Journal of Infection

BackgroundTuberculous meningitis (TBM) is the most sinister form of extrapulmonary tuberculosis (EPTB), associated with high mortality due to delayed diagnosis and limited sensitivity of conventional and molecular tests. Current study evaluated the diagnostic utility of Lipoarabinomannan antigen (LAM) detection in CSF and urine and explored host inflammatory biomarkers for diagnosis and prognosis of TBM. MethodsThis prospective observational study enrolled 80 patients with presumptive TBM at a tertiary care centre. CSF samples were subjected to AFB microscopy, liquid culture(MGIT-960), GeneXpert MTB/RIF (GX), and LAM lateral flow assay. Urine LAM was performed at baseline. Serum and CSF levels of IL-1{beta}, IL-6, TNF-, IFN-{gamma}, IL-17A, and IP-10 were measured at baseline and after 1 month treatment. ResultsAmong 80 participants, 23 (28.7%) had definite TBM and 46 (57.5%) had probable TBM. CSF LAM sensitivity and specificity against microbiological reference standards was 43.5% and 80.7%, while urine LAM sensitivity (60.9%) and specificity 82.5% was higher. Against composite reference standards, both CSF and urine LAM showed reduced sensitivity but achieved 100% specificity. Serum IL-1{beta} showed the best diagnostic performance (AUC 0.943; sensitivity 88.9%, specificity 90.9%). Elevated serum and CSF IP-10 levels were associated with poor outcomes, whereas declining IL-6 and TNF- levels correlated with treatment response. ConclusionLAM detection in CSF and urine may serve as a highly specific, rapid rule-in test for TBM. Host inflammatory biomarkers, especially IL-1{beta} and IP-10, show additional diagnostic and prognostic value. Combining LAM testing with cytokine biomarkers may improve early diagnosis and efficient clinical management of TBM.

Background: The choice of hand-drying method affects microbial contamination levels but its economic consequences have not been systematically quantified. Methods: By applying a quantitative microbial risk assessment framework, we translated the documented contamination differential between jet air dryers and paper towels into infection risk estimates, and embedded these into an established health economic model of healthcare-associated infections in NHS hospitals and an illustrative productivity analysis for the EU workforce. Results: The median estimated avoidable HCAI cost attributable to jet air dryer presence in UK NHS clinical areas was 58 million pounds per year, representing 2.1% of total HCAI expenditure for the affected hospital population, with a 50% certainty interval of 33-84 million pounds. Extended to the EU workforce, the same contamination differential implied a median of 1.7 billion euros in annual productivity gains, due to reduced absenteeism, for a shift to use of paper towels in public restrooms. Conclusions: These findings suggest that hand-drying method selection carries measurable economic implications that are not currently reflected in facility management practice. The evidence supports the prioritisation of paper towels in clinical and public settings as a cost-effective infection control measure

Large epidemics of invasive meningococcal disease are rare in temperate regions. Here, we analyse administrative data on the largely forgotten epidemic of bacterial meningococcal meningitis that occurred in Glasgow in 1907, probably the largest on record in the UK. The epidemic, predominantly confined to the city, killed around 1,000 people, had a case fatality rate of nearly 70%, and hit infants and young children the hardest. We show the rapid rise and fall in cases and the spatial distribution of incidence and mortality rates within the city. We find that within-household overcrowding was a key driver of incidence whereas between-household geographic proximity was not. We also find that the spatial distribution of disease risk during the epidemic persisted in the post-epidemic period and during a later outbreak. The findings suggest that interventions should prioritise populations in areas that have experienced higher incidence rates to mitigate the risk of future outbreaks.

The Epic Sepsis Model version 2 (ESMv2) is a prediction model embedded into the electronic medical record used to warn clinicians which hospitalized patients are at risk for sepsis. We conducted a retrospective cohort study of 31,951 hospitalizations of 25,760 patients to compare analyses conducted at the commonly used patient-level (where a maximum prediction prior to the onset of sepsis is used to measure performance) vs novel prediction-level (where each prediction is used to measure performance). Sepsis, defined by the Sepsis 3 criteria occurred during 1,049 hospitalizations (3.3%). Patient-level analyses suggested excellent discrimination AUC 0.86; [IQR 0.85, 0.87], whereas prediction-level analyses demonstrated lower performance AUC 0.62; [IQR 0.57, 0.65]. Low estimates of the positive predictive value (14.5% at the patient level vs 4% at the prediction level) imply a high number of false alerts. Common evaluation approaches may overstate the performance of dynamic prediction models and mislead clinical decision-making.

