Escherichia coli O157Pennington H. (2010) The Lancet 376 (9750): 1428-1435

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 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

JAN 19 23 15 12 9 17 21 27 32 24FEB 14 25 13 13 18 16 24 23 27 11MAR 32 25 27 19 23 22 37 17 28 29APR 43 24 24 27 34 38 27 36 68 43MAY 94 49 49 44 56 61 71 118 101 56JUN 110 88 46 61 78 96 111 83 106 126JUL 134 107 79 94 91 129 234 145 105 145AUG 111 127 114 154 144 109 160 125 122 137SEP 176 118 92 152 129 182 124 86 210 230OCT 119 81 58 60 62 123 113 70 76 107NOV 25 68 53 28 33 125 57 66 48 89DEC 19 33 25 11 22 32 22 32 27 37

TOTAL 896 768 595 675 699 950 1001 828 950 1034

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 15x109 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

Transmission of E. coli O157

Source of transmission

Outbreaks

Food 42.2%Dairy products 12.2%Animal contact 7.8%Water 6.7%Environmental 2.2%Unknown 28.9%

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 1984-2008

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 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)

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

OutcomeReceived peritoneal dialysis, haemodialysis, or haemofiltration

53%

Recovered and were released 48%Renal impairment 13%Became dependent on dialysis 7%Had neurological impairment 4%Died 4%

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)