Linking epidemiological and genomic data in cases of enteric fever in England to inform clinical management and public health action.

OBJECTIVES: To explore the feasibility of linking data from enhanced surveillance patient questionnaires from each enteric fever case in England with genome sequencing data, including antimicrobial resistance (AMR) profiles, from the corresponding isolate of typhoidal salmonellae. METHODS: After linking data we interrogated the merged dataset and assessed the utility of passive surveillance data to match and monitor antimicrobial treatment regimens in enteric fever patients with the AMR profiles of the infectious agent. RESULTS: A high proportion of cases were given antibiotics (n = 1230/1415; 86.9%); half of the cases stated the class of antibiotic they were given (n = 630/1239) and half were prescribed cephalosporins (n = 316/630). Reported treatment with a combination of antibiotics increased with symptom severity. Nearly half of isolates (n = 644/1415; 45.5%) had mutations conferring resistance to ciprofloxacin. Based on genome-derived AMR profiles, typhoidal salmonellae isolates inferred to be susceptible to the recommended first-line antimicrobials were twice as likely to be isolated from individuals residing in the least deprived areas compared with the most deprived (n = 26/169; 15.4% versus n = 32/442; 7.2%). CONCLUSIONS: Due to the high proportion of missing data obtained from patient interviews, we recommend a more transparent and systematic approach to recording the antibiotic prescription details by healthcare professionals in primary and secondary care. A more robust approach to data capture at this point in the care pathway would enable us to audit inconsistencies in the prescribing algorithms across England and ensure equitable treatment across all sections of society. Integrating prescribing data with the genome-derived AMR profiles of the causative agent at the individual patient level provides an opportunity to monitor the impact of treatment on clinical outcomes, and to promote best practice in real time.

Association between socioeconomic deprivation and incidence of infectious intestinal disease by pathogen and linked transmission route: An ecological analysis in the UK.

Infectious intestinal disease (IID) studies conducted at different levels of the surveillance pyramid have found heterogeneity in the association of socioeconomic deprivation with illness. The aim of this study was to analyse the association between socioeconomic deprivation and incidence of IID by certain gastrointestinal pathogens reported to UKHSA. Data were extracted from 2015 to 2018 for Salmonella, Campylobacter, Shigella, Giardia species, and norovirus. Rates were calculated per 100,000 person-years by the index of multiple deprivation quintile, and an ecological analysis was conducted using univariant and multvariable regression models for each pathogen. Incidence of Campylobacter, and Giardia species decreased with increasing deprivation. Conversely, the incidence of norovirus, non-typhoidal Salmonella, Salmonella typhi/paratyphi, Shigella species increased with increasing deprivation. Multivariable analysis results showed that higher deprivation was significantly associated with higher odds of higher number of cases for Shigella flexneri, norovirus and S. typhi/paratyphi. Infections most associated with deprivation were those transmitted by person-to-person spread, and least associated were those transmitted by zoonotic contamination of the environment. Person-to-person transmission can be contained by implementing policies targeting over-crowding and poor hygiene. This approach is likely to be the most effective solution for the reduction of IID.

Socioeconomic and ethnic inequalities in incidence and severity of enteric fever in England 2015-2019: analysis of a national enhanced surveillance system.

There is limited research on whether inequalities exist among individuals from different ethnicities and deprivation status among enteric fever cases. The aim of the study was to investigate the association between the enteric fever incidence rates, ethnicity and deprivation for enteric fever cases in England. Additionally, it was assessed if ethnicity and deprivation were associated with symptom severity, hospital admission and absence from school/work using logistic regression models. Incidence rates were higher in the two most deprived index of multiple deprivation quintiles and those of Pakistani ethnicity (9.89, 95% CI 9.08-10.75) followed by Indian (7.81, 95% CI 7.18-8.49) and Bangladeshi (5.68, 95% CI 4.74-6.76) groups: the incidence rate in the White group was 0.07 (95% CI 0.06-0.08). Individuals representing Pakistani (3.00, 95% CI 1.66-5.43), Indian (2.05, 95% CI 1.18-3.54) and Other/Other Asian (3.51, 95% CI 1.52-8.14) ethnicities had significantly higher odds of hospital admission than individuals representing White (British/Other) ethnicity, although all three groups had statistically significantly lower symptom severity scores. Our results show that there are significant ethnic and socioeconomic inequalities in enteric fever incidence that should inform prevention and treatment strategies. Targeted, community-specific public health interventions are needed to impact on overall burden.

Outbreak of Shiga toxin-producing Escherichia coli O157 linked with consumption of a fast-food product containing imported cucumbers, United Kingdom, August 2020.

