BackgroundThere is a significant hidden burden of infectious intestinal disease (IID) in the UK community, which has increased over time. In the late 2000s, the Second Study of Infectious Intestinal Disease (IID2 study) estimated 17 million IID cases annually in the United Kingdom. However, only a small proportion of cases present to health care, and even those are often not tested for causative organisms. ObjectiveThe Third Study of Infectious Intestinal Disease (IID3 study) aims to determine the IID burden in the UK community, estimate the underreporting level in routine practice and the general population, and recalibrate UK national surveillance based on the new incidence rates. MethodsWe will follow methods of previous studies, along with modern pathogen detection methods and digital platforms for recruitment and follow-up. Participants will be recruited to three population-based prospective cohorts: cohort 1 (the general population), cohort 2 (patients with IID presenting to general practices [GPs]), and cohort 3 (enumeration study of IID cases presenting to GPs). Microbiological analysis of stool samples in cohorts 1 and 2 will include testing for a wide range of causative organisms using molecular assays, including pathogen targets not routinely sought by National Health Service (NHS) laboratories. Additional characterization of pathogens will be conducted at national reference laboratories. The incidence rates of IID and organisms detected in cohorts 1-3 will be compared to national surveillance systems, both laboratory and syndromic. Descriptive statistics and analysis will allow comparison of IID rates within each cohort, estimate the overall burden of disease caused by different pathogens, and compare findings to earlier IID studies. ResultsA favorable ethical opinion was obtained from the UK Health Research Authority on August 4, 2022. A pilot phase to test the sampling process was conducted from January to August 2023. Participant recruitment commenced on September 1, 2023, for cohort 2 and on March 16, 2024, for cohort 1; recruitment ceased on August 31, 2025. Data collection is complete, and data analysis is to begin. The study is expected to end in September 2026. ConclusionsSince the first and second IID studies, changes have occurred within national surveillance systems, the NHS structure, and public recommendations about when to consult a GP and where to seek health care advice, which may have altered the extent of IID reporting and the perceived burden in the community, creating greater uncertainty about the representativeness of IID rates. The IID3 study results will provide insight into trends in disease incidence over time and help quantify inequalities in IID in the UK community. Revised estimates can inform policy related to prevention, including food standards and disease management. Furthermore, advances in molecular diagnostics will significantly enhance pathogen detection, increasing our understanding of the causes of IID. International Registered Report Identifier (IRRID)DERR1-10.2196/88759

Introduction While visiting open farms and farm attractions is a valuable experience for the public, exposure to the farm environment and farm animals can increase the risk of infection. Although public health advice is available for both farms and farm visitors, the extent to which this advice is understood and implemented is unclear. Method An ethnographic approach was adopted to explore understanding and adherence to public health advice and guidance from the perspectives of key stakeholders. This included on-site observations on open farms and farm attractions in North-West England, informal conversations with farm staff and visitors, formal focus groups with key stakeholders and analysis of relevant documents identified during data collection. Data was analysed using a qualitative inductive framework approach. Results Three key themes were identified that informed public health practices: (i) the influence of the farm environment (e.g., the layout and behaviour of others) (ii) perceptions of risk and (iii) the way in which public and professional stakeholders engaged with and understood public health advice and guidance. Conclusions Our findings outline important considerations for the development and dissemination of public health advice and guidance for open farms and farm attractions, with recommendations related to both the content of guidance and approaches to dissemination. Key recommendations include emphasising the importance of all site visitors engaging in protective behaviours and optimising the design and layout of farm environments to support engagement with public health measures. Future work should explore the development and evaluation of interventions and public health campaigns to support stakeholders to engage with this guidance.

Norovirus incidence increased in England during 2022-2025, when GII.17 replaced GII.4 as the dominant genotype. By using nationally linked norovirus testing and fatality data, we found age and care setting, but not genotype, were associated with case-fatality risk. Increased incidence might reflect changes in transmissibility or population immunity.

This chapter provides a broad definition of surveillance in relation to health protection, including infections, environmental hazards, and health delivery. Surveillance systems include active, passive, and sentinel surveillance, and guidelines are provided for assessing the quality of surveillance data. Surveillance tools include the statutory notification of diseases, laboratory reporting, and prevalence surveys. In addition, syndromic surveillance, the (near) real-time collection of data has become increasingly used, facilitated by increasing use of digital data collection within health care settings and the availability of other digital data sources (e.g. social media). Other surveillance types include event-based surveillance (e.g. during major sporting events), and environmental surveillance, including food related disease, air pollution and chemical hazards. The chapter finally brings these together in integrated surveillance and the use of such surveillance in health planning and assessment.

Background Norovirus causes substantial burden to healthcare systems. England experienced high activity in recent seasons alongside a shift in the dominant genotype from GII.4 to GII.17. It remains unclear whether this increased burden reflects changes in severity or other transmission mechanisms associated with the strain replacement. Methods Individual-level testing and mortality data in England from 2022/23-2024/25 seasons were linked from national surveillance systems. Piece-wise exponential additive mixed models estimated all-cause case-fatality risk (CFR) for death within 28 days of a positive test, adjusting for age, location, primary or secondary care case identification and temporal effects. Additional analysis tested the effect of the death linkage threshold. Results CFR did not differ significantly between GII.4 and GII.17, but increased markedly with age and was substantially higher for cases detected in secondary versus primary care. At the 2024/25 season peak, the CFR for the average cohort case (age 75) was 8.01% (95% CI: 6.88-9.33%) for cases identified in secondary care compared with 1.18% (95% CI: 0.61-2.25%) for primary care, likely driven by different case mixes and unmeasured confounding between patients managed in these settings. Interpretation We found no evidence that the newly dominant GII.17 genotype had higher CFR than GII.4 among test-positive cases. The increased burden is therefore more consistent with changes in transmissibility, population immunity, or testing dynamics than increased genotype-specific severity. Norovirus remains a major public health threat, and understanding genotype switching supports enhanced surveillance, expanded genotyping, routine clinical data linkage and advanced modelling to inform control strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research did not receive any specific funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: UKHSA have an exemption under regulation 3 of Sect. 251 of the National Health Service Act (2006) to allow identifiable patient information to be processed to diagnose, control, prevent, or recognise trends in, communicable diseases and other risks to public health. The use of electronic health records complied with an approved Data Protection Impact Assessment, Caldicott Agreement, and Data Sharing Agreement, with approvals granted by the UKHSA Information Management and Privacy Office and the UKHSA Caldicott Office. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes An application for data access can be made to the UK Health Security Agency. UKHSA operates a robust governance process for applying to access protected data that considers: - the benefits and risks of how the data will be used, - compliance with policy, regulatory and ethical obligations, - data minimisation, - how the confidentiality, integrity, and availability will be maintained, - retention, archival, and disposal requirements, - best practice for protecting data, including the application of 'privacy by design and by default', emerging privacy conserving technologies and contractual controls. Access to protected data is always strictly controlled using legally binding data sharing contracts. UKHSA welcomes data applications from organisations looking to use protected data for public health purposes. To request an application pack or discuss a request for UKHSA data you would like to submit, contact DataAccess{at}ukhsa.gov.uk.

Background: Rotavirus vaccination programmes for infants have significantly reduced the incidence of rotavirus gastroenteritis. Vaccines which decrease disease incidence can reduce antibiotic prescribing and may help combat antimicrobial resistance. A US cohort study found a significant association between rotavirus vaccination and reduced antibiotic prescribing. However, no studies have investigated this association in the UK, where infant rotavirus vaccination was introduced in 2013. Methods: We conducted a retrospective cohort study using the Clinical Practice Research Datalink Aurum, a large representative dataset of UK primary care health records. Between 2010 and 2020, children were assessed for rotavirus vaccination status and followed from six months to seven years of age. The outcome was an antibiotic prescription within seven days following an all-cause acute gastroenteritis (AGE) diagnosis. Recurrent time-to-event modelling was used to estimate adjusted hazard ratios (aHR) accounting for sex, deprivation, urban-rural status, seasonality and health-seeking behaviour. Model estimates were used to predict the prescribing events averted by rotavirus vaccination. Results: Of 429,009 participants eligible for inclusion, 2.4% (10,328 participants) experienced an AGE-linked antibiotic prescribing event. For participants who received one or more rotavirus vaccines, after adjusting for covariates, the aHR was 0.74 (95% CI 0.71–0.77). This finding was robust across several sensitivity analyses, including changing the outcome definition to an antibiotic prescription within 3 days of an acute gastroenteritis diagnosis aHR 0.74 (95% CI 0.71–0.77). We also estimated that in a UK birth cohort born between 2014 and 2019 rotavirus vaccination has averted 12,635 (95%CI 11,363 − 14,109) AGE-linked prescriptions. Conclusions: Rotavirus vaccination was associated with a significantly lower rate of antibiotic prescribing in UK primary care. This is the first UK study to investigate this association, and our findings are consistent with the US cohort study and studies in low and middle-income countries. Our study provides further evidence that rotavirus vaccines are effective against disease in primary care and may contribute to antimicrobial stewardship.

