Campylobacteriosis

Acute gastroenteritis associated with Campylobacter  infections in humans is in most cases self-limiting after a few days to weeks, but for some patients the disease may be fatal. When available, information on duration of illness mainly relates to cases having requested medical help. These cases are often the most severe cases of longer duration. For example, the overall mean duration of illness due to Campylobacter infection observed in the GP[*] case control component of the IID study in England and Wales was 9.34 days, whereas it was only 6.52 days for all cases observed in the community component (Adak, 2002). About 47% of the community component cases would have visited their GP (Food Standards Agency, 2000). Based on the IID study, it is has been assumed that gastroenteritis caused by campylobacteriosis would last 3.22 days (no medical help), 9.72 days (visiting GP) and 14.39 days (hospitalised) (Mangen, 2004; Mangen, 2005). In our current model we chose to apply 3.22–9.72 days for all uncomplicated cases and 14.39 days for the complicated ones.

Bacteraemia is highlighted in many reports as a possible extra-intestinal complication of campylobacteriosis. For example, Skirrow et al. (Skirrow, 1993) estimated a bacteraemia incidence of 1.5 per 1 000 reported campylobacteriosis cases, whereas Ternhag et al. (Ternhag, 2008) reported an absolute risk of bacteraemia/sepsis of 0.02% for laboratory-confirmed campylobacteriosis cases.

Assuming that GP visits represent an indication of moderate diarrhoea and that the proportion of hospitalised cases represents severe diarrhoea, we divided cases into the following groups: uncomplicated (mild diarrhoea) 75.5%, complicated (GP, moderate diarrhoea) 23.5% and complicated hospitalised (severe diarrhoea) cases 1% (Kemmeren, 2006; Kwong, 2012; redistributing to total 100%).

Estimates of campylobacteriosis case fatality proportions range from 0.001% to 0.05%: 0.05% (Mead, 1999), 0.024% of all foodborne campylobacteriosis cases in the IID study (Adak, 2002), 2–6% of the hospitalised cases (Buzby, 1996; corresponding to 0.012–0.036% of all cases, considering that 0.6% of cases are hospitalised according to Mangen et al. 2004), 1.3 fatal cases per year, corresponding to 0.001% of the estimated 123 000 Campylobacter cases (Cressey & Lake, 2007), 0.038% of all symptomatic cases (Mangen, 2004).

We chose to estimate the overall case fatality proportion as being within the range 0.001–0.05% and assumed a different age-group distribution of this risk based on the age-group distribution of reported deaths to TESSy between 2009 and 2013 (see Table 3). This table is based on all TESSy notified cases from EU Member States except Bulgaria, reporting only aggregate data, Greece, Portugal and Liechtenstein which do not report.

Risk of complications

Reactive arthritis (ReA), irritable bowel syndrome (IBS) (but not inflammatory bowel disease due to lack of confirmation of a biological link and limited evidence) and Guillain-Barré syndrome (GBS) may be associated with campylobacteriosis.

Reactive arthritis (ReA)

ReA is a significant long-term sequelae following campylobacteriosