Retrospective assessment of rapid outbreak investigation for gastrointestinal diseases using only cases and background exposure data.

For outbreaks of gastrointestinal disease, rapid identification of the source is crucial to enable public health intervention and prevent further cases. Outbreak investigation comprises analyses of exposure information from cases and, if required, undertaking analytical epidemiological studies. Hypothesis generation has been reliant on empirical knowledge of exposures historically associated with a given pathogen. Epidemiology studies are resource-intensive and prone to bias, one of the reasons being the difficulties in recruiting appropriate controls. For this paper, the information from cases was compared against pre-defined background exposure information. As exemplars, three past outbreaks were used, one of common and two of rare exposures. Information from historical case trawling questionnaires was used to define background exposure having removed any exposures implicated with the outbreak. The case-background approach showed good sensitivity and specificity, identifying correctly all outbreak-related exposures. One additional exposure related to a retailer was identified and four food items where all cases had been exposed. In conclusion, the case-background method, a development of the case-case design, can be used to assist with hypothesis generation or when a case-control study may not be possible to carry out.

Campylobacter outbreak associated with raw drinking milk, North West England, 2016.

In December 2016, Public Health England investigated an outbreak of campylobacteriosis in North West England, with 69 cases in total. Epidemiological, microbiological and environmental investigations associated the illness with the consumption of unpasteurised cows' milk from Farm X, where milk was predominantly sold from a vending machine. Campylobacter was detected in milk samples which, when sequenced, were identical in sequence type as pathogens isolated from cases (Clonal Complex ST-403, Sequence Type 7432). The farm was served with a Hygiene Emergency Prohibition Order to prevent further cases. To our knowledge, this is the first outbreak of campylobacter associated with unpasteurised milk in England since 1996. Our findings highlighted several important lessons, including that the current testing regime in England for unpasteurised milk is not fit for purpose and that the required warning label should include additional wording, underscoring the risk to vulnerable groups. There has been a substantial increase in both the volume of unpasteurised milk consumed in England and the use of vending machines to sell unpasteurised milk over the last 10 years, making unpasteurised milk more readily accessible to a wider population. The evidence generated from outbreaks like this is therefore critical and should be used to influence policy development.

Are food exposures obtained through commercial market panels representative of the general population? Implications for outbreak investigations.

Current methods of control recruitment for case-control studies can be slow (a particular issue for outbreak investigations), resource-intensive and subject to a range of biases. Commercial market panels are a potential source of rapidly recruited controls. Our study evaluated food exposure data from these panel controls, compared with an established reference dataset. Market panel data were collected from two companies using retrospective internet-based surveys; these were compared with reference data from the National Diet and Nutrition Survey (NDNS). We used logistic regression to calculate adjusted odds ratios to compare exposure to each of the 71 food items between the market panel and NDNS participants. We compared 2103 panel controls with 2696 reference participants. Adjusted for socio-demographic factors, exposure to 90% of foods was statistically different between both panels and the reference data. However, these differences were likely to be of limited practical importance for 89% of Panel A foods and 79% of Panel B foods. Market panel food exposures were comparable with reference data for common food exposures but more likely to be different for uncommon exposures. This approach should be considered for outbreak investigation, in conjunction with other considerations such as population at risk, timeliness of response and study resources.

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.

An outbreak of Shiga toxin-producing Escherichia coli O157:H7 associated with contaminated salad leaves: epidemiological, genomic and food trace back investigations.

In August 2015, Public Health England detected an outbreak of Shiga toxin-producing Escherichia coli (STEC) serotype O157:H7 caused by contaminated salad leaves in a mixed leaf prepacked salad product from a national retailer. The implicated leaves were cultivated at five different farms and the zoonotic source of the outbreak strain was not determined. In March 2016, additional isolates from new cases were identified that shared a recent common ancestor with the outbreak strain. A case-case study involving the cases identified in 2016 revealed that ovine exposures were associated with illness (n = 16; AOR 8·24; 95% CI 1·55-39·74). By mapping the recent movement of sheep and lambs across the United Kingdom, epidemiological links were established between the cases reporting ovine exposures. Given the close phylogenetic relationship between the outbreak strain and the isolates from cases with ovine exposures, it is plausible that ovine faeces may have contaminated the salad leaves via untreated irrigation water or run-off from fields nearby. Timely and targeted veterinary and environmental sampling should be considered during foodborne outbreaks of STEC, particularly where ready to eat vegetables and salads are implicated.

An outbreak of norovirus GI-6 infection following a wedding in North West England.

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19-20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

Prospective use of whole genome sequencing (WGS) detected a multi-country outbreak of Salmonella Enteritidis.

