STEC/VTEC

The current disease model relies strongly on publications focused around STEC/VTEC O157 infections. Shiga toxin-producing Escherichia coli O157 (STEC/VTEC O157) infection may be asymptomatic, or may result in acute gastroenteritis (GE), and potentially in haemorrhagic colitis: 44.5% of cases had bloody diarrhoea (Michel, 2000). Duration is assumed to be longer than for non-bloody diarrhoea (Havelaar, 2004): median duration of five days and three days for bloody and non-bloody diarrhoea respectively (Cressey & Lake, 2007), which are proposed in the model as a uniform distribution.

There is little information on STEC/VTEC-associated mortality. Study findings range from 0.083% of the total estimated/VTEC O157:H7 (Mead, 1999), 0.03% (Buzby & Roberts, 2009), 0.04% (Walkerton outbreak, one fatal case in 2 321 patients, Bruce-Grey-Owen Sound Health Unit, 2000) and 0.045 (Havelaar, 2004). We therefore assume a uniformly distributed case-fatality proportion of between 0.03% and 0.045% for this study.

Fatal cases occur mainly in elderly people (Bauch, 2007); therefore, we assumed that the case fatality proportion of 0.03–0.045% is distributed across age-groups in accordance with the observed age-group distribution of TESSy-reported deaths between 2009 and 2013 (see Table 3). This table is based on all TESSy-notified cases from EU Member States except Bulgaria and Lithuania, because they report only aggregate data, and Italy because it has sentinel surveillance for STEC/VTEC for which we do not have the coverage.

Risk of complications

STEC/VTEC infection has been associated with post-diarrhoeal haemolytic uremic syndrome (HUS), which may result in death, end-stage renal disease (ESRD) or other sequelae. HUS and ESRD are the most frequently occurring sequelae of STEC and will be considered in the outcome tree. Irritable Bowel Syndrome (IBS) is another frequently occurring sequelae of bacteria-triggered gastroenteritis (Haagsma, 2010; Marshall, 2010; Thabane, 2009) and was considered for inclusion in the outcome tree (see below). The frequency of other post-infectious complications following STEC is low and they were therefore disregarded (Havelaar, 2004; Frenzen, 2005; Cressey & Lake, 2007; Buzby, 2009; McPherson, 2011; Tariq, 2011).

Haemolytic uraemic syndrome (HUS)

Haemolytic Uraemic Syndrome (HUS) is ‘a condition in which sudden rapid destruction of red blood cells causes acute renal failure’ (Oxford Medical Dictionary, 2003). HUS may occur following a respiratory or gastrointestinal infection, especially by pathogenic Escherichia coli or Shigella spp.

The risk of developing HUS after STEC/VTEC infection has been found to be 3–7% (McPherson, 2011), 1% (Havelaar, 2004), 0.94–1.25% (Cressey & Lake, 2007) and 1.6% of laboratory-confirmed EHEC infections although authors mention under-estimation due to misclassification (13/820; Ternhag, 2008). In the current study we assume that the probability of developing HUS after a VTEC/STEC symptomatic infection is 0.94–1.25%.

HUS occurs mainly in children between the ages of one and five years, and less frequently in children over five years. In one study, 72% of all HUS cases were under 15 years of age and 28% were older (Havelaar, 2003). Member States report HUS outcomes relating to STEC/VTEC infections and we therefore redistributed the age-group risk of developing HUS (0.94–1.24%) based on the age-group of HUS cases reported to TESSy between 2009 and 2013 (all Member States except Bulgaria, Italy and Lithuania) (see Table 4).

Duration is reported to be seven days (range 3–31 days) and 41% (19/46) of patients were admitted to hospital (McPherson, 2011); hospitalisation is reported to last two to four weeks for HUS patients (Havelaar, 2003).

The case fatality proportion was found to be 3.7% (Cressey & Lake, 2007; Oxford Medical Dictionary, 2003; Havelaar, 2003). This low case-fatality may be valid for cases up to 65 years and then as high as 56% for cases ≥65 years, as indicated by data from an outbreak in Scotland (Dundas, 1999). Other studies assume age-specific fatality rates, as reported by Havelaar et al. (Havelaar, 2003). We estimated the age-group case fatality proportion from HUS based on STEC/VTEC infections notified to TESSy between 2009 and 2013 from all Member States, except Bulgaria, Italy and Lithuania (see Table 5).

End-stage renal disease (ESRD)

ESRD is one of the most serious outcomes associated with HUS and is the most advanced stage of kidney failure (Oxford Medical Dictionary, 2003). HUS cases may develop ESRD briefly after HUS or after a long latency period. In the current study we assume that 13.4% develop ESRD, 2.9% of whom develop it briefly after HUS and 10.5% after a latency period of 20 years (Havelaar, 2004; Cressey & Lake, 2007). We also assume that all cases experiencing ESRD undergo dialysis treatment until transplantation occurs.

