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Background: Shiga toxin-producing Escherichia coli (STEC) infections are a significant public health concern as they can cause serious illness and outbreaks. In England, STEC incidence is highest among children and guidance recommends that children under six diagnosed with STEC are excluded from childcare until two consecutive stool cultures are negative. We aimed to describe the barriers and facilitators to implementing exclusion and the impact of exclusion policies on young children and their families., Methods: Individual level data was obtained from a wider study focusing on shedding duration among STEC cases aged < 6 years between March 2018 - March 2022. Data was extracted from England's public health case management system. The case management system includes notes on telephone conversations, email correspondence and meeting minutes relating to the case. Collected data consisted of free text in three forms: (1) quotes from parents, either direct or indirect, (2) direct quotes from the case record by health protection practitioners or environmental health officers, and (3) summaries by the data collector after reviewing the entire case record. We analysed free text comments linked to 136 cases using thematic analysis with a framework approach., Results: The median age of included cases was 3 years (IQR 1.5-5), with males accounting for 49%. Nine key themes were identified. Five themes focused on barriers to managing exclusion, including (i) financial losses, (ii) challenges with communication, engagement and collaboration, (iii) issues with sampling, processing, and results, (iv) adverse impact on children and their families and (v) conflicting exclusion advice. Four themes related to facilitators to exclusion, including (i) good communication with parents and childcare settings, (ii) support with childcare, (iii) improvements to sampling, testing, and reporting of results, and (iv) provision of supervised control measures., Conclusions: Qualitative analysis of public health case records can provide evidence-based insights around complex health protection issues to inform public health guidelines. Our analysis highlights the importance of considering wider social and economic consequences of exclusion when developing policies and practices for the management of STEC in children., (© 2024. The Author(s).)

International travel is thought to be a major risk factor for developing gastrointestinal (GI) illness for UK residents. Here, we present an analysis of routine laboratory and exposure surveillance data from North East (NE) England, describing the destination-specific contribution that international travel makes to the regional burden of GI infection.Laboratory reports of common notifiable enteric infections were linked to exposure data for cases reported between 1 January 2013 and 31 December 2022. Demographic characteristics of cases were described, and rates per 100,000 visits were determined using published estimates of overseas visits from the Office for National Statistics (ONS) International Passenger Survey (IPS).About 34.9% of cases reported international travel during their incubation period between 2013 and 2022, although travel-associated cases were significantly reduced (>80%) during the COVID-19 pandemic. Between 2013 and 2019, half of Shigella spp. and non-typhoidal Salmonella infections and a third of Giardia sp. , Cryptosporidium spp. , and Shiga toxin-producing Escherichia coli (STEC) infections were reported following travel. Rates of illness were highest in travellers returning from Africa and Asia (107.8 and 61.1 per 100,000 visits), with high rates also associated with tourist resorts like Turkey, Egypt, and the Dominican Republic (386.4-147.9 per 100,000 visits).International travel is a major risk factor for the development of GI infections. High rates of illness were reported following travel to both destinations, which are typically regarded as high-risk and common tourist resorts. This work highlights the need to better understand risks while travelling to support the implementation of guidance and control measures to reduce the burden of illness in returning travellers.

The underreporting of laboratory-reported cases of community-based gastrointestinal (GI) infections poses a challenge for epidemiologists understanding the burden and seasonal patterns of GI pathogens. Syndromic surveillance has the potential to overcome the limitations of laboratory reporting through real-time data and more representative population coverage. This systematic review summarizes the utility of syndromic surveillance for early detection and surveillance of GI infections. Relevant articles were identified using the following keyword combinations: 'early warning', 'detection', 'gastrointestinal activity', 'gastrointestinal infections', 'syndrome monitoring', 'real-time monitoring', 'syndromic surveillance'. In total, 1820 studies were identified, 126 duplicates were removed, and 1694 studies were reviewed. Data extraction focused on studies reporting the routine use and effectiveness of syndromic surveillance for GI infections using relevant GI symptoms. Eligible studies ( n = 29) were included in the narrative synthesis. Syndromic surveillance for GI infections has been implemented and validated for routine use in ten countries, with emergency department attendances being the most common source. Evidence suggests that syndromic surveillance can be effective in the early detection and routine monitoring of GI infections; however, 24% of the included studies did not provide conclusive findings. Further investigation is necessary to comprehensively understand the strengths and limitations associated with each type of syndromic surveillance system.

