A spatial and temporal analysis of risk factors associated with sporadic Shiga toxin-producing Escherichia coli O157 infection in England between 2009 and 2015.

Infection with STEC O157 is relatively rare but has potentially serious sequelae, particularly for children. Large outbreaks have prompted considerable efforts designed to reduce transmission primarily from food and direct animal contact. Despite these interventions, numbers of infections have remained constant for many years and the mechanisms leading to many sporadic infections remain unclear.Here, we show that two-thirds of all cases reported in England between 2009 and 2015 were sporadic. Crude rates of infection differed geographically and were highest in rural areas during the summer months. Living in rural areas with high densities of cattle, sheep or pigs and those served by private water supplies were associated with increased risk. Living in an area of lower deprivation contributed to increased risk but this appeared to be associated with reported travel abroad. Fresh water coverage and residential proximity to the coast were not risk factors.To reduce the overall burden of infection in England, interventions designed to reduce the number of sporadic infections with STEC should focus on the residents of rural areas with high densities of livestock and the effective management of non-municipal water supplies. The role of sheep as a reservoir and potential source of infection in humans should not be overlooked.

Shiga Toxin-Producing Escherichia coli O157, England and Wales, 1983-2012.

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.

Public Health Investigation of Two Outbreaks of Shiga Toxin-Producing Escherichia coli O157 Associated with Consumption of Watercress.

An increase in the number of cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 2 (PT2) in England in September 2013 was epidemiologically linked to watercress consumption. Whole-genome sequencing (WGS) identified a phylogenetically related cluster of 22 cases (outbreak 1). The isolates comprising this cluster were not closely related to any other United Kingdom strain in the Public Health England WGS database, suggesting a possible imported source. A second outbreak of STEC O157 PT2 (outbreak 2) was identified epidemiologically following the detection of outbreak 1. Isolates associated with outbreak 2 were phylogenetically distinct from those in outbreak 1. Epidemiologically unrelated isolates on the same branch as the outbreak 2 cluster included those from human cases in England with domestically acquired infection and United Kingdom domestic cattle. Environmental sampling using PCR resulted in the isolation of STEC O157 PT2 from irrigation water at one implicated watercress farm, and WGS showed this isolate belonged to the same phylogenetic cluster as outbreak 2 isolates. Cattle were in close proximity to the watercress bed and were potentially the source of the second outbreak. Transfer of STEC from the field to the watercress bed may have occurred through wildlife entering the watercress farm or via runoff water. During this complex outbreak investigation, epidemiological studies, comprehensive testing of environmental samples, and the use of novel molecular methods proved invaluable in demonstrating that two simultaneous outbreaks of STEC O157 PT2 were both linked to the consumption of watercress but were associated with different sources of contamination.

Salmonella enterica serovar Enteritidis, England and Wales, 1945-2011.

In England and Wales, the emergence of Salmonella enterica serovar Enteritidis resulted in the largest and most persistent epidemic of foodborne infection attributable to a single subtype of any pathogen since systematic national microbiological surveillance was established. We reviewed 67 years of surveillance data to examine the features, underlying causes, and overall effects of S. enterica ser. Enteritidis. The epidemic was associated with the consumption of contaminated chicken meat and eggs, and a decline in the number of infections began after the adoption of vaccination and other measures in production and distribution of chicken meat and eggs. We estimate that >525,000 persons became ill during the course of the epidemic, which caused a total of 6,750,000 days of illness, 27,000 hospitalizations, and 2,000 deaths. Measures undertaken to control the epidemic have resulted in a major reduction in foodborne disease in England and Wales.

The "case-chaos study" as an adjunct or alternative to conventional case-control study methodology.

Case-control studies are important in infectious disease epidemiology for rapidly identifying and controlling risks, but challenges, including the need for speed, can place practical restrictions on control selection and recruitment. The biased comparisons that result can hamper or, worse, mislead investigators. Following a 2009 outbreak of Shiga-like toxin-producing Escherichia coli O157 infection associated with a petting farm in southeast England, it was hypothesized that case behavior alone could be used to identify risks. Case-patients' exposures were randomized on a case-by-case basis, and the resulting permuted data were compared with the actual events preceding illness by conditional logistic regression analysis. There was good agreement between the risks identified by using our new method and the risks elicited in the original outbreak case-control studies. This was also the case in analysis of 2 further historical outbreaks. These initial findings suggest that the technique, which we have called the "case-chaos" technique, appeared to be useful in this setting. Analysis of simulated data supports this view. Circumventing the need for traditional control data has the potential to reduce outbreak investigation lead times, leading to earlier interventions and reduced morbidity and mortality. However, further validation is necessary, coupled with an awareness of limitations of the method.