BACKGROUND: In August 2020, an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 occurred in the United Kingdom. Whole genome sequencing revealed that these cases formed a genetically distinct cluster. METHODS: Hypotheses generated from case interviews were tested in analytical studies, and results informed environmental sampling and food chain analysis. A case-case study used non-outbreak 'comparison' STEC cases; a case-control study used a market research panel to recruit controls. RESULTS: A total of 36 cases were identified; all cases reported symptom onset between August 3 and August 16, 2020. The majority of cases (83%) resided in the Midlands region of England and in Wales. A high proportion of cases reported eating out, with one fast-food restaurant chain mentioned by 64% (n = 23) of cases. Both the case-case study (adjusted odds ratio (aOR) 31.8, 95% confidence interval (CI) 1.6-624.9) and the case-control study (aOR 9.19, 95% CI 1.0-82.8) revealed statistically significant results, showing that the consumption of a specific fast-food product was independently associated with infection. CONCLUSIONS: Consumption of a specific fast-food product was a likely cause of this outbreak. The only ingredient specific to the product was cucumbers. The supply of cucumbers was immediately halted, and no further cases have been identified.

Utility of whole-genome sequencing during an investigation of multiple foodborne outbreaks of Shigella sonnei.

In April 2018, Public Health England was notified of cases of Shigella sonnei who had eaten food from three different catering outlets in England. The outbreaks were initially investigated as separate events, but whole-genome sequencing (WGS) showed they were caused by the same strain. The investigation included analyses of epidemiological data, the food chain and microbiological examination of food samples. WGS was used to determine the phylogenetic relatedness and antimicrobial resistance profile of the outbreak strain. Ultimately, 33 cases were linked to this outbreak; the majority had eaten food from seven outlets specialising in Indian or Middle Eastern cuisine. Five outlets were linked to two or more cases, all of which used fresh coriander although a shared supplier was not identified. An investigation at one of the venues recorded that 86% of cases reported eating dishes with coriander as an ingredient or garnish. Four cases were admitted to hospital and one had evidence of treatment failure with ciprofloxacin. Phylogenetic analysis showed that the outbreak strain was part of a wider multidrug-resistant clade associated with travel to Pakistan. Poor hygiene practices during cultivation, distribution or preparation of fresh produce are likely contributing factors.

Neighbourhood unemployment and other socio-demographic predictors of emergency hospitalisation for infectious intestinal disease in England: A longitudinal ecological study.

BACKGROUND: Previous studies have observed that infectious intestinal disease (IID) related hospital admissions are higher in more deprived neighbourhoods. These studies have mainly focused on paediatric populations and are cross-sectional in nature. This study examines recent trends in emergency IID admission rates, and uses longitudinal methods to investigate the effects of unemployment (as a time varying measure of neighbourhood deprivation) and other socio-demographic characteristics on IID admissions for adults and children in England. METHODS: A longitudinal ecological analysis was performed using Hospital Episode Statistics on emergency hospitalisations for IID, collected over the time period 2012-17 across England. Analysis was conducted at the neighbourhood (Lower-layer Super Output Area) level for three age groups (0-14; 15-64; 65+ years). Mixed-effect Poisson regression models were used to assess the relationship between trends in neighbourhood unemployment and emergency IID admission rates, whilst controlling for measures of primary and secondary care access, underlying morbidity and the ethnic composition of each neighbourhood. RESULTS: From 2012-17, declining trends in emergency IID admission rates were observed for children and older adults overall, while rates increased for some sub-groups in the population. Each 1 percentage point increase in unemployment was associated with a 6.3, 2.4 and 4% increase in the rate of IID admissions per year for children [IRR=1.06, 95%CI 1.06-1.07], adults [IRR=1.02, 95%CI 1.02-1.03] and older adults [IRR=1.04, 95%CI 1.036-1.043], respectively. Increases in poor primary care access, the percentage of people from a Pakistani ethnic background, and the prevalence of long-term health problems, in a neighbourhood, were also associated with increases in IID admission rates. CONCLUSIONS: Increasing trends in neighbourhood deprivation, as measured by unemployment, were associated with increases in emergency IID admission rates for children and adults in England, despite controlling for measures of healthcare access, underlying morbidity and ethnicity. Research is needed to improve understanding of the mechanisms that explain these inequalities, so that effective policies can be developed to reduce the higher emergency IID admission rates experienced by more disadvantaged communities.

Syndromic surveillance: two decades experience of sustainable systems - its people not just data!

Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of 'big data', but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.

