Shigellosis

Acute gastroenteritis associated with Shigella spp. infections in humans is, in most cases, self-limiting within days to weeks, but for a few patients the disease may be severe and fatal.

We assume that more complicated cases visit their doctor or are hospitalised and will subsequently be laboratory-tested and reported as confirmed. The proportion of reported cases over the total symptomatic cases is 5.45% (2.18–40%) (Haagsma, 2010).

We assumed a similar duration of symptoms as for salmonellosis: 5.58 days for uncomplicated cases and 10.65–16.15 for complicated ones (Kemmeren, 2006).

On average, patients aged 65 years and over are hospitalised for a greater number of days and are more likely to die of shigellosis than other patients (van Pelt, 2010; Barton Behravesh, 2011). We assumed that only complicated cases lead to fatalities and set the case fatality proportion for complicated cases as 0.06–0.97% (Van Pelt, 2010; Barton Behravesh, 2011). Assuming a different age-group distribution of this risk, we distributed the case fatality proportion based on the age-group distribution of deaths reported to TESSy between 2009 and 2013 (see Table 3). This table is based on all TESSy-notified cases from EU Member States except Bulgaria, Lithuania and Poland, because they report only aggregate data, and Liechtenstein, Luxembourg and Italy which do not report on the death outcome.

Risk of complications

Reactive arthritis (ReA), Post-Infectious Irritable Bowel Syndrome (PI-IBS), Haemolytic Uraemic Syndrome (HUS) and End-stage Renal Disease (ESRD) are possible sequelae of shigellosis.

Asymptomatic cases, which themselves do not have a disease burden for acute illness, might also develop sequelae. However neither the number of asymptomatic cases in the population, nor the percentage of asymptomatic cases that develop sequelae is known and these are therefore not included in the model.

Reactive arthritis (ReA)

The risk of developing ReA has been found to be 6.6% of all laboratory-confirmed cases of shigellosis (Hannu, 2005), 1.2% (Rees, 2004) and 9.8% (Schiellerup, 2008). However, severity of the acute infection and duration of diarrhoea are associated with a higher risk of developing ReA (Townes, 2008; Hannu, 2005; Rees, 2004; Schiellerup, 2008); moreover, these figures relate to laboratory-confirmed cases only. Therefore, we assume that only ‘complicated’ cases have a risk of 6.6% (1.2-9.8%) of developing ReA.

Little is known about the duration of ReA; the average duration is set between 1.5 months (Hannu, 2005) and 222 days (Kemmeren, 2006).

Irritable bowel syndrome (IBS)

In a recent literature review, 8.8% (7.2–10.4%) of symptomatic infections involving foodborne pathogens (salmonellosis, campylobacteriosis and shigellosis) were associated with a risk of developing IBS, irrespective of age and gender. The duration of IBS was set to five 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 shigellosis outcome tree in our study.

Haemolytic uraemic syndrome (HUS)

>HUS is characterised by haemolytic anaemia (severe anaemia due to increased destruction of red blood cells), thrombocytopenia (reduced platelet count) and impaired kidney function (acute renal failure). Haemolytic anaemia and thrombocytopenia often occur after bloody diarrhoea. Acute renal failure may then follow.

Several studies have associated HUS with shigellosis infections, in particular Shigella dysenteriae type 1, a species which occurs mainly in tropical countries and accounts for approximately 30% of S. dysenteriae isolates in those countries (Mark Taylor, 2008; Chopra, 1997; Bennis, 2006; Kotloff, 1999; Ekdahl, 2005).

In Europe, based on data reported to TESSy, S. dysenteriae accounts for less than 3% of laboratory-confirmed shigellosis cases, whereas S. sonnei is the most common Shigella species (ECDC, 2013 a & b). This means that around 0.9% of the shigellosis cases occurring in Europe, caused by Shigella dysenteriae type 1, are at risk of developing HUS; however, the risk varies according to EU Member State.

The incidence of S. dysenteriae-induced HUS is unknown and it is affected by antibiotic treatment (Bennish, 2006). HUS caused by S. dysenteriae type 1 is often perceived as more severe than HUS caused by enterohaemorrhagic E. coli (EHEC), however this is probably due to the fact that such infections mainly occur in countries with limited access to high-quality healthcare. Though the age range of Shigella-induced-HUS is wider and the ‘median time from the onset of diarrhoea to the presentation of HUS’ is longer, HUS caused by Shigella and EHEC is very similar (Mark Taylor, 2008). Therefore, we assume that the risk of developing HUS after symptomatic infection with Shigella dysenteriae type 1 is the same as the risk for symptomatic infections with Shiga-toxin producing E. coli O157 (STEC), around 0.94–1.25% (Cressey & Lake, 2007).

