Influence of socio-economic status on Shiga toxin-producing Escherichia coli (STEC) infection incidence, risk factors and clinical features.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010-2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19-2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10-1.75) and hospitalisation (OR 1.71, 95% CI 1.36-2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16-2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40-2.27; OR 1.85, 95% CI 1.35-2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22-2.70; soil contact, OR 1.52, 95% CI 2.13-1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Large outbreak of multiple gastrointestinal pathogens associated with fresh curry leaves in North East England, 2013.

A total of 592 people reported gastrointestinal illness following attendance at Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in February/March 2013. Epidemiological, microbiological and environmental investigations were undertaken to identify the source and prevent further cases. Several epidemiological analyses were conducted; a cohort study; a follow-up survey of cases and capture re-capture to estimate the true burden of cases. Indistinguishable isolates of Salmonella Agona phage type 40 were identified in cases and on fresh curry leaves used in one of the accompaniments served at the event. Molecular testing indicated entero-aggregative Escherichia coli and Shigella also contributed to the burden of illness. Analytical studies found strong associations between illness and eating food from a particular stall and with food items including coconut chutney which contained fresh curry leaves. Further investigation of the food supply chain and food preparation techniques identified a lack of clear instruction on the use of fresh uncooked curry leaves in finished dishes and uncertainty about their status as a ready-to-eat product. We describe the investigation of one of the largest outbreaks of food poisoning in England, involving several gastrointestinal pathogens including a strain of Salmonella Agona not previously seen in the UK.

Online market research panel members as controls in case-control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK.

Established methods of recruiting population controls for case-control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case-control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.

Investigation of a national outbreak of STEC Escherichia coli O157 using online consumer panel control methods: Great Britain, October 2014.

In October 2014, Public Health England (PHE) identified cases of Shiga toxin-producing Escherichia coli (STEC) serogroup O157 sharing a multiple locus variable-number tandem repeat analysis (MLVA) profile. We conducted a case-control study using multivariable logistic regression to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) testing a range of exposures. Cases were defined as laboratory-confirmed STEC O157 with the implicated MLVA profile, were UK residents aged ⩾18 years with symptom onset between 25 September and 30 October 2014, and had no history of travel abroad within 5 days of symptom onset. One hundred and two cases were identified. Cases were mostly female (65%; median age 49, range 2-92 years). It was the second largest outbreak seen in England, to date, and a case-control study was conducted using market research panel controls and online survey methods. These methods were instrumental in the rapid data collection and analysis necessary to allow traceback investigations for short shelf-life products. This is a new method of control recruitment and this is the first in which it was a standalone recruitment method. The case-control study suggested a strong association between consumption of a ready-to-eat food and disease (aOR 28, 95% CI 5·0-157) from one retailer. No reactive microbiological testing of food items during the outbreak was possible due to the short shelf-life of the product. Collaboration with industrial bodies is needed to ensure timely traceback exercises to identify contamination events and initiate appropriate and focused microbiological testing and implement control measures.

Disease severity of Shiga toxin-producing E. coli O157 and factors influencing the development of typical haemolytic uraemic syndrome: a retrospective cohort study, 2009-2012.

OBJECTIVES: Assess the disease severity of Shiga toxin-producing Escherichia coli (STEC) O157 infection and factors influencing the development of typical haemolytic uraemic syndrome (tHUS). DESIGN: A retrospective cohort study using data collected through routine surveillance questionnaires between 2009 and 2012. PARTICIPANTS: 3323 symptomatic cases of STEC O157. MAIN OUTCOME MEASURES: Incidence of human STEC O157 and tHUS, proportion of cases reporting bloody diarrhoea, hospitalisation, tHUS and death. Odds of progression to tHUS and predicted percentage chance of developing tHUS based on case demographics, STEC O157 strain characteristics and clinical symptoms. RESULTS: From 2009 to 2012, 3323 cases of symptomatic STEC O157 with completed questionnaires were reported, of which 172 developed tHUS (5.18%). Being aged 1-4 years (OR 8.65, 95% CI 5.01 to 14.94, p=0.004) or female (OR 1.61, 95% CI 1.12 to 2.30, p=0.009), being infected with phage type (PT) 21/28 (OR 2.07, 95% CI 1.25 to 3.42, p=0.005) or PT 2 (OR 2.18, 95% CI 1.06 to 4.50, p=0.034), receiving ß-lactam antibiotics (OR 4.08, 95% CI 1.43 to 11.68, p=0.009) and presenting with vomiting (OR 3.16, 95% CI 2.16 to 4.62, p<0.001) or bloody diarrhoea (OR 2.10, 95% CI 1.38 to 3.20, p=0.001) were found to be significant risk factors for progression to tHUS. The predicted percentage chance of developing tHUS varied from under 1% to 50% if all risk factors were present. CONCLUSIONS: The data from this study indicate the use of ß-lactam antibiotics should be avoided in suspected cases of STEC infection in all age groups, particularly in those under the age of 5.

