Eurosurveillance

Background Ecological surveillance indicates (regional) establishment of West Nile virus (WNV) and Usutu virus (USUV) in the Netherlands. However, the incidence of human infections remains unknown. Methods We identified WNV and USUV infections in the Netherlands in 2020-2023, using a longitudinal, nationwide population-based cohort, applying a two-tiered serology approach based on protein micro-array and virus neutralization. IgG data were used to estimate overall seroprevalence and infection incidence, and to study antibody longevity. Study set-up enabled tracking of the period of seroconversion and linking of self-reported travel history. The analyses took account of the survey design and weights were incorporated to match the Dutch population distribution following census data. Findings Among 4290 participants, we identified 113 probable WNV and/or USUV cases, including 55 seroconversions. Thirty-six cases were confirmed by antibody neutralization, of which 12 seroconverted. Six confirmed seroconverters were identified as autochthonous infections. The overall weighted seroprevalence was estimated at 0.54% (0.21-0.87%) for WNV and 0.25% (0.09-0.40%) for USUV. The weighted incidence for autochthonous WNV and USUV infection was estimated as respectively 0.06% (95% CI 0-0.12%) and 0.04% (95% CI 0-0.09%). Interpretation The estimated infection incidence and seroprevalence of WNV and USUV indicate a substantial underdiagnosis of clinical cases in the Netherlands in 2020-2023. These observations highlight the need for increased awareness among physicians to identify cases and the need for continued paired syndromic-laboratory surveillance for these viruses.

Objectives: To evaluate the epidemiological evolution of unique pneumococcal serotypes covered by either PCV20 or PCV21, common serotypes by both vaccines and non-vaccine serotypes in adults. Methods: We characterized all national IPD clinical isolates from January 2009 to June 2026. Results: The highest burden of IPD was caused by serotypes shared between PCV20 and PCV21 with serotypes 3 and 8 the most prevalent in adults of all ages. During the pre-pandemic period, IPD caused by unique-PCV20 serotypes declined probably due to herd protection by paediatric vaccination with PCVs. In contrast, unique-PCV21 serotypes increased in incidence accounting for more cases than unique-PCV20 serotypes. However, after the COVID-19 pandemic, a different pattern was observed with unique-PCV20 serotypes increasing in incidence due a marked rise in IPD caused by serotypes 4 and 14 that has progressively reduced the gap in disease coverage. In adults aged 18-64 years, the fraction of disease that could be prevented with PCV20/PCV21 changed from 5% in favour of PCV21 (years 2022/2023) to 15% in favour of PCV20 (year 2026) whereas in adults [≥]65 years the vaccine contribution declined from 20% in favour of PCV21 (year 2022) to 8% in 2026. Conclusions: IPD trends in adults have changed after the COVID-19 pandemic, especially in recent years. Our study emphasizes the rapid re-emergence of infections caused by traditional PCV7 serotypes especially serotypes 4 and 14 and reinforce the idea that the use of broader PCVs must be accompanied by an increase in the uptake rates in adults of all ages.

Background: Following the global resurgence of cholera in 2022, 51 cholera cases were reported by European countries. We previously characterised 49 Vibrio cholerae O1 isolates from these cases using whole genome sequencing. In 2023 and 2024, 59 additional cholera cases were reported by 11 European countries. Aim: We aimed to confirm that V. cholerae O1 isolates associated with cholera cases reported in Europe in 2023-2024 belonged to the epidemic seventh pandemic El Tor (7PET) lineage rather than to non-epidemic V. cholerae O1 lineages, and to characterise their virulence, antimicrobial resistance (AMR) determinants and phylogenetic relationships. Methods: Fifty V. cholerae O1 isolates were available for whole genome sequencing, of which 49 yielded genomes of sufficient quality for analysis. Genomes were analysed together with more than 1,500 publicly available 7PET genomes to place the European isolates into a global phylogenetic context. Results: All 49 genomes belonged to the 7PET lineage and Wave 3. Four sub-lineages were identified: BD1.2 (2/49), AFR12 (6/49), AFR13 (8/49) and Pre-AFR15 (33/49). The predominance of Pre-AFR15 confirms its continued contribution to the ongoing global cholera resurgence. In contrast to our 2022 survey, eight highly drug-resistant AFR13 isolates were detected, documenting the international spread of this highly drug-resistant clone resistant to multiple first-line antimicrobial agents. Conclusion: Whole genome sequencing should be routinely used by reference laboratories to distinguish epidemic 7PET from non-epidemic V. cholerae O1 lineages and to monitor the emergence and international spread of AMR clones. Continued collaborative genomic surveillance of travel-associated cholera cases can provide early insights into the emergence, international spread and antimicrobial resistance of 7PET sub-lineages.

