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

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

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

MONTH JAN FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC TOTAL E. coli O157 in England & Wales

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

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

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

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)

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)

Transmission of E. coli O157

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

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)

Isolation rates, UK

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

Disease caused by E. coli O , 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)

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

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%

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

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

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

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

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)