Background: Wearing facemasks and practising social distancing slow the spread of respiratory pathogens. However, in the event of a new pandemic emerging, the willingness of populations to voluntarily adopt these behaviours is unclear. Methods: A discrete choice experiment was conducted among 2,006 UK-based adults. Participants were presented with hypothetical scenarios describing the emergence of a respiratory virus pandemic and were asked to choose when they would wear facemasks and practise social distancing. A mixed multinomial logit model was used to jointly estimate how disease severity and prevalence, uncertainty in these quantities, and individual-level characteristics influence behavioural choices. Findings: Participants were averse to facemasks and social distancing in the absence of pandemic risk. For each ten-unit increase in severity (10 additional hospitalisations/1,000 infections), the odds of always wearing a facemask outside the home increased by 15.9% (95%CI: 14.3%, 17.5%), relative to rarely/never, and the odds of avoiding all people as much as possible increased by 16.4% (14.6%, 18.2%), relative to not avoiding anyone. Greater disease prevalence, uncertainty in disease severity or disease prevalence, a university education, prior COVID-19 vaccination and non-white ethnicity were also associated with choosing to always wear facemasks and avoid all people as much as possible. The probability of participants choosing to rarely/never wear facemasks varied from 13.4% (11.9%, 14.9%) in the lowest-risk scenario to 1.4% (1.2%, 1.7%) in the highest-risk scenario. Interpretation: Perceived risks of disease and associated uncertainty drive intention of UK adults to adapt their behaviour in a future pandemic.

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

Background Gastric cancer management is heterogeneous, and although the treating surgeon leads decisions across the pathway, surgeon level outcome variation remains poorly quantified. This study assessed surgeon identity as an independent predictor of survival after risk adjustment, introducing the Surgical Assessment and Healthcare (SAH) Index. Methods This single institution retrospective study (Ruijin Hospital, Shanghai Jiao Tong University; NCT07180966) included 692 patients undergoing curative-intent resection for gastric adenocarcinoma (pStage I ,II, III) in 2019 by eight consultant surgeons. Overall survival was modelled by multivariable Cox regression (primary model, 199 events, EPV 16.6; complete-case sensitivity model, N = 647). The SAH Index expressed surgeon * stage observed-to-expected ratios for five-year mortality and major morbidity (Clavien Dindo [≥] IIIa). Median follow up was 74.3 months. Results Independent predictors of survival were tumour stage (HR 2.979/step), age (HR 1.030/year), and non-distal gastrectomy (HR 1.498; all p [≤] .006). After full adjustment, surgeon identity remained significant (Wald = 14.58, df = 7, p = .042): two surgeons carried roughly double the reference hazard S6 (HR 2.219, p = .003) and S8 (HR 2.034, p = .031) both with the cohort's lowest neoadjuvant chemotherapy rates (3.0% and 7.0% versus 17.6%), implicating pre-operative pathway decisions. The effect persisted in the sensitivity model (MSI also prognostic, HR 3.162, p = .007). Morbidity benchmarking flagged no surgeon for excess complications (no Tier 2 flags) and one survival-outlier cell (S6, Stage II; Tier 3). Conclusion Surgeon identity is independently associated with survival in gastric cancer beyond measurable case mix. The SAH Index offers a reproducible tool for institutional and inter-hospital benchmarking, with tier assignments stable across all four prespecified weighting scenarios confirming tier classification is independent of weight specification.