Stepwise non-pharmaceutical interventions and health system changes implemented as part of the COVID-19 response have had implications on the incidence, diagnosis, and reporting of other communicable diseases. Here, we established the impact of the COVID-19 outbreak response on gastrointestinal (GI) infection trends using routinely collected surveillance data from six national English laboratory, outbreak, and syndromic surveillance systems using key dates of governmental policy to assign phases for comparison between pandemic and historic data. Following decreases across all indicators during the first lockdown (March-May 2020), bacterial and parasitic pathogens associated with foodborne or environmental transmission routes recovered rapidly between June and September 2020, while those associated with travel and/or person-to-person transmission remained lower than expected for 2021. High out-of-season norovirus activity was observed with the easing of lockdown measures between June and October 2021, with this trend reflected in laboratory and outbreak systems and syndromic surveillance indicators. Above expected increases in emergency department (ED) attendances may have reflected changes in health-seeking behaviour and provision. Differential reductions across specific GI pathogens are indicative of the underlying routes of transmission. These results provide further insight into the drivers for transmission, which can help inform control measures for GI infections.

BackgroundYersiniosis is one of the most common food-borne zoonoses in Europe, but there are large variations in the reported incidence between different countries.AimWe aimed to describe the trends and epidemiology of laboratory-confirmed Yersinia infections in England and estimate the average annual number of undiagnosed Yersinia enterocolitica cases, accounting for under-ascertainment.MethodsWe analysed national surveillance data on Yersinia cases reported by laboratories in England between 1975 and 2020 and enhanced surveillance questionnaires from patients diagnosed in a laboratory that has implemented routine Yersinia testing of diarrhoeic samples since 2016.ResultsThe highest incidence of Yersinia infections in England (1.4 cases per 100,000 population) was recorded in 1988 and 1989, with Y. enterocolitica being the predominant species. The reported incidence of Yersinia infections declined during the 1990s and remained low until 2016. Following introduction of commercial PCR at a single laboratory in the South East, the annual incidence increased markedly (13.6 cases per 100,000 population in the catchment area between 2017 and 2020). There were notable changes in age and seasonal distribution of cases over time. The majority of infections were not linked to foreign travel and one in five patients was admitted to hospital. We estimate that around 7,500 Y. enterocolitica infections may be undiagnosed in England annually.ConclusionsFindings suggest a considerable number of undiagnosed yersiniosis cases in England, with possibly important changes in the epidemiology. The apparently low incidence of yersiniosis in England is probably due to limited laboratory testing.

Background: In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus., Methods: We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing., Findings: Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%)., Interpretation: DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections., Funding: UK Government Department of Health and Social Care., Competing Interests: Declaration of interests IO, GJR, and LY participate in the UK Scientific Advisory Group for Emergencies and its subgroups, where this and related work were discussed. CT also contributed to these groups, presenting analysis as part of work on the COVID response. GJR has been paid by Bayer as a legal expert witness, not related to this manuscript. GJR received payment for peer review of research grants and manuscripts related to COVID-19, but not related to this manuscript. Several authors (IO, SH, NL, DR, AFM, SD, LY, GJR, RA, and CT) carried out previous studies funded by the Department of Health and Social Care investigating testing of contacts of COVID-19 cases by PCR or LFD. Several authors (IO, LY, and JR) were funded by UK Research and Innovation or the National Institute for Health and Care Research (NIHR) to undertake research related to COVID-19, outside of the current study. IO, DR, CEF, IO, RA, SD, and LY receive funding from the NIHR Health Protection Research Unit (HPRU) in Behavioural Science and Evaluation at the University of Bristol. NL receives funding from the NIHR HPRU in Gastrointestinal Infections at the University of Liverpool. LY is an NIHR Senior Investigator, and her research programme is partly supported by NIHR Applied Research Collaboration West and NIHR Biomedical Research Centre at the University of Southampton. RA and GJR receive payments from the NIHR HPRU in Emergency Preparedness and Response. LY, SD, and IO receive payments from the Department of Health and Social Care. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction. Evidence suggests that although people modify their behaviours, full adherence to self-isolation guidance in England may be suboptimal, which may have a detrimental impact on COVID-19 transmission rates. Hypothesis. Testing asymptomatic contacts of confirmed COVID-19 cases for the presence of SARS-CoV-2 could reduce onward transmission by improving case ascertainment and lessen the impact of self-isolation on un-infected individuals. Aim. This study investigated the feasibility and acceptability of implementing a 'test to enable approach' as part of England's tracing strategy. Methodology. Contacts of confirmed COVID-19 cases were offered serial testing as an alternative to self-isolation using daily self-performed lateral flow device (LFD) tests for the first 7 days post-exposure. Asymptomatic participants with a negative LFD result were given 24 h of freedom from self-isolation between each test. A self-collected confirmatory PCR test was performed on testing positive or at the end of the LFD testing period. Results. Of 1760 contacts, 882 consented to daily testing, of whom 812 individuals were within 48 h of exposure and were sent LFD testing packs. Of those who declined to participate, 39.1% stated they had already accessed PCR testing. Of the 812 who were sent LFD packs, 570 (70.2%) reported one or more LFD results; 102 (17.9%) tested positive. Concordance between reported LFD result and a supplied LFD image was 97.1%. In total, 82.8% of PCR-positive samples and 99.6% of PCR-negative samples were correctly detected by LFD. The proportion of secondary cases from contacts of those who participated in the study and tested positive (6.3%; 95% CI: 3.4-11.1%) was comparable to a comparator group who self-isolated (7.6%; 95% CI: 7.3-7.8%). Conclusion. This study shows a high acceptability, compliance and positivity rates when using self-administered LFDs among contacts of confirmed COVID-19 cases. Offering routine testing as a structured part of the contact tracing process is likely to be an effective method of case ascertainment.

Objective: To establish the impact of the first 6 months of the COVID-19 outbreak response on gastrointestinal (GI) infection trends in England., Design: Retrospective ecological study using routinely collected national and regional surveillance data from seven UK Health Security Agency coordinated laboratory, outbreak and syndromic surveillance systems using key dates of UK governmental policy change to assign phases for comparison between 2020 and historic data., Results: Decreases in GI illness activity were observed across all surveillance indicators as COVID-19 cases began to peak. Compared with the 5-year average (2015-2019), during the first 6 months of the COVID-19 response, there was a 52% decrease in GI outbreaks reported (1544 vs 3208 (95% CI 2938 to 3478)) and a 34% decrease in laboratory confirmed cases (27 859 vs 42 495 (95% CI 40 068 to 44 922)). GI indicators began to rise during the first lockdown and lockdown easing, although all remained substantially lower than historic figures. Reductions in laboratory confirmed cases were observed across all age groups and both sexes, with geographical heterogeneity observed in diagnosis trends. Health seeking behaviour changed substantially, with attendances decreasing prior to lockdown across all indicators., Conclusions: There has been a marked change in trends of GI infections in the context of the COVID-19 pandemic. The drivers of this change are likely to be multifactorial; while changes in health seeking behaviour, pressure on diagnostic services and surveillance system ascertainment have undoubtably played a role, there has likely been a true decrease in the incidence for some pathogens resulting from the control measures and restrictions implemented. This suggests that if some of these changes in behaviour such as improved hand hygiene were maintained, then we could potentially see sustained reductions in the burden of GI illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Between August 2016 and November 2019, a cluster of babies colonized with meticillin-resistant Staphylococcus aureus (MRSA) was reported in a special care baby unit in northern England., Aim: A case-control study was performed to identify the source and prevent further cases., Methods: Cases were admitted neonates colonized or infected with MRSA (spa type t316). A retrospective case-control study was performed with two matched controls per case. Exposures were determined by medical record review. Cases were compared with controls using conditional logistic regression. Environmental investigations and staff screening were undertaken., Findings: Thirty-one colonized cases were identified across the 3-year period, with no infections reported. Thirteen of the 31 cases were sequenced and were within a cluster of 25 single nucleotide polymorphisms, consistent with exposure to a common source over a prolonged period. Most MRSA cases had a prior negative screen (N=22, 71%). Environmental sampling and staff screening were performed on several occasions. In the analytical study, 31 cases were compared with 62 controls. One ward location and one healthcare worker were identified as significant exposures in the multi-variable analysis., Conclusions: Due to the sporadic nature of the colonizations, it was hypothesized that MRSA was being introduced intermittently, likely by a colonized healthcare worker, with possible transmission between infants also occurring within each temporal cluster. It is recommended that transiently colonized healthcare workers should be considered as a source of MRSA during outbreaks. This study highlights the importance of analytic epidemiological studies in persistent outbreaks of MRSA., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

