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Abstract Background Children are important transmitters of norovirus infection and there is evidence that laboratory reports in children increase earlier in the norovirus season than in adults. This raises the question as to whether cases and outbreaks in children could provide an early warning of seasonal norovirus before cases start increasing in older, more vulnerable age groups. Methods This study uses weekly national surveillance data on reported outbreaks within schools, care homes and hospitals, general practice (GP) consultations for infectious intestinal disease (IID), telehealth calls for diarrhoea and/or vomiting and laboratory norovirus reports from across England, UK for nine norovirus seasons (2010/11–2018/19). Lagged correlation analysis was undertaken to identify lead or lag times between cases in children and those in adults for each surveillance dataset. A partial correlation analysis explored whether school outbreaks provided a lead time ahead of other surveillance indicators, controlling for breaks in the data due to school holidays. A breakpoint analysis was used to identify which surveillance indicator and age group provided the earliest warning of the norovirus season each year. Results School outbreaks occurred 3-weeks before care home and hospital outbreaks, norovirus laboratory reports and NHS 111 calls for diarrhoea, and provided a 2-week lead time ahead of NHS 111 calls for vomiting. Children provided a lead time ahead of adults for norovirus laboratory reports (+ 1–2 weeks), NHS 111 calls for vomiting (+ 1 week) and NHS 111 calls for diarrhoea (+ 1 week) but occurred concurrently with adults for GP consultations. Breakpoint analysis revealed an earlier seasonal increase in cases among children compared to adults for laboratory, GP and NHS 111 data, with school outbreaks increasing earlier than other surveillance indicators in five out of nine surveillance years. Conclusion These findings suggest that monitoring cases and outbreaks of norovirus in children could provide an early warning of seasonal norovirus infection. However, both school outbreak data and syndromic surveillance data are not norovirus specific and will also capture other causes of IID. The use of school outbreak data as an early warning indicator may be improved by enhancing sampling in community outbreaks to confirm the causative organism.

Abstract Background Infection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. The incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project aimed to explore potential transmission in the home and attempt to identify asymptomatic infections, which might play a role in transmission. Risk factors and characteristics associated with spread of infection in the home were described including any differences between Cryptosporidium species. Methods The study identified cryptosporidiosis cases from North West England and Wales over a year and invited them and their household to take part. Each household was sent a study pack containing study information and a questionnaire, and stool sample kits to provide samples from consenting household members. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, were characterised using molecular methods to help describe any patterns of transmission. Characteristics of households with and without additional cases were described, and compared using odds ratios (OR) and a multivariable logistic regression identified independent risk factors for household transmission. Data collection ran for one year, beginning in September 2018 with an initial pilot phase. Results We enrolled 128 index cases and their households. Additional illness occurred in over a quarter of homes, each reporting an average of two additional cases. The majority of these were undiagnosed and unreported to surveillance. This burden was even greater in households where the index case was infected with C. hominis versus C. parvum, or the index case was under five years old, with mums and siblings most at risk of secondary infection. Only having an index case of C. hominis was independently associated with transmission in the multivariable model (OR 4.46; p = 0.01). Conclusions Cryptosporidium was a considerable burden in the home. At-risk homes were those where the index was less than five years old and/or infected with C. hominis. Of particular risk were female caregivers and siblings. Hygiene advice should be specifically directed here. This work provides evidence for humans as sources of C. hominis infection and that person-person is a key pathway. We recommend that all stools submitted for the investigation of gastrointestinal pathogens are tested for Cryptosporidium to better capture cases, inclusion of speciation data in routine surveillance, and the consideration of specific clinical advice on prevention for high-risk homes.

Abstract Background Syndromic surveillance provides public health intelligence to aid in early warning and monitoring of public health impacts (e.g. seasonal influenza), or reassurance when an impact has not occurred. Using information collected during routine patient care, syndromic surveillance can be based on signs/symptoms/preliminary diagnoses. This approach makes syndromic surveillance much timelier than surveillance requiring laboratory confirmed diagnoses. The provision of healthcare services and patient access to them varies globally. However, emergency departments (EDs) exist worldwide, providing unscheduled urgent care to people in acute need. This provision of care makes ED syndromic surveillance (EDSyS) a potentially valuable tool for public health surveillance internationally. The objective of this study was to identify and describe the key characteristics of EDSyS systems that have been established and used globally. Methods We systematically reviewed studies published in peer review journals and presented at International Society of Infectious Disease Surveillance conferences (up to and including 2017) to identify EDSyS systems which have been created and used for public health purposes. Search criteria developed to identify “emergency department” and “syndromic surveillance” were applied to NICE healthcare, Global Health and Scopus databases. Results In total, 559 studies were identified as eligible for inclusion in the review, comprising 136 journal articles and 423 conference abstracts/papers. From these studies we identified 115 EDSyS systems in 15 different countries/territories across North America, Europe, Asia and Australasia. Systems ranged from local surveillance based on a single ED, to comprehensive national systems. National EDSyS systems were identified in 8 countries/territories: 2 reported inclusion of ≥85% of ED visits nationally (France and Taiwan). Conclusions EDSyS provides a valuable tool for the identification and monitoring of trends in severe illness. Technological advances, particularly in the emergency care patient record, have enabled the evolution of EDSyS over time. EDSyS reporting has become closer to ‘real-time’, with automated, secure electronic extraction and analysis possible on a daily, or more frequent basis. The dissemination of methods employed and evidence of successful application to public health practice should be encouraged to support learning from best practice, enabling future improvement, harmonisation and collaboration between systems in future. Prospero number CRD42017069150 .

