1. Escherichia coli O157 Pennington H. (2010) The Lancet 376 (9750): 1428-1435 Dr. Claudio Scotti

2. Campylobacter Rotavirus Salmonella Norovirus Cryptosporidium Giardia Shigella Escherichia coli O157 GI tract infections in the UK

3. Escherichia coli Six different groups of pathogenic E. coli: - EPEC: enteropathogenic - ETEC: enterotoxigenic - EHEC: enterohaemorrhagic (VTEC) - EIEC: enteroinvasive - EAEC: enteroaggregative - DAEC: diffuse-aggregative

4. MONTH2000200120022003200420052006200720082009 JAN1923151291721273224 FEB142513 181624232711 MAR32252719232237172829 APR4324 27343827366843 MAY9449 4456617111810156 JUN110884661789611183106126 JUL134107799491129234145105145 AUG111127114154144109160125122137 SEP1761189215212918212486210230 OCT119815860621231137076107 NOV256853283312557664889 DEC19332511223222322737 TOTAL89676859567569995010018289501034 E. coli O157 in England & Wales

5. Typical features Abdominal pain Five or more bowel movements in the day before presentation Non-bloody diarrhoea, becoming bloody after 1-4 days No fever 10-15% of patients develop haemolytic uraemic syndrome (HUS) 5-13 days after the onset of diarrhoea

6. Haemolytic uraemic syndrome Acute onset of renal impairment with oliguria or anuria and high concentrations of serum urea and creatinine Platelet counts less than 15x10 9 cells/L Microangiopathic haemolytic anaemia with haemoglobin <10 g/dL and with fragmented red cells in a peripheral blood smear

7. The first oubreak 1982, in Oregon and Michigan, USA Bloody diarrhoea and severe abdominal cramps after eating hamburgers in a restaurant chain First outbreak in the UK: 1983

8. The largest outbreak Sakai City, Japan, in 1996 Associated with white radish sprouts served as school meals 7,966 cases 2,764 microbiologically confirmed 106 with haemolytic uraemic syndrome (HUS)

9. The source of E. coli O157 Ruminants, particularly cattle (prevalence between 0.2 and 48.8%) and sheep 80% of transmission arise from the 20% of animals that are most infectious (supershedders) Secondary spread (20% of outbreak cases)

10. Transmission of E. coli O157

11. Source of transmission Outbreaks Food42.2% Dairy products12.2% Animal contact7.8% Water6.7% Environmental2.2% Unknown28.9%

12. Transmission of E. coli O157 Quantitative microbial risk assessment showed that the risk is 100 times greater for visits to pastures than for consumption of burgers in the northeast of Scotland Heavy rain is frequently associated with outbreaks (e.g. Glastonbury festival in 1997)

13. Isolation rates, UK 1984-2008

14. Incidence of infection Per 100,000: –4.7 in Scotland –4 in Canada –2.87 in Ireland –2.74 in Japan –2.1 in England and Wales –1.3 in the USA –0.43 in Germany –0.08 in France

15. Disease caused by E. coli O157 1996, in central Scotland, associated with meat from a butcher: 279 individuals, 17 people died from the direct effects of infection Irish outbreak, water-borne spread: 18 individuals, 2 children with HUS 2010 English outbreak on an open farm: 17 developed HUS (8 of them receiving dialysis)

16. Typical features HUS is most common in children younger than 5 years In England and Scotland, between 1997 and 2001, 226 (65%) of the 350 cases occurred in this age group Once an infection has been established, no therapeutic interventions are available to lessen the risk of the development of the HUS

17. Outcomes of HUS Outcome Received peritoneal dialysis, haemodialysis, or haemofiltration 53% Recovered and were released48% Renal impairment13% Became dependent on dialysis7% Had neurological impairment4% Died4%

18. Extrarenal effects Increase in pancreatic enzymes and oedema Necrosis of the colon wall Myocardial damage CNS damage (25% of cases), with seizures, paralysis, coma Deaths are usually associated with severe extra-renal complications

19. Virulence factors Two different Shiga toxins (Stx1, Stx2) Correlation with bloody diarrhoea and HUS Shiga toxin binds to glycosphingolipid globotriaosylceramide (Gb3), a cell surface receptor In the human kidney, Gb3 is present on glomerular endothelial cell types and various tubular epithelial cell types

20. Virulence factors Enterocyte effacement genes: mediate the intimate attachment of bacteria to the intestinal epithelium Several plasmid-encoded genes promoting adherence Upregulation of flagellar and chemotaxis genes

21. Prevention (failure points) Failure during or after milk pasteurisation Rare and light cooking of hamburger patties Failure in municipal water chlorination Failure to prevent cross-contamination or ready-to-eat foods by direct or indirect contact with raw meat Handwashing

22. Conclusion Ground beef outbreaks still occur in the USA but are now associated with home- made burgers A vaccine that shows promise has been developed Investigation of “supershedders” (> reduction of ruminant carriage)