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Human papillomavirus (HPV)-associated high-grade vulvar intraepithelial lesion (HSIL) is a precursor of vulvar squamous cell carcinoma (VSCC). Because of the 8% cancer risk, many vulvar HSIL patients undergo aggressive and mutilating treatments. Characterizing HSIL by their progression risk can help individualize treatment strategies. Accordingly, copy number alterations (CNAs) and DNA methylation have been identified as biomarkers for cancer risk stratification of HSIL. Here, we assessed their potential correlation, and relation to HPV16 (sub)lineages and progression to vulvar cancer. Eighty-two vulvar formalin-fixed paraffin-embedded (FFPE) samples, including controls, HSIL, HSIL adjacent to VSCC and VSCC, with previously determined DNA methylation profiles, were analysed for CNAs using mFAST-SeqS. Genome-wide z-scores were calculated to determine overall aneuploidy (aneuploidy scores), and compared to the methylation levels and status of marker panel ZNF582/SST/miR124-2. For 52 HPV16-positive cases, HPV (sub)lineages were determined by Sanger sequencing. HPV16 lineage A was predominant (86.4%), followed equally by lineages B, C, and D. Frequent chromosomal alterations included chr1pq, chr3q, chr9q gains, and chr2q, chr4q losses. Median aneuploidy scores increased across disease categories, from 0 in controls, to 3 in HSIL, 16 in HSIL adjacent to VSCC and 29 in VSCC. A positive relationship between aneuploidy scores and DNA methylation levels was found (ρ = 0.61, Spearman's rank correlation test). Aneuploidy scores were significantly higher in methylation-positive samples (p < .001). In conclusion, we showed that DNA methylation and CNAs both rise with increasing severity of disease, indicating their prognostic value for cancer risk stratification of HSIL, while no relation to HPV16 (sub)lineages was found., (© 2025 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Symptom-only case definitions are insufficient to discriminate COVID-like illness from acute respiratory infection (ARI) or influenza-like illness (ILI), due to the overlap in case definitions. Our objective was to develop a statistical method that does not rely on case definitions to determine the contribution of influenza virus and SARS-CoV-2 to the ARI burden during periods when both viruses are circulating. Data sources used for testing the approach were weekly ARI syndrome reports from the Infectieradar participatory syndromic surveillance system during the analysis period (the first 25 weeks of 2022, in which SARS-CoV-2 and influenza virus co-circulated in the Netherlands) and data from virologically tested ARI (including ILI) patients who consulted a general practitioner in the same period. Estimation of the proportions of ARI attributable to influenza virus, SARS-CoV-2, or another cause was framed as an inference problem, through which all data sources are combined within a Bayesian framework to infer the weekly numbers of ARI reports attributable to each cause. Posterior distributions for the attribution proportions were obtained using Markov Chain Monte-Carlo methods. Application of the approach to the example data sources indicated that, of the total ARI reports (total of 11,312; weekly mean of 452) during the analysis period, the model attributed 35.4% (95% CrI: 29.2-40.0%) and 27.0% (95% CrI: 19.3-35.2%) to influenza virus and SARS-CoV-2, respectively. The proposed statistical model allows the attribution of respiratory syndrome reports from participatory surveillance to either influenza virus or SARS-CoV-2 infection in periods when both viruses are circulating, but comparability of the participatory surveillance and virologically tested populations is important. Portability for use by other countries with established participatory respiratory surveillance systems is an asset., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 McDonald et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although older people in nursing homes have a larger susceptibility to infectious diseases, the extent to which infectious diseases contribute to their mortality is unknown. Therefore, we quantified the associations between seasonal infectious diseases and all-cause mortality in Dutch nursing homes., Methods: We analyzed time series (January 2009 to December 2021) of the weekly sentinel surveillance of infectious diseases in Dutch nursing homes. A generalized linear model with binomial distribution and identity link was used to associate the proportion of all-cause mortality with the incidence of infections: COVID-19 (2020-2021), gastroenteritis (GE), influenza-like illness (ILI), and lower respiratory tract infections (LRTIs) at 0- to 4-week time-lags (mortality incidence at 0 to 4 weeks after infections incidence)., Results: Over 13 years, 81 nursing homes participated, with 20 to 35 homes each year (mean: 26). A total of 11,555 all-cause deaths occurred over 1,864,667 resident weeks, averaging a mortality incidence of 6.2 per 1000 resident weeks. All 4 tested infectious diseases exhibited a significant association with all-cause mortality in nursing homes (P ≤ .01). Collectively, these infectious diseases were associated with 18.6% (95% CI, 17.8%-19.3%) of all deaths. The association between mortality and ILI was significant in 7 of 12 ILI seasons. Yearly mortality associated with the specific infectious diseases was as follows: LRTI (10.2%; 95% CI, 9.6%-10.8%), ILI (8.2%; 95% CI, 7.5%-8.9%) (over the 7 of 12 significant seasons), COVID-19 (6.5%; 95% CI, 5.4%-7.7%) (over 2019-2021 as there was no previous SARS-CoV-2 circulation), and GE (2.3%; 95% CI, 2.0%-2.5%)., Conclusion and Implications: In nursing homes, the occurrence of seasonal respiratory and gastrointestinal infections is associated with nearly one-fifth of all-cause deaths. Although infection prevention and surveillance may already be performed in some nursing homes, it is vital to implement, and enhance targeted strategies like (hand) hygiene protocols, environmental cleaning practices, reducing droplet and aerosol transmission, and vaccination to effectively address specific infections., Competing Interests: Disclosure H.v.W. declares financial and nonfinancial research support from DaVolterrra and bioMérieux; financial research support from LimmaTech; and consultancy fees from MSD and Sanofi-Pasteur. All payments to the University Medical Centre Utrecht. The other authors declare no conflict of interest., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Alternative data sources for surveillance have gained importance in maintaining coronavirus disease 2019 (COVID-19) situational awareness as nationwide testing has drastically decreased. Therefore, we explored whether rates of sick-leave from work are associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) notification trends and at which lag, to indicate the usefulness of sick-leave data for COVID-19 surveillance., Methods: We explored trends during the COVID-19 epidemic of weekly sick-leave rates and SARS-CoV-2 notification rates from 1 June 2020 to 10 April 2022. Separate time series were inspected visually. Then, Spearman correlation coefficients were calculated at different lag and lead times of zero to four weeks between sick-leave and SARS-CoV-2 notification rates. We distinguished between four SARS-CoV-2 variant periods, two labour sectors and overall, and all-cause sick-leave versus COVID-19-specific sick-leave., Results: The correlation coefficients between weekly all-cause sick-leave and SARS-CoV-2 notification rate at optimal lags were between 0.58 and 0.93, varying by the variant period and sector (overall: 0.83, lag -1; 95% CI [0.76, 0.88]). COVID-19-specific sick-leave correlations were higher than all-cause sick-leave correlations. Correlations were slightly lower in healthcare and education than overall. The highest correlations were mostly at lag -2 and -1 for all-cause sick-leave, meaning that sick-leave preceded SARS-CoV-2 notifications. Correlations were highest mostly at lag zero for COVID-19-specific sick-leave (coinciding with SARS-CoV-2 notifications)., Conclusion: All-cause sick-leave might offer an earlier indication and evolution of trends in SARS-CoV-2 rates, especially when testing is less available. Sick-leave data may complement COVID-19 and other infectious disease surveillance systems as a syndromic data source., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Background: Multidrug-resistant (MDR) bacteria are a growing global threat, especially in healthcare facilities. Faecal microbiota transplantation (FMT) is an effective prevention strategy for recurrences of Clostridioides difficile infections and can also be useful for other microbiota-related diseases., Methods: We study the effect of FMT in patients with multiple recurrent C. difficile infections on colonisation with MDR bacteria and antibiotic resistance genes (ARG) on the short (3 weeks) and long term (1-3 years), combining culture methods and faecal metagenomics., Results: Based on MDR culture (n = 87 patients), we notice a decrease of 11.5% in the colonisation rate of MDR bacteria after FMT (20/87 before FMT = 23%, 10/87 3 weeks after FMT). Metagenomic sequencing of patient stool samples (n = 63) shows a reduction in relative abundances of ARGs in faeces, while the number of different resistance genes in patients remained higher compared to stools of their corresponding healthy donors (n = 11). Furthermore, plasmid predictions in metagenomic data indicate that patients harboured increased levels of resistance plasmids, which appear unaffected by FMT. In the long term (n = 22 patients), the recipients' resistomes are still donor-like, suggesting the effect of FMT may last for years., Conclusions: Taken together, we hypothesise that FMT restores the gut microbiota to a composition that is closer to the composition of healthy donors, and potential pathogens are either lost or decreased to very low abundances. This process, however, does not end in the days following FMT. It may take months for the gut microbiome to re-establish a balanced state. Even though a reservoir of resistance genes remains, a notable part of which on plasmids, FMT decreases the total load of resistance genes., (© 2024. The Author(s).)