Shigellosis is a gastrointestinal illness caused by bacteria belonging to one of four species of Shigella. Sexually transmissible (ST) shigellosis was first reported in 1974, but recently there has been a global increase in the transmission of extensively drug-resistant (XDR) strains. Here, we sought to characterise the natural history of ST shigellosis through literature review and genomic epidemiological analysis of early outbreaks. The literature review revealed a significant gap in reporting of ST shigellosis between the first report in 1974 and the early 2000s, after which reporting increased. To better understand this sustained emergence of ST shigellosis in the 21st century, we explored potential pathogen factors and linked these with changes in host populations. Specifically, we analysed the genomic epidemiology of preserved strains from outbreaks in both Berlin (2000-2002) and London (2004-2006). Both outbreaks were Shigella sonnei Genotype 3.1, an ancestral branch of the globally disseminated lineage III subtype, which is distinct from the currently globally dominant XDR forms (Genotypes 3.6.1.1.2 and 3.6.1.1) circulating in sexual transmission networks. We also describe the variable antimicrobial resistance, conserved colicin genes and differing virulence and plasmid profiles between the London and Berlin outbreaks. Finally, we conducted temporal reconstruction of Genotype 3.1 and found that the most recent common ancestor occurred in 1999 (95% highest posterior density 1997-2000), which is coincident with the introduction of highly active antiretroviral therapy (HAART) for human immunodeficiency virus. This suggests that changes associated with the introduction of HAART may have contributed to the re-emergence of ST shigellosis in the 21st century.

Wastewater-based surveillance (WBS) can monitor for the presence of human health pathogens in the population. During COVID-19, WBS was widely used to determine wastewater SARS-CoV-2 RNA concentration (concentrations) providing information on community COVID-19 cases (cases). However, studies examining the relationship between concentrations and cases tend to be localised or focussed on small-scale institutional settings. Few have examined this relationship in multiple settings, over long periods, with large sample numbers, nor attempted to quantify the relationship between concentrations and cases or detail how catchment characteristics affected these.This 18-month study (07/20–12/21) explored the correlation and quantitative relationship between concentrations and cases using censored regression. Our analysis used >94,000 wastewater samples collected from 452 diverse sampling sites (259 Sewage Treatment Works (STW) and 193 Sewer Network Sites (SNS)) covering ~65 % of the English population. Wastewater concentrations were linked to ~6 million diagnostically confirmed COVID-19 cases.High correlation coefficients were found between concentrations and cases (STW: median r = 0.66, IQR: 0.57–0.74; SNS: median r = 0.65, IQR: 0.54–0.74). The quantitative relationship (regression coefficient) between concentrations and cases was variable between catchments. Catchment and sampling characteristics (e.g. size of population and grab vs automated sampling) had significant but small effects on correlation and regression coefficients.During the last six months of the study correlation coefficients reduced and regression coefficients became highly variable between catchments. This coincided with a shift towards younger cases, a highly vaccinated population and rapid emergence of the variant Omicron.The English WBS programme was rapidly introduced at scale during COVID-19. Laboratory methods evolved and study catchments were highly diverse in size and characteristics. Despite this diversity, findings indicate that WBS provides an effective proxy for establishing COVID-19 dynamics across a wide variety of communities. While there is potential for predicting COVID-19 cases from wastewater concentration, this may be more effective at smaller scales.