Overview: SeptiCyte RAPID is an FDA-cleared gene expression test that quantifies host immune response to aid in the diagnosis of sepsis. The test yields a score (the SeptiScore) ranging from 0-15, distributed across four bands (1-4) based on increased likelihood of sepsis. Each band can be characterized by average positive and negative likelihood ratios (LR+, LR- respectively) for the discrimination of sepsis versus the non-infectious systemic inflammatory response syndrome (SIRS). Methods: A retrospective analysis of prospectively collected data from a combined cohort of critically ill patients suspected of sepsis (N=889), recruited across 19 hospitals in the USA and Europe. The analysis quantified the LR+ and LR- parameters as a function of SeptiScore, for discrimination of sepsis vs. SIRS in patients admitted to ICU. Hypotheses: (1) The likelihood ratio (LR) framework provides a clinically useful interpretive approach that complements the previously used SeptiScore banding scheme; (2) Low Band 1 SeptiScores are associated with sufficiently small LR- to support the use of SeptiCyte RAPID as a rule-out test for sepsis; (3) High Band 4 SeptiScores are associated with sufficiently large LR+ to support the use of SeptiCyte RAPID as a rule-in test for sepsis; and (4) SeptiScore-derived LR+ and LR- values can be combined with estimates of pre-test probability (derived from patient characteristics and/or other diagnostic tests) to generate individualized, patient-specific post-test probabilities of sepsis. Results: The SeptiCyte RAPID test demonstrates strong diagnostic performance in distinguishing sepsis from SIRS. The likelihood ratios across different score bands provide clear clinical utility: the median LR+ was 3.26 (range 2.57-4.24) for Band 3, and 6.97 (range 4.35-15.57) for Band 4 providing evidence toward ruling in sepsis at high SeptiScores. Conversely, the median LR- was 0.16 (range 0.14-0.20) for Band 2 and 0.085 (range 0.014-0.16) for Band 1, providing evidence toward ruling out sepsis at low SeptiScores. A higher-resolution analysis of SeptiCyte RAPID performance confirmed these trends by evaluating LR+ and LR- at specific values within each band. The sepsis group was further stratified according to whether patients were classified as blood-culture positive (BC+) or blood culture negative (BC-), and the detailed LR+ and LR- analyses were repeated. A monotonic increase in likelihood ratio with increasing SeptiScore was consistently observed, independent of whether sepsis patients were culture-positive, culture-negative, or unstratified with respect to blood culture status. Conclusion: High SeptiScores have correspondingly high LR+ values, and low SeptiScores have correspondingly low LR- values, both of which may have clinical utility. High likelihood ratios for band 4 SeptiScores, which precede traditional microbiology results, may provide clinicians with early confidence of a sepsis diagnosis and microbiology diagnostic stewardship. Low likelihood ratios for band 1 SeptiScores may prompt clinicians to consider an alternate diagnosis to sepsis. Such results, obtained early in the diagnostic workup process, may lead to fewer missed diagnoses and more efficient use of hospital resources.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of lepromatous leprosy characterised by recurrent inflammatory episodes often requiring prolonged immunosuppression. The severity of ENL can be quantified using the validated and reliable ENLIST ENL Severity Scale (EESS). The longitudinal course of ENL and how it is captured using standardised severity measures has not been well described. We prospectively evaluated the changes in ENL severity over time using the EESS in a randomised clinical trial. Methods We conducted a post-hoc analysis of participants enrolled in the Methotrexate and Prednisolone Study in ENL, an international multicentre randomised controlled trial conducted in Ethiopia, India, Indonesia, and Nepal. Adults with severe ENL (EESS score [&ge;]9) were followed for 60 weeks with repeated EESS assessments. Longitudinal trajectories were analysed using mixed-effects regression models. Item-level analyses characterised the clinical phenotype captured by the scale. Associations between EESS score, prednisolone exposure, and dermatology-specific health-related quality of life measured using the Dermatology Life Quality Index (DLQI) were examined. Findings A total of 135 participants contributed 1,958 EESS assessments. Mean EESS declined rapidly during the first four weeks of treatment (-2.10 points/week; 95% CI -2.36 to -1.84; p<0.001), increased modestly during reduction in corticosteroid dose (weeks 4-20), and gradually declined thereafter. Severe ENL (EESS score [&ge;]9) occurred in 20.6% of visits and was characterised primarily by pain and cutaneous inflammatory manifestations. Participants who required additional prednisolone had persistently higher EESS scores and showed limited improvement compared with those who did not receive additional prednisolone. Longitudinal EESS scores were strongly correlated with the DLQI score (Spearmans {rho}=0.75; p<0.001). Conclusion The EESS captures clinically meaningful changes in ENL severity, aligns with treatment decisions, and reflects patient-reported severity over time. These findings support the use of the EESS as a robust tool for monitoring ENL severity in both clinical research and routine care.

BackgroundMicrobial colonisation of the human body begins immediately after birth, with each body site forming a distinct ecological niche. While early gut microbial dynamics and their links to paediatric health have been considerably studied, the bacterial colonisation of the early infant respiratory system remains poorly understood, particularly at the species and strain level. ResultsHere, we generated and analysed whole genome sequencing of 925 isolates from six dominant genera in nasopharyngeal samples from 58 healthy infants enrolled in the Childhood Asthma Study (CAS) in Western Australia, collected longitudinally from birth (2, 6, and 12 months old). Our results expanded genomic reference catalogues and uncovered substantial strain-level diversity in dominant infant airway taxa. Plate-sweep metagenomics identified four microbiome profile groups (MPGs) with age-dependent membership, confirming prior observations while enabling high-resolution species and strain analyses. Community maturation was characterised by a shift from early Staphylococcus aureus dominance to increased Moraxella catarrhalis dominance by 12 months of age, alongside marked temporal changes in prevalence and cohort-level strain diversity. ConclusionsThese findings resolve infant nasopharyngeal microbiota composition at the species and strain level, revealing taxon-specific colonisation patterns. By substantially expanding publicly available reference genomes for underrepresented airway taxa, this work also provides a foundation for functional follow-up studies of the early respiratory microbiota and respiratory outcomes.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460). Conclusions Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.

Background Reactivation of human herpesviruses (HHVs), particularly EBV, is associated with more severe acute SARS-CoV-2 infections and the development of Long COVID (LC). Observations of higher anti-EBV antibody levels in individuals with LC support the idea that chronic reactivation of HHVs could contribute to LC pathology. HHV shedding in saliva has also been previously associated with saliva hormone levels. This study aims to examine the relationship between salivary shedding of HHV DNA and LC symptoms, as well as cortisol, testosterone, and estradiol levels. Methods We enrolled 45 participants with LC, and 45 age-sex-matched controls. Surveys and validated health questionnaires were used to collect demographics, medical history, and symptom profiles. Saliva was self-collected at waking, 15, 30, and 45 minutes, and 8 and 16 hours after waking, across two consecutive days. Salivary cortisol, testosterone and estradiol were measured, and extracted nucleic acid was tested for EBV, HSV 1/2, HCMV and HHV-6 A/B using multiplex qPCR, plus SARS-CoV-2 and RNaseP using RT-qPCR. Findings Detection of salivary EBV and HHV-6 DNA was highest early in the morning. There were no significant differences in salivary cortisol, testosterone, or estradiol, or in EBV or HHV-6 shedding between the LC and control groups. However, salivary HHV-6 DNA levels were positively associated with a greater aggregated LC propensity score, as well as anxiety and depression scores. Interpretation The observed correlation between salivary HHV-6 shedding and symptom severity suggests HHV-6 may contribute to post-acute disease, though mechanisms remain unclear. While our study did not identify a relationship between salivary EBV shedding and LC, EBV may still play a role at earlier time points in the disease course, or in compartments not sampled here. These findings highlight the potential importance of HHV-6 in LC pathophysiology and underscore the need for longitudinal, multi-compartment studies of herpesvirus reactivation in LC.

