Journal of Clinical Virology Plus

BackgroundImmunocompromised (IC) individuals are at increased risk for persistent SARS-CoV-2 infections and can develop new viral mutations and lineages not seen in the community. In this case report, a persistent SARS-CoV-2 infection (330 days) in an IC patient is examined for viral mutations and mutations associated with cryptic lineages. Case PresentationThe patient was followed in a longitudinal study examining persistent SARS-CoV-2 in IC patients. The patient provided stool and nasal swab samples biweekly until 28 days post-enrollment, then monthly, and then quarterly after 12 month post enrollment until the participant was no longer positive for SARS-CoV-2. Staff performed RT-qPCR and viral sequencing on the samples. Viral mutations from the XBK lineage were already present in the initial sample. By the end of the infection period, there were 40 fixed consensus changes from XBK of which two mutations were typical for cryptic lineages. Mutations increased steadily over time, with most mutations fixed by day 253, including the cryptic typical mutations. ConclusionThis case demonstrates the potential for persistent SARS-CoV-2 infections to develop mutations and lineages in IC patients and highlights the need for continued SARS-CoV-2 monitoring and treatment in this vulnerable population.

IntroductionHemophagocytic lymphohistiocytosis (HLH) is a serious condition induced by Dengue virus which becomes fatal if not detected early and treated appropriately. So objectives of the present study are to observe the different patterns of presentations, clinical features and outcome of HLH induced by Dengue. MethodsIn this observational study, 14 patients admitted and diagnosed HLH as per diagnostic criteria, were included after informed written consent. Study conducted in a period of six months from 01/07/2025 to 31/12/2025. All patients were followed up till discharge. After collection, all data were analyzed by Microsoft Excel 2010. Ethical clearance was taken from Ethical Review Board of the Medical College. ResultsAmong 14 cases, male were more affected then the female (78.6% VS 21.4%) and majority were in between 20 to 50 years age groups. Clinical data showed, all 14 cases had fever for >7 days, joint pain 3(21.4%), headache 11(78.6%), skin rashes 10(71.4%), retro-orbital pain 2(14.3%), vomiting 11(78.6%),bleeding 10(71.4%), cough 4(28.6%), loose motion 9(64.3%), abdominal pain 7(50.0%), anorexia 2(14.3%), Melaena 2(14.3%), jaundice 4(28.6%) and spleenomegaly 9(64.3%). One(7.1%) case had history of Hypertension. Laboratory data showed different level of Bi or Pancytopenia, high ferritin, high TG, low fibrinogen, raised liver enzymes and low sodium. Dengue RT PCR and serology results showed 8(42.9%) cases were both IG M and Ig G dengue antibody positive, 6 cases were RT PCR positive, 2 cases were IgM and another 4 cases were IgG positive. Outcome of patients revealed, among all 14 cases12(85.8%) patients improved uneventfully and 2 were shifted to ICU where one improved and one died. ConclusionDengue is prevailing for long time and different complications are evolving and HLH is a relatively newer incident among the dengue patients. Infection by different serotypes at different time or multiple dengue serotype infection may be related with HLH and it might be a future subject to explore and to evaluate.