The genus Neisseria includes two major human pathogens: N. meningitidis causing bacterial meningitis/septicemia and N. gonorrhoeae causing gonorrhoea. Mathematical models have been used to simulate their transmission and control strategies, and the recent observation of a meningococcal B (MenB) vaccine being partially effective against gonorrhoea has led to an increased modeling interest. Here we conducted a systematic review of the literature, focusing on studies that model vaccination strategies with MenB vaccines against Neisseria incidence and antimicrobial resistance. Using journal, preprint, and grey literature repositories, we identified 52 studies that we reviewed for validity, model approaches and assumptions. Most studies showed a good quality of evidence, and the variety of approaches along with their different modeling angles, was assuring especially for gonorrhoea studies. We identified options for future research, including the combination of both meningococcal and gonococcal infections in studies to have better estimates for vaccine benefits, and the spill over of gonorrhoea infections from the heterosexual to the MSM community and vice versa. Cost-effectiveness studies looking at at-risk and the wider populations can then be used to inform vaccine policies on gonorrhoea, as they have for meningococcal disease.

OBJECTIVES:Acute hepatitis B affects over a million people a year globally. Follow up for public health purposes involves vaccination or advising prophylaxis of contacts to reduce transmission. Those lost to follow up are more likely to transmit infection. This study investigated the socio-demographic factors potentially associated with being lost to public health follow up in cases with acute hepatitis B infection. STUDY DESIGN:This was a retrospective cohort study of all acute hepatitis B cases in England followed up by UKHSA in 2022 and 2023. METHODS:We reviewed case notes from the UKHSA case management system. The outcome variable was the completion of public health follow up. Independent variables were index of multiple deprivation quintile, age, gender, ethnicity, history of sex between men or sex between women, intravenous drug usage, and geographical region. RESULTS:Out of 226 cases with acute hepatitis B infection, 6.6 % of cases were lost to follow up. Exploratory analyses suggested that males and cases in two regions may be at greater risk of being lost to follow up, although these findings were based on small numbers. CONCLUSIONS:This study found that in England most cases of acute hepatitis B are appropriately followed up from a public health perspective. The study suggests that males had a marginally increased risk of being lost to follow up.

BACKGROUNDIn Scotland, the number of pertussis infections recorded in children in 2024 was the highest of any year in the last decade. The protective role of vaccination against severe infection and associated hospitalisations has not been assessed.AIMTo investigate the effect of vaccination and sociodemographic factors on pertussis-related hospitalisations in Scottish children aged under 18 years.METHODSIn a retrospective cohort study, laboratory-confirmed pertussis cases from January 2013 to July 2024 were extracted from the national electronic surveillance system and linked to hospitalisation data from Scottish Morbidity Records and vaccination data from the national immunisations database. The outcome was a pertussis-associated hospitalisation. Multivariable logistic regression was used to calculate odds ratios (OR) for the association between vaccination status and hospitalisation, adjusted for age, sex, ethnicity and deprivation status.RESULTSThere were 3,982 laboratory-confirmed cases of pertussis during the study period. Children fully vaccinated for age had significantly lower odds of hospitalisations than unvaccinated children (adjusted OR (aOR): 0.31; 95% CI: 0.21-0.46). Being partially vaccinated for age did not significantly reduce hospitalisations relative to unvaccinated children (aOR: 0.80; 95% CI: 0.47-1.33). In the univariable analysis, children living in the most deprived areas had significantly more hospitalisations than those in the least deprived areas (OR: 3.90; 95% CI: 2.41-6.56). This association was not significant when adjusted for the effect of vaccination (aOR: 1.47; 95% CI: 0.84-2.66).CONCLUSIONSFully vaccinated children had significantly lower odds of hospitalisation, indicative of less severe disease. This emphasises the importance of fully vaccinating children according to the childhood immunisation schedule.