Sociodemographic and clinical risk factors for paediatric typical haemolytic uraemic syndrome: retrospective cohort study.

OBJECTIVES: Haemolytic uraemic syndrome (HUS) following Shiga toxin-producing Escherichia coli (STEC) infection is the the most common cause of acute renal failure among children in the UK. This study explored differential progression from STEC to HUS by social, demographic and clinical risk factors. METHODS: We undertook a retrospective cohort study linking two datasets. We extracted data on paediatric STEC and HUS cases identified in the Public Health England National Enhanced Surveillance System for STEC and British Paediatric Surveillance Unit HUS surveillance from 1 October 2011 to 31 October 2014. Using logistic regression, we estimated the odds of HUS progression by risk factors. RESULTS: 1059 paediatric STEC cases were included in the study, of which 207 (19.55%, 95% CI 17% to 22%) developed HUS. In the fully adjusted model, the odds of progression to HUS were highest in those aged 1-4 years (OR 4.93, 95% CI 2.30 to 10.56, compared with 10-15 years), were infected with an Shiga toxin (stx) 2-only strain (OR 5.92, 95% CI 2.49 to 14.10), were prescribed antibiotics (OR 8.46, 95% CI 4.71 to 15.18) and had bloody diarrhoea (OR 3.56, 95% CI 2.04 to 6.24) or vomiting (OR 4.47, 95% CI 2.62 to 7.63), but there was no association with progression to HUS by socioeconomic circumstances or rurality. CONCLUSION: Combining data from an active clinical surveillance system for HUS with the national enhanced STEC surveillance system suggests that 20% of diagnosed paediatric STEC infections in England resulted in HUS. No relationship was found with socioeconomic status or rurality of cases, but differences were demonstrated by age, stx type and presenting symptoms.

Social patterning of telephone health-advice for diarrhoea and vomiting: analysis of 24 million telehealth calls in England.

OBJECTIVES: Gastrointestinal (GI) infections are common and most people do not see a physician. There is conflicting evidence of the impact of socioeconomic status (SES) on risk of GI infections. We assessed the relationship between SES and GI calls to two National Health Service (NHS) telephone advice services in England. METHODS: Over 24 million calls to NHS Direct (2010-13) and NHS 111 (2013-15) were extracted from Public Health England (PHE) syndromic surveillance systems. The relationship between SES and GI calls was assessed using generalised linear models (GLM). RESULTS: Adjusting for rurality and age-sex interactions, in NHS Direct, children in disadvantaged areas were at lower risk of GI calls; in NHS 111 there was a higher risk of GI calls in disadvantaged areas for all ages (0-4 years RR 1.27, 95% CI 1.25-1.29; 5-9 years RR 1.43, 95% CI 1.36-1.51; 10-14 years RR 1.36, 95% CI 1.26-1.41; 15-19 years RR 1.59, 95% CI 1.52-1.67; 20-59 years RR 1.50, 95% CI 1.47-1.53, 60 years and over RR 1.12, 95% CI 1.09-1.14). CONCLUSIONS: Disadvantaged areas had higher risk of GI calls in NHS 111. This may relate to differences in exposure or vulnerability to GI infections, or propensity to call about GI infections.

An outbreak of Shigella boydii serotype 20 in January 2015 amongst United Kingdom healthcare workers involved in the Ebola response in Sierra Leone.

In January 2015, Public Health England and the United Kingdom (UK) Ministry of Defence investigated cases of diarrhoea and fever in military personnel recently returned to the UK after supporting the response to the Ebola epidemic in Sierra Leone. Tests for Ebola virus infection were negative. PCR tests detected the ipaH gene in 10/12 faecal specimens, and Shigella boydii serotype 20 was isolated from 7 patients. A case control study was undertaken and analysed using multivariable logistic regression. Consumption of a coronation chicken lunch at the transit camp in Sierra Leone (SL) 24-48 h prior to departure for the UK was significantly associated with disease [adjusted odds ratio (OR) 28.15, 95 % CI: 1.87-422.65]. In the context of heightened concern during the Ebola epidemic, this outbreak highlights the importance of rapid and effective microbiological and epidemiological investigations to identify the aetiological agent in patients presenting with fever and diarrhoea.

Use of an ingredient-based analysis to investigate a national outbreak of Escherichia coli O157, United Kingdom, July 2016.