Abstract Background Outbreaks of infectious gastroenteritis are common in care homes for the elderly. Norovirus can cause these outbreaks, but diagnosis is frequently based solely on clinical characteristics. Our objective in this study was to describe the epidemiology of norovirus and other gastrointestinal pathogens in these settings. Methods We analysed surveillance data from gastroenteritis outbreaks reported in North East England between 04 July 2016 to 01 July 2018. Stool samples taken during these outbreaks were tested for a range of viral and bacterial pathogens. We described the epidemiology of these outbreaks and explored the characteristics of norovirus outbreaks versus from other viral causes using multivariable logistic regression. Results From the 566 care home gastroenteritis outbreaks in this study, we found that norovirus was the pathogen most frequently isolated. Norovirus was detected in 64% of outbreaks with a pathogen identified. Sapovirus was found in 13%; rotavirus in 11%. We found that norovirus outbreaks were associated with higher attack rates (aOR 1.03, 95% CI 1.01–1.05) and fewer cases sampled (aOR 0.74, 95% CI 0.60–0.91), compared to outbreaks caused by other viral pathogens. Conclusions These results are important as they quantify the contribution of norovirus to gastroenteritis outbreaks in care homes. Given this evidence, we emphasize the importance of non-specific outbreak interventions that can affect the impact of all such outbreaks. We further recommend that these findings are used to inform the implementation strategies of any norovirus-specific interventions such as a norovirus vaccine.

Abstract Background With over 800 million cases globally, campylobacteriosis is a major cause of food borne disease. In temperate climates incidence is highly seasonal but the underlying mechanisms are poorly understood, making human disease control difficult. We hypothesised that observed disease patterns reflect complex interactions between weather, patterns of human risk behaviour, immune status and level of food contamination. Only by understanding these can we find effective interventions. Methods We analysed trends in human Campylobacter cases in NE England from 2004 to 2009, investigating the associations between different risk factors and disease using time-series models. We then developed an individual-based (IB) model of risk behaviour, human immunological responses to infection and environmental contamination driven by weather and land use. We parameterised the IB model for NE England and compared outputs to observed numbers of reported cases each month in the population in 2004–2009. Finally, we used it to investigate different community level disease reduction strategies. Results Risk behaviours like countryside visits (t = 3.665, P

Abstract Background Norovirus is the commonest cause of infectious intestinal disease (IID) worldwide. In the UK community incidence of norovirus has been estimated at 59/1000 population, equating to four million cases a year. Whilst norovirus infects people of all ages, a substantial burden occurs in infants and young children. The population of viruses found in sporadic cases among infants has been observed to be more diverse than that associated with outbreaks. In this study, we analysed norovirus-positive specimens collected during the second study of infectious intestinal diseases (IID2 Study) a national community cohort study conducted between April 2008 and August 2009 We examined the data for differences in circulating norovirus strains between two arms of a community cohort, and differences between genotypes and disease outcomes such as illness duration and symptom profiles. Methods Analysis was conducted to assess genetic diversity of noroviruses in the community. We also assessed differences in the cycle threshold (Ct) value, as a proxy for viral load, between norovirus genogroups and genotypes, and differences in reported symptoms or length of illness in relation to genogroup and genotype. Results There were 477 samples where norovirus was detected. Whilst 85% of people recovered within two days for vomiting; diarrhoea symptoms were reported to day 4 for 83% of the cases, and 10% of people reported symptoms of diarrhoea lasting between five and six days. Both diarrhoea and vomiting symptoms lasted longer in children aged