The 2026 multinational Andes virus (ANDV) outbreak linked to cruise-ship travel from Argentina triggered extensive contact tracing and quarantine. Whether intervention on this scale was necessary or sufficient depends on the risk of onward transmission, which can be difficult to estimate early in an outbreak. Using transmission-pair data from the 2018--2019 outbreak in Epuyen, Argentina, and a mechanistic model linking viral growth, symptom onset, and transmission, we estimated that 42.4% (95% CrI: 18.2-69.7\%) of transmission occurs before symptom onset and that the median incubation period is 18.5 days (95% CrI: 16.5-19.5). We simulated outbreaks under an Epuyen-calibrated estimate (R = 2.12, k = 0.316) and a pooled estimate from 15 prior ANDV investigations (R = 0.24, k = 0.39), with intervention beginning after two generations, as in the cruise-associated event. Under the higher-transmission scenario, missing 10% of exposed individuals or downstream contacts resulted in a 29.9% probability of continued spread and a 20.6% probability that at least 5,000 ultimately uninfected people would be quarantined. Under lower transmission, continued spread stayed below 8%. However, the risk of onward transmission could not be estimated precisely from the first several detected cases. These findings therefore support rapid, comprehensive contact tracing and quarantine after large international exposure events despite substantial costs.

BackgroundHuman Mastadenovirus B (HAdV-B) causes ocular and respiratory infections and is capable of causing outbreaks in healthcare settings. HAdV-B114, a recombinant genotype only formally recognised in 2023, has been reported predominantly from Germany, the USA, China and Japan; genomic data from UK clinical settings remain limited. This study analysed 68 HAdV-B whole genomes from ocular and respiratory-associated samples collected at a Nottingham hospital across the pre- and post-COVID-19 restriction periods (2017-2023). MethodsClinical samples typed positive for HAdV-B by partial hexon Sanger sequencing were selected for whole-genome sequencing using a novel overlapping PCR amplicon strategy, sequenced on the Oxford Nanopore Technologies PromethION platform. Phylogenetic and pairwise difference analyses were used to characterise genotype composition and genomic relatedness. SimPlot and amino-acid comparison characterised divergence between sub-lineages. ResultsWhole-genome phylogenetics confirmed that two species B genotypes were detected in Nottingham University Hospitals between 2017-23: HAdV-B114 (n=56) and HAdV-B7 (n=12). HAdV-B114 was detected before and after COVID-19 restrictions, with an increase in 2022-2023, consistent with post-restriction expansion of a pre-existing lineage. Pairwise difference analysis identified 24 genomically identical B114 sequences; associated metadata argued against a single nosocomial transmission chain interpretation, with the pattern more consistent with repeated detection of a widely circulating community strain, with the possibility of localised onward transmission. Within the B114 clade, multiple monophyletic groups were identified by whole-genome phylogenetics. ConclusionsThis study adds whole-genome resolution to the existing UK HAdV-B114 data, demonstrates the utility of WGS for clinical adenovirus surveillance and shows the benefits of combining epidemiological data with genomic analysis.

Background: Optimising sampling frames for genomic surveillance of E. coli and Klebsiella may support interventions to mitigate bloodstream infections (BSIs), but approaches to estimating sample size and how these relate to bacterial population diversity at multiple genetic levels (strain/plasmid/antimicrobial resistance genes [ARGs]) are lacking. Methods: Using systematically collected, regionally-stratified, whole genome sequencing data from a 6-month genomic survey of English E. coli/Klebsiella BSI isolates (n=1,939; NEKSUS), we used Bayesian approaches to estimate the sample sizes required to capture genetic diversity at strain- (MLST, fastBAPS clusters), plasmid- and ARG-levels, using two diversity measures: 'coverage' (i.e. proportion of the bacterial population/plasmids/ARGs represented by features observed in the sample), and the number/proportion of unique features observed at varying surveillance sample sizes. Our method is available as a user-friendly R Shiny application, EpiSENTRY (https://01a0c3dd-90d2-e597-58a5-51391a468387.share.connect.posit.cloud/). Findings: Randomly sampling 1,400 E. coli/Klebsiella BSI isolates each achieved [≥]80% coverage of bacterial lineages and ARGs (i.e. capture features constituting [≥]80% of the population) at 95% certainty, but captured lower proportions of unique features (28% MLSTs, 59% fastBAPS clusters, 19% plasmid subcommunities, and 57% ARGs for E. coli; 49%, 87%, 50% and 83% for Klebsiella, respectively). Sample sizes required for 80% coverage of E. coli plasmid populations were higher than MLSTs (1,928 [95% CrI: 1,837-2,025] vs 1,351 [1,230-1,472]), while for Klebsiella, estimates were lower for plasmids (1,115 [1,052-1,181] vs 1,422 [1,331-1,515] for MLSTs). Lower sample sizes adequately captured 80% coverage of fastBAPS clusters and ARGs (649 [575-727] and 27 [23-30], respectively, for E. coli; 113 [84-145] and 83 [72-96] for Klebsiella), due to feature-specific frequency distributions. Klebsiella BSIs were more diverse than E. coli, with sampling 10.9% vs 3.2% of total annual BSIs in England needed to reach 80% MLST coverage. Plasmid populations and Klebsiella MLSTs were region-specific, emphasising the need for regionally-representative sampling. Interpretation: Bayesian analysis facilitates estimates of context-specific genomic surveillance sample sizes. Cost-effective targets for coverage require further optimisation.