Methods for determining disease burden and calibrating national surveillance data in the United Kingdom: the second study of infectious intestinal disease in the community (IID2 study).

BACKGROUND: Infectious intestinal disease (IID), usually presenting as diarrhoea and vomiting, is frequently preventable. Though often mild and self-limiting, its commonness makes IID an important public health problem. In the mid 1990s around 1 in 5 people in England suffered from IID a year, costing around pound0.75 billion. No routine information source describes the UK's current community burden of IID. We present here the methods for a study to determine rates and aetiology of IID in the community, presenting to primary care and recorded in national surveillance statistics. We will also outline methods to determine whether or not incidence has declined since the mid-1990s. METHODS/DESIGN: The Second Study of Infectious Intestinal Disease in the Community (IID2 Study) comprises several separate but related studies. We use two methods to describe IID burden in the community - a retrospective telephone survey of self-reported illness and a prospective, all-age, population-based cohort study with weekly follow-up over a calendar year. Results from the two methods will be compared. To determine IID burden presenting to primary care we perform a prospective study of people presenting to their General Practitioner with symptoms of IID, in which we intervene in clinical and laboratory practice, and an audit of routine clinical and laboratory practice in primary care. We determine aetiology of IID using molecular methods for a wide range of gastrointestinal pathogens, in addition to conventional diagnostic microbiological techniques, and characterise isolates further through reference typing. Finally, we combine all our results to calibrate national surveillance data. DISCUSSION: Researchers disagree about the best method(s) to ascertain disease burden. Our study will allow an evaluation of methods to determine the community burden of IID by comparing the different approaches to estimate IID incidence in its linked components.

Listeria monocytogenes infection in the over-60s in England between 2005 and 2008: a retrospective case-control study utilizing market research panel data.

A retrospective case-control study of listeriosis in patients in England aged over 60 years is described. The incidence of listeriosis in patients aged ≥60 years in England has doubled since 2001; hence, the investigation of risk factors for infection in this group is important to inform on prevention and control. Standardized epidemiological information has been sought on cases since 2005, but the value of the data accrued is limited without some perception of exposure prevalence in the population at risk of listeriosis. The exposures of listeriosis cases aged ≥60 years reported in England from 2005 to 2008 were compared to those of market research panel members representing the same population (i.e., residents of England aged ≥60 years) and time period. Exposures were grouped to facilitate comparison. Odds ratios and 95% confidence intervals were calculated. Cases were more likely than panel members to report the consumption of cooked meats (beef and ham/pork, but not poultry), cooked fish (specifically smoked salmon) and shellfish (prawns), dairy products (most noticeably milk but also certain cheeses), and mixed salads. They were less likely to report the consumption of other forms of seafood, dairy spread, other forms of dairy, sandwiches, and fresh vegetables. The diversity of high-risk food exposures reflects the ubiquity of the microorganism in the environment and/or the susceptibility of those at risk, and suggests that a wider variety of foods can give rise to listeriosis. Food safety advice on avoiding listeriosis should be adapted accordingly. While not inexpensive, the application of market research data to infectious disease epidemiology can add value to routine surveillance data.

Modelling study to estimate the health burden of foodborne diseases: cases, general practice consultations and hospitalisations in the UK, 2009.