Abstract Background Outbreaks of infectious gastroenteritis in care homes are common, with norovirus a frequent cause. In England there is no co-ordinated national surveillance system. We aimed to estimate the burden of these outbreaks. Methods Using a generalised linear mixed effects regression model we described the relationship between the observed number of care home outbreaks and covariates. Estimated model parameters were used to infer uplift in the number of outbreaks expected if all areas were subjected to enhanced surveillance. From this we then estimated the total burden of care home gastroenteritis outbreaks in this period. Results We estimated a total of 14,146 care home gastroenteritis outbreaks in England during 2014–2016; this is 47% higher than the reported total and a rate of 32.4 outbreaks per 100 care homes per year. The median number of outbreaks from the model estimates was 31 (IQR 20–46) compared to 19 (IQR 12–34) reported from routine surveillance. Conclusions This estimated care home gastroenteritis burden in England indicates that current surveillance substantially underestimates the number of outbreaks, by almost half. Improving this surveillance could provide better epidemiological knowledge of the burden of norovirus to inform public health policy, particularly with the advent of norovirus vaccines.

Abstract Background Cryptosporidium is a protozoan parasite of humans and other animals worldwide and is one of the greatest contributors to human diarrhoeal illness. Transmission can occur indirectly via contaminated food or water, or directly via contact with animals or other infected people. Risk exposures are often identified from outbreak investigations, but a subset of cases remains unexplained, and sources for sporadic disease and pathways to infection are still unclear. Given the few systematic syntheses of reported evidence in industrialised populations, the aim of this review is to consolidate the literature to describe exposures associated with human cryptosporidiosis in industrialised countries, specifically including the UK, and describe any differences between outbreak-associated and sporadic disease. Methods/design Where relevant, methods will follow the recommendations made in the Cochrane Handbook for Systematic Reviews of Interventions. Three steps will be used to identify the literature including electronic database searching using PubMed, Scopus, Embase and Web of Science; reference list trawling; and an exploration of the grey literature. Screening of results will be undertaken by two reviewers using pre-defined criteria. Studies conducted in industrialised countries and reporting on human subjects will be included. All observational studies will be included where they report exposures and relevant quantitative results. Data will be extracted using a standardised form. Study quality will be assessed using the ROBINS-I tool. Data will be summarised presenting the papers’ main findings including population under study, outcomes, and exposures, and whether these were considered outbreak or sporadic cases. A narrative summary will also be included. Where populations are appropriate, available data will be pooled in a meta-analysis combining the significant exposures across studies. Discussion This review aims to consolidate the evidence for transmission routes and exposures for Cryptosporidium in industrialised countries, with particular reference to how these may apply to the UK. In addition, the review will seek to describe differences between outbreak and sporadic cases. This will help to identify those most vulnerable, highlighting pathways where interventions and public health response may be appropriate. Systematic review registration PROSPERO number CRD42017056589.

Abstract Background Data on outbreaks of infectious gastroenteritis in care homes have been collected using an internet-based surveillance system in North West England since 2012. We analysed the burden and characteristics of care home outbreaks to inform future public health decision-making. Methods We described characteristics of care homes and summary measures of the outbreaks such as attack rate, duration and pathogen identified. The primary analysis outcome was duration of closure following an outbreak. We used negative binomial regression to estimate Incidence Rate Ratios (IRR) and confidence intervals (CI) for each explanatory variable. Results We recorded 795 outbreaks from 379 care homes (37.1 outbreaks per 100 care homes per year). In total 11,568 cases, 75 hospitalisations and 29 deaths were reported. Closure within three days of the first case (IRR = 0.442, 95%CI 0.366–0.534) was significantly associated with reduced duration of closure. The total size of the home (IRR = 1.426, 95%CI = 1.275–1.595) and the total attack rate (IRR = 1.434, 95%CI = 1.257–1.595) were significantly associated with increased duration of closure. Conclusions Care homes that closed promptly had outbreaks of shorter duration. Care home providers, and those advising them on infection control, should aim to close homes quickly to prevent lengthy disruption to services.

During winter 2014–15, England experienced severe strains on acute health services. We investigated whether syndromic surveillance could contribute to understanding of the unusually high level of healthcare needs. We compared trends for several respiratory syndromic indicators from that winter to historical baselines. Cumulative and mean incidence rates were compared by winter and age group. All-age influenza-like illness was at expected levels; however, severe asthma and pneumonia levels were above those expected. Across several respiratory indicators, cumulative incidence rates during 2014–15 were similar to those of previous years, but higher for older persons; we saw increased rates of acute respiratory disease, including influenza like illness, severe asthma, and pneumonia, in the 65–74- and >75-year age groups. Age group–specific statistical algorithms may provide insights into the burden on health services and improve early warning in future winters.

