BACKGROUND:Escherichia coli (E. coli) O157 is a virulent zoonotic strain of enterohaemorrhagic E. coli. In Scotland (1998-2008) the annual reported rate of human infection is 4.4 per 100,000 population which is consistently higher than other regions of the UK and abroad. Cattle are the primary reservoir. Thus understanding infection dynamics in cattle is paramount to reducing human infections.A large database was created for farms sampled in two cross-sectional surveys carried out in Scotland (1998-2004). A statistical model was generated to identify risk factors for the presence of E. coli O157 on farms. Specific hypotheses were tested regarding the presence of E. coli O157 on local farms and the farms previous status. Pulsed-field gel electrophoresis (PFGE) profiles were further examined to ascertain whether local spread or persistence of strains could be inferred.RESULTS:The presence of an E. coli O157 positive local farm (average distance: 5.96 km) in the Highlands, North East and South West, farm size and the number of cattle moved onto the farm 8 weeks prior to sampling were significant risk factors for the presence of E. coli O157 on farms. Previous status of a farm was not a significant predictor of current status (p = 0.398). Farms within the same sampling cluster were significantly more likely to be the same PFGE type (p < 0.001), implicating spread of strains between local farms. Isolates with identical PFGE types were observed to persist across the two surveys, including 3 that were identified on the same farm, suggesting an environmental reservoir. PFGE types that were persistent were more likely to have been observed in human clinical infections in Scotland (p < 0.001) from the same time frame.CONCLUSIONS:The results of this study demonstrate the spread of E. coli O157 between local farms and highlight the potential link between persistent cattle strains and human clinical infections in Scotland. This novel insight into the epidemiology of Scottish E. coli O157 paves the way for future research into the mechanisms of transmission which should help with the design of control measures to reduce E. coli O157 from livestock-related sources.

An increase in the number of cases of Shiga toxin-producing Escherichia coli O157 PT 2 stx2 infection was reported in the United Kingdom on 9 September 2013. Of the 19 cases, 13 were interviewed, of which 10 reported consuming watercress purchased from one retailer. The retailer recalled pre-packed bagged salads containing watercress on 12 September. The descriptive epidemiology was supported by a case–case study performed after control measures were implemented.

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is Escherichia coli O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle-human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker stx2. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human-animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human E. coli O157 cases.

Escherichia coli O26 and O157 have similar overall prevalences in cattle in Scotland, but in humans, Shiga toxin-producing E. coli O26 infections are fewer and clinically less severe than E. coli O157 infections. To investigate this discrepancy, we genotyped E. coli O26 isolates from cattle and humans in Scotland and continental Europe. The genetic background of some strains from Scotland was closely related to that of strains causing severe infections in Europe. Nonmetric multidimensional scaling found an association between hemolytic uremic syndrome (HUS) and multilocus sequence type 21 strains and confirmed the role of stx(2) in severe human disease. Although the prevalences of E. coli O26 and O157 on cattle farms in Scotland are equivalent, prevalence of more virulent strains is low, reducing human infection risk. However, new data on E. coli O26-associated HUS in humans highlight the need for surveillance of non-O157 enterohemorrhagic E. coli and for understanding stx(2) phage acquisition.

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome.