Ebola virus disease (EVD), caused by the Ebola virus (EBOV), is characterized by high morbidity and mortality, with 16 distinct EVD outbreaks reported in the Democratic Republic of the Congo (DRC), alone. As part of the formal response to the 2018 outbreaks in Equateur and North Kivu provinces, a recombinant vesicular stomatitis virus-Zaire Ebolavirus envelope glycoprotein vaccine (rVSV-ZEBOV-GP) vaccine was deployed under emergency use. While clinical trials have evaluated vaccine safety and efficacy, there is a paucity of real-world data documenting antibody durability for longer periods post-vaccination. Here, we present serologic data from 1081 individuals in Beni, North Kivu (n = 599) and Mbandaka, Equateur (n = 482) who were vaccinated during the outbreaks--with samples from baseline up to five-years following vaccination. Using a multiplexed immunoassay, we show sustained anti-EBOV GP reactivity: at year-5 collection, 72% of individuals naive at time of vaccination remained seroreactive to EBOV GP. Stratifying by site, antibody titers remained significantly elevated after baseline across all post-vaccination timepoints in both linear and logistic mixed-effects models. Pre-existing EBOV GP reactivity at baseline was the strongest independent predictor of antibody response in Mbandaka, associated with higher titers and greater odds of seropositivity (OR = 3.87, 95% CI: 2.50-6.01, p-value < 0.001), consistent with a boosting effect among previously exposed individuals. However, this was not replicated in Beni (OR: 0.66, 95% CI: 0.27-1.58, p-value = 0.348). In Mbandaka, among those recipients who reported receiving a booster dose, the odds of seroreactivity were 12.75-fold (p-value < 0.001) and 3.68-fold higher (p-value = 0.04) at 4.2 and 5-years post-vaccination, respectively, in comparison to odds of reactivity at three weeks following administration of the initial dose. Occupational groups with zoonotic or community-level exposure had trending lower odds of seroreactivity relative to healthcare workers, most consistently in Beni. Ultimately, these data indicate that five years following administration of the rVSV-ZEBOV-GP vaccine, most vaccinated individuals retain detectable anti-EBOV GP antibodies. While correlates of protection for EVD are not well established, sustained IgG seroreactivity to EBOV GP may serve as a marker for future understandings of the durability of and variation in immune responses to this high-consequence pathogen.

Background: The ongoing Bundibugyo virus disease (BDBV) outbreak in Central Africa highlights the absence of approved vaccines specifically targeting BDBV. Whether licensed Zaire ebolavirus (EBOV) vaccines induce cross-reactive immunity against BDBV remains largely unknown. Methods: We performed an immunogenicity analysis using serum samples from participants enrolled in the PREVAC randomized clinical trial evaluating licensed Ebola vaccine strategies in West Africa. Samples collected at day 28 (D28) and month 3 (M3) following vaccination with rVSV{Delta}G-ZEBOV-GP or Ad26.ZEBOV/MVA-BN-Filo were assessed using a multiplex Luminex assay against glycoproteins from multiple filoviruses, including EBOV Kikwit, EBOV Mayinga, BDBV, Sudan virus, Reston virus, and Marburg virus. Results: A total of 179 samples were analysed. Detectable cross-reactive antibody responses against BDBV were observed across vaccine groups, timepoints, and age categories. However, BDBV responses remained substantially lower than homologous EBOV responses. In rVSV recipients, median BDBV responses (net MFI) reached 282 (IQR 164-644) at D28 compared with 1788 (832-3311) against the homologous Kikwit antigen. Similar patterns were observed following rVSV booster vaccination and Ad26.ZEBOV/MVA-BN-Filo vaccination. The heterologous Ad26/MVA regimen demonstrated increasing BDBV responses between D28 and M3. Conclusions: Licensed EBOV vaccines induced detectable but quantitatively reduced cross-reactive antibody responses against BDBV. Although no direct assessment of vaccine efficacy against BDBV disease was possible, these findings support the plausibility of partial heterologous immunity following EBOV vaccination. In the absence of approved BDBV-specific vaccines, these data support the urgent evaluation of currently available Ebola vaccines during BDBV outbreaks and reinforce the importance of developing broadly protective pan-filovirus vaccines.