Abstract Background The burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or the extent to which they relate to disease severity. Methods We performed a cross-sectional analysis using IID cases identified from a large population-based survey, to explore the association between socioeconomic status (SES) and symptom severity and sickness absence; and to assess the role of symptom severity on the relationship between SES and absence. Regression modelling was used to investigate these associations, whilst controlling for potential confounders such as age, sex and ethnicity. Results Among 1164 cases, those of lower SES versus high had twice the odds of experiencing severe symptoms (OR 2.2, 95%CI;1.66–2.87). Lower SES was associated with higher odds of sickness absence (OR 1.8, 95%CI;1.26–2.69), however this association was attenuated after adjusting for symptom severity (OR 1.4, 95%CI;0.92–2.07). Conclusions In a large sample of IID cases, those of low SES versus high were more likely to report severe symptoms, and sickness absence; with greater severity largely explaining the higher absence. Public health interventions are needed to address the unequal consequences of IID identified.

In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs’ ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public’s preference for rareness and thus preferred to serve them more rare. We estimated that 19%–52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%–98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections.

We evaluated clinical Shiga toxin–producing Escherichia coli O157 infections in England and Wales during 1983–2012 to describe changes in microbiological and surveillance methods. A strain replacement event was captured; phage type (PT) 2 decreased to account for just 3% of cases by 2012, whereas PT8 and PT21/28 strains concurrently emerged, constituting almost two thirds of cases by 2012. Despite interventions to control and reduce transmission, incidence remained constant. However, sources of infection changed over time; outbreaks caused by contaminated meat and milk declined, suggesting that interventions aimed at reducing meat cross-contamination were effective. Petting farm and school and nursery outbreaks increased, suggesting the emergence of other modes of transmission and potentially contributing to the sustained incidence over time. Studies assessing interventions and consideration of policies and guidance should be undertaken to reduce Shiga toxin–producing E. coli O157 infections in England and Wales in line with the latest epidemiologic findings.

Disability adjusted life years (DALYs) have been used since the 1990s. It is a composite measure of years of life lost with years lived with disability. Essentially, one DALY is the equivalent of a year of healthy life lost if a person had not experienced disease. Norovirus is the most common cause of gastrointestinal diseases worldwide. Norovirus activity varies from one season to the next for reasons not fully explained. Infection with norovirus is generally not severe, and is normally characterized as mild and self-limiting with no long-term sequelae. In this study, we model a range of estimates of DALYs for community cases of norovirus in England and Wales. We estimated a range of DALYs for norovirus to account for mixing of the severity of disease and the range of length of illness experienced by infected people. Our estimates were between 1159 and 4283 DALYs per year, or 0.3⁻1.2 years of healthy life lost per thousand cases of norovirus. These estimates provide evidence that norovirus leads to a considerable level of ill health in England and Wales. This information will be helpful should candidate norovirus vaccines become available in the future.

The epidemiology of listeriosis in England and Wales changed during 2001–2008; more patients >60 years of age had bacteremia than in previous years. To investigate these changes, we calculated risk for listeriosis by concurrent condition for non–pregnancy-associated listeriosis cases reported to the national surveillance system in England during 1999–2009. Conditions occurring with L. monocytogenes infection were coded according to the International Classification of Diseases, 10th Revision, and compared with appropriate hospital episode statistics inpatient denominator data to calculate incidence rates/million consultations. Malignancies (especially of the blood), kidney disease, liver disease, diabetes, alcoholism, and age >60 years were associated with an increased risk for listeriosis. Physicians should consider a diagnosis of listeriosis when treating patients who have concurrent conditions. Providing cancer patients, who accounted for one third of cases, with food safety information might help limit additional cases.

In a case–control study of Campylobacter spp. risk factors in England during 2005–2006, we identified recent consumption of commercially prepared chicken as an important risk factor. The risk for illness associated with recent chicken consumption was much lower for persons who regularly ate chicken than in those who did not, which suggests that partial immunologic protection may follow regular chicken preparation or consumption. Chicken-related risk factors accounted for 41% of cases; acid-suppressing medication, for 10%; self-reported past Campylobacter enteritis, 2%; and recent acquisition of a pet dog, 1%. Understanding the risks associated with chicken from different sources will benefit strategies to reduce Campylobacter infections. Better characterization of immune correlates for Campylobacter infection is necessary to assess the relative importance of immunity and behavioral factors in determining risk.

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in polio-free regions. Considerable evidence links Campylobacter infection with GBS, but evidence that implicates other pathogens as triggers remains scarce. We conducted a time-series analysis to investigate short-term correlations between weekly laboratory-confirmed reports of putative triggering pathogens and weekly hospitalizations for GBS in England from 1993 through 2002. We found a positive association between the numbers of reports of laboratory-confirmed influenza A in any given week and GBS hospitalizations in the same week. Different pathogens may trigger GBS in persons of different ages; among those 35 years, positive associations were with influenza. Further studies should estimate the relative contribution of different pathogens to GBS incidence, overall and by age group, and determine whether influenza is a real trigger for GBS or a marker for influenza vaccination.