Pneumococcal carriage studies have suggested that pneumococcal colonization in adults is largely limited to the oral cavity and oropharynx. In this study, we used total abundance-based β-diversity (dissimilarity) and β-diversity components to characterize age-related differences in pneumococcal serotype composition of respiratory samples. quantitative PCR (qPCR) was applied to detect pneumococcal serotypes in nasopharyngeal samples collected from 946 toddlers and 602 adults, saliva samples collected from a subset of 653 toddlers, and saliva and oropharyngeal samples collected from a subset of 318 adults. Bacterial culture rates from nasopharyngeal samples were used to characterize age-related differences in rates of colonizing bacteria. Dissimilarity in pneumococcal serotype composition was low among saliva and nasopharyngeal samples from children. In contrast, respiratory samples from adults exhibited high serotype dissimilarity, which predominantly consisted of abundance gradients and was associated with reduced nasopharyngeal colonization. Age-related serotype dissimilarity was high among nasopharyngeal samples and relatively low for saliva samples. Reduced nasopharyngeal colonization by pneumococcal serotypes coincided with significantly reduced Moraxella catarrhalis and Haemophilus influenzae and increased Staphylococcus aureus nasopharyngeal colonization rates among adults. Findings from this study suggest that within-host environmental conditions, utilized in the upper airways by pneumococcus and other bacteria, undergo age-related changes. It may result in a host-driven ecological succession of bacterial species colonizing the nasopharynx and lead to competitive exclusion of pneumococcus from the nasopharynx but not from the oral habitat. This explains the poor performance of nasopharyngeal samples for pneumococcal carriage among adults and indicates that in adults saliva more accurately represents the epidemiology of pneumococcal carriage than nasopharyngeal samples., Competing Interests: UKHSA provides vaccine manufacturers (GSK, Pfizer, and Sanofi) with postmarketing surveillance reports on pneumococcal infection which the companies are required to submit to the UK licensing authority in compliance with their Risk Management Strategy. A cost recovery charge is made for these reports. UKHSA has received unrestricted research grants from Pfizer to participate in pneumococcal surveillance projects. K.T. received funds for an unrestricted research grant from GlaxoSmithKline Biologicals SA, consultation fees, fees for participation in advisory boards, speaking fees, and funds for unrestricted research grants from Pfizer, funds for an unrestricted research grant, and fees for participating in advisory boards from Merck Sharp & Dohme, all paid directly to his home institution. Except for the funds from GlaxoSmithKline Biologicals SA, none was received in relation to the work reported here. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) [2024]. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background: We describe how rates of two frequently occurring notifiable diseases-diphtheria and scarlet fever-varied between regions of The Netherlands in the early twentieth century, and identify potential factors underlying this variation., Methods: Digitized weekly mandatory notification data for 1905-1925, municipality level, were aggregated into 27 'spatial units' defined by unique combinations of province and population density category (high: more than 4500; mid : 1250-4500; low: less than 1250 inhabitants km - ). Generalized additive regression models were fitted to estimate the associations between notification rates and population density, infant mortality rate and household income, while adjusting for temporal trends per spatial unit.2 ). Generalized additive regression models were fitted to estimate the associations between notification rates and population density, infant mortality rate and household income, while adjusting for temporal trends per spatial unit., Results: Annual per capita notification rates for both diphtheria and scarlet fever tended to rise from the beginning of the period 1905-1925 until peaking around 1918/1919. Adjusted diphtheria notification rates were higher for high- and mid- compared with low-density municipalities (by 71.6 cases per 100 000, 95% confidence interval (CI) : 52.7-90.5; 39.0/100 k, 95% CI : 24.7-53.3, respectively). Scarlet fever showed similar associations with population density (35.7 cases per 100 000, 95% CI : 9.4-62.0; 21.4/100 k, 95% CI: 1.5-41.3)., Conclusions: There was considerable spatial variation in notification rates for both diseases in early twentieth century Netherlands, which could partly be explained by factors capturing variation in living conditions and socio-economic circumstances. These findings aid understanding of contemporary respiratory infection transmission., Competing Interests: All authors declare that they have no competing interests., (© 2023 The Authors.)