BackgroundThe epidemiology of suspected pediatric meningoencephalitis has shifted in the era of conjugate vaccines and multiplex PCR diagnostics, with viral pathogens now predominating over bacterial causes. Updated epidemiologic data are essential to adapt diagnostic and therapeutic algorithms to current clinical practice. MethodsThis retrospective single-center study included children and adolescents <18 years who underwent lumbar puncture with cerebrospinal fluid multiplex PCR for suspected central nervous system infection at a tertiary-care pediatric hospital in Germany between 2016 and 2024. Clinical, laboratory, and outcome data were extracted from electronic medical records. Cerebrospinal fluid was analyzed using the BioFire(R) FilmArray(R) Meningitis/Encephalitis Panel. Statistical analyses included descriptive statistics, nonparametric group comparisons, receiver operating characteristic analyses. ResultsAmong 1,198 included children, definite bacterial meningitis was diagnosed in 13 (1.1%), definite viral meningitis in 80 (6.7%), aseptic meningitis of unknown etiology in 131 (11.0%), confirmed/probable encephalitis in 53 (4.4%), and possible encephalitis in 34 (2.8%). Bacterial meningitis accounted for 5.8% of all meningitis cases. A causative pathogen was identified in all bacterial meningitis cases, most commonly Streptococcus pneumoniae (n = 7). Enterovirus (n = 52) and parechovirus (n = 9) predominated in viral meningitis, whereas an infectious etiology was identified in only 13 of 53 confirmed/probable encephalitis cases. The Bacterial Meningitis Score showed a sensitivity of 80.0% and a specificity of 57.6%. The recently published UK-ChiMES-pre- and post-lumbar puncture scores demonstrated sensitivities of 84.6% and 76.9% and specificities of 86.3% and 92.7%, respectively. DiscussionBacterial meningitis was rare in this contemporary cohort, while viral and etiologically unresolved infections predominated despite routine multiplex PCR diagnostics. Clinical prediction scores supported risk stratification, with the UK-ChiMES-pre-lumbar puncture score showing the most favorable balance between sensitivity and specificity and potential to guide diagnostic decisions and antiinfective therapy.

A number of vaccines and long-acting monoclonal antibodies have been shown to be effective in the prevention of respiratory syncytial virus (RSV) disease. However, an immune correlate of protection for RSV has not yet been identified. We conducted a systematic review to identify published reports of immunogenicity and/or efficacy in vaccines and long-acting monoclonal antibodies against RSV and performed a meta-analysis on extracted data to identify any relationship between antibody increase and protection against RSV disease. We identified 130 relevant reports which we classified into an open access evidence map of RSV immunisation products. We found a strong correlation between the immunisation induced rise in neutralising antibody titres and efficacy ({rho}>0.7 for all comparisons, Spearman). For infants, we estimated that each 10-fold increase in neutralising antibody titre rise provides an additional 31% [95% CI 10%-47%], 47% [95% CI 36%-56%] and 57% [95% CI 45%-66%] reduction in the relative risk of symptomatic, moderate and severe disease respectively. For older adults, a 10-fold rise in antibody levels was associated with a 34% [95% CI -2%-57%], 50% [95% CI 22%-67%] and 63% [95% CI 36%-79%] reduction in the relative risk of RSV disease with 1, 2 and 3 symptoms respectively. These results align extremely well with findings from natural history studies and individual-based analysis of correlates of protection studies. This work paves the way for use of neutralising antibodies as a correlate of protection to guide the development, approval, and deployment of RSV vaccines and monoclonal antibodies.

In the past decade, dengue fever has emerged as a major public health on Reunion Island in the Southwest Indian Ocean. During the 2018-2022 outbreak, an unusual increase in ocular complications was reported in some patients. To investigate a potential viral cause, we analysed 447 blood samples from hospitalized patients with and without ophthalmic symptoms. Genetic sequencing revealed the co-circulation of two strains of dengue virus serotype 1, both genetically linked to strains previously identified in Asia. Notably, all patients with ophthalmic symptoms were infected with viruses from a single cluster within genotype I, which harbored several unique mutations. These findings suggest that the rare ocular complications observed during this outbreak may be associated with specific viral cluster. Further laboratory studies are required to confirm this potential link.

Influenza A(H3N2) subclade K virus was detected in Canada early in the 2025/26 influenza season, bearing an antigenic transition in the hemagglutinin (HA) glycoprotein. Analysis of 396 HA sequences from Canada showed antigenic divergence from 2025/26 influenza vaccine strains, consistent with partial mismatch. Phylodynamic analysis revealed sustained pre-vaccine transmission without clear post-vaccine expansion. Phylogenetic and phylogeographic analyses indicated interprovincial mixing within a highly connected metapopulation, highlighting the value of genomic surveillance for real-time epidemiologic inference and public health decision-making.