We conducted prospective surveillance of childhood hemolytic uremic syndrome (HUS) from 1997 to 2001 to describe disease incidence and clinical, epidemiologic and microbiologic characteristics. We compared our findings, where possible, with those of a previous study conducted from 1985 to 1988. The average annual incidence of HUS for the United Kingdom and Ireland (0.71/100,000) was unchanged from 1985 to 1988. The overall early mortality had halved, but the reduction in mortality was almost entirely accounted for by improved outcome in patients with diarrhea-associated HUS. The principal infective cause of diarrhea-associated HUS was Shiga toxin–producing Escherichia coli O157 (STEC O157), although in the 1997–2001 survey STEC O157 phage type (PT) 21/28 had replaced STEC O157 PT2 as the predominant PT. The risk of developing diarrhea-associated HUS was significantly higher in children infected with STEC O157 PT 2 and PT 21/28 compared with other PTs. Hypertension as a complication of HUS was greatly reduced in patients with diarrhea-associated HUS.

Preventing campylobacteriosis depends on a thorough understanding of its epidemiology. We used case-case analysis to compare cases of Campylobacter coli infection with cases of C. jejuni infection, to generate hypotheses for infection from standardized, population-based sentinel surveillance information in England and Wales. Persons with C. coli infection were more likely to have drunk bottled water than were those with C. jejuni infection and, in general, were more likely to have eaten pâté. Important differences in exposures were identified for these two Campylobacter species. Exposures that are a risk for infection for both comparison groups might not be identified or might be underestimated by case-case analysis. Similarly, the magnitude or direction of population risk cannot be assessed accurately. Nevertheless, our findings suggest that case-control studies should be conducted at the species level.

To explore hypotheses for age-related changes in the incidence of Campylobacter infections in England and Wales during 1990–2007, we analyzed electronic laboratory data. Disease incidence was reduced among children, and the greatest increase in risk was for those >60 years of age. Risk factors for campylobacteriosis in the elderly population should be identified.

From July through September 2000, patients in five European countries were infected with a multidrug-resistant strain of Salmonella Typhimurium DT204b. Epidemiologic investigations were facilitated by the transmission of electronic images (Tagged Image Files) of pulsed-field gel electrophoresis profiles. This investigation highlights the importance of standardized protocols for molecular typing in international outbreaks of foodborne disease.

In a prospective, unmatched case-control study of sporadic Shiga toxin (Vero cytotoxin)-producing Escherichia coli O157 (STEC O157) infection in England, exposure to the farming environment emerged strongly as a risk factor (adjusted odds ratio = 2.45; 95% confidence intervals = 1.49-4.02; p=0.0004) posing further challenges and opportunities for prevention.

BackgroundInfectious intestinal disease (IID) is common, and children are more likely than adults both to have IID and to transmit infection onto others. Before the introduction of the vaccine, rotavirus was the leading cause of severe childhood diarrhea, with norovirus and Campylobacter predominate pathogens. Public health surveillance of IID is primarily based on health care data, and as such, illness that is managed within the community will often go undetected. School attendance registers offer a novel data set that has the potential to identify community cases and outbreaks of IID that would otherwise be missed by current health surveillance systems. Although studies have explored the role of school attendance registers in the monitoring of influenza among children, no studies have been identified that consider this approach in the surveillance of IID. ObjectiveThe aim of this study is to explore the role and utility of school attendance registers in the detection and surveillance of IID in children. The secondary aims are to estimate the burden of IID on school absenteeism and to assess the impact of the rotavirus vaccine on illness absence among school-aged children. MethodsThis study is a retrospective analysis of school attendance registers to investigate whether school absences due to illness can be used to capture seasonal trends and outbreaks of infectious intestinal disease among school-aged children. School absences in Merseyside, United Kingdom will be compared and combined with routine health surveillance data from primary care, laboratories, and telehealth services. These data will be used to model spatial and temporal variations in the incidence of IID and to apportion likely causes to changes in school absenteeism trends. This will be used to assess the potential utility of school attendance data in the surveillance of IID and to estimate the burden of IID absenteeism in schools. It will also inform an analysis of the impact of the rotavirus vaccine on disease within this age group. ResultsThis study has received ethical approval from the University of Liverpool Research Ethics Committee (reference number 1819). Use of general practice data has been approved for the evaluation of rotavirus vaccination in Merseyside by NHS Research Ethics Committee, South Central-Berkshire REC Reference 14/SC/1140. ConclusionsThis study is unique in considering whether school attendance registers could be used to enhance the surveillance of IID. Such data have multiple potential applications and could improve the identification of outbreaks within schools, allowing early intervention to reduce transmission both within and outside of school settings. These data have the potential to act as an early warning system, identifying infections circulating within the community before they enter health care settings. School attendance data could also inform the evaluation of vaccination programs, such as rotavirus and, in time, norovirus. International Registered Report Identifier (IRRID)DERR1-10.2196/30078