Background Neisseria meningitidis is a commensal bacterium which can cause invasive disease. Colonisation studies are important to guide vaccination strategies.AimThe study's aim was to determine the prevalence of meningococcal colonisation, duration of carriage and distribution of genogroups in Iceland.MethodsWe collected samples from 1 to 6-year-old children, 15-16-year-old adolescents and 18-20-year-old young adults. Carriers were sampled at regular intervals until the first negative swab. Conventional culture methods and qPCR were applied to detect meningococci and determine the genogroup. Whole genome sequencing was done on groupable meningococci.ResultsNo meningococci were detected among 460 children, while one of 197 (0.5%) adolescents and 34 of 525 young adults (6.5 %) carried meningococci. Non-groupable meningococci were most common (62/77 isolates from 26/35 carriers), followed by genogroup B (MenB) (12/77 isolates from 6/35 carriers). Genogroup Y was detected in two individuals and genogroup W in one. None carried genogroup C (MenC). The longest duration of carriage was at least 21 months. Serial samples from persistent carriers were closely related in WGS.ConclusionsCarriage of pathogenic meningococci is rare in young Icelanders. Non-groupable meningococci were the most common colonising meningococci in Iceland, followed by MenB. No MenC were found. Whole genome sequencing suggests prolonged carriage of the same strains in persistent carriers.

The gut microbiome of humans and animals acts as a reservoir of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC). Dogs are known for having a high prevalence of ESBL-EC in their gut microbiota, although their ESBL-EC carrier status often shifts over time. We hypothesized that the gut microbiome composition of dogs is implicated in ESBL-EC colonization status. Therefore, we assessed whether ESBL-EC carriage in dogs is associated with changes in the gut microbiome and resistome. Fecal samples were collected longitudinally from 57 companion dogs in the Netherlands every 2 weeks for a total of 6 weeks ( n  = 4 samples/dog). Carriage of ESBL-EC was determined through selective culturing and PCR and in line with previous studies, we observed a high prevalence of ESBL-EC carriage in dogs. Using 16s rRNA gene profiling we found significant associations between detected ESBL-EC carriage and an increased abundance of Clostridium sensu stricto 1 , Enterococcus , Lactococcus , and the shared genera of Escherichia -Shigella in the dog microbiome. A resistome capture sequencing approach (ResCap) furthermore, revealed associations between detected ESBL-EC carriage and the increased abundance of the antimicrobial resistance genes: cmlA , dfrA , dhfR , floR , and sul3 . In summary, our study showed that ESBL-EC carriage is associated with a distinct microbiome and resistome composition. IMPORTANCE The gut microbiome of humans and animals is an important source of multidrug resistant pathogens, including beta-lactamase-producing Escherichia coli (ESBL-EC). In this study, we assessed if the carriage of ESBL-EC in dogs was associated with changes in gut composition of bacteria and antimicrobial resistant genes (ARGs). Therefore, stool samples from 57 dogs were collected every 2 weeks for a total of 6 weeks. Sixty eight percent of the dogs carried ESBL-EC during at least one of the time points analyzed. By investigating the gut microbiome and resistome composition, we observed specific changes at time points when dogs were colonized with ESBL-EC compared to time points whenESBL-EC were not detected. In conclusion, our study highlights the importance to study the microbial diversity in companion animals, as gut colonization of particular antimicrobial resistant bacteria might be an indication of a changed microbial composition that is associated with the selection of particular ARGs., Competing Interests: The authors declare no conflict of interest.