Selection of population controls for a Salmonella case-control study in the UK using a market research panel and web-survey provides time and resource savings.

Timely recruitment of population controls in infectious disease outbreak investigations is challenging. We evaluated the timeliness and cost of using a market research panel as a sampling frame for recruiting controls in a case-control study during an outbreak of Salmonella Mikawasima in the UK in 2013. We deployed a web-survey by email to targeted members of a market research panel (panel controls) in parallel to the outbreak control team interviewing randomly selected public health staff by telephone and completing paper-based questionnaires (staff controls). Recruitment and completion of exposure history web-surveys for panel controls (n = 123) took 14 h compared to 15 days for staff controls (n = 82). The average staff-time cost per questionnaire for staff controls was £13·13 compared to an invoiced cost of £3·60 per panel control. Differences in the distribution of some exposures existed between these control groups but case-control studies using each group found that illness was associated with consumption of chicken outside of the home and chicken from local butchers. Recruiting market research panel controls offers time and resource savings. More rapid investigations would enable more prompt implementation of control measures. We recommend that this method of recruiting controls is considered in future investigations and assessed further to better understand strengths and limitations.

Association between use of proton pump inhibitors and non-typhoidal salmonellosis identified following investigation into an outbreak of Salmonella Mikawasima in the UK, 2013.

In November 2013, national public health agencies in England and Scotland identified an increase in laboratory-confirmed Salmonella Mikawasima. The role of proton pump inhibitors (PPIs) as a risk factor for salmonellosis is unclear; we therefore captured information on PPI usage as part of our outbreak investigation. We conducted a case-control study, comparing each case with two controls. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Thirty-nine of 61 eligible cases were included in the study. The median age of cases was 45 years; 56% were female. Of these, 33% were admitted to hospital and 31% reported taking PPIs. We identified an association between PPIs and non-typhoidal salmonellosis (aOR 8·8, 95% CI 2·0-38·3). There is increasing evidence supporting the existence of an association between salmonellosis and PPIs; however, biological studies are needed to understand the effect of PPIs in the pathogenesis of Salmonella. We recommend future outbreak studies investigate PPI usage to strengthen evidence on the relevance of PPIs in Salmonella infection. These findings should be used to support the development of guidelines for patients and prescribers on the risk of gastrointestinal infection and PPI usage.

A large Great Britain-wide outbreak of STEC O157 phage type 8 linked to handling of raw leeks and potatoes.

Between December 2010 and July 2011, 252 cases of STEC O157 PT8 stx1 + 2 infection were reported in England, Scotland and Wales. This was the largest outbreak of STEC reported in England and the second largest in the UK to date. Eighty cases were hospitalized, with two cases of haemolytic uraemic syndrome and one death reported. Routine investigative data were used to generate a hypothesis but the subsequent case-control study was inconclusive. A second, more detailed, hypothesis generation exercise identified consumption or handling of vegetables as a potential mode of transmission. A second case-control study demonstrated that cases were more likely than controls to live in households whose members handled or prepared leeks bought unwrapped [odds ratio (OR) 40, 95% confidence interval (CI) 2·08-769·4], and potatoes bought in sacks (OR 13·13, 95% CI 1·19-145·3). This appears to be the first outbreak of STEC O157 infection linked to the handling of leeks.

A multi-country Salmonella Enteritidis phage type 14b outbreak associated with eggs from a German producer: 'near real-time' application of whole genome sequencing and food chain investigations, United Kingdom, May to September 2014.

We report an outbreak of Salmonella Enteritidis phage type 14b (PT14b) in the United Kingdom (UK) between May and September 2014 where Public Health England launched an investigation to identify the source of infection and implement control measures. During the same period, outbreaks caused by a Salmonella Enteritidis strain with a specific multilocus variable-number tandem repeat analysis (MLVA) profile occurred in other European Union Member States. Isolates from a number of persons affected by the UK outbreak, who had initially been tested by MLVA also shared this particular profile. Cases were defined as any person infected with S. Enteritidis PT14b, resident in England or Wales and without history of travel outside of this geographical area during the incubation period, reported from 1 June 2014 onwards, with a MLVA profile of 2­11­9-7­4-3­2-8­9 or a single locus variant thereof. In total, 287 cases met the definition. Food traceback investigations in the UK and other affected European countries linked the outbreaks to chicken eggs from a German company. We undertook whole genome sequencing of isolates from UK and European cases, implicated UK premises, and German eggs: isolates were highly similar. Combined with food traceback information, this confirmed that the UK outbreak was also linked to a German producer.