Symptom profiles have previously been identified for infectious intestinal disease (IID) which distinguish bacterial from viral organisms. However, there is evidence that the seasonality, severity, and duration of IID may differ between children, adults and elderly. A secondary data analysis was undertaken to explore whether symptom profiles for bacterial and viral IID vary across different age groups. Data from 844 cases of IID were divided into three age categories: 65 years. Multivariable logistic regression modelling was used to compare the significance of different symptoms across the three age groups. The odds of bacterial IID in children were increased by onset in the summer, diarrhoea in the absence of vomiting and fever. These symptoms were also associated with lower odds of a viral pathogen. In adults, diarrhoea but no vomiting, bloody diarrhoea and diarrhoea lasting more than 3 days were associated with increased odds of a bacterial organism, whilst onset in the winter or spring and a loss of appetite were associated with viral IID. In the elderly, diarrhoea in the absence of vomiting and diarrhoea lasting more than 3 days were associated with higher odds of bacterial IID and lower odds of a viral cause. Only diarrhoea in the absence of vomiting emerged as a key symptom across all three age groups. Variation in symptom profiles by age has implications for clinicians, public health specialists and epidemiologists who use symptoms to guide presumptive diagnoses in the absence of microbiological confirmation.

BackgroundRotavirus infection is a common cause of gastroenteritis in children worldwide, with a high mortality burden in developing countries, particularly during the first two years of life. Rotavirus vaccination was introduced into the United Kingdom childhood vaccination schedule in July 2013, with high coverage (>90%) achieved by June 2016. We used an emergency department (ED) syndromic surveillance system to assess the impact of the rotavirus vaccination programme, specifically through the demonstration of any immediate and continuing impact on ED gastroenteritis visits in England.MethodsThis retrospective, observational study used syndromic surveillance data collected from 3 EDs in the two years before (July 2011-June 2013) and 3 years post (July 2013-June 2016) introduction of rotavirus vaccination. The weekly levels of ED visits for gastroenteritis (by age group and in total) during the period before rotavirus vaccination was first described alongside the findings of laboratory surveillance of rotavirus during the same period. An interrupted time-series analysis was then performed to demonstrate the impact of rotavirus vaccination introduction on gastroenteritis ED visit levels.ResultsDuring the two years before vaccine introduction ED visits for gastroenteritis in total and for the 0-4 years age group were seen to rise and fall in line with the seasonal rotavirus increases reported by laboratory surveillance. ED gastroenteritis visits by young children were lower in the three years following introduction of rotavirus vaccination (reduced from 8% of visits to 6% of visits). These attendance levels in young children (0-4years) remained higher than in older age groups, however the previously large seasonal increases in children were greatly reduced, from peaks of 16% to 3-10% of ED visits per week.ConclusionsED syndromic surveillance demonstrated a reduction in gastroenteritis visits following rotavirus vaccine introduction. This work establishes ED syndromic surveillance as a platform for rapid impact assessment of future vaccine programmes.

BackgroundCampylobacter jejuni is the most common bacterial cause of human infectious intestinal disease.MethodsWe genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993-1996; n = 293] and IID2 [isolates from 2008-2009; n = 93]), the INTEGRATE project [isolates from 2016-2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163].ResultsThere was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation.DiscussionFour population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation.

IntroductionInfection with the Cryptosporidium parasite causes over 4000 cases of diagnosed illness (cryptosporidiosis) in England and Wales each year. Risk factors are often estimated from outbreak investigations, and in the UK include ingestion of contaminated water and food, farm/animal contact and person-to-person spread in institutions. However, reported outbreaks only represent about 10% of cases and the transmission routes for sporadic disease may not be the same. Contact with other people has been highlighted as a factor in the transmission of Cryptosporidium, but the incidence of sporadic disease has not been sufficiently established, and how frequently this arises from contact with other infected people is not well documented. This project will estimate the amount of secondary spread that occurs in the home and potentially identify asymptomatic infections which might have a role in transmission. Risk factors and characteristics associated with secondary spread will be described including any differences in transmission between Cryptosporidium species.Methods and analysisThe study will prospectively identify cryptosporidiosis cases from North West England and Wales over 1 year and invite them and their household to take part. Each household will complete a questionnaire and each household member will be asked to provide a stool sample. Clinical, demographic and home variables will be described, and further analyses undertaken to investigate associations with secondary spread in the home. Cryptosporidium-positive stool samples, identified by immunofluorescence microscopy, will be characterised using molecular methods to describe patterns of transmission. Data collection is expected to take 1 year, beginning in September 2018.Ethics and disseminationThe study has been approved by the North West–Liverpool East NHS Research Ethics Committee (Reference: 18/NW/0300) and the Confidentiality and Advisory Group (Reference 18/CAG/0084). Outputs will include scientific conferences and peer-reviewed publications. In addition, a short, lay report of findings will be produced for participants, who can opt to receive this when they take part.Trial registration numberCPMS ID: 39458.