Since April 2015, whole genome sequencing (WGS) has been the routine test for Salmonella identification, surveillance and outbreak investigation at the national reference laboratory in England and Wales. In May 2015, an outbreak of Salmonella Enteritidis cases was detected using WGS data and investigated. UK cases were interviewed to obtain a food history and links between suppliers were mapped to produce a food chain network for chicken eggs. The association between the food chain network and the phylogeny was explored using a network comparison approach. Food and environmental samples were taken from premises linked to cases and tested for Salmonella. Within the outbreak single nucleotide polymorphism defined cluster, 136 cases were identified in the UK and 18 in Spain. One isolate from a food containing chicken eggs was within the outbreak cluster. There was a significant association between the chicken egg food chain of UK cases and phylogeny of outbreak isolates. This is the first published Salmonella outbreak to be prospectively detected using WGS. This outbreak in the UK was linked with contemporaneous cases in Spain by WGS. We conclude that UK and Spanish cases were exposed to a common source of Salmonella-contaminated chicken eggs.

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.

Service evaluation of selected risk factors for extended-spectrum beta-lactamase Escherichia coli urinary tract infections: a case-control study.

In the context of the increasing incidence of extended-spectrum beta-lactamase (ESBL) Escherichia coli infection, this prospective frequency-matched case-control study aimed to identify risk factors that would provide information and guidance for local clinical practice. One hundred and twelve participants were recruited: 54 cases and 58 controls. Univariate analysis indicated that isolation of an ESBL-producing E. coli in the previous 12 months and diabetes were significantly associated with the outcome. This study demonstrates the utility of service evaluation studies for producing epidemiological information to inform clinical practice.

Outbreak of Salmonella enterica Goldcoast infection associated with whelk consumption, England, June to October 2013.

An increase in the number of cases of Salmonella enterica serotype Goldcoast infection was observed in England during September 2013. A total of 38 cases were reported, with symptom onset dates between 21 June and 6 October 2013. Epidemiological, environmental, microbiological and food chain evidence all support the conclusion that this outbreak was associated with eating whelks processed by the same factory. Whelks are a novel vehicle of Salmonella infection and should be considered when investigating future outbreaks.

Effect of ribotype on all-cause mortality following Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) is significantly associated with subsequent all-cause mortality. Although a number of studies have investigated mortality associated with CDI, few have compared all-cause mortality between ribotypes. AIM: We aimed to estimate all-cause mortality following CDI and to investigate the relationship between mortality, ribotype and other available variables. METHODS: We undertook a retrospective cohort study. All patients with toxin-positive CDI in North East England between July 2009 and June 2011 were matched to death registration data. Differences in all-cause 30-day case fatality were explored using Poisson regression with robust error variances. For survival analysis, an accelerated failure time model with generalized gamma distribution was chosen. FINDINGS: In total, 1426 patients were included. All-cause case fatality was 10.2%, 16.4%, 25.7% and 38.1% at 7, 14, 30 and 90 days respectively. In multivariate analysis, ribotype 027 (risk ratio: 1.34; 95% confidence interval: 1.02-1.75) and ribotype 015 (0.46; 0.26-0.82) were significantly associated with higher and lower all-cause 30-day case fatality rates, respectively. In survival analysis, only ribotype 015 had significantly lower predicted mortality (P = 0.008). Patients whose infection was hospital-acquired had significantly higher predicted mortality (P < 0.001). CONCLUSION: This is the first population-based study of comparative mortality between multiple ribotypes. Our study identified a high rate of all-cause mortality following CDI. We found evidence of variability in mortality between ribotypes in this cohort with mortality significantly higher for ribotype 027 at 30 days following diagnosis and significantly lower for ribotype 015.

Epidemiological survey of Clostridium difficile ribotypes in the North East of England during an 18-month period.

During an 18-month period, 1606 stool specimens from laboratory-confirmed cases of Clostridium difficile infection in the North East of England were ribotyped using unrestricted polymerase chain reaction. Of these, 87.6% grew C. difficile on culture; 70% had one of 10 recognizable ribotypes of which 001, 106 and 027 were the most prevalent. The proportions of ribotypes 002 and 015 declined during the study period, whereas ribotypes 016 and 023 increased. Ribotype 005 was significantly more numerous in males and ribotype 027 was associated with significantly higher mean age. Our findings differ from national data derived from more selective testing.

Cohort study of a campylobacteriosis outbreak associated with chicken liver parfait, United Kingdom, June 2010.

In an outbreak of 24 cases of gastroenteritis among guests at a wedding reception, 13 cases had confirmed Campylobacter infection. In a cohort study, univariate analysis revealed a strong association with consumption of chicken liver parfait: risk ratio (RR): 30.08, 95% confidence interval (CI): 4.34-208.44, p<0.001, which remained after adjustment for potential confounders in a multivariable model: RR=27.8, 95% CI=3.9-199.7, p=0.001. These analyses strongly support the hypothesis that this outbreak was caused by the consumption of chicken liver parfait.