Background: Estimates of Lyme disease incidence in England are based on reporting of cases with a laboratoryconfirmed diagnosis only, underestimating total cases. In 2017 - 2018, two independent reviews commissioned by the UK Government highlighted the lack of official data on Lyme disease prevalence and incidence as a critical knowledge gap. Aim: To estimate the prevalence of IgG antibodies in the English adult population specific for Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease. Methods: The prevalence of Bbsl-specific antibodies in the English population was estimated in a cross-sectional cohort, selected from an archive of residual NHS blood donor plasma samples (age range 17 - 84, collected between 2021 - 2022). 10,000 samples were randomly selected proportionate to the population size of each of the nine English administrative regions. 9,994 samples were tested using a standard two-tiered testing strategy, with an IgG/IgM ELISA followed by an IgG immunoblot (array) test for any sera with positive or indeterminate reactivity in the ELISA. Results: Out of the 9,994 samples tested, 482 were seroreactive by screening ELISA. After two-tier testing, 49 were confirmed positive. Regional and demographic differences in seroprevalence were observed after two-tier testing, but due to the low overall seroprevalence, were not significant upon multivariable analysis. Conclusion: The seroprevalence of Borrelia burgdorferi sensu lato-specific IgG in the English adult population (2021 - 2022), determined using two-tier testing was estimated at 0.49 % (95 % CI 0.36 - 0.65). This is lower than neighbouring UK nation Scotland and other northern European countries.

Our study assessed the link between gastrointestinal (GI) infections in England and the Eat Out to Help Out scheme (EOHO), a government subsidy created to encourage people to eat out during COVID-19 pandemic (03-30 August 2020). We studied national laboratory data between January 2015 and December 2020. We used time series change point analysis to see if there were shifts in reported cases of specific GI infections (Campylobacter spp., Escherichia coli O157, and non-typhoidal Salmonella spp.) associated with the timing of the scheme. Our analysis uniquely applied the Pruned Exact Linear Time method, with generalized linear models to a national dataset of GI infections. This revealed increases in cases closely aligned to the timing of the easing of COVID-19 restrictions, prior to the introduction of the EOHO scheme. Our study showed the scheme had no measurable impact, as there was no significant change on reported cases. Substantial reductions in cases after the first lockdown, followed by an increase as restrictions were phased out, show the wider impact of COVID-19 control measures, for example, public information campaigns aimed at improving hand-hygiene. These findings highlight the complicated interactions between COVID-19 control measures, the public's behaviour, and the spread of GI infections.

The Flexible Farrington Algorithm (FFA) is widely used to detect infectious disease outbreaks at national/regional levels on a weekly basis. The rapid spread of SARS-CoV-2 alongside the speed at which diagnostic and public health interventions were introduced made the FFA of limited use. We describe how the methodology was adapted to provide a daily alert system to support local health protection teams (HPTs) working in the 316 English lower-tier local authorities. To minimize the impact of a rapidly changing epidemiological situation, the FFA was altered to use 8 weeks of data. The adapted algorithm was based on reported positive counts using total tests as an offset. Performance was assessed using the root mean square error (RMSE) over a period. Graphical reports were sent to local teams enabling targeted public health action. From 1 July 2020, results were routinely reported. Adaptions accommodated the impact on reporting because of changes in diagnostic strategy (introduction of lateral flow devices). RMSE values were relatively small compared to observed counts, increased during periods of increased reporting, and were relatively higher in the northern and western areas of the country. The exceedance reports were well received. This presentation should be considered as a successful proof-of-concept.