BackgroundThe association between socioeconomic status (SES) and health is well-documented; however limited evidence on the relationship between SES and gastrointestinal (GI) infections exists, with published studies producing conflicting results. This systematic review aimed to assess the association between SES and GI infection risk, and explore possible sources of heterogeneity in effect estimates reported in the literature.MethodsMEDLINE, Scopus, Web of Science and grey literature were searched from 1980 to October 2015 for studies reporting an association between GI infections and SES in a representative population sample from a member-country of the Organisation for Economic Co-operation and Development. Harvest plots and meta-regression were used to investigate potential sources of heterogeneity such as age; level of SES variable; GI infection measurement; and predominant mode of transmission. The protocol was registered on PROSPERO: CRD42015027231.ResultsIn total, 6021 studies were identified; 102 met the inclusion criteria. Age was identified as the only statistically significant potential effect modifier of the association between SES and GI infection risk. For children, GI infection risk was higher for those of lower SES versus high (RR 1.51, 95% CI;1.26-1.83), but there was no association for adults (RR 0.79, 95% CI;0.58-1.06). In univariate analysis, the increased risk comparing low and high SES groups was significantly higher for pathogens spread by person-to-person transmission, but lower for environmental pathogens, as compared to foodborne pathogens.ConclusionsDisadvantaged children, but not adults, have greater risk of GI infection compared to their more advantaged counterparts. There was high heterogeneity and many studies were of low quality. More high quality studies are needed to investigate the association between SES and GI infection risk, and future research should stratify analyses by age and pathogen type. Gaining further insight into this relationship will help inform policies to reduce inequalities in GI illness in children.

Foodborne disease poses a serious threat to public health. In the UK, half a million cases are linked to known pathogens and more than half of all outbreaks are associated with catering establishments. The UK Food Standards Agency (FSA) has initiated the UK Food Hygiene Rating Scheme in which commercial food establishments are inspected and scored with the results made public. In this study we investigate the prevalence of food risk increasing behaviours among chefs, catering students and the public. Given the incentive for respondents to misreport when asked about illegal or illicit behaviours we employed a Randomised Response Technique designed to elicit more accurate prevalence rates of such behaviours. We found 14% of the public not always hand-washing immediately after handling raw meat, poultry or fish; 32% of chefs and catering students had worked within 48 hours of suffering from diarrhoea or vomiting. 22% of the public admitted having served meat "on the turn" and 33% of chefs and catering students admitted working in kitchens where such meat was served; 12% of the public and 16% of chefs and catering students admitted having served chicken at a barbeque when not totally sure it was fully cooked. Chefs in fine-dining establishment were less likely to wash their hands after handling meat and fish and those who worked in award winning restaurants were more likely to have returned to work within 48 hours of suffering from diarrhoea and vomiting. We found no correlation between the price of a meal in an establishment, nor its Food Hygiene Rating Score, and the likelihood of any of the food malpractices occurring.

Noroviruses are endemic in the human population, and are recognised as a leading cause of acute gastroenteritis worldwide. Although they are a highly diverse group of viruses, genogroup-II genotype-4 (GII-4) noroviruses are the most frequently identified strains worldwide. The predominance of GII-4 norovirus strains is driven by the periodic emergence of antigenic variants capable of evading herd protection. The global molecular epidemiology of emerging GII-4 strains is largely based on data from outbreak surveillance programmes, but the epidemiology of GII-4 strains among sporadic or community cases is far less well studied. To understand the distribution of GII-4 norovirus strains associated with gastroenteritis in the wider population, we characterised the GII-4 norovirus strains detected during studies of sporadic cases of infectious gastroenteritis collected in the UK and Malawi between 1993 and 2009. Our data shows that GII-4 norovirus strains that have emerged as strains of global epidemic importance have circulated in the community up to 18 years before their recognition as pandemic strains associated with increases in outbreaks. These data may suggest that more comprehensive surveillance programmes that incorporate strains associated with sporadic cases may provide a way for early detection of emerging strains with pandemic potential. This may be of particular relevance as vaccines become available.