At a cellular level, nutrients are sensed by the mechanistic Target of Rapamycin (mTOR). The response of cells to hypoxia is regulated via action of the oxygen sensor Hypoxia-Inducible Factor 1 (HIF-1). During development, injury and disease, tissues might face conditions of both low nutrient supply and low oxygen, yet it is not clear how cells adapt to both nutrient restriction and hypoxia, or how mTOR and HIF-1 interact in such conditions. Here we explore this question in vivo with respect to cell proliferation using the ciliary marginal zone (CMZ) of Xenopus . We found that both nutrient-deprivation and hypoxia cause retinal progenitors to decrease their proliferation, yet when nutrient-deprived progenitors are exposed to hypoxia there is an unexpected rise in cell proliferation. This increase, mediated by HIF-1 signalling, is dependent on glutaminolysis and reactivation of the mTOR pathway. We discuss how these findings in non-transformed tissue may also shed light on the ability of cancer cells in poorly vascularised solid tumours to proliferate.

In many growing tissues, slowly dividing stem cells give rise to rapidly proliferating progenitors that eventually exit the cell cycle and differentiate. Growth rates are limited by nutrient availability, but it is unclear which steps of the proliferation-differentiation programme are particularly sensitive to fuel supplies. We examined how nutrient deprivation (ND) affects stem and progenitor cells in the ciliary marginal zone (CMZ) of the amphibian retina, a well-characterised neurogenic niche. We show that ND specifically blocks the proliferation and differentiation of progenitor cells through an mTOR-mediated mechanism. By contrast, the identity and proliferation of retinal stem cells are insensitive to ND and mTOR inhibition. Re-feeding starved retinas in vitro rescues both proliferation and differentiation, and activation of mTOR is sufficient to stimulate differentiation even in ND retinas. These results suggest that an mTOR-mediated restriction point operates in vivo to couple nutrient abundance to the proliferation and differentiation programme in retinal progenitor cells.

Unlike healthy adult tissues, cancers produce energy mainly by aerobic glycolysis instead of oxidative phosphorylation. This adaptation, called the Warburg effect, may be a feature of all dividing cells, both normal and cancerous, or it may be specific to cancers. It is not known whether, in a normally growing tissue during development, proliferating and postmitotic cells produce energy in fundamentally different ways. Here we show in the embryonic Xenopus retina in vivo, that dividing progenitor cells depend less on oxidative phosphorylation for ATP production than non-dividing differentiated cells, and instead use glycogen to fuel aerobic glycolysis. The transition from glycolysis to oxidative phosphorylation is connected to the cell differentiation process. Glycolysis is indispensable for progenitor proliferation and biosynthesis, even when it is not used for ATP production. These results suggest that the Warburg effect can be a feature of normal proliferation in vivo, and that the regulation of glycolysis and oxidative phosphorylation is critical for normal development.