IntroductionDengue has been prevalent in a regular fashion in Bangladesh and Chattogram for the last 6-7 years and is showing some serotype twisting. So, the objectives of the present study were to explore the burden of dengue serotypes in Chattogram. MethodsIn this study, 223 Dengue RT-PCR positive patients were evaluated for serotyping. Gender and age group, along with cycle threshold (CT) values, were also collected. Data after collection were compiled, analyzed, and plotted in Microsoft Excel and GraphPad Prism 10.4. Ethical clearance was taken to conduct the study. ResultsAmong 223 patients analyzed, males and females were found near equal (113 and 110). Middle-aged patients were more than the extremes of age. The mean {+/-} SD of age was 33.55 {+/-} 13.67 years. Regarding serotype distributions, isolated Den 1, Den 2 and Den 3 were found 1.3%, 73.1% and 6.7%, respectively. Concurrent infections with multiple serotypes were observed in several patients, most notably the Den 2 and Den 3 combination, which accounted for 14.3% (n=32) of the cases. Other co-infections were less frequent: the Den 1 and Den 2 pairing appeared in 3.6% (n=8) of the cohort, while triple-serotype infections (Den 1, 2, and 3) and Den 3/Den 4 pairings were rare, each occurring in only 0.4% of patients. Statistical analysis of CT values revealed no significant sex-based differences for Den 2 and Den 3. However, significant variations in CT values were observed when comparing Den 1 against both Den 2 and Den 3 (p < 0.05). In contrast, the difference between Den 2 and Den 3 Ct values remained statistically insignificant. ConclusionIn the year 2025, Dengue serotypes 2 and 3 were found to be the most prevalent, both in isolated or in combinations and Den 1 and Den 4 were found minimum. Exposure to multiple serotypes and twisting from one serotype to another might influence the dengue outcome in future, which needs further exploration.

BackgroundHeartland virus (HRTV) is an emerging tick-borne virus capable of causing severe illness and death. The burden of disease is likely underestimated due to limited seroprevalence studies, lack of commercially available diagnostic tests, and an overlapping clinical syndrome with more commonly diagnosed bacterial diseases such as spotted fever group rickettsiosis or ehrlichiosis. MethodsActive surveillance for Heartland virus disease was conducted at a large academic center from March to September 2024. Enrolled subjects included those who had testing sent for Ehrlichia polymerase chain reaction (PCR) along with fever and 2 of the 3 criteria: leukopenia, thrombocytopenia, and/or elevated liver function tests. Specimens with detectable RNA underwent whole genome sequencing and analysis. FindingsOver 800 specimens were received with 53 individuals meeting enrollment criteria. Among these 53, two (3.8%) had detectable HRTV RNA in whole blood during the time of Ehrlichia PCR testing. The two cases had disparate clinical manifestations: one with mild disease which was identified in an outpatient setting, while a second case required intensive care unit-level support. Heartland virus genome sequences from the two cases were more similar to viruses from other states than they were to one another. InterpretationDespite only two prior reported cases of Heartland virus disease in North Carolina, we identified two individuals with acute HRTV viremia. Further surveillance for HRTV disease is necessary to understand the burden of disease and to facilitate further studies of virus pathogenesis and host responses. FundingFunding for the study was provided by a Creativity Hub Award to Dr. Boyce from the UNC Office of the Vice Chancellor for Research. Dr. Zychowskis effort was supported by the T32 NIAD grant AI070114.