In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands ( n  = 61) and Spain ( n  = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes ( ureAD ). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages- ybt  9, ybt  10, ybt  13, ybt  14, ybt  16, ybt  17, and ybt  27-which were chromosomally embedded in seven integrative conjugative elements (ICE Kp ): ICE Kp3 , ICE Kp4 , ICE Kp2 , ICE Kp5 , ICE Kp12 , ICE Kp10 , and ICE Kp22 , respectively. Multidrug-resistant lineages-ST11, ST101, and ST405-were associated with ybt  10/ICE Kp4 , ybt  9/ICE Kp3 , and ybt  27/ICE Kp22 , respectively. The fimbrial adhesin kpi operon ( kpiABCDEFG ) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC , which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICE Kp10 ). In this study, the integrative conjugative element, ICE Kp , was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections., Competing Interests: The authors declare a conflict of interest. J.W.A.R. was employed by IDbyDNA and is currently consulting for ARES-genetics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Carriage of Neisseria meningitidisis an accepted endpoint in monitoring meningococcal vaccine effects. We applied molecular methods to assess the impact of menACWY vaccine implementation on meningococcal carriage and genogroup-specific prevalence in young adults in Fall of 2022, four years after the introduction of the tetravalent vaccine in the Netherlands. The overall carriage rate of genogroupable meningococci was not significantly different compared to a pre-menACWY cohort investigated in 2018 (20.8 % or 125 of 601 versus 17.4 % or 52 of 299 individuals, p = 0.25). Of 125 carriers of genogroupable meningococci, 122 (97.6 %) were positive for either vaccine-types menC, menW, menY or genogroups, menB, menE, and menX, which are not targeted by the menACWY vaccine. Compared with a pre-vaccine-implementation cohort, there was 3.8-fold reduction (p < 0.001) in vaccine-type carriage rates and 9.0-fold increase (p < 0.0001) in non-vaccine type menE prevalence. We observe a reduction in menW and menY and an increase in menE, which suggest that implementation of menACWY vaccine affected carriage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains are of particular concern, especially strains with mobilizable carbapenemase genes such as blaKPC, blaNDM or blaOXA-48, given that carbapenems are usually the last line drugs in the β-lactam class and, resistance to this sub-class is associated with increased mortality and frequently co-occurs with resistance to other antimicrobial classes., Objectives: To characterize the genomic diversity and international dissemination of CRKP strains from tertiary care hospitals in Lisbon, Portugal., Methods: Twenty CRKP isolates obtained from different patients were subjected to WGS for species confirmation, typing, drug resistance gene detection and phylogenetic reconstruction. Two additional genomic datasets were included for comparative purposes: 26 isolates (ST13, ST17 and ST231) from our collection and 64 internationally available genomic assemblies (ST13)., Results: By imposing a 21 SNP cut-off on pairwise comparisons we identified two genomic clusters (GCs): ST13/GC1 (n = 11), all bearing blaKPC-3, and ST17/GC2 (n = 4) harbouring blaOXA-181 and blaCTX-M-15 genes. The inclusion of the additional datasets allowed the expansion of GC1/ST13/KPC-3 to 23 isolates, all exclusively from Portugal, France and the Netherlands. The phylogenetic tree reinforced the importance of the GC1/KPC-3-producing clones along with their rapid emergence and expansion across these countries. The data obtained suggest that the ST13 branch emerged over a decade ago and only more recently did it underpin a stronger pulse of transmission in the studied population., Conclusions: This study identifies an emerging OXA-181/ST17-producing strain in Portugal and highlights the ongoing international dissemination of a KPC-3/ST13-producing clone from Portugal., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations., Methods: Recommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD. After a systematic literature review, separate recommendations were formulated for paediatric and adult patients. For pedAIIRD, six overarching principles and seven recommendations were formulated and provided with the level of evidence, strength of recommendation and Task Force level of agreement., Results: In general, the National Immunisation Programmes (NIP) should be followed and assessed yearly by the treating specialist. If possible, vaccinations should be administered prior to immunosuppressive drugs, but necessary treatment should never be postponed. Non-live vaccines can be safely given to immunosuppressed pedAIIRD patients. Mainly, seroprotection is preserved in patients receiving vaccinations on immunosuppression, except for high-dose glucocorticoids and B-cell depleting therapies. Live-attenuated vaccines should be avoided in immunosuppressed patients. However, it is safe to administer the measles-mumps-rubella booster and varicella zoster virus vaccine to immunosuppressed patients under specific conditions. In addition to the NIP, the non-live seasonal influenza vaccination should be strongly considered for immunosuppressed pedAIIRD patients., Conclusions: These recommendations are intended for paediatricians, paediatric rheumatologists, national immunisation agencies, general practitioners, patients and national rheumatology societies to attain safe and effective vaccination and optimal infection prevention in immunocompromised pedAIIRD patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background. Scarlet fever, an infectious disease caused by Streptococcus pyogenes , largely disappeared in developed countries during the twentieth century. In recent years, scarlet fever is on the rise again, and there is a need for a better understanding of possible factors driving transmission. Methods. Using historical case notification data from the three largest cities in The Netherlands (Amsterdam, Rotterdam and The Hague) from 1906 to 1920, we inferred the transmission rate for scarlet fever using time-series susceptible-infected-recovered (TSIR) methods. Through additive regression modelling, we investigated the contributions of meteorological variables and school term times to transmission rates. Results. Estimated transmission rates varied by city, and were highest overall for Rotterdam, the most densely populated city at that time. High temperature, seasonal precipitation levels and school term timing were associated with transmission rates, but the roles of these factors were limited and not consistent over all three cities. Conclusions. While weather factors alone can only explain a small portion of the variability in transmission rates, these results help understand the historical dynamics of scarlet fever infection in an era with less advanced sanitation and no antibiotic treatment and may offer insights into the driving factors associated with its recent resurgence., (© 2022 The Authors.)