OBJECTIVE: To generate estimates of the burden of UK-acquired foodborne disease accounting for uncertainty. DESIGN: A modelling study combining data from national public health surveillance systems for laboratory-confirmed infectious intestinal disease (IID) and outbreaks of foodborne disease and 2 prospective, population-based studies of IID in the community. The underlying data sets covered the time period 1993-2008. We used Monte Carlo simulation and a Bayesian approach, using a systematic review to generate Bayesian priors. We calculated point estimates with 95% credible intervals (CrI). SETTING: UK, 2009. OUTCOME MEASURES: Pathogen-specific estimates of the number of cases, general practice (GP) consultations and hospitalisations for foodborne disease in the UK in 2009. RESULTS: Bayesian approaches gave slightly more conservative estimates of overall health burden (∼511 000 cases vs 566 000 cases). Campylobacter is the most common foodborne pathogen, causing 280 400 (95% CrI 182 503-435 693) food-related cases and 38 860 (95% CrI 27 160-55 610) GP consultations annually. Despite this, there are only around 562 (95% CrI 189-1330) food-related hospital admissions due to Campylobacter, reflecting relatively low disease severity. Salmonella causes the largest number of hospitalisations, an estimated 2490 admissions (95% CrI 607-9631), closely followed by Escherichia coli O157 with 2233 admissions (95% CrI 170-32 159). Other common causes of foodborne disease include Clostridium perfringens, with an estimated 79 570 cases annually (95% CrI 30 700-211 298) and norovirus with 74 100 cases (95% CrI 61 150-89 660). Other viruses and protozoa ranked much lower as causes of foodborne disease. CONCLUSIONS: The 3 models yielded similar estimates of the burden of foodborne illness in the UK and show that continued reductions in Campylobacter, Salmonella, E. coli O157, C. perfringens and norovirus are needed to mitigate the impact of foodborne disease.

Estimating the burden of acute gastroenteritis, foodborne disease, and pathogens commonly transmitted by food: an international review.

The burden of foodborne disease is not well defined in many countries or regions or on a global level. The World Health Organization (WHO), in conjunction with other national public health agencies, is coordinating a number of international activities designed to assist countries in the strengthening of disease surveillance and to determine the burden of acute gastroenteritis. These data can then be used to estimate the following situations: (1) the burden associated with acute gastroenteritis of foodborne origin, (2) the burden caused by specific pathogens commonly transmitted by food, and (3) the burden caused by specific foods or food groups. Many of the scientists collaborating with the WHO on these activities have been involved in quantifying the burden of acute gastroenteritis on a national basis. This article reviews these key national studies and the international efforts that are providing the necessary information and technical resources to derive national, regional, and global burden of disease estimates.

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012.

BACKGROUND: We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. METHODS: Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. RESULTS: Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle.

A summertime peak of "winter vomiting disease": surveillance of noroviruses in England and Wales, 1995 to 2002.

BACKGROUND: Noroviruses are the most common cause of gastroenteritis outbreaks in industrialised countries. Gastroenteritis caused by Norovirus infection has been described as a highly seasonal syndrome, often referred to as "winter vomiting disease". METHODS: The Public Health Laboratory Service Communicable Disease Surveillance Centre has systematically collected reports of laboratory confirmed cases of Norovirus-gastroenteritis since 1995. We analysed these data for annual and seasonal trends and age distribution. RESULTS: A mid-summer peak in reported cases of Norovirus was observed in 2002, unlike all six previous years when there was a marked summer decline. Total reports from 2002 have also been higher than all previous years. From the first 10 months of 2002, a total of 3029 Norovirus diagnoses were reported compared the previous peak in 1996 of 2437 diagnoses for the whole 12-month period. The increase in 2002 was most marked in the 65 and older age group. CONCLUSION: This surveillance data challenges the view that Noroviruses infections exclusively have wintertime seasonality.

To close or not to close? Analysis of 4 year's data from national surveillance of norovirus outbreaks in hospitals in England.

OBJECTIVE: To assess the impact of ward or bay closures, specifically, whether prompt closure of an affected ward shortens the duration of norovirus outbreaks and the resulting disruption in hospitals. DESIGN: Analysis of summary data from hospitals on outbreaks of norovirus from 2009 to 2012. METHODS: Using a large outbreak surveillance dataset, we examined the duration of outbreaks, duration of disruption, ward closures, the number of patients and staff affected and the number of lost bed-days, as functions of the timing of closure. We conducted Quasi-Poisson regression analyses to assess the effect of ward closure (timing of closure) on outcome measures, controlling for time of year (winter or summer), ward size and ward type (elderly care wards). RESULTS: Regression analysis indicates that after controlling for season ward size and type, the duration of outbreak and duration of disruption were shorter, fewer patients were affected by the time of closure and fewer patients were affected overall, when closure occurred promptly (within 3 days of the first case becoming ill) compared with non-prompt closure groups. However, in outbreaks where wards were not closed, the length of outbreaks were similar to the prompt closure group and also had fewer patients and staff affected and fewer cases per day of outbreak compared with prompt closure. CONCLUSIONS: Closing a bay or ward promptly in an outbreak of norovirus leads to a shorter duration of outbreaks, a shorter duration of disruption and fewer patients being affected compared with outbreaks where wards were not promptly closed. However, the interpretation of these results is not straightforward. The outbreaks where the ward was not closed at all have similar characteristics in terms of the duration of outbreak and fewer people were affected compared with the baseline prompt closure group.