RationaleObstructive sleep apnea (OSA) is linked to cardiovascular, metabolic, and cognitive morbidity. Although COVID-19 has been associated with long-term respiratory and neurological sequelae, its role in precipitating new-onset OSA remains unclear. ObjectivesTo evaluate whether SARS-CoV-2 infection increases risk of developing OSA up to 4.5 years post-infection and how risk varies by hospitalization status, demographics, comorbidities, and vaccination status. MethodsThis retrospective cohort study used electronic health records from the Montefiore Health System in the Bronx. Adults tested for SARS-CoV-2 between March 1, 2020, and August 17, 2024, were classified as hospitalized COVID+, non-hospitalized COVID+, or COVID-. Patients with prior OSA or inadequate follow-up were excluded. Inverse probability weighting adjusted for demographic, clinical, socioeconomic, and vaccination covariates. New-onset OSA was assessed using weighted Cox proportional hazards models. Secondary outcomes including hypertension, myocardial infarction, heart failure, stroke, arrhythmia, pulmonary hypertension, type 2 diabetes, and obesity were evaluated with Poisson regression. Sensitivity analysis used a pre-pandemic control cohort. ResultsAmong 910,393 eligible patients, hospitalized [HR 1.41 (95% CI 1.14-1.73)] and non-hospitalized [HR 1.33 (95% CI 1.22-1.46)] COVID+ patients had higher adjusted risk of new-onset OSA versus COVID- controls. Similar findings were observed using historical controls (n=621046). After OSA onset, hospitalized COVID+ patients had higher risks of heart failure and pulmonary hypertension, while non-hospitalized COVID+ patients had higher risk of obesity vs COVID- patients. ConclusionsSARS-CoV-2 infection is independently associated with increased risk of new-onset OSA. These findings support targeted screening in post-COVID populations.

BackgroundSevere Fever with Thrombocytopenia Syndrome (SFTS) is an acute infectious disease with high mortality. This study aimed to develop a quantitative scoring system for grading SFTS severity using dynamic clinical data. MethodsA retrospective study included 547 confirmed SFTS patients from two hospitals. Clinical data were collected over a 14-day course (divided into four phases). Patients were grouped into survivors (n=451) and non-survivors (n=96). Statistical analyses, including Kaplan-Meier curves and log-rank tests, were performed. An external validation cohort of 44 new patients was used to validate the scoring system via C-statistic, calibration curves, and decision curve analysis (DCA). ResultsOf 547 patients, 96 (17.55%) were non-survivors. Multivariate logistic regression identified six independent prognostic factors across phases: age, platelet (PLT), aspartate aminotransferase (AST), and creatinine (Cr) (days 5-7); age, red blood cell distribution width (RDW), Cr, and lactate dehydrogenase (LDH) (days 8-10); Cr and LDH (days 11-14). A scoring system (0-11 points) was developed, stratifying patients into low (0-3), intermediate (4-7), and high (8-11) risk groups, with adverse outcome rates of 1.04%, 22.92%, and 76.04%, respectively. Kaplan-Meier curves showed significant prognostic differences (log-rank P<0.001). External validation (44 cases) confirmed excellent performance: AUC 0.810-0.952, good calibration (Hosmer-Lemeshow P>0.05), and net clinical benefit (DCA Eavg 0.068-0.098, Emax 0.422-0.559). ConclusionA dynamic SFTS severity scoring system was developed and validated. Internal and external validation confirmed its reliability and clinical utility, providing a simple, practical tool for timely assessment and early intervention.

Household transmission of EV-D68 was identified in 35 of 1040 households (3.4%) in the Pacific Northwest between 2022-2024, with an estimated secondary attack rate of 15%. Sequences from within households clustered closely with 0 to 2 pairwise nucleotide differences (median 1) between cases 6-14 days apart (median 7).