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.

To deal with the COVID-19 pandemic, Denmark implemented an aggressive program aimed at controlling the pandemic which included both testing and contact tracing programs. The large amount of data collected in Denmark on the pandemic and its integrated nature made it possible to investigate the effectiveness of the testing and contact tracing effort. The results of that investigation and a discussion of the effectiveness and limitations of the different control efforts are reported herein, as are lessons learned concerning possible improvements for the future. The analysis is limited to the period from the start of the COVID-19 pandemic in Denmark (late Feb. 2020) into May 2021, at which time the impact of vaccination intervention was already playing a role with ~25% of the Danish population at least partially vaccinated. From the available data sets we estimate the national Infection Detection Efficiency (IDE) starting around July 1, 2020, the time at which the national infection detection program started to be implemented in a more robust form. The results rely on daily COVID-19 hospital admissions, PCR test results, and anti-body prevalence values for the Danish population. We find that for the long-term average, the combined Danish national testing and contact tracing program identified on average about 55 to 60% of the infected individuals during the period from Sept. 1, 2020, into early May 2021. However, higher infection detection efficiencies were achieved in localized areas for short time intervals. Our investigations further indicate that the Danish testing and contact tracing program, which was among the most ambitious in the world, could have had a better balance between voluntary probing on the one hand and focused contact tracing and targeted testing on the other hand. As typically implemented, it proved to be largely ineffective in controlling the pandemic. However, in at least one case when it was implemented in an enhanced and focused mode, it was able to bring a large local outbreak that dominated the country's cases under control. We have compiled a list of lessons learned regarding the use of contact tracing procedures to control potential future pandemics before vaccinations become available.

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: 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.

Objectives- Among clinical methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) strains, we sought to determine the prevalence of {beta}-lactam-{beta}-lactamase inhibitor (BLBLI) susceptibility, and its association with oxacillin susceptibility, genotypic factors, and patient characteristics. Methods- Clinical MRSA BSI strains were tested for susceptibility to penicillin-clavulanate by Etest (n=117, 36% of the dataset) and to oxacillin by disk diffusion assay (n=328, 100%). Penicillin-clavulanate susceptibility was defined as MIC [&le;]2mg/L and oxacillin disk susceptibility as an inhibition zone > 6mm. All strains were whole-genome sequenced, and alleles of mecA annotated. The sensitivity and specificity of the oxacillin disk to predict penicillin-clavulanate 'susceptibility' were assessed. Clinical and genomic associations with BLBLI 'susceptibility' were assessed by calculating odds-ratios (OR). Results -We found 73/117 (62%) and 205/328 (62%) strains to be 'susceptible' to penicillin-clavulanate and oxacillin disk, respectively. Oxacillin disk susceptibility and penicillin-clavulanate susceptibility were highly correlated (sensitivity 97.3% and specificity 95.5%). We therefore used oxacillin disk susceptibility as a proxy for penicillin-clavulanate susceptibility. Comparative genomics of the mecA gene uncovered 8 alleles. The oxacillin disk 'susceptible' phenotype was associated with specific mecA alleles, community-associated MRSA sequence-types (OR 72.8, 95%CI 35.4-162), community acquisition of infection (OR 2.09, 95% CI 1.03-4.27), lower Charlson Comorbidity Index (OR 0.90, 95% CI 0.82-0.98) and SOFA (sequential organ failure assessment) scores at presentation (OR 0.88, 95% CI 0.79-0.98). Conclusion - BLBLI 'susceptibility' is common among MRSA strains and is strongly associated with the strain genotype. Infections caused by BLBLI 'susceptible' strains are associated with specific patients' characteristics, namely younger age, fewer comorbidities, acquisition in the community and milder presentations.