The epidemiology, microbiology and clinical impact of Shiga toxin-producing Escherichia coli in England, 2009-2012.

Between 1 January 2009 and 31 December 2012 in England, a total of 3717 cases were reported with evidence of Shiga toxin-producing E. coli (STEC) infection, and the crude incidence of STEC infection was 1·80/100 000 person-years. Incidence was highest in children aged 1-4 years (7·63/100 000 person-years). Females had a higher incidence of STEC than males [rate ratio (RR) 1·24, P < 0·001], and white ethnic groups had a higher incidence than non-white ethnic groups (RR 1·43, P < 0·001). Progression to haemolytic uraemic syndrome (HUS) was more frequent in females and children. Non-O157 STEC strains were associated with higher hospitalization and HUS rates than O157 STEC strains. In STEC O157 cases, phage type (PT) 21/28, predominantly indigenously acquired, was also associated with more severe disease than other PTs, as were strains encoding stx2 genes. Incidence of STEC was over four times higher in people residing in rural areas than urban areas (RR 4·39, P < 0·001). Exposure to livestock and/or their faeces was reported twice as often in cases living in rural areas than urban areas (P < 0·001). Environmental/animal contact remains an important risk factor for STEC transmission and is a significant driver in the burden of sporadic STEC infection. The most commonly detected STEC serogroup in England was O157. However, a bias in testing methods results in an unquantifiable under-ascertainment of non-O157 STEC infections. Implementation of PCR-based diagnostic methods designed to detect all STEC, to address this diagnostic deficit, is therefore important.

Pregnancy-associated listeriosis in England and Wales.

Listeriosis is a rare but severe foodborne disease with low morbidity and high case-fatality rates. Pregnant women, unborn and newborn babies are among the high-risk groups for listeriosis. We examined listeriosis cases reported to the enhanced surveillance system in England and Wales from 1990 to 2010 to identify risk factors influencing outcome. Cases were defined as pregnancy-associated if Listeria monocytogenes was isolated from a pregnant woman or newborn infants aged <28 days. Of the 3088 cases reported, pregnancy-associated listeriosis accounted for 462 (15%) cases and 315 cases resulted in a live birth. Several factors were identified as affecting the severity and outcome of listeriosis in pregnancy in both mother and child including: presence or absence of maternal symptoms, gestational age at onset of symptoms, and clinical presentation in the infant (meningitis or septicaemia). Deprivation, ethnicity and molecular serotype had no effect on outcome.

Identification of verocytotoxin-producing Escherichia coli O117:H7 in men who have sex with men, England, November 2013 to August 2014.

Between November 2013 and August 2014, nine cases of verocytotoxin-producing Escherichia coli O117:H7 VT1 were confirmed in adult men. Further investigation using semi-structured interviews revealed that eight cases were United Kingdom (UK)-born men who have sex with men (MSM) who had sexually acquired infection in the UK. Most were HIV-positive with high numbers of sexual partners. This behavioural profile resembles that associated with the recent rapid increase in other sexually acquired infections in MSM.

National outbreaks of Salmonella infection in the UK, 2000-2011.

Over a 12-year period, the Health Protection Agency's (now Public Health England's) Department of Gastrointestinal and Emerging Infections (GEZI) investigated over 100 potential national outbreaks of Salmonella enterica. These ranged from a cluster of cases requiring data interrogation and monitoring of the situation, to full blown case-control studies involving hundreds of interviews, many staff, multi-agency collaboration and the media. Vehicles of infection ranged from the usual suspects of chicken and eggs, to the less frequently implicated snake feed and chocolate. This has forced us to alter our preconceptions of disease transmission. The way in which GEZI investigate outbreaks and conduct case-control studies is constantly evolving as we learn and adapt to the changing aetiology of S. enterica. We present the findings and lessons learned during the last 12 years of investigating S. enterica outbreaks in England and Wales.

The development of Web-based surveillance provides new insights into the burden of norovirus outbreaks in hospitals in England.