Given that 0.9% of shigellosis cases occurring in Europe are caused by Shigella dysenteriae type 1, the overall risk of developing HUS after symptomatic shigellosis is set to 0.008–0.011%.

HUS occurs mainly in children aged one to five years, and less frequently in children over five years. In one study (Havelaar, 2003) 72% of all HUS cases were under 15 years of age, and 28% were older. The distribution of HUS patients admitted to the Paediatric Nephrology Department of University Hospital Nijmegen from 1974–1993 was used for cases under 15 years (Havelaar, 2003). For the current study we distributed the age risk of developing HUS (0.008-0.011%) according to TESSy-notified cases of HUS by age due to VTEC infection from 2009 to 2013 (see Table 4). Cases were from all EU Member States except Bulgaria and Lithuania, because they report only aggregate data, and Italy because it has sentinel surveillance for STEC/VTEC which does not provide sufficient coverage.

Duration of HUS 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 2–4 weeks for HUS patients (Havelaar, 2003).

The case fatality proportion is assumed to be 3.7% (Cressey & Lake, 2007; Oxford Medical Dictionary, 2003; Havelaar, 2003). This low case-fatality might be valid for cases up to 65 years and be as high as 56% for those aged ≥65 years as data from an outbreak in Scotland suggests (Dundas, 1999). For the current study we use age-specific fatality proportions as reported by Havelaar et al. (Havelaar, 2003; 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, of which 2.9% 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 are in dialysis treatment until transplantation occurs.

The case-fatality proportion is based on the assumption that in the first year after starting dialysis mortality ratios are relatively high and differ between 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).

Model input summary

Table 1. Transition probabilities used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Symptomatic infection
(Uncomplicated)
(Complicated)


Rem. cases
5.45% (2.18–40%)

 

Haagsma, 2010

Fatal cases following complicated symptomatic infection

 

0.06–0.97
Age dep.Table 3

Van Pelt, 2010; Barton Behravesh, 2011; TESSy 2009–2013

ReA

 

6.6% (1.2–9.8%)

Hannu, 2005; Rees, 2004; Townes, 2008; Schiellerup, 2008

HUS

 

0.008–0.011%
Age dep.
Table 4

Mark Taylor, 2008; Chopra, 1997; Bennis, 2006; Kotloff, 1999; Ekdahl, 2005; ECDC, 2013 a & b; Cressey & Lake, 2007

Latency period before ESRD

 

10.5%

Havelaar, 2004; Cressey & Lake, 2007

ESRD after HUS

 

2.9%

Havelaar, 2004; Cressey and Lake, 2007

ESRD after latency period

 

100%

 

Fatal cases following HUS

 

< 65 years: 3.7%

>=65 years: 56%

Table 5

Haavelar, 2004; Dundas, 1999

Fatal cases following ESRD

 

Age dep. & different for dialysis and transplantation
See 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/assumption

Symptomatic infection
(Uncomplicated)
(Complicated)



0.073–0.149
0.239 (0.202–0.285)



Diarrhoea, from mild to moderate
Diarrhoea, severe



0.015
0.029–0.044

Kemmeren, 2006

ReA

0.344 (0.3–0.391)

Musculoskeletal problems, generalised, moderate

0.131-0.608

Estimated from Hannu, 2005; Kemmeren, 2006

HUS

0.108 (0.09–0.132)

Chronic kidney disease (stage IV)

0.019 (0.008-0.085)

McPherson, 2011

ESRD

0.487 (0.432–0.544)

End-stage renal disease, on dialysis

See Table 7

Assuming that all ESRD are in dialysis

Transplanted

0.070 (0.057–0.088)

Generic uncomplicated disease: worry and daily medication

Remaining life expectancy

Assuming no risk of re-transplantation

Table 3. Age group distribution of the case fatality proportion (0.06–0.97%)

Age groups

%

0

0.00

1–4

10.00

5–9

10.00

10–14

0.00

15–19

0.00

20–24

0.00

25–29

0.00

30–34

10.00

35–39

0.00

40–44

10.00

45–49

20.00

50–54

0.00

55–59

0.00

60–64

10.00

65–69

0.00

70–74

0.00

75–79

10.00

80–84

10.00

>85

10.00

All ages

100.00

Table 4. Age-group redistribution of risk of developing HUS (0.008–0.011%) following infection (TESSy 2009–2013)

Age groups

%

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. HUS case-fatality proportion per age group

Age groups

CFR

0–65

3.7%

>65

56%

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 to remaining life expectancy

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