Public Health England was alerted to a national outbreak of Shiga toxin-producing Escherichia coli O157 PT34 in July 2016. Early investigations suggested that the likely source was a salad item consumed outside of the home. A number of cases reported consuming meals at a staff canteen (Venue A) and a garden café (Venue B). Both venues shared a common salad supplier. An investigation was undertaken to measure associations between salad items and illness using an 'ingredient-based analysis'. A retrospective case-control study was conducted using an online questionnaire to collect information on menu items consumed at each venue. Chefs at both venues were interviewed to identify ingredients contained within each menu item. Both venues were pooled together for multivariable analysis measuring associations at the ingredient level. Among 203 responses, 24 cases were identified (13 confirmed, two probable and nine possible). Case onsets ranged between 7 and 25 June 2016. Multivariable analysis identified strong evidence that only baby mixed-leaf salad from the common supplier was a vehicle of infection (adjusted odds ratio = 13.1; 95% confidence interval: 1.6-106.5). Identifying the specific salad ingredient associated with illness was made possible by using an ingredient-based analysis. We recommend the increased use of ingredient-based analyses.

National outbreak of Shiga toxin-producing Escherichia coli O157:H7 linked to mixed salad leaves, United Kingdom, 2016.

We investigated a large outbreak of Escherichia coli O157 in the United Kingdom (UK) with 165 cases between 31 May and 29 July 2016. No linked cases were reported in other countries. Cases were predominately female (n = 128) and adult (n = 150), 66 attended hospital and nine had features of haemorrhagic uraemic syndrome. A series of epidemiological studies (case-control, case-case, ingredients-based and venue-based studies) and supply chain investigations implicated mixed salad leaves from Supplier A as the likely outbreak vehicle. Whole genome sequencing (WGS) indicated a link with strains from the Mediterranean and informed the outbreak control team to request that Supplier A cease distributing salad leaves imported from Italy. Microbiological tests of samples of salad leaves from Supplier A were negative. We were unable to confirm the source of contamination or the contaminated constituent leaf although our evidence pointed to red batavia received from Italy as the most likely vehicle. Variations in Shiga toxin-producing E.coli surveillance and diagnosis may have prevented detection of cases outside the UK and highlights a need for greater standardisation. WGS was useful in targeting investigations, but greater coverage across Europe is needed to maximise its potential.

Novel application of the matched case-control design to compare food supply chains during an Escherichia coli O157 outbreak, United Kingdom, 2016.

There is a need for innovative methods to investigate outbreaks of food-borne infection linked to produce with a complex distribution network. The investigation of a large outbreak of Escherichia coli O157 PT34 infection in the United Kingdom in 2016 indicated that catering venues associated with multiple cases had used salad leaves sourced from one supplier. Our aim was to investigate whether catering venues linked to cases were more likely to have used salad leaves from this supplier. We conducted a matched case-control study, with catering venues as the units of analysis. We compared venues linked to cases to those without known linked cases. We included 43 study pairs and obtained information on salad leaf products received by each venue. The odds of a case venue being supplied with salad leaves by Supplier A were 7.67 times (95% confidence interval: 2.30-25.53) those of control venues. This association provided statistical evidence to support the findings of the other epidemiological investigations undertaken for this outbreak. This is a novel approach which is labour-intensive but which addresses the challenge of investigating exposures to food across a complex distribution network.

Relationship between socioeconomic status and gastrointestinal infections in developed countries: A systematic review and meta-analysis.

BACKGROUND: The 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. METHODS: MEDLINE, 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. RESULTS: In 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. CONCLUSIONS: Disadvantaged 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.

Whole genome sequencing reveals an outbreak of Salmonella Enteritidis associated with reptile feeder mice in the United Kingdom, 2012-2015.

Analysis of whole genome sequencing data uncovered a previously undetected outbreak of Salmonella Enteritidis that had been on-going for four years. Cases were resident in all countries of the United Kingdom and 40% of the cases were aged less than 11 years old. Initial investigations revealed that 30% of cases reported exposure to pet snakes. A case-control study was designed to test the hypothesis that exposure to reptiles or their feed were risk factors. A robust case-definition, based on the single nucleotide polymorphism (SNP) profile, increased the power of the analytical study. Following univariable and multivariable analysis, exposure to snakes was the only variable independently associated with infection (Odds ratio 810 95% CI (85-7715) p < 0.001). Isolates of S. Enteritidis belonging to the outbreak profile were recovered from reptile feeder mice sampled at the retail and wholesale level. Control measures included improved public health messaging at point of sale, press releases and engagement with public health and veterinary counterparts across Europe. Mice destined to be fed to reptiles are not regarded as pet food and are not routinely tested for pathogenic bacteria. Routine microbiological testing to ensure feeder mice are free from Salmonella is recommended.

A standardized methodology for the surveillance of antimicrobial prescribing linked to clinical indications in primary care.

Background: A key component of strategies to reduce antimicrobial resistance is better antimicrobial prescribing. The majority of antibiotics are prescribed in primary care. While many existing surveillance systems can monitor trends in the quantities of antibiotics prescribed in this setting, it can be difficult to monitor the quality of prescribing as data on the condition for which prescriptions are issued are often not available. We devised a standardized methodology to facilitate the monitoring of condition-specific antibiotic prescribing in primary care. Methods: We used a large computerized general practitioner database to develop a standardized methodology for routine monitoring of antimicrobial prescribing linked to clinical indications in primary care in the UK. Outputs included prescribing rate by syndrome and percentages of consultations with antibiotic prescription, for recommended antibiotic, and of recommended treatment length. Results: The standardized methodology can monitor trends in proportions of common infections for which antibiotics were prescribed, the specific drugs prescribed and duration of treatment. These data can be used to help assess the appropriateness of antibiotic prescribing and to assess the impact of prescribing guidelines. Conclusions: We present a standardized methodology that could be applied to any suitable national or local database and adapted for use in other countries.

Socioeconomic status and infectious intestinal disease in the community: a longitudinal study (IID2 study).

Background: Infectious intestinal diseases (IID) are common, affecting around 25% of people in UK each year at an estimated annual cost to the economy, individuals and the NHS of £1.5 billion. While there is evidence of higher IID hospital admissions in more disadvantaged groups, the association between socioeconomic status (SES) and risk of IID remains unclear. This study aims to investigate the relationship between SES and IID in a large community cohort. Methods: Longitudinal analysis of a prospective community cohort in the UK following 6836 participants of all ages was undertaken. Hazard ratios for IID by SES were estimated using Cox proportional hazard, adjusting for follow-up time and potential confounding factors. Results: In the fully adjusted analysis, hazard ratio of IID was significantly lower among routine/manual occupations compared with managerial/professional occupations (HR 0.74, 95% CI 0.61-0.90). Conclusion: In this large community cohort, lower SES was associated with lower IID risk. This may be partially explained by the low response rate which varied by SES. However, it may be related to differences in exposure or recognition of IID symptoms by SES. Higher hospital admissions associated with lower SES observed in some studies could relate to more severe consequences, rather than increased infection risk.

Recurrent seasonal outbreak of an emerging serotype of Shiga toxin-producing Escherichia coli (STEC O55:H7 Stx2a) in the south west of England, July 2014 to September 2015.

The first documented British outbreak of Shiga toxin-producing Escherichia coli (STEC) O55:H7 began in the county of Dorset, England, in July 2014. Since then, there have been a total of 31 cases of which 13 presented with haemolytic uraemic syndrome (HUS). The outbreak strain had Shiga toxin (Stx) subtype 2a associated with an elevated risk of HUS. This strain had not previously been isolated from humans or animals in England. The only epidemiological link was living in or having close links to two areas in Dorset. Extensive investigations included testing of animals and household pets. Control measures included extended screening, iterative interviewing and exclusion of cases and high risk contacts. Whole genome sequencing (WGS) confirmed that all the cases were infected with similar strains. A specific source could not be identified. The combination of epidemiological investigation and WGS indicated, however, that this outbreak was possibly caused by recurrent introductions from a local endemic zoonotic source, that a highly similar endemic reservoir appears to exist in the Republic of Ireland but has not been identified elsewhere, and that a subset of cases was associated with human-to-human transmission in a nursery.

Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK.

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.

Novel public health risk assessment process developed to support syndromic surveillance for the 2012 Olympic and Paralympic Games.

Background: Syndromic surveillance aims to provide early warning and real time estimates of the extent of incidents; and reassurance about lack of impact of mass gatherings. We describe a novel public health risk assessment process to ensure those leading the response to the 2012 Olympic Games were alerted to unusual activity that was of potential public health importance, and not inundated with multiple statistical 'alarms'. Methods: Statistical alarms were assessed to identify those which needed to result in 'alerts' as reliably as possible. There was no previously developed method for this. We identified factors that increased our concern about an alarm suggesting that an 'alert' should be made. Results: Between 2 July and 12 September 2012, 350 674 signals were analysed resulting in 4118 statistical alarms. Using the risk assessment process, 122 'alerts' were communicated to Olympic incident directors. Conclusions: Use of a novel risk assessment process enabled the interpretation of large number of statistical alarms in a manageable way for the period of a sustained mass gathering. This risk assessment process guided the prioritization and could be readily adapted to other surveillance systems. The process, which is novel to our knowledge, continues as a legacy of the Games.