International travel as a risk factor for gastrointestinal infections in residents of North East England.

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.

Shedding and exclusion from childcare in children with Shiga toxin-producing Escherichia coli, 2018-2022.

Excluding children with Shiga toxin-producing Escherichia coli (STEC) from childcare until microbiologically clear of the pathogen, disrupts families, education, and earnings. Since PCR introduction, non-O157 STEC serotype detections in England have increased. We examined shedding duration by serotype and transmission risk, to guide exclusion advice. We investigated STEC cases aged <6 years, residing in England and attending childcare, with diarrhoea onset or sample date from 31 March 2018 to 30 March 2022. Duration of shedding was the interval between date of onset or date first positive specimen and earliest available negative specimen date. Transmission risk was estimated from proportions with secondary cases in settings attended by infectious cases. There were 367 cases (STEC O157 n = 243, 66.2%; STEC non-O157 n = 124, 33.8%). Median shedding duration was 32 days (IQR 20-44) with no significant difference between O157 and non-O157; 2% (n = 6) of cases shed for ≥100 days. Duration of shedding was reduced by 17% (95% CI 4-29) among cases reporting bloody diarrhoea. Sixteen settings underwent screening; four had secondary cases (close contacts' secondary transmission rate = 13%). Shedding duration estimates were consistent with previous studies (median 31 days, IQR 17-41). Findings do not warrant guidance changes regarding exclusion and supervised return of prolonged shedders, despite serotype changes.

Facilitators and barriers to implementing successful exclusion among children with shiga toxin-producing Escherichia coli: a qualitative analysis of public health case management records.

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.

Understanding the impact of the COVID-19 pandemic response on GI infection surveillance trends in England, January 2020-April 2022.

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.

Forgotten but not gone: Yersinia infections in England, 1975 to 2020.

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.

Preliminary investigation of a significant national Cryptosporidium exceedance in the United Kingdom, August 2023 and ongoing.

Routine laboratory surveillance has identified an unprecedented and ongoing exceedance of Cryptosporidium spp. across the United Kingdom, notably driven by C. hominis transmission, since 14 August 2023. Information from 477 reported cases in England and Wales, followed up with a standardised exposure questionnaire as of 25 September 2023, identified foreign travel in 250 (54%) of 463 respondents and swimming in 234 (66%) of 353 cases. A significant, common exposure has not yet been identified in first analyses.

A qualitative process analysis of daily contact testing as an alternative to self-isolation following close contact with a confirmed carrier of SARS-CoV-2.

BACKGROUND: In July 2021, a randomised controlled trial was conducted to compare the effect on SARS-CoV-2 transmission of seven days of Daily Contact Testing (DCT) using Lateral Flow Test (LFT) and two Polymerase Chain Reaction (PCR) tests as an alternative to 10 days of standard self-isolation with one PCR, following close contact with a SARS-CoV-2 carrier. In this qualitative study, we used a nested process evaluation to aid interpretation of the trial and provide insight into factors influencing use of tests, understanding of test results, and how tests were used to inform behavioural decisions. METHODS: Interviews were conducted with 60 participants (42 randomised to DCT and 18 randomised to self-isolation) who had been in close contact with a confirmed SARS-CoV-2 carrier and had consented to take part in the trial. RESULTS: Data were organised into three overarching themes: (1) assessing the risks and benefits of DCT (2) use of testing during the study period and (3) future use of testing. Attitudes toward DCT as an alternative to self-isolation and behaviour during the testing period appeared to be informed by an assessment of the associated risks and benefits. Participants reported how important it was for them to avoid isolation, how necessary self-isolation was considered to be, and the ability of LFTs to detect infection. Behaviour during the testing period was modified to reduce risks and harms as much as possible. Testing was considered a potential compromise, reducing both risk of transmission and the negative impact of self-isolation, and was regarded as a way to return to normal. CONCLUSION: Participants in this study viewed DCT as a sensible, feasible, and welcome means of avoiding unnecessary self-isolation. Although negative LFTs provided reassurance, most people still restricted their activity as recommended. DCT was also highly valued by those in vulnerable households as a means of providing reassurance of the absence of infection and as an important means of detecting infection and prompting self-isolation when necessary.

Engagement with daily testing instead of self-isolating in contacts of confirmed cases of SARS-CoV-2.

BACKGROUND: In December 2020, Public Health England with NHS Test and Trace initiated a pilot study in which close contacts of people with confirmed COVID-19 were given the option to carryout lateral flow device antigen tests at home, as an alternative to self-isolation for 10-14 days. In this study, we evaluated engagement with daily testing, and assessed levels of adherence to the rules relating to behaviour following positive or negative test results. METHODS: We conducted a service evaluation of the pilot study, examining survey responses from a subset of those who responded to an evaluation questionnaire. We used an online cross-sectional survey offered to adult contacts of confirmed COVID-19 cases who consented to daily testing. We used a comparison group of contacts who were not offered testing and instead self-isolated. RESULTS: Acceptability of daily testing was lower among survey respondents who were not offered the option of testing and among people from ethnic minority groups. Overall, 52% of respondents reported being more likely to share details of people that they had been in contact with following a positive test result, if they knew that their contacts would be offered the option of daily testing. Only 2% reported that they would be less likely to provide details of their contacts. On the days that they were trying to self-isolate, 19% of participants reported that they left the house, with no significant group differences. Following a negative test, 13% of respondents reported that they increased their contacts, but most (58%) reported having fewer risky contacts. CONCLUSIONS: Our data suggest that daily testing is potentially acceptable, may facilitate sharing contact details of close contacts among those who test positive for COVID-19, and promote adherence to self-isolation. A better understanding is needed of how to make this option more acceptable for all households. The impact of receiving a negative test on behaviour remains a risk that needs to be monitored and mitigated by appropriate messaging. Future research should examine attitudes and behaviour in a context where infection levels are lower, testing is more familiar, and restrictions on activity have been reduced.