The case-fatality proportion is based on the assumption that in the first year after starting dialysis mortality is relatively high and differs among age-groups (see Table 6) and that only few fatalities occur after renal transplantation (Havelaar, 2003). Duration of dialysis (time to transplantation) is age-dependent and is applied to the duration of ESRD – see Table 7 (Havelaar, 2003).

Irritable bowel syndrome (IBS)

In a recent literature review, 8.8% (7.2-10.4%) of symptomatic infections with foodborne pathogens were considered at risk of developing IBS, irrespective of age and gender; the duration was set to 5 years (Haagsma, 2010). However, the causality is largely debated and the impact of concurrent factors significant. Therefore, IBS is not considered as part of the STEC/VTEC outcome tree in our study.

Model input summary

Table 1. Transition probabilities and distributions used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Fatal cases following symptomatic infection

 

0.03-0.045%
Age-dependent (Table 3)

Buzby & Roberts, 2009; TESSy 2009-2013

Haemolytic uraemic syndrome (HUS)

 

0.94-1.25%
Age-dependent (Table 4)

Havelaar, 2004; Cressey and Lake, 2007; TESSy 2009-2013

Latency period before ESRD

 

10.5%

Havelaar, 2004; Cressey and Lake, 2007

ESRD after HUS

 

2.9%

Havelaar, 2004; Cressey and Lake, 2007

ESRD after latency period

 

100%

 

Fatal cases following HUS

 

Age-dependent (Table 5)

TESSy 2009-2013

Fatal cases following ESRD

 

Age-dependent, different for dialysis and transplantation (Table 6)

Havelaar, 2003 see Table 6

Transplanted

 

Remaining %

 

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Symptomatic infection (Gastroenteritis)

HUS

ESRD

Transplanted

0.149 (0.12-0.182)

0.108 (0.09–0.132)

0.487 (0.432–0.544)

0.070 (0.057–0.088)

Diarrhoea, moderate

Chronic kidney disease (stage IV)

End-stage renal disease, on dialysis

Generic uncomplicated disease: worry and daily medication

0.008-0.014

0.019 (0.008–0.085)

Age dependent(See Table 7)

Remaining life expectancy

Havelaar, 2004; Cressey & Lake, 2007

McPherson, 2011

Assuming that all ESRD are in dialysis

Table 3. Age-group redistribution of case fatality proportion (0.03–0.045%)

Age groups

%

0

4.30

1-4

9.68

5-9

4.30

10-14

0.00

15-19

0.00

20-24

2.15

25-29

0.00

30-34

0.00

35-39

3.23

40-44

3.23

45-49

2.15

50-54

1.08

55-59

4.30

60-64

8.60

65-69

4.30

70-74

10.75

75-79

10.75

80-84

15.05

>85

16.13

All ages

100.00

Table 4. Age-group redistribution of risk of developing haemolytic uraemic syndrome (0.94–1.25%)

Age

%

0

5.67

1-4

33.74

5-9

13.09

10-14

6.62

15-19

2.88

20-24

2.27

25-29

3.83

30-34

3.54

35-39

2.88

40-44

3.40

45-49

3.45

50-54

2.36

55-59

2.88

60-64

3.02

65-69

2.27

70-74

3.36

75-79

1.89

80-84

1.65

85+

0.99

All ages

100

Table 5. Age-group case fatality proportion from haemolytic uraemic syndrome (TESSy 2009–2013)

Age

%

0

6.06

1-4

2.63

5-9

3.25

10-14

0.00

15-19

0.00

20-24

5.13

25-29

0.00

30-34

0.00

35-39

3.64

40-44

3.28

45-49

3.17

50-54

2.13

55-59

2.00

60-64

4.44

65-69

8.33

70-74

4.62

75-79

17.86

80-84

25.93

85+

28.57

All ages

3.91

Table 6. Case-fatality proportions in the first year after starting dialysis and after renal transplantation

Age class

Case-fatality ratio dialysis

Case-fatality ratio renal transplantation

0–14

4.1% (0.9–11.1%)

7% (2.2–16%)

15–44

8.7% (5.8–12.4%)

7% (2.2–16%)

45–64

37% (31–44%)

7% (2.2–16%)

65–74

65% (58–72%)

7% (2.2–16%)

75+

79% (70–87%)

7% (2.2–16%)

Table 7 .Age specific duration of dialysis

Age class

Duration of dialysis

0-14

1.7 (0.2-5.3)

15-44

2.5 (0.2-9.6)

45-64

6.7 (0.5-30)

>65

5 years to remaining life expectancy

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