A new surveillance system for outbreaks of norovirus in English hospitals, the hospital norovirus outbreak reporting system (HNORS), was launched in January 2009. On site investigators were enabled to enter data on outbreaks of norovirus directly onto a tailored system via an Internet-based front end. A standard dataset was designed to collect information describing the key epidemiological characteristics of each outbreak. In the period 1992-2008, 1817 suspected and confirmed outbreaks of norovirus in English hospitals were reported to national surveillance. After introduction of the new system there were 3980 reports of outbreaks of suspected and confirmed norovirus received in the years 2009-2011. Data from the new reporting system demonstrates that transmission of norovirus levies a heavy burden on English hospitals. On average, reported outbreaks are associated with 13,000 patients and 3400 staff becoming ill, 8900 days of ward closure and the loss of over 15,500 bed-days annually.

The serotype case-case design: a direct comparison of a novel methodology with a case-control study in a national Salmonella Enteritidis PT14b outbreak in England and Wales.

Societal and technological changes render traditional study designs less feasible for investigation of outbreaks. We compared results obtained from case-case and case-control designs during the investigation of a Salmonella Enteritidis PT14b (SE14b) outbreak in Britain to provide support for validation of this approach. Exposures of cases were compared to concurrent non-Enteritidis Salmonella cases and population controls recruited through systematic digit phone dialling. Infection with SE14b was associated with eating in oriental restaurants [odds ratio (OR) 35·8, 95% confidence interval (CI) 4·4-290·9] and consuming eggs away from home (OR 13·8, 95% CI 1·5-124·5) in the case-case study and was confirmed through a concurrent case-control study with similar effect estimates and microbiological findings of SE14b in eggs from a specific chicken flock on a Spanish farm. We found that the case-case design was feasible, quick and inexpensive, potentially minimized recall bias and made use of already interviewed cases with subtyping results. This approach has potential for use in future investigations.

A large foodborne outbreak of norovirus in diners at a restaurant in England between January and February 2009.

An outbreak of gastroenteritis affected at least 240 persons who had eaten at a gourmet restaurant over a period of 7 weeks in 2009 in England. Epidemiological, microbiological, and environmental studies were conducted. The case-control study demonstrated increased risk of illness in those who ate from a special 'tasting menu' and in particular an oyster, passion fruit jelly and lavender dish (odds ratio 7·0, 95% confidence interval 1·1-45·2). Ten diners and six staff members had laboratory-confirmed norovirus infection. Diners were infected with multiple norovirus strains belonging to genogroups I and II, a pattern characteristic of molluscan shellfish-associated outbreaks. The ongoing risk from dining at the restaurant may have been due to persistent contamination of the oyster supply alone or in combination with further spread via infected food handlers or the restaurant environment. Delayed notification of the outbreak to public health authorities may have contributed to outbreak size and duration.

A Salmonella Typhimurium phage type (PT) U320 outbreak in England, 2008: continuation of a trend involving ready-to-eat products.

In March 2008, the Health Protection Agency in England conducted a retrospective case-control study to investigate the cause of 179 cases of the newly recognized, fully antimicrobial-sensitive Salmonella Typhimurium PT U320. Forty-three symptomatic laboratory-confirmed case-patients and 84 asymptomatic location-matched controls were interviewed by telephone about exposures in the 3 days prior to illness or interview. Multivariate logistic analysis indicated consumption of pre-packaged egg sandwiches (odds ratio 3·29, 95% confidence interval 1·19-9·09) was independently associated with illness. Eight of the 15 case-patients who consumed egg sandwiches did so from retail chain A (53·3%) whereas none of the eight controls consumed similar sandwiches (χ2=7·20, P≤0·01). A review of the pre-packaged egg sandwich ingredients suggested this outbreak was probably caused by exposure to an ingredient common to pre-packaged sandwiches and prepared salads but we established a definitive epidemiological link with only the former. Short shelf-life, product diversity and investigation lag hinder epidemiological investigations of such popular products, providing continued challenges for food safety enforcement of freshly prepared produce.

An outbreak of Salmonella Typhimurium DT191a associated with reptile feeder mice.

In December 2008 an increase of tetracycline-resistant Salmonella Typhimurium definitive phage-type 191a (DT191a) was identified in England and Wales by the reference laboratory. This was confirmed to have a phage-typing pattern that had not previously been seen. Strong statistical evidence for an association between illness and keeping reptiles was demonstrated by a matched case-case study (mOR 16·82, 95% CI 2·78-∞). Questionnaires revealed an association with frozen reptile feeder mice, and mice representing 80% of the UK supply lines were tested for the presence of Salmonella. DT191a was found in three pools of sampled mice, which were traced back to a single supplier in the USA. Imports from this supplier were halted, and tighter regulations are now in place. A leaflet detailing how to prevent contracting Salmonella from pet reptiles has been published as well as updated advice on the Health Protection Agency's website.