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

Background Despite the significant impact of longstanding paediatric pneumococcal conjugate vaccine (PCV) use in the United Kingdom (UK), pneumococcal disease burden remains substantial and is primarily driven by nonPCV13 serotypes. Higher valent vaccines such as the 20 valent PCV (PCV20) may provide additional public health and economic benefits, yet their value in the contemporary UK setting has not been fully assessed using recent data. Methods We updated an age structured dynamic transmission model using post COVID 19 UK epidemiology (2001 to 2023) to compare pediatric PCV20 with PCV13 and PCV15. Over a 10 year horizon, we assessed cost effectiveness and number needed to vaccinate (NNV), capturing invasive and non invasive disease cases, deaths, costs, quality adjusted life years, and incremental cost effectiveness ratios. PCV20 was evaluated under 1+1 and 2+1 schedules; PCV13 and PCV15 were assessed under 1+1. Scenario analyses examined key uncertainties. Results PCV20 was estimated to avert more cases and deaths than PCV13 or PCV15, driven by broader serotype coverage and indirect effects. Both PCV20 schedules were dominant or cost saving versus lower valent comparators, with lower NNVs. PCV20s higher vaccination costs were offset by reductions in downstream healthcare expenditures. Conclusion Paediatric PCV20 implementation in the UK could deliver substantial health gains while improving economic efficiency, supporting timely adoption.

Background: Community-acquired pneumonia (CAP) remains a major global health burden disproportionately affecting older adults and people with comorbidities, with Streptococcus pneumoniae as one of the leading bacterial causes in Europe. The Hungarian Occurrence and Burden of PnEumonia (Hungarian-HOPE) study examined the incidence, hospitalization rates, and mortality of CAP between 2016 and 2020 in Hungary. Methods: The National Health Insurance Fund database was used to identify adult CAP patients (all-cause) based on ICD-10 codes J10-18. Outcomes included CAP incidence, 0-15-day hospitalization, and 0-30-day mortality after hospitalization, stratified by age, sex, and comorbidities (chronic obstructive pulmonary disease [COPD], asthma, cardiovascular disease [CVD], and type 1 and 2 diabetes [T1DM, T2DM]). Risk maps visualized relative risk gradients across population strata. Results: During the pre-pandemic period (2016-2019), over 100,000 CAP cases and more than 50,000 hospitalizations were recorded annually. In 2020, recorded cases fell to approximately 98,000, while hospitalizations increased to 66,200. Hospitalization rates increased from 25.1% in 2016 to 29.1% in 2019, then increased to 43.1% in 2020. The 30-day mortality among hospitalized patients rose from 22.7% in 2016 to 23.6% in 2019. Incidence, hospitalization, and mortality all increased with age. Relative to healthy males aged 30-39 years, CAP risk escalated steeply in the [&ge;]80 years cohort (incidence 5-15-fold; hospitalization >3-fold; mortality 11-24-fold) and was further amplified by COPD, CVD, or T2DM, with a lesser effect for T1DM. Conclusions: The results highlight the substantial age- and comorbidity-driven CAP burden in Hungary and support prioritization of preventive strategies including pneumococcal vaccination for older adults and high-risk groups.

Shigella sonnei is a human-adapted enteric pathogen with a very low infectious dose and increasing antimicrobial resistance. In high-income settings, transmission is multimodal including sporadic cases/outbreaks associated with food and travel, as well as sustained transmission among sexual networks of men who have sex with men (MSM). Whole-genome sequencing (WGS) now underpins national shigellosis surveillance in the United Kingdom. Hence, consistent, communicable genotyping is essential for case linkage and trend detection across heterogeneous transmission modes. Here, we evaluate the performance of WGS genotyping approaches for granulating outbreaks of S. sonnei shigellosis, particularly considering differential performance in dense sexual transmission where highly clonal MSM-associated sublineages pose distinct clustering challenges. Specifically, we compare performance of the current practice approach (10 SNP-distance clustering based on SNP address [t10]), allele-based methods (EnteroBase cgMLST/HierCC [HC5]), a pathogen-specific genotyping scheme (sonneityper), and two k-mer based approaches (PopPUNK and KPop), on a bona fide UK surveillance dataset (n = 3,639 isolates from between 2016 and 2022), and stratify analyses by demographics (i.e. presumptive MSM [pMSM] versus non-pMSM). Comparison metrics indicate that t10 clustering method groups data more broadly than HC5, and k-mer-based methods may capture genetic variation independent from SNP or allele-based approaches. Clusters derived from k-mer-based methods offer similar resolution to HC5 and reflect different demographics, but had unconvincing utility for this pathogen. These findings suggest a transmission context-aware surveillance workflow for shigellosis in high income settings: anchor routine communication on a portable allele-based backbone and augment with more granular, complementary methods (e.g., k-mer-based micro-partitioning or phylogenetic analysis) in comparatively low genomic-density regions of population structure (e.g., pMSM transmission lineages) to stabilise clusters and reduce artefactual chaining.