Evaluating the use of multilocus variable number tandem repeat analysis of Shiga toxin-producing Escherichia coli O157 as a routine public health tool in England.

Multilocus variable number tandem repeat analysis (MLVA) provides microbiological support for investigations of clusters of cases of infection with Shiga toxin-producing E. coli (STEC) O157. All confirmed STEC O157 isolated in England and submitted to the Gastrointestinal Bacteria Reference Unit (GBRU) during a six month period were typed using MLVA, with the aim of assessing the impact of this approach on epidemiological investigations. Of 539 cases investigated, 341 (76%) had unique (>2 single locus variants) MLVA profiles, 12% of profiles occurred more than once due to known household transmission and 12% of profiles occurred as part of 41 clusters, 21 of which were previously identified through routine public health investigation of cases. The remaining 20 clusters were not previously detected and STEC enhanced surveillance data for associated cases were retrospectively reviewed for epidemiological links including shared exposures, geography and/or time. Additional evidence of a link between cases was found in twelve clusters. Compared to phage typing, the number of sporadic cases was reduced from 69% to 41% and the diversity index for MLVA was 0.996 versus 0.782 for phage typing. Using MLVA generates more data on the spatial and temporal dispersion of cases, better defining the epidemiology of STEC infection than phage typing. The increased detection of clusters through MLVA typing highlights the challenges to health protection practices, providing a forerunner to the advent of whole genome sequencing as a diagnostic tool.

Epidemiology and microbiology of Shiga toxin-producing Escherichia coli other than serogroup O157 in England, 2009-2013.

The implementation of direct testing of clinical faecal specimens for gastrointestinal (GI) pathogens by PCR offers a sensitive and comprehensive approach for the detection of Shiga toxin-producing Escherichia coli (STEC). The introduction of a commercial PCR assay, known as GI PCR, for the detection of GI pathogens at three frontline hospital laboratories in England between December 2012 and December 2013 led to a significant increase in detection of STEC other than serogroup O157 (non-O157 STEC). In 2013, 47 isolates were detected in England, compared with 57 in the preceding 4 years (2009-2012). The most common non-O157 STEC serogroup detected was O26 (23.2 %). A total of 47 (47.5 %) STEC isolates had stx2 only, 28 (28.3 %) carried stx1 and stx2, and the remaining 24 (24.2 %) had stx1 only. Stx2a (64.0 %) was the most frequently detected Stx2 subtype. The eae (intimin) gene was detected in 52 (52.5 %) non-O157 STEC isolates. Six strains of STEC O104 had aggR, but this gene was not detected in any other STEC serogroups in this study. Haemolytic ureamic syndrome was significantly associated with STEC strains possessing eae [odds ratio (OR) 5.845, P = 0.0235] and/or stx2a (OR 9.56, P = 0.0034) subtypes. A matched case-control analysis indicated an association between non-O157 STEC cases and contact with farm animals. Widespread implementation of the PCR approach in England will determine the true incidence of non-O157 STEC infection, highlight the burden in terms of morbidity and mortality, and facilitate the examination of risk factors to indicate whether there are niche risk exposures for particular strains.

Disease risks from foods, England and Wales, 1996-2000.

Data from population-based studies and national surveillance systems were collated and analyzed to estimate the impact of disease and risks associated with eating different foods in England and Wales. From 1996 to 2000, an estimated 1,724,315 cases of indigenous foodborne disease per year resulted in 21,997 hospitalizations and 687 deaths. The greatest impact on the healthcare sector arose from foodborne Campylobacter infection (160,788 primary care visits and 15,918 hospitalizations), while salmonellosis caused the most deaths (209). The most important cause of indigenous foodborne disease was contaminated chicken (398,420 cases, risk [cases/million servings] = 111; case-fatality rate [deaths/100,000 cases] = 35, deaths = 141). Red meat (beef, lamb, and pork) contributed heavily to deaths, despite lower levels of risk (287,485 cases, risk = 24, case-fatality rate = 57, deaths = 164). Reducing the impact of indigenous foodborne disease is mainly dependent on controlling the contamination of chicken.