Introduction: Influenza vaccination, besides protecting traditional risk groups, can protect employees and reduce illness-related absence, which is especially relevant in sectors with staff shortages. This study describes current knowledge of influenza vaccination in teachers and estimates its potential impact., Methods: We conducted a scoping review of the considerations for and impact of influenza vaccination of schoolteachers (grey and scientific literature up to 2020 March, complemented with interviews). We then estimated the potential impact of teacher vaccination in the Netherlands, with different scenarios of vaccine uptake for 3 influenza seasons (2016-2019). Using published data on multiple input parameters, we calculated potentially averted absenteeism notifications, averted absenteeism duration and averted doctor visits for influenza., Results: Only one scientific paper reported on impact; it showed lower absenteeism in vaccinated teachers, whereas more knowledge of vaccination impact was deemed crucial by 50% of interviewed experts. The impact for the Netherlands of a hypothetical 50% vaccine uptake was subsequently estimated: 74-293 potentially averted physician visits and 11,178-28,896 potentially averted days of influenza absenteeism (on ≈200,000 total teacher population). An estimated 12-32 vaccinations were required to prevent one teacher sick-leave notification, or 3.5-9.1 vaccinations to prevent one day of teacher absenteeism (2016-2019)., Conclusion: Scientific publications on influenza vaccination in teachers are few, while public interest has increased to reduce teacher shortages. However, school boards and public health experts indicate requiring knowledge of impact when considering this vaccination. Estimations of 3.5-9.1 vaccinated teachers preventing one day of influenza-related sick leave suggest a possible substantial vaccination impact on absenteeism. Financial incentives, more accessible on-site vaccinations at workplaces, or both, are expected to increase uptake, but more research is needed on teachers' views and vaccine uptake potential and its cost-effectiveness. Piloting free on-site influenza vaccination in several schools could provide further information on teacher participation., Competing Interests: The authors have declared that no competing interests exist.

The human gut microbiome plays a central role in health and disease. Environmental factors, such as lifestyle and diet, are known to shape the gut microbiome as well as the reservoir of resistance genes that these microbes harbour; the resistome. In this study we assessed whether long-term dietary habits within a single geographical region (the Netherlands) impact the human gut resistome. Faecal samples from Dutch omnivores, pescatarians, vegetarians and vegans were analysed by metagenomic shotgun sequencing (MSS) (n = 149) and resistome capture sequencing approach (ResCap) (n = 64). Among all diet groups, 119 and 145 unique antibiotic resistance genes (ARGs) were detected by MSS or ResCap, respectively. Five or fifteen ARGs were shared between all diet groups, based on MSS and ResCap, respectively. The total number of detected ARGs by MSS or ResCap was not significantly different between the groups. MSS also revealed that vegans have a distinct microbiome composition, compared to other diet groups. Vegans had a lower abundance of Streptococcus thermophilus and Lactococcus lactis compared to pescatarians and a lower abundance of S. thermophilus when compared to omnivores. In summary, our study showed that long-term dietary habits are not associated with a specific resistome signature., (© 2022. The Author(s).)