Background Influenza imposes a significant health burden on older adults, with influenza-like illness (ILI) a key driver of antibiotic prescribing, contributing to unnecessary antibiotic use and antimicrobial resistance (AMR). Influenza vaccination may reduce antibiotic prescribing; however, robust evidence remains limited. To address this, we examined the association between influenza vaccination and antibiotic prescribing in individuals aged 65 and older in England, using a self-controlled case series (SCCS) approach. Methods We conducted a SCCS analysis using electronic primary care health records from the Clinical Practice Research Datalink (CPRD), covering eight influenza seasons (2011 to 2019). Eligible individuals had at least one influenza season in which they were both vaccinated and unvaccinated. The primary outcome was days prescribed antibiotics, focusing on respiratory tract infection (RTI) linked prescribing. To account for seasonal variation in influenza circulation, we initially examined antibiotic prescribing from September to April and further restricted the analysis to January to April to assess the vaccine's effect during peak influenza activity. Incidence rate ratios (IRRs) were estimated using conditional Poisson regression models, adjusting for comorbidities, healthcare interactions, and other vaccinations. Results The analysed extract included 250,344 individuals, of whom 48,329 met the inclusion criteria. On average, individuals were prescribed antibiotics for 8 days per influenza season. Findings suggest influenza vaccination may reduce overall and RTI related antibiotic prescribing, particularly during peak influenza season. The IRR for RTI linked prescribing decreased from 0.96 (95% CI: 0.95 to 0.98) for September-April to 0.91 (95% CI: 0.89 to 0.93) for January-April. Conclusion Influenza vaccination contributes to reduced RTI related antibiotic prescribing in older adults during the influenza season. ### Competing Interest Statement Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the Wellcome Trust for the submitted work; financial relationships with organisations that might have an interest in the submitted work in the previous three years; DH, DS and NF are currently in receipt of grant support from Seqirus UK for the evaluation of influenza vaccines in the UK, ; NF is in receipt of funding from GSK in relation to malaria vaccines; DH has also received grants from Merck and Co (Kenilworth, NJ) for rotavirus strain surveillance, received honorariums for presentation at a Merck Sharp and Dohme (UK) symposium on vaccines and has consulted on rotavirus strain surveillance; TS, VD, MH have no competing interests to disclose, and no other relationships or activities that could appear to have influenced the submitted work. ### Funding Statement Funding: This work was funded by a Wellcome Trust (UK) Impact of Vaccines on Antimicrobial Resistance project grant (219798/Z/19/Z). DH was funded by a National Institute for Health and Care Research (NIHR) postdoctoral fellowship (PDF-2018-11-ST2-006. DH, are affiliated with the NIHR Health Protection Research Unit (HPRU) in Gastrointestinal Infections at the University of Liverpool in partnership with the UK Health Security Agency (UKHSA), in collaboration with the University of Warwick. NF are affiliated with the NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool in partnership with the UKHSA, in collaboration with University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UKHSA. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability: The datasets used in this study were extracted from Clinical Practice Research Datalink (CPRD) following CPRD approval of the study protocol (reference 21_000457: available at https://cprd.com/protocol/) and through a multi-study license and data sharing agreement between the University of Liverpool and CPRD. The Medicines and Healthcare products Regulatory Agency and National Institute for Health and Care Research sponsor CPRD. The authors are not authorised to share the datasets and are obliged to destroy the datasets according to the data-sharing agreement between the University of Liverpool and CPRD.

BackgroundLaboratory surveillance detected an unprecedented increase in Cryptosporidium spp. (predominantly Cryptosporidium hominis) in England and Wales in August 2023. Cases are not routinely followed up in all of England and Wales, and initial investigations identified no common exposures.AimTo perform a retrospective case-case study investigation of the increase in Cryptosporidium spp. in England and Wales.MethodsWe conducted an unmatched case-case study with 203 cases of laboratory-confirmed C. hominis and 614 comparator cases of laboratory-confirmed Campylobacter spp. reported between 14 August and 30 September 2023. We fitted a multilevel logistic regression model, with random intercepts for geographical region, to estimate adjusted odds ratios (aOR) for exposures. We present the final model as aOR and 95% confidence intervals (CI).ResultsMultivariable analysis identified associations with swimming pool use (aOR: 5.3, 95% CI: 2.3-9.3), travel to Spain (aOR: 6.5, 95% CI: 3.5-12.3) and young age, with children 0-4 years having the strongest association of being a case (aOR: 3.6, 95% CI: 1.5-8.6). We also identified associations with swimming in a river, and travel to France or Türkiye, but there was low frequency of exposure among cases and comparator cases.ConclusionsFollowing the largest recorded increase of Cryptosporidium spp. and in particular C. hominis cases in England and Wales, we identified several exposures, suggesting that causation was likely to be multifactorial. We recommend development of a standardised questionnaire to enable rapid investigation of future case increases, which will improve existing surveillance and inform public health actions.