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.

Bordetella pertussis is the main aetiological agent of pertussis (whooping cough), with a global resurgence of cases reported in 2024. As current pertussis diagnostics are predominantly based on molecular methods, cultured isolates are increasingly scarce, limiting traditional culture-based surveillance. To address these challenges, this study evaluated culture-independent approaches for B. pertussis surveillance and their feasibility for implementation in public health laboratory settings in Victoria, Australia. The Microbiological Diagnostic Unit Public Health Laboratory received 356 nasopharyngeal clinical specimens that were PCR-positive for Bordetella spp. from diagnostic laboratories for further characterisation during the 2024-2025 epidemic period. Culture-based approaches yielded only five B. pertussis isolates, largely due to limitations associated with specimen transport media. Four culture-independent approaches were evaluated for B. pertussis characterisation: real-time PCR assay for high-resolution Bordetella spp. differentiation (n=356), multiplex PCR amplicon sequencing assay for lineage typing (n=38), in-house laboratory developed test implemented on Panther Fusion(R) System for macrolide resistance screening (n=92) and shotgun metagenomic sequencing (n=5). The dataset was dominated by B. pertussis (330/356; 92.7%) with most strains harbouring ptxP3 (35/38; 92.1%) allele and the macrolide resistance rate was reported as 4.3% (4/92). Shotgun metagenomics was able to detect B. pertussis directly from clinical samples, but the genomic recovery was limited. Evaluation of operational performance and workflow integration highlighted method-specific strengths and limitations, informing suitability for implementation in public health laboratories. This study demonstrates the potential to integrate culture-independent approaches into public health laboratory settings to strengthen B. pertussis surveillance and inform feasible workflow design amid limited culture availability.

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.

Macrolides remain the first-line antimicrobial treatment for pertussis, primarily caused by Bordetella pertussis. Emergence of macrolide-resistant B. pertussis in Australia and globally presents a growing concern for clinical management. As molecular diagnosis predominates for pertussis, limited numbers of cultures are available for antimicrobial susceptibility testing. The A2037G mutation in the 23S rRNA gene is most commonly associated with macrolide resistance in B. pertussis, yet no commercial molecular assay is available for its detection. In this study, we adapted and validated a previously published real-time PCR assay as a laboratory developed test (LDT) on the Panther Fusion(R) system using Open Access functionality to detect the macrolide resistance-associated mutation in B. pertussis from culture isolates and clinical specimens. Total turnaround time was ~2.5 h for the first result and 2-3 min for subsequent results in the same batch, with an estimated cost of AUD 18 per sample, excluding labour. A total of 30 samples were included in the validation panel to assess assay performance. All isolates and clinical specimens in the validation panel produced results concordant with the expected mutation status, demonstrating 100% accuracy, sensitivity and specificity. The assay demonstrated a limit of detection of 1.5 x 103 CFU/mL (22 CFU/reaction). This Panther Fusion(R) LDT provides a rapid and fully automated approach for molecular detection of the targeted mutation associated with macrolide resistance in B. pertussis. Its integration into routine molecular workflows as a reflex test following identification of B. pertussis may facilitate timely identification of resistant infections.

Background: Both over- and under-antibiotic use pose major global health challenges, yet there is no consensus on how to quantify deviations from optimal prescribing or set evidence-based targets. We developed a benchmarking tool for inpatient antibiotic use and evaluated its application in 10 countries. Methods: We developed decision-tree models to estimate expected empiric antibiotic use for 11 indications, based on the WHO AWaRe book for two age groups: 28 days to 12 years and >12 years. We parameterised the models using country-specific antimicrobial resistance estimates in the 10 countries and cross-sectional Global Point Prevalence Survey (Global-PPS) case-mix data from 2021 for 10 countries and from 2015-2022 in a subset of five countries. We then compared estimated expected antibiotic use with observed empiric use (from Global-PPS) in defined daily doses for adults and days of therapy for children, across indications and AWaRe categories. Findings: In 2021, among patients aged >12 years, in all countries but one, observed empiric Access antibiotic use, as a proportion of total antibiotic use, was lower than expected and empiric Watch antibiotic use was higher than expected. Similar patterns were observed in all countries but one in patients aged 28 days to 12 years. The magnitude of discrepancies between expected and observed Access and Watch antibiotic use varied across indications and countries. The median observed-to-expected ratios of usage across countries ranged from 0.3-0.8 for Access antibiotics, and 0.7-5.3 for Watch antibiotics in patients aged >12 years in 2021. Temporal trends from repeated surveys from 2015 to 2022 showed little change in observed-to-expected ratios for Access and Watch antibiotics. Interpretation: This benchmarking tool uses Global-PPS data to quantify differences between observed antibiotic use and WHO AWaRe recommendations. Our tool can be adaptable to local guidelines, provides policy-relevant estimates of expected antibiotic use to support monitoring, procurement planning, and targeted stewardship intervention.