BackgroundThere is a need for synthetic peptide-based serologic assays that exploit avidity to replace whole antigens while enabling low-cost diagnostics in resource-limited settings. ObjectiveTo evaluate the diagnostic accuracy of a polymeric peptide-based ELISA leveraging avidity to enhance signal. MethodA 15-member SARS-CoV-2 peptide library corresponding to multiple epitope clusters and proteins was screened by indirect ELISA using pooled sera from RT-PCR-confirmed COVID-19 patients to identify peptides with possible diagnostic utility. The identified lead candidate, S559, possessed terminal cysteine-substitution to allow disulfide polymerization, and the resulting avidity gain was evaluated by comparing the apparent dissociation constant (KDapp) before and after depolymerization with N-acetylcysteine. The performance of an optimized ELISA using S559 was evaluated on 1,222 prospectively collected COVID-19 serum samples and 218 biobanked pre-COVID control serum samples. ResultsPolymeric S559 with a KDapp of 29.26 nM-1was demonstrated to have a 218% avidity gain relative to the completely depolymerized form. At pre-defined thresholds, the optimized S559 ELISA has a sensitivity and specificity of 83.39% (95%CI: 81.18% and 85.43%) and 96.79% (95%CI: 93.50% and 98.70%), respectively. At post hoc thresholds determined by Youden index, sensitivity and specificity reached 95.01 (95% CI: 93.63% - 96.16%) and 100.00% (95% CI: 98.32% - 100.00%), respectively. ConclusionHomomultivalent epitope presentation using polymeric S559 allows a highly specific immunoassay using human sera that may have important value in detecting antibodies, whether for diagnosing infection, confirming vaccination status or conducting surveillance.

Serological surveillance is fundamental to infectious disease research and informed public-health decision making. Immunoassays used in the study of pathogen-specific immunity have historically relied on the collection of venous blood. While critical for many public-health applications, this sample collection method is invasive and resource intensive. The costs and logistical barriers associated with venous blood collection are exacerbated in resource-limited regions, and the shift to less invasive sampling methods would increase sample availability for pathogen surveillance and study of pathogen-specific immunity. To this end, we have developed and optimized a self-collected, saliva-based immunoassay capable of quantifying pathogen-specific antibody binding in saliva samples. Using samples collected from geographically and epidemiologically diverse regions of the world, we compared antigen-specific IgG levels in paired plasma and saliva samples. We observed that levels of IgG against multiple pathogens of public health concern - including SARS-CoV-2 and dengue virus (DENV) - were highly correlated in plasma and swab-collected saliva. In addition, the decay of maternally derived antibodies in saliva samples collected from infants was readily observed using this immunoassay, demonstrating the assay's sensitivity and potential for use in measuring antibody kinetics. We posit that this assay represents a climate stable, non-invasive tool that can aid in the surveillance and study of pathogen-specific immunity across a broad range of public-health indications.

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting antibodies were absent, we detected widespread binding and functional NA antibodies against N1 neuraminidases from clade 2.3.4.4b H5N1 viruses. Neuraminidase inhibition (NI) titers were highest against North American D1.1 genotype N1 viruses and correlated strongly with neutralizing activity, whereas HA-binding antibodies did not. An additional N-linked glycosylation site, as found in the NA of a human D1.1 isolate from British Columbia, reduced susceptibility to NI antibodies. Antibodies to N5 from H5N5 were minimal. These findings indicate that population-level immunity to clade 2.3.4.4b H5 viruses is dominated by NA-directed antibodies, with important implications for pandemic risk assessment. ImportanceUnderstanding how pre-existing human immunity shapes susceptibility to emerging influenza viruses is central to pandemic preparedness. Here, we determined that human sera contain widespread, functional antibodies targeting H5N1 neuraminidase, which correlate with virus neutralization, whereas HA directed responses are limited. We further show that acquisition of an NA glycosylation site reduces antibody inhibition, highlighting a potential pathway for immune evasion. These results identify neuraminidase-specific immunity as a major immunological barrier to severe H5N1 disease in humans and emphasize the need to incorporate NA antigenicity into influenza surveillance, risk assessment, and next-generation vaccine design.