To the Editor: Hemolytic uremic syndrome (HUS) is a rare disorder characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan injury. HUS is one of the commonest causes of acute renal failure in children worldwide and is most frequently precipitated by infection with verotoxin-producing Escherichia coli (VTEC) such as E. coli O157 (1). However, non-O157 VTEC serotypes have been increasingly found in the development of HUS (2–4). Although previous surveillance of childhood HUS in Scotland identified E. coli O157 in >90% of cases, non-O157 serotypes have also been associated with HUS (5). In 2010, several particularly severe cases of HUS were reported to Health Protection Scotland by a consultant pediatric nephrologist. Subsequent tests identified the pathogen in these cases as E. coli O26. However, in a recent study of pediatric HUS cases in Europe, children infected with E. coli O26 did not exhibit different clinical signs and symptoms from patients infected with other VTEC serotypes (6). To establish whether the host pathophysiologic responses to E. coli O157 and E. coli O26 strains differed, we analyzed a cohort of children with HUS who were infected with these VTEC serotypes. In Scotland, most patients with pediatric thrombotic microangiopathy are referred to a specialist pediatric hospital, which immediately reports cases of HUS to Health Protection Scotland as part of national surveillance. To test the hypothesis that E. coli O26 was more virulent than E. coli O157, we performed an age-matched, nested case–case study of HUS patients and compared host clinical markers, treatment, and outcomes from pediatric cases in 2010. Data collection has been described elsewhere (5). The statistical significances of associations between categorical variables were investigated by using χ2, Fisher exact, Mann-Whitney, or t tests. All analyses were performed by using SPSS version 11 (SPSS Inc., Chicago, IL, USA) with a significance level of 5%. Although initial signs and symptoms were similar for both sets of cases, i.e., bloody diarrhea and abdominal pain, statistical analysis showed that children with O26-HUS were more likely to have neurologic complications and diabetes mellitus and require admission to the intensive care unit than O157-HUS patients (p = 0.02 for neurologic complications and diabetes and p = 0.04 for admission to an intensive treatment unit; Table). Table Characteristics of infection in children with Escherichia coli O157 versus E. coli O26, Scotland, 2010* All patients with HUS were oligoanuric, and the 2 groups did not differ with respect to this parameter. However, O26-HUS patients had significantly longer periods of anuria than O157-HUS patients (p = 0.04; Table) and were more likely to require treatment with hemofiltration than with peritoneal or hemodialysis (p = 0.001; Table). One patient with O26-HUS also experienced cardiomyopathy resulting in reduced left ventricular function. Our study illustrates the potential for increased severity of E. coli O26 infection in children. In Scotland, HUS is more commonly associated with E. coli O157 infection, and the outcome for children infected with this pathogen is much better than that reported in other studies (7,8). In this study, the clinical severity and outcomes for the children with O26-HUS were worse than for children requiring treatment for O157-HUS. We investigated the prehospital management of E. coli O157 and O26 patients in this cohort and found no difference in pharmacologic intervention or duration of delay in admission to hospital. In our cohort, vtx1 and vtx2 genes were detected in isolates from 2 of 3 patients. A diagnosis was made in the third patient by detection of E. coli O26 lipopolysaccharide–specific immunoglobulin M in serum; it was therefore not possible to confirm the presence of vtx genes. However, it is not unusual for VTEC to be undetectable in stool samples from patients with HUS, most likely because of intrahost bacteriophage lysis. Therefore, serodiagnosis of VTEC is considered a necessary adjunct to bacteriological confirmation of infection (9). A recent study suggests E. coli O26 exists as a highly dynamic group of organisms that can undergo verotoxin gene loss and be transferred during infection in humans, resulting in new pathogenic clones (10). Therefore, vtx2 gene acquisition by E. coli O26 may have contributed to increased virulence. Our study was limited by the small number of patients with pediatric O26-HUS. However, given the severity of the complications experienced by the children in this cohort, we believe it is necessary to communicate these findings promptly to the international community. We suggest that infection with E. coli O26 in children can result in more severe and complicated forms of HUS than those caused by E. coli O157. In contrast to the findings of Gerber et al., we found that there was a significant difference in neurologic complications between the 2 groups (2). Epidemiologic investigations found that 2 of the 3 children lived on farms and may have acquired infection while playing near their homes (the other was acquired through foreign travel). Risk communication of VTEC infection to parents of young children who live in farming communities remains problematic, perhaps because of the perception that immunity has been acquired. Although this suggestion may be true for adults, children are likely to be immunologically naive. Salient public health messages on simple precautionary behavior need to be regularly reinforced because prevention of VTEC infection prevents HUS.