Patient movement within and between hospitals creates a complex hospital network that facilitates the spread of antimicrobial-resistant bacteria and contributes to healthcare-associated infections. Yet most national-scale studies infer spread from aggregated hospital-to-hospital patient sharing, leaving patient-to-patient contact pathways and the role of routine patient mobility in shaping colonization risk poorly characterized. Using Frances 2023-2024 national hospital-discharge data, we reconstructed a temporal patient-based network of 10.4 million patients across 1,408 acute-care hospitals, comprising 326.6 million overnight ward co-location interactions. We simulated colonization over 365 days on the observed day-by-day temporal network using a stochastic susceptible-colonized-susceptible model, with a mean colonization duration of 180 days. We used national carbapenemase-producing Enterobacterales (CPE) surveillance data to calibrate differences in transmission risk across clinical settings. Across 2,000 simulations initiated on randomly selected dates in 2023, we calculated patient-level colonization probabilities and summarized risk across patients residential areas, wards, and hospitals. We further assessed hospital-level consistency between simulated risk and recorded CPE occurrence. Simulated risk was highly heterogeneous across patients and care settings. When mapped by place of residence, hospital-associated colonization risk showed strong spatial clustering in both urban and rural areas. Multivariable regression analyses identified patient- and hospital-level characteristics associated with heterogeneity in simulated colonization risk. Sensitivity analyses varying initial seeding and colonization duration showed that relative risk patterns remained highly stable. This nationwide framework shows how patient mobility and ward co-location patterns can reveal patterns of hospital-associated colonization risk and could support pathogen-specific surveillance and intervention evaluation. Significance StatementAsymptomatic carriage allows antimicrobial-resistant bacteria to spread through healthcare systems while colonized patients may remain unrecognized in the absence of active screening. We reconstructed a nationwide, time-resolved network of ward co-location among hospitalized patients in France. We accounted for differences in transmission risk across clinical settings using national surveillance data on carbapenemase-producing Enterobacterales. Using a transmission model, we characterized colonization-risk patterns and identified patient- and hospital-level features associated with variation in risk. This framework offers health authorities a way to examine where patient movement and hospital care may contribute to concentrations of colonization risk, although pathogen- and context-specific adaptation and evaluation remain necessary to guide surveillance or interventions. Author contributionsS.B., L.C., L.T., A.K., T.D., V.C., and P.C. designed research; S.B. and P.C. performed research; S.B. and P.C. analyzed data; S.B. and P.C. wrote the paper; all authors reviewed and edited the final manuscript.

Background Evidence on {beta}-thalassaemia carrier prevalence is fragmented across heterogeneous surveys and national summaries, leaving within-country variation and geographic concentration of carriers poorly resolved. This study characterises {beta}-thalassaemia carrier prevalence and carrier populations at high spatial resolution and identifies where additional data would most improve geographic coverage. Methods Using carrier-prevalence records curated through ITHANET, a global haemoglobinopathy resource, Bayesian geostatistical modelling generated high-resolution predictions across 25 countries. Predictions were integrated with population data to estimate national and subnational carrier numbers. Prediction uncertainty and gaps in existing survey coverage informed prioritisation of healthcare sites for additional surveys. Findings Predicted prevalence varied markedly within countries, and highest-prevalence areas did not coincide with the largest carrier populations. National mean prevalence was highest in Cyprus (12.99%), whereas India, China, and Pakistan had the largest carrier populations, together accounting for 81.21% of estimated carriers. Random five-fold cross-validation favoured a model capturing broad geographic patterns and location-specific variation. Predictive performance deteriorated when geographically clustered records were withheld together, indicating reduced reliability across larger gaps in geographic sampling and the need for additional data from poorly characterised areas. Survey prioritisation identified 183 healthcare sites across 17 countries for future carrier-prevalence surveys. Interpretation By distinguishing areas of high carrier prevalence, large carrier populations, and evidence gaps, this updatable framework provides a subnational evidence base to inform {beta}-thalassaemia prevention planning and guide future data collection, screening, and genetic counselling.

