Escherichia coli O157
Pennington H. (2010) The Lancet 376 (9750): 1428-1435
Dr. Claudio Scotti
GI tract infections in the UK
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Campylobacter
Rotavirus
Salmonella
Norovirus
Cryptosporidium
Giardia
Shigella
Escherichia coli O157
Escherichia coli
• Six different groups of pathogenic E. coli:
- EPEC: enteropathogenic
- ETEC: enterotoxigenic
- EHEC: enterohaemorrhagic (VTEC)
- EIEC: enteroinvasive
- EAEC: enteroaggregative
- DAEC: diffuse-aggregative
E. coli O157 in England & Wales
MONTH
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
NOV
DEC
19
14
32
43
94
110
134
111
176
119
25
19
23
25
25
24
49
88
107
127
118
81
68
33
15
13
27
24
49
46
79
114
92
58
53
25
12
13
19
27
44
61
94
154
152
60
28
11
9
18
23
34
56
78
91
144
129
62
33
22
17
16
22
38
61
96
129
109
182
123
125
32
21
24
37
27
71
111
234
160
124
113
57
22
27
23
17
36
118
83
145
125
86
70
66
32
32
27
28
68
101
106
105
122
210
76
48
27
24
11
29
43
56
126
145
137
230
107
89
37
TOTAL
896
768
595
675
699
950
1001
828
950
1034
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
Food
Dairy products
Animal contact
Water
Environmental
Unknown
Outbreaks
42.2%
12.2%
7.8%
6.7%
2.2%
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
Outcome
Received peritoneal dialysis,
haemodialysis, or haemofiltration
Recovered and were released
Renal impairment
Became dependent on dialysis
Had neurological impairment
Died
53%
48%
13%
7%
4%
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 homemade burgers
• A vaccine that shows promise has been
developed
• Investigation of “supershedders” (>
reduction of ruminant carriage)