To the Editor: Verotoxin-producing Escherichia coli (VTEC) of serogroup O157 causes severe gastrointestinal and renal illness; clinical signs may be mild diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome (HUS). Typically, 10%–15% of reported VTEC infections quickly progress to HUS (1). Sorbitol-fermenting (SF)–O157 strains have emerged in continental Europe (2,3). Some evidence suggests that SF-O157 is more frequently associated with HUS than are non-sorbitol–fermenting strains (3–6). SF-O157 shows increased adherence to colonic epithelial cells and may in turn cause a more potent inflammatory host response, resulting in a higher risk for HUS (4). The potentially greater virulence of SF-O157 requires urgent identification of its reservoir(s) and vehicle(s) of infection, as well as determination of genetic or other predisposing factors for infection with this strain. To understand whether the host pathophysiologic responses to SF-O157 and non–SF-O157 strains differ, we analyzed a cohort of children with HUS who were infected with E. coli O157. During April and May 2006, Health Protection Scotland (HPS) identified 18 cases of verotoxin-producing SF-O157 infection in Scotland, 13 of which were associated with a nursery. HUS developed in 8 of the 18 patients; those with thrombotic microangiopathy were admitted to the renal unit of a specialist pediatric hospital, which immediately reports cases of HUS to HPS as part of national surveillance (7). To test the hypothesis that SF-O157 was more virulent than non–SF-O157, we performed an age-matched, nested case–case study of HUS case-patients and analyzed host clinical markers, treatment, and outcomes from SF-O157 and non–SF-O157 cases in 2006. Clinical questionnaires, patient information sheets, and consent forms were completed by clinicians for each case-patient and returned to HPS; data were entered into a database in Epi Info version 6 (Centers for Disease Control and Prevention, Atlanta, GA, USA). Statistical analysis by t test showed that nadirs for serum albumin were significantly higher for children with SF-O157 HUS (p = 0.03; Table) than for children with non–SF-O157 HUS and that children with SF-O157 HUS had significantly more sessions of hemodialysis than did children with non–SF-O157 HUS (p = 0.01; Table). All case-patients were oligoanuric; the 2 groups did not differ with respect to this parameter. Initial signs and symptoms were similar for both sets of patients, i.e., classic VTEC symptoms of bloody diarrhea and abdominal pain. This finding is in acccordance with those of other studies of SF-O157 outbreaks, which also noted signs and symptoms compatible with VTEC-associated gastroenteritis (5,6). Table Characteristics of patients infected with non–SF-O157 versus SF-O157 Escherichia coli, Scotland, 2006* Our study highlights a number of lessons. Medical practitioners rarely have the opportunity to recognize patients at such an appreciable and predictable risk of progressing rapidly to anuric renal failure as they do when they see children with early O157 infection. Failure to appreciate the potential gravity of O157 infection and the possible development of HUS may result in avoidable illness and even death. Our investigation of the prehospital management of SF-O157 and non–SF-O157 in this cohort found no difference in pharmacologic intervention or duration of delay in admission to hospital. Our study has limitations. A number of patients in the cohort were prescribed antimicrobial drugs and/or antimotility drugs or were sent home from the local hospital without hospital admission or further monitoring; such actions potentially exacerbate clinical outcomes (1,8). We recognize that comparison of the SF-O157 outbreak strain with non–SF-O157 strains (some of which caused sporadic cases) may be a potential confounding factor in the analysis. However, recently published work has indicated no statistically significant differences in the verotoxin proteins encoded by SF-O157 or non–SF-O157 strains or in their level of toxicity (9). Other virulence factors may contribute to increased likelihood of HUS (4). Our data suggest that infection with SF-O157 results in less severe colitis than does the more common non–SF-O157 infection. Less severe colitis could result in a lower risk for renal disease because less verotoxin would be translocated into the bloodstream and bound to the kidneys. However, patients infected with SF-O157 had anuria for longer periods and consequently had longer sessions of peritoneal and hemodialysis. Although unknown bacterial or host inflammatory cytokines may contribute to enhanced disease progression, this observation is surprising and requires further investigation. Additional research is needed to learn more about the virulence of SF-O157 strains and establish other host factors that contribute to disease progression.