Introduction: This study compared the health and economic impact of the 21-valent pneumococcal conjugate vaccine (aPCV21) vs the 20-valent pneumococcal conjugate vaccine (PCV20) on invasive pneumococcal disease (IPD) and post-meningitis sequelae (PMS) among adults aged 65 years and older in the United Kingdom (UK). Methods: A published Markov model was used to simulate a single-cohort of vaccine-naive adults who became eligible for age-based vaccination at age 65 years, with uptake occurring over time. The cohort was followed until a maximum age of 100 years. Model inputs were derived from publicly available national health data and published reports. Outcomes were discounted at 3.5% annually, and costs were adjusted to the 2024 Great Britain Pound ({pound}). Additional analyses explored the impact of changing the age-based recommendation from 65 years to 75 years. Scenarios involving instantaneous vaccine uptake rates were included as part of the sensitivity analyses. A deterministic sensitivity analysis was performed on the incremental direct medical costs between vaccinating with aPCV21 vs PCV20 under the age-based recommendation of 65 years. Results: Using an age-based recommendation of 65 years, aPCV21 led to fewer cases, deaths, and costs than PCV20. Compared with PCV20, aPCV21 averted an additional 138 IPD cases, 1 PMS case, and 22 IPD deaths, saving {pound}1.2 million in direct medical costs. Raising the age-based recommendation from 65 to 75 years and using aPCV21 (or PCV20, respectively), resulted in 120 (92) additional IPD cases, 2 (1) additional PMS case(s), 19 (14) additional IPD death(s), and an extra {pound}1.1 ({pound}0.8) million in direct medical costs. The deterministic sensitivity analysis showed that aPCV21 reduced direct medical costs across all parameter ranges. Conclusions: Compared with PCV20, aPCV21 prevented more IPD cases, IPD deaths, and direct medical costs among older adults in the UK. Changing the age-based recommendation from age 65 to 75 resulted in worse health and economic outcomes. Key words. Pneumococcal infections; pneumococcal vaccines; vaccines, conjugate; serotype; United Kingdom; health costs

Importance Several influenza vaccine products are available for older adults, but evidence combining both their absolute effectiveness and head-to-head comparisons within the same large population remains scarce, limiting product-specific vaccination guidance for this high-risk group. Objective To estimate the relative and absolute effectiveness of influenza vaccines against influenza-related hospitalization and in-hospital mortality among older adults. Design, Setting, and Participants Nationwide cohort study using the French National Health Data System (SNDS), including all adults born in 1958 or earlier, living in metropolitan France, at the start of the 2023-2024 campaign. Relative effectiveness (rVE) was assessed using a landmark design with exposure fixed before epidemic onset. Absolute effectiveness (VE) was assessed using a sequential trial emulation with weekly matching of newly vaccinated individuals to yet unvaccinated controls. Follow-up ran from December 5, 2023 to April 19, 2024. Exposures Vaccination with a high-dose (Efluelda) or one of three standard-dose quadrivalent vaccines (Influvac, Fluarix, Vaxigrip), compared individually or by dosage category, and against no vaccination. Main Outcomes and Measures Hospitalization with a diagnosis of influenza and death during such hospitalization. Effectiveness was estimated as 1 minus the hazard ratio from weighted Cox models, with corresponding numbers needed to vaccinate to prevent one case. Results Among 13.8 million eligible individuals, 5.7 million (41%) were vaccinated at the beginning of follow-up. The high-dose vaccine showed greater rVE than standard-dose vaccines against hospitalization (27% [95%CI, 23 to 31%]) and in-hospital death (27% [95%CI,14 to 38%]). Absolute VE was 39% (95%CI, 38 to 41%) against hospitalization and 45% (95%CI, 40 to 49%) against in-hospital death, and was higher for the high-dose vaccine (50%) than standard-dose vaccines (36%) against hospitalization. This difference was most evident among adults 70 years and older, while overall effectiveness declined with age. Conclusions and Relevance In this study, influenza vaccination conferred moderate protection against severe outcomes in older adults, and high-dose vaccination was associated with significantly greater effectiveness than standard-dose vaccines, particularly among adults 70 years and older. These findings support product-level differentiation in vaccination strategy for this population.