OBJECTIVES:In 2022, a global outbreak of mpox was reported. In the UK, it predominantly affected gay, bisexual and men who have sex with men (GBMSM). The study objectives were to describe the impact of the mpox outbreak on healthcare service usage in England in 2022, particularly emergency department (ED) attendance, inpatient admission and a number of bed days. Additionally, we wanted to explore whether pre-exposure prophylaxis (PrEP) usage, as a marker of condomless anal intercourse, which increases the risk of sexually transmitted infections associated with compromised skin integrity, was associated with higher ED attendance or hospital attendance. METHODS:Data on adult males with laboratory-confirmed mpox were linked with hospital records and described. Using routinely collected data and self-reported exposure data (including PrEP usage) from surveillance questionnaires, multinomial regression was used to estimate adjusted relative risk ratios (aRRRs) with 95% CIs for ED attendance and hospital admission compared with those not admitted. RESULTS:Among 3542 adult males with mpox during May to December 2022, 544 (15.4%) attended ED and 202 (5.7%) were admitted to the hospital. London had the most cases (2393, 68.7%), ED attendances (391, 71.9%) and hospital admissions (121, 59.9%). In multinomial regression, we found strong evidence that compared with people living with HIV, the aRRR for hospital admissions was higher in those not using PrEP (6.9 (95% CI 2.3 to 20.6) vs 4.9 (95% CI 1.7 to 14.1)). The aRRR for ED attendance was 0.63 (95% CI 0.36 to 1.1) for those not using PrEP versus 0.49 (95% CI 0.31 to 0.79). CONCLUSIONS:This outbreak had a considerable impact on health services, particularly in high-incidence areas. Commissioners of sexual and healthcare services should review plans for healthcare provision for similar sexually transmitted infection or novel outbreaks among GBMSM or naïve populations in the future. Further studies are needed to confirm and identify reasons for the higher likelihood of hospital admission seen for GBMSM without HIV infection.

Background Whole-genome sequencing (WGS) is the gold standard diagnostic tool to identify and genetically characterise emerging pathogen mutations (variants), but cost, capacity, and timeliness limit its use when large populations need rapidly assessing. We assessed the potential of genotyping assays to provide accurate and timely variant information at scale by retrospectively examining surveillance for SARS-CoV-2 variants in England between March and September, 2021, when genotyping assays were used widely for variant detection. Methods We chose a panel of four RT-PCR genotyping assays to detect circulating variants of SARS-COV-2 in England and developed a decision algorithm to assign a probable SARS-CoV-2 variant to samples using the assay results. We extracted surveillance data from the UK Health Security Agency databases for 115 934 SARS-CoV-2-positive samples (March 1-Sept 6, 2021) when variant information was available from both genotyping and WGS. By comparing the genotyping and WGS variant result, we calculated accuracy metrics (ie, sensitivity, specificity, and positive predictive value [PPV]) and the time difference between the sample collection date and the availability of variant information. We assessed the number of samples with a variant assigned from genotyping or WGS, or both, over time. Findings Genotyping and an initial decision algorithm (April 10-May 11, 2021 data) were accurate for key variant assignment: sensitivities and PPVs were 0.99 (95% CI 0.99-0.99) for the alpha, 1.00 (1.00-1.00) for the beta, and 0.91 (0.80-1.00) for the gamma variants; specificities were 0.97 (0.96-0.98), 1.00 (1.00-1.00), and 1.00 (1.00-1.00), respectively. A subsequent decision algorithm over a longer time period (May 27-Sept 6, 2021 data) remained accurate for key variant assignment: sensitivities were 0.91 (95% CI 0.74-1.00) for the beta, 0.98 (0.98-0.99) for the delta, and 0.93 (0.81-1.00) for the gamma variants; specificities were 1.00 (1.00-1.00), 0.96 (0.96-0.97), and 1.00 (1.00-1.00), respectively; and PPVs were 0.83 (0.62-1.00), 1.00 (1.00-1.00), and 0.78 (0.59-0.97), respectively. Genotyping produced variant information a median of 3 days (IQR 2-4) after the sample collection date, which was faster than with WGS (9 days [8-11]). The flexibility of genotyping enabled a nine-times increase in the quantity of samples tested for variants by this method (from 5000 to 45 000). Interpretation RT-PCR genotyping assays are suitable for high-throughput variant surveillance and could complement WGS, enabling larger scale testing for known variants and timelier results, with important implications for effective public health responses and disease control globally, especially in settings with low WGS capacity. However, the choice of panels of RT-PCR assays is highly dependent on database information on circulating variants generated by WGS, which could limit the use of genotyping assays when new variants are emerging and spreading rapidly.