A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation.

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.

Early Detection and Monitoring of Gastrointestinal Infections Using Syndromic Surveillance: A Systematic Review.

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.

The acceptability of testing contacts of confirmed COVID-19 cases using serial, self-administered lateral flow devices as an alternative to self-isolation.

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.

Daily use of lateral flow devices by contacts of confirmed COVID-19 cases to enable exemption from isolation compared with standard self-isolation to reduce onward transmission of SARS-CoV-2 in England: a randomised, controlled, non-inferiority trial.

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.

Impact of the COVID-19 pandemic on gastrointestinal infection trends in England, February-July 2020.

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.

Engagement With Daily Testing Instead of Self-Isolating in Contacts of Confirmed Cases of SARS-CoV-2: A Qualitative Analysis.

Introduction: In December 2020 and January 2021 Public Health England (PHE) with NHS Test and Trace conducted a study to explore the feasibility and acceptability of daily testing as an alternative to self-isolation following close contact with a confirmed COVID-19 case. This qualitative paper aims to identify factors influencing uptake among those offered daily testing, and the subsequent impact on behaviour. Methods: We conducted in-depth interviews with 52 participants who had taken part in the feasibility study. Participants were asked about their experiences of daily testing or self-isolating, their reasons for choosing to test or isolate, and their behaviour during the study period. Data were analysed using inductive thematic analysis. Results: Results are presented under two main headings: (1) factors influencing acceptance of testing and (2) impact of test results. Participants appeared highly motivated to engage in behaviours that would protect others from the virus. Factors influencing the decision to accept testing included (1) needing to avoid self-isolation, (2) concerns about test sensitivity, and (3) perceived benefits of detecting infection. Participants who were taking tests reported: (1) positive consequences following confirmation of COVID status, (2) engaging in essential activities, (3) uncertainty, and (4) self-isolating whilst testing. Conclusions: This study has identified a range of factors that appear to influence the decision to engage in daily testing or to self-isolate following close contact with a positive case, many of which could be addressed by clear communications. Covid-19 infection rates and government restrictions influenced experiences, and so further research is needed to explore perceptions of daily testing and behaviour following close contact with a positive case among a wider range of individuals, in the context of lower rates of COVID-19, few government restrictions on general population behaviour and more widespread testing.

Environmental sampling for SARS-CoV-2 in long term care facilities: lessons from a pilot study.

Background: The SARS-CoV-2 pandemic has highlighted the risk of infection in long-term care facilities (LTCF) and the vulnerability of residents to severe outcomes. Environmental surveillance may help detect pathogens early and inform Infection Prevention and Control (IPC) measures in these settings. Methods: Upon notification of SARS-CoV-2 outbreaks, LTCF within a local authority in South West England were approached to take part in this pilot study. Investigators visited to swab common touch-points and elevated 'non-touch' surfaces (>1.5m above ground level) and samples were analysed for presence of SARS-CoV-2 genetic material (RNA). Data were collected regarding LTCF infrastructure, staff behaviours, clinical and epidemiological risk factors for infection (staff and residents), and IPC measures. Criteria for success were: recruitment of three LTCF; detection of SARS-COV-2 RNA; variation in proportion of SARS-CoV-2 positive surfaces by sampling zone; and collection of clinical and epidemiological data for context. Results: Three LTCFs were recruited, ranging in size and resident demographics. Outbreaks lasted 63, 50 and 30 days with resident attack rates of 53%, 40% and 8%, respectively. The proportion of sample sites on which SARS-CoV-2 was detected was highest in rooms occupied by infected residents and varied elsewhere in the LTCF, with low levels in a facility implementing enhanced IPC measures. The heterogeneity of settings and difficulty obtaining data made it unfeasible to assess association between environmental contamination and infection. A greater proportion of elevated surfaces tested positive for SARS-CoV-2 RNA than common touch-points. Conclusions: SARS-CoV-2 RNA can be detected in a variety of LTCF outbreak settings, both on common-touch items and in elevated sites out of reach. This suggests that further work is justified, to assess feasibility and utility of environmental sampling for infection surveillance in LTCF.

Nutrient-Deprived Retinal Progenitors Proliferate in Response to Hypoxia: Interaction of the HIF-1 and mTOR Pathway.

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.

Metabolic differentiation in the embryonic retina.

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.