ObjectivesListeria monocytogenes is an opportunistic pathogen, associated with foodborne infections that disproportionately affect newborns, elderly and immunocompromised patients. L. monocytogenes can be classified on the antigenic and related structural variation of cell-associated wall teichoic acid (WTA) molecules through conventional serotyping techniques. The WTA structure of serovars (SV) 1/2, 1/2*, 3 and 7 consists of a linear poly-ribitolphosphate (RboP) polymer either with or without decoration with rhamnose (Rha) and/or N-acetylglucosamine (GlcNAc). Of these four SVs, SV1/2 (WTA with GlcNAc and Rha) causes [~] 99% of all listeriosis cases. However, conventional serotyping cannot accurately discriminate between these four SVs, particularly SVs1/2* (WTA with Rha). MethodsHere we applied two identified monoclonal antibodies (mAb), with specificity for the RboP backbone or GlcNAc modification to develop a discriminatory serotyping scheme for SV1/2, 1/2*, 3 and 7. Isogenic mutants for the different SVs were created in L. monocytogenes SV1/2 strain EGD-e. The typing scheme was then adapted to an immnoblot assay and applied to a collection of 317 previously classified listeriosis isolates from the Netherlands Reference Laboratory for Bacterial Meningitis. ResultsBinding of the RboP-specific mAb was limited to EGD-e wild type (SV1/2), but increased significantly for isogenic EGD-e mutants representing SV1/2*, 3 and 7. In contrast, the GlcNAc-specific mAb only recognized EGD-e mutants representing SVs 1/2 and 3. The combined staining profiles of the two mAbs allowed accurate discrimination of the four SVs as verified on clinical isolates. Applying this typing scheme to 317 listeriosis isolates previously typed as SV1/2, we confirmed SV designation in >90% of isolates, but also identified SV1/2* (5.4%), SV3 (0.6%) and SV7 (0.3%) isolates. SV1/2* isolates were also identified among meningitis patients. ConclusionThe increased discriminatory capacity of L. monocytogenes serotyping provides a more detailed insight of the epidemiological landscape and the critical factors for L. monocytogenes infections.

Estimates of population prevalence and genetic diversity of bloodborne viruses in healthy humans are essential to support population-scale monitoring for transfusion transmission risk. In the UK and globally, blood donations are routinely screened for a limited number of high-consequence pathogens, but the full composition of the plasma virome remains to be characterised. Using a novel quantitative targeted metagenomics sequencing approach, we analysed previously unscreened plasma donations collected by NHS Blood and Transplant in England for all major pathogenic and known commensal human bloodborne viruses, and quantified their viral burden. Here we show that in a representative sample of 5,064 UK blood donors in pools of 24 collected over a one-month period, the virome was dominated by a small number of largely persistent species, representing ~11% (12/106) of previously identified human bloodborne viruses. Anelloviruses (TTV, TTMV and TTMDV) was detected in 89.0% of pools, albeit at low read count inconsistent with measured anellovirus viral loads. In contrast, human pegivirus type 1 (HPgV-1), had estimated population prevalence of 3.7% (95% CI 3.0-4.4%), with high read count and complete genome recovery in around one half of positive pools, consistent with high titre in plasma. Estimated prevalences for less common detections included one species of gemykibovirus (0.12%), hepatitis C virus (genotype 1a, 0.04%) and various polyomaviruses and herpesviruses between 0.04% (parvovirus 4, BK polyomavirus) and 0.41% (human herpesvirus 6). Phylogenetic analyses revealed mixed TTV, TTMV and TTMDV populations and almost exclusively genotype 2 HPgV-1, consistent with known genotype distributions in Europe. Our results provide a baseline for describing the healthy plasma virome in UK blood donors.