The emergence of vaccine covered serotypes causing invasive pneumococcal disease (IPD) is a serious concern worldwide. We investigated the unexpected rise of serotype 4 causing IPD primarily in non-vaccinated young adults after the COVID-19 pandemic that further spread to adults [&ge;] 65 years in recent years. For this purpose, we conducted a retrospective study of serotype 4 IPD cases (n=827) reported in Spain between 2009 and 2024. Whole-genome sequencing was performed to assess clonal lineages and phylogenetic relationships. Clinical and epidemiological data were compared between serotype 4 and all other serotypes causing IPD. Epidemiological and genomic analysis confirmed that the rise started as an abrupt cluster of IPD cases in Seville (Andalusia) in the year 2022 due to the ST15063 within GPSC12 lineage. This outbreak initially caused pneumonia episodes that required hospitalization in young individuals associated with high rates of tobacco smoking, alcohol, and inhaled drugs such as cannabis and cocaine, followed by a general distribution pattern throughout the country in the following years, affecting the elderly population. Experimental studies to evaluate potential underlying mechanisms confirmed that ST15063 serotype 4 strains displayed enhanced infection rates of human lung cells that significantly increased in the presence of cigarette smoke exposure and by influenza H3N2 virus coinfection, but not with H1N1. These findings highlight the need for targeted vaccination strategies not only against pneumococcus but also against respiratory viruses such as influenza, RSV and COVID-19 and demonstrate the importance of molecular surveillance to establish effective interventions in high-risk populations.

BackgroundTalaromycosis, caused by the fungus Talaromyces marneffei, is a leading cause of HIV-associated death in Southeast Asia. Current culture-based diagnosis only identifies late-stage infection, limiting understanding of disease burden and disease spectrum. We evaluated the clinical performance of anti-Mp1p IgM and IgG enzyme immunoassays (EIA) for talaromycosis diagnosis. MethodsThis diagnostic study included 423 adults with advanced HIV disease and culture-confirmed talaromycosis as cases, and 206 non-talaromycosis individuals with and without HIV who have never traveled to Asia as controls. Anti-Mp1p IgM and IgG antibodies were measured using conventional double-sandwich EIA. Diagnostic performance was assessed using the healthy control group and the HIV control group separately. Assay cut-offs were based on both the Youden index generated from the receiver operating characteristic curves, and separately using a pre-defined specificity of 95%. ResultsAt the pre-defined 95% specificity, IgM had low to moderate accuracy of 62.3% and 87.9%, and a low sensitivity of 8.3% and 21.3%, when evaluated with healthy and HIV controls, respectively. IgG had similarly low accuracy of 52.2% and 78.4%, and a low sensitivity of 21.5% and 30.5%, when evaluated using healthy and HIV controls, respectively. Both IgM and IgG assays performed better in HIV controls than healthy controls. ConclusionsThe anti-Mp1p IgM and IgG EIAs show low utility for the diagnosis of acute talaromycosis. However, at the high specificity cut-off of 95%, the assays have utility in the detection of T. marneffei exposure at both individual and population levels, and. provides a foundation for future sero-epidemiological studies. IMPORTANCETalaromycosis, caused by the dimorphic fungus Talaromycosis marneffei endemic in Southeast Asia, southern China, and northeastern India, is an invasive fungal infection that causes over 25,000 cases and 6,000 deaths annually but remains neglected in the global health community. Current diagnosis requiring culture-based testing is too slow, often resulting in patient death before treatment can begin. This study presents the first large-scale clinical evaluation of antibody tests for talaromycosis. While the antibody tests showed limited sensitivity for diagnosing acute disease, the high specificity makes them useful in determining prior exposure to T. marneffei, providing a new tool for public health investigation of disease prevalence at a population level, and for clinicians to identify individuals at risk for disease reactivation who may benefit from prevention strategies. The research provides important groundwork for improving disease control efforts in regions where this neglected infection is endemic.

Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady-state levels, functional properties, and changes in these parameters over time. Using longitudinal samples from adolescents, adults, and older adults, collected before and after the 2009 swine flu pandemic, we comprehensively characterized the specificity and functionality of nnAB responses against H1N1 pandemic 2009 (H1N1pdm09) virus. Remarkably, all participants exhibited cross-reactive antibodies to this virus before having encountered it through infection or vaccination, with the highest baseline levels observed in older adults. The levels of these IgG antibodies showed a strong correlation with engagement of fragment crystallizable {gamma} receptor IIIa (Fc{gamma}RIIIa) and ADCC activity, both of which were notably lower in adolescents compared to adults and older adults. Without infection or vaccination, average amounts of H1N1pdm09-reactive antibodies remained relatively stable on population level over the 5-year study period. However, on an individual level, substantial increases and decreases occurred. H1N1pdm09 infection or vaccination significantly enhanced specific antibody levels and the Fc{gamma}RIIIa-engaging capacity of these antibodies in all age groups. ADCC-mediating antibodies increased however only in adolescents, reaching the same level as observed in the adult groups. Taken together, our results demonstrate the presence of cross-reactive, non-neutralizing, functional, and boostable antibodies against a never-encountered influenza virus strain across all age groups. These antibodies can potentially contribute to protection from severe disease. Accordingly, in case of a newly emerging virus, their further enhancement by vaccination could be beneficial as an immediate protective measure before a strain-specific vaccine becomes available. Author summaryNearly everyone has contracted influenza and/or has been vaccinated against influenza several times over the years. While the antibodies raised during these earlier encounters will not prevent infection by a newly emerging influenza virus strain, they can help to protect from severe disease. Therefore, it is important to determine the prevalence and quantity of these antibodies, understand their mechanisms of action, assess their persistence over time, and examine potential age-related differences in these parameters. We studied antibody responses to the H1N1pdm09 virus in blood samples of young, adult, and older adult individuals from a large cohort study. Irrespective of age, all blood samples contained antibodies that reacted with a never-before-encountered influenza virus strain. The amounts of these antibodies were initially lower in adolescents but with time increased, reaching the same levels as observed in adults. Importantly, infection with or vaccination against the new virus strengthened the responses in all age groups. We conclude that boosting such broadly-reactive antibodies through vaccination could serve as an immediate strategy when a new virus emerges, buying critical time to develop a more specific vaccine.

BackgroundPreoperative biliary stenting alters biliary colonization and may reduce the effectiveness of perioperative antibiotic prophylaxis in pancreatoduodenectomy. Although broader-spectrum regimens have been associated with improved infectious outcomes, their microbiological adequacy in routine clinical practice remains poorly defined. We therefore evaluated the real-world adequacy of a prolonged ampicillin-sulbactam protocol, its association with infectious outcomes and survival, and the potential impact of a universal piperacillin-tazobactam strategy. MethodsWe analyzed all consecutive patients who underwent elective pancreatoduodenectomy from 2002 to 2023 at our tertiary center. Demographic, operative, microbiological, and outcome data were retrieved from a prospectively maintained database. Patients were stratified by stent status. Adequacy of prophylaxis was defined as the full in vitro susceptibility of all bile isolates. The outcomes included 30-day infectious morbidity, clinically relevant POPF, PPH, DGE, reoperation, 30- and 90-day mortality and long-term survival. A coverage simulation was performed to compare ampicillin-sulbactam with a hypothetical universal piperacillin-tazobactam. Statistical methods included chi-square/Fishers exact tests, Mann-Whitney U tests, Cox models, McNemars test and Poisson regression. ResultsOf 956 patients, 424 (44%) had a biliary stent. Technical complications were comparable between groups, and rates of POPF and PPH were not increased. However, infectious morbidity was higher in stented patients, including sepsis (RR 1.62, 95% CI 1.05-2.51) and postoperative cholangitis (RR 2.20, 95% CI 1.36-3.56). Thirty- and 90-day mortality were increased (RR 2.88 and 2.73) but lost significance after adjustment. Bile cultures predominantly yielded Enterococcus and Enterobacterales with low ampicillin-sulbactam susceptibility. Overall adequacy was 21.7%. Among patients with bile cultures (n = 474), ampicillin-sulbactam covered 43.7% (207/474) versus 81.2% (385/474) with piperacillin-tazobactam; in stented patients with cultures (n = 397), coverage increased from 41.8% to 78.1%. Adequate ampicillin-sulbactam coverage was not associated with reduced infectious outcomes in Poisson models. ConclusionPreoperative stenting creates a polymicrobial, partially resistant biliary niche that ampicillin-sulbactam does not sufficiently cover. Our data shows that a piperacillin-tazobactam strategy substantially improves coverage and was therefore implemented at our center. Core message- Stented patients exhibit a distinct infectious risk profile characterized by Enterococcus-and Enterobacterales-dominated bile colonization rather than increased rates of technical complications. - In stented patients, real-world microbiological coverage of ampicillin-sulbactam was limited, and in vitro susceptibility did not independently translate into reduced postoperative infectious morbidity. - Broader prophylaxis, such as piperacillin/tazobactam, aligns with the actual flora and nearly doubles theoretical coverage, addressing the mismatch between stent-associated biofilms and narrow regimens.