To estimate the annual cost to patients, the health service and society of infectious intestinal disease (IID) from Campylobacter, norovirus and rotavirus.Secondary data analysis.The United Kingdom population, 2008-9.Cases and frequency of health services usage due to these three pathogens; associated healthcare costs; direct, out-of-pocket expenses; indirect costs to patients and caregivers.The median estimated costs to patients and the health service at 2008-9 prices were: Campylobacter £50 million (95% CI: £33m-£75m), norovirus £81 million (95% CI: £63m-£106m), rotavirus £25m (95% CI: £18m-£35m). The costs per case were approximately £30 for norovirus and rotavirus, and £85 for Campylobacter. This was mostly borne by patients and caregivers through lost income or out-of-pocket expenditure. The cost of Campylobacter-related Guillain-Barré syndrome hospitalisation was £1.26 million (95% CI: £0.4m-£4.2m).Norovirus causes greater economic burden than Campylobacter and rotavirus combined. Efforts to control IID must prioritise norovirus. For Campylobacter, estimated costs should be considered in the context of expenditure to control this pathogen in agriculture, food production and retail. Our estimates, prior to routine rotavirus immunisation in the UK, provide a baseline vaccine cost-effectiveness analyses.

To estimate the burden of intestinal infectious disease (IID) in the UK and determine whether disease burden estimations using a retrospective study design differ from those using a prospective study design.A retrospective telephone survey undertaken in each of the four countries comprising the United Kingdom. Participants were randomly asked about illness either in the past 7 or 28 days.14,813 individuals for all of whom we had a legible recording of their agreement to participate.Self-reported IID, defined as loose stools or clinically significant vomiting lasting less than two weeks, in the absence of a known non-infectious cause.The rate of self-reported IID varied substantially depending on whether asked for illness in the previous 7 or 28 days. After standardising for age and sex, and adjusting for the number of interviews completed each month and the relative size of each UK country, the estimated rate of IID in the 7-day recall group was 1,530 cases per 1,000 person-years (95% CI: 1135-2113), while in the 28-day recall group it was 533 cases per 1,000 person-years (95% CI: 377-778). There was no significant variation in rates between the four countries. Rates in this study were also higher than in a related prospective study undertaken at the same time.The estimated burden of disease from IID varied dramatically depending on study design. Retrospective studies of IID give higher estimates of disease burden than prospective studies. Of retrospective studies longer recall periods give lower estimated rates than studies with short recall periods. Caution needs to be exercised when comparing studies of self-reported IID as small changes in study design or case definition can markedly affect estimated rates.

Campylobacter species are the most common cause of bacterial gastroenteritis in the developed world. However, comparatively few studies have determined the epidemiological features of campylobacteriosis in resource-poor settings.A total of 1,941 faecal specimens collected from symptomatic (diarrhoeic) children and 507 specimens from asymptomatic (non-diarrhoeic) children hospitalised in Blantyre, Malawi, between 1997 and 2007, and previously tested for the presence of rotavirus and norovirus, was analysed for C. jejuni and C. coli using a real time PCR assay.Campylobacter species were detected in 415/1,941 (21%) of diarrhoeic children, with C. jejuni accounting for 85% of all cases. The median age of children with Campylobacter infection was 11 months (range 0.1-55 months), and was significantly higher than that for children with rotavirus and norovirus (6 months and 7 months respectively; P

A number of infectious agents have previously been suggested as risk factors for the development of Guillain-Barré syndrome (GBS), but robust epidemiologic evidence for these associations is lacking.We conducted a nested case-control study using data from the United Kingdom General Practice Research Database between 1991 and 2001. Controls were matched to cases on general practice clinic, sex, year of birth and date of outcome diagnosis in their matched case. We found positive associations between GBS and infection with Campylobacter, Epstein-Barr virus and influenza-like illness in the previous two months, as well as evidence of a protective effect of influenza vaccination. After correction for under-ascertainment of Campylobacter infection, the excess risk of GBS following Campylobacter enteritis was 60-fold and 20% of GBS cases were attributable to this pathogen.Our findings indicate a far greater excess risk of GBS among Campylobacter enteritis patients than previously reported by retrospective serological studies. In addition, they confirm previously suggested associations between infection due to Epstein-Barr virus infection and influenza-like illness and GBS. Finally, we report evidence of a protective effect of influenza vaccination on GBS risk, which may be mediated through protection against influenza disease, or result from a lower likelihood of vaccination among those with recent infection. Cohort studies of GBS incidence in this population would help to clarify the burden of GBS due to influenza, and any potential protective effect of influenza vaccination.