14.391 in 2021. Segmented log-linear regression identified four temporal phases: 1999-2004 (annual percent change [APC],-1.76%), 2004-2018 (APC, 2.57%), 2018-2021 (APC, 6.54%), and 2021-2024 (APC, -5.98%). Encephalopathy was listed as the underlying cause in only 21.6% of deaths in 2024. Unspecified encephalopathy surged more than 3.6-fold, while anoxic brain injury remained stable. Mortality remained higher in males than females (13.973 versus 9.778 per 100,000), and rates among non-Hispanic Black individuals were 1.90-fold those of non-Hispanic White individuals. Geographically, mortality clustered in the Midwest and South (13.144 and 13.120 per 100,000 in 2024), with persistent state-level dispersion across the study period. COVID-19 accounted for 10.9% of associated deaths in 2021 before falling to 1.4% in 2024. These findings reveal a nonlinear trajectory shaped by diagnostic shifts, pandemic disruption, and persistent demographic and geographic disparities.

Background: Half of US children are prescribed an antibiotic by age 2. Maternal education and socio-economic factors influence prescribing but the role of other factors, such as age of solid food introduction is unknown. Objectives: We assessed risk factors for time to first antibiotic use between birth to age 2 to identify modifiable drivers of antibiotic use. Methods: We analyzed interviews from mothers of 1032 children participating in the mother-child Center for Oral Health Research in Appalachia cohort 2 between 2011 and 2017. The cohort enrolled healthy, English-speaking, pregnant White women > 18 years with singleton pregnancies. We used time-to-event analyses and a Cox Proportional Hazards model to describe and estimate hazard ratios (HRs) for time to first antibiotic. Results: By age 2, 78% of children received at least one antibiotic (median age at first antibiotic: 12.5 months). Over half (58%) of antibiotics prescribed were for ear infections. After adjustment for household income and birth quarter as fixed variables, time of solid food introduction (aHR: 4.75; 95% CI: 3.19, 7.07), time of first ear infection (aHR: 3.28; 95% CI: 2.58,4.17), and time of first illness (aHR: 4.60; 95% CI: 3.32,6.36) were significantly associated with time of first antibiotic use. Conclusions: Earlier time of solid food introduction was associated with earlier antibiotic use. Childhood illnesses, especially ear infections, also strongly influence antibiotic initiation. These modifiable factors offer targets to reduce unnecessary early antibiotic use.

Serious pertussis infections disproportionately affect infants but the biological basis for this age-dependent susceptibility remains unclear. Infant mouse models recapitulate features of severe human infant pertussis. We investigated the role of interferon lambda (IFN-{lambda}), a key regulator of mucosal immunity, in Bordetella pertussis infection of infant mice. While infected adult mice upregulate lung IFN-{lambda}, infant mice inoculated at P7 fail to upregulate IFN-{lambda} and succumb to infection. We hypothesized that failure to produce IFN-{lambda} during infection represents a critical immunological deficit in infant mice, and that restoring IFN-{lambda} signaling would improve survival outcomes. Whereas wild-type mice gained complete protection from lethal B. pertussis infection by P10, mice lacking the IFN-{lambda} receptor component IFNLR1 did not achieve full protection until P21. Loss of IFNLR1 was associated with enhanced bacterial dissemination to systemic organs. Infant mice possessed a functional IFN-{lambda} receptor in the lungs but failed to upregulate IFN-{lambda} during infection, and supplementing IFN-{lambda} exogenously extended survival. RNA sequencing of lung tissue from infected and uninfected wild-type and IFNLR1-deficient mice inoculated at different ages identified an immune transcriptional framework distinguishing susceptible from resistant animals at a systems level and revealed IFN-{lambda} signaling as a critical driver of immunological maturation in the infant lung. Infected infant IFNLR1-deficient mice had dysregulated immune cell recruitment to the lungs, indicating a quantitatively expanded but qualitatively impaired response. These findings demonstrate that IFN-{lambda} affects immune maturation accounting for a critical window of age-dependent resistance to lethal pertussis with novel therapeutic possibilities for human infants with this disease.