The rapid diagnosis of Campylobacter infections is important for the management of infectious gastroenteritis. Although stool culture is considered the gold standard, its sensitivity is limited and it requires prolonged incubation times. We performed a prospective multicenter study at nine healthcare facilities in Japan to evaluate a Campylobacter rapid antigen test using stool specimens between March 2024 and August 2025. Patients with suspected infectious gastroenteritis were consecutively enrolled and tested using QuickNavi-Campylobacter and compared with the FilmArray Gastrointestinal Panel as the reference method. Discordant results were further evaluated by culturing and additional PCR assays. In total, 410 patients were included in the final analysis. The positive, negative, and total concordance rates between QuickNavi-Campylobacter and FilmArray Gastrointestinal Panel were 79%, 99%, and 93%, respectively. The positive concordance rate decreased in specimens collected [&ge;] 6 days after the onset of symptoms (50%). QuickNavi-Campylobacter demonstrated relatively good concordance with the FilmArray Gastrointestinal Panel in a real-world multicenter setting. These results suggest that this rapid antigen test may be particularly useful for the early diagnosis of suspected campylobacteriosis.

BACKGROUND AND OBJECTIVESSeasonal influenza vaccination has been shown to reduce the risk of influenza and severe complications among children 6 months and older. Since 2010, reported numbers of influenza-associated pediatric deaths among children aged <18 years have ranged from 37 during the 2011-2012 season to 289 during 2024-2025. We estimated influenza vaccine effectiveness (VE) against pediatric death from 2016-2017 through 2024-2025. METHODSWe conducted a case-cohort analysis comparing current season influenza vaccination status among reported influenza-associated pediatric deaths with survey estimates of influenza vaccination coverage in pediatric age groups. Underlying medical conditions and current seasonal influenza vaccination were obtained from surveillance case reports. We estimated vaccination odds ratios (OR) and 95% confidence intervals (CI) from logistic regression comparing influenza vaccination among children who died with vaccination coverage in comparison cohorts. VE was calculated as (1 - OR) x 100. RESULTSFrom August 2016 through July 2025, 1234 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months--17 years. Of 1086 reported deaths including influenza vaccination information, 124 (23%) of 530 children with underlying medical conditions and 70 (13%) of 556 children without known conditions were fully vaccinated against influenza. Average influenza vaccination coverage in survey cohorts was 49%. VE was 80% (95% CI, 75% to 84%) overall, 77% (95% CI, 71% to 82%) among children with underlying medical conditions and 87% (95% CI, 84% to 89%) among children without known conditions. CONCLUSIONSInfluenza vaccination reduced risk of fatal influenza among children with or without known underlying medical conditions.