To the Editor: Verotoxin-producing Escherichia coli (VTEC) of serogroup O157 causes severe gastrointestinal and renal illness; clinical signs may be mild diarrhea, hemorrhagic colitis, or hemolytic uremic syndrome (HUS). Typically, 10%–15% of reported VTEC infections quickly progress to HUS (1). Sorbitol-fermenting (SF)–O157 strains have emerged in continental Europe (2,3). Some evidence suggests that SF-O157 is more frequently associated with HUS than are non-sorbitol–fermenting strains (3–6). SF-O157 shows increased adherence to colonic epithelial cells and may in turn cause a more potent inflammatory host response, resulting in a higher risk for HUS (4). The potentially greater virulence of SF-O157 requires urgent identification of its reservoir(s) and vehicle(s) of infection, as well as determination of genetic or other predisposing factors for infection with this strain. To understand whether the host pathophysiologic responses to SF-O157 and non–SF-O157 strains differ, we analyzed a cohort of children with HUS who were infected with E. coli O157. During April and May 2006, Health Protection Scotland (HPS) identified 18 cases of verotoxin-producing SF-O157 infection in Scotland, 13 of which were associated with a nursery. HUS developed in 8 of the 18 patients; those with thrombotic microangiopathy were admitted to the renal unit of a specialist pediatric hospital, which immediately reports cases of HUS to HPS as part of national surveillance (7). To test the hypothesis that SF-O157 was more virulent than non–SF-O157, we performed an age-matched, nested case–case study of HUS case-patients and analyzed host clinical markers, treatment, and outcomes from SF-O157 and non–SF-O157 cases in 2006. Clinical questionnaires, patient information sheets, and consent forms were completed by clinicians for each case-patient and returned to HPS; data were entered into a database in Epi Info version 6 (Centers for Disease Control and Prevention, Atlanta, GA, USA). Statistical analysis by t test showed that nadirs for serum albumin were significantly higher for children with SF-O157 HUS (p = 0.03; Table) than for children with non–SF-O157 HUS and that children with SF-O157 HUS had significantly more sessions of hemodialysis than did children with non–SF-O157 HUS (p = 0.01; Table). All case-patients were oligoanuric; the 2 groups did not differ with respect to this parameter. Initial signs and symptoms were similar for both sets of patients, i.e., classic VTEC symptoms of bloody diarrhea and abdominal pain. This finding is in acccordance with those of other studies of SF-O157 outbreaks, which also noted signs and symptoms compatible with VTEC-associated gastroenteritis (5,6). Table Characteristics of patients infected with non–SF-O157 versus SF-O157 Escherichia coli, Scotland, 2006* Our study highlights a number of lessons. Medical practitioners rarely have the opportunity to recognize patients at such an appreciable and predictable risk of progressing rapidly to anuric renal failure as they do when they see children with early O157 infection. Failure to appreciate the potential gravity of O157 infection and the possible development of HUS may result in avoidable illness and even death. Our investigation of the prehospital management of SF-O157 and non–SF-O157 in this cohort found no difference in pharmacologic intervention or duration of delay in admission to hospital. Our study has limitations. A number of patients in the cohort were prescribed antimicrobial drugs and/or antimotility drugs or were sent home from the local hospital without hospital admission or further monitoring; such actions potentially exacerbate clinical outcomes (1,8). We recognize that comparison of the SF-O157 outbreak strain with non–SF-O157 strains (some of which caused sporadic cases) may be a potential confounding factor in the analysis. However, recently published work has indicated no statistically significant differences in the verotoxin proteins encoded by SF-O157 or non–SF-O157 strains or in their level of toxicity (9). Other virulence factors may contribute to increased likelihood of HUS (4). Our data suggest that infection with SF-O157 results in less severe colitis than does the more common non–SF-O157 infection. Less severe colitis could result in a lower risk for renal disease because less verotoxin would be translocated into the bloodstream and bound to the kidneys. However, patients infected with SF-O157 had anuria for longer periods and consequently had longer sessions of peritoneal and hemodialysis. Although unknown bacterial or host inflammatory cytokines may contribute to enhanced disease progression, this observation is surprising and requires further investigation. Additional research is needed to learn more about the virulence of SF-O157 strains and establish other host factors that contribute to disease progression.

Within outbreaks of Escherichia coli O157 (E. coli O157), at least 10–15% of cases are thought to have been acquired by secondary transmission. However, there has been little systematic quantification or characterisation of secondary outbreak cases worldwide. The aim of this study was to characterise secondary outbreak cases, estimate the overall proportion of outbreak cases that were the result of secondary transmission and to analyse the relationships between primary and secondary outbreak cases by mode of transmission, country and median age.

Early clinical diagnosis and outbreak identification are essential to prevent serious sequelae and further transmission

Background: Escherichia coli O157 is an important cause of acute diarrhoea, haemorrhagic colitis and, especially in children, haemolytic uraemic syndrome (HUS). Incidence rates for human E. coli O157 infection in Scotland are higher than most other United Kingdom, European and North American countries. Cattle are considered the main reservoir for E. coli O157. Significant associations between livestock related exposures and human infection have been identified in a number of studies.Results: Animal Studies: There were no statistically significant differences (P = 0.831) in the mean farm-level prevalence between the two studies (SEERAD: 0.218 (95% CI: 0.141-0.32); IPRAVE: 0.205 (95% CI: 0.135-0.296)). However, the mean pat-level prevalence decreased from 0.089 (95% CI: 0.075-0.105) to 0.040 (95% CI: 0.028-0.053) between the SEERAD and IPRAVE studies respectively (P < 0.001). Highly significant (P < 0.001) reductions in mean pat-level prevalence were also observed in the spring, in the North East and Central Scotland, and in the shedding of phage type (PT) 21/28. Human Cases: Contrasting the same time periods, there was a decline in the overall comparative annual reported incidence of human cases as well as in all the major PT groups except 'Other' PTs. For both cattle and humans, the predominant phage type between 1998 and 2004 was PT21/28 comprising over 50% of the positive cattle isolates and reported human cases respectively. The proportion of PT32, however, was represented by few (<5%) of reported human cases despite comprising over 10% of cattle isolates. Across the two studies there were differences in the proportion of PTs 21/28, 32 and 'Other' PTs in both cattle isolates and reported human cases; however, only differences in the cattle isolates were statistically significant (P = 0.002).Conclusion: There was no significant decrease in the mean farm-level prevalence of E. coli O157 between 1998 and 2004 in Scotland, despite significant declines in mean pat-level prevalence. Although there were declines in the number of human cases between the two study periods, there is no statistically significant evidence that the overall rate (per 100,000 population) of human E. coli O157 infections in Scotland over the last 10 years has altered. Comparable patterns in the distribution of PTs 21/28 and 32 between cattle and humans support a hypothesized link between the bovine reservoir and human infections. This emphasizes the need to apply and improve methods to reduce bovine shedding of E. coli O157 in Scotland where rates appear higher in both cattle and human populations, than in other countries.

Scotland has higher rates of Escherichia coli O157 infection than other countries in the United Kingdom (UK) and Europe.

The three main pathways of Escherichia coli O157 infection are foodborne, environmental (including direct contact with animals and their faeces and contaminated water supplies) or person to person contact. The disease is often nicknamed the 'burger bug' but it appears that environmental risk factors may be more important. In this study we use four techniques (outbreak analysis, case-control studies, disease mapping and quantitative microbial risk assessment (QMRA)) to determine whether burgers or environmental pathways present the greater risk in Scotland. Analysis of E. coli O157 outbreaks in Scotland from 1994 to 2003 associated with either meat or dairy foods, or with environmental transmission shows that approximately 40% [M1] of these outbreaks were foodborne, 54% were environmental and 6% involved both transmission routes. However, the largest outbreaks tend to be foodborne accounting for 83% of outbreak cases. Case-control studies indicate strong risk associations with environmental exposure in Scotland, the UK as a whole and the USA, but burgers appear to be more of a risk in the USA. Canadian, Scottish and Swedish disease mapping studies found positive association with indicators of cattle density. In Grampian (North-East Scotland) we found that there was a positive association with cattle and sheep density (divided by human population density) as well as percentage of population on private water supplies. We found 63% of cases in rural postcodes compared with 37% urban after correcting for population differences suggesting that at least 26% of cases may be classified as environmental. QMRA showed that on average, the risk was 100 times greater when visiting a pasture than eating a burger in Grampian. However, it is difficult to determine which pathway actually causes most illnesses as it is unknown how many burgers are consumed daily and what is the frequency of human visits to pasture. The implementation of hygienic food processing post-1996 Central Scotland outbreak and the preference for 'well done' burgers may account for this food being a relatively low risk thus making the 'burger bug' term less appropriate in the UK.

Scotland generally reports higher rates of infection with verotoxin-producing Escherichia coli O157 (VTEC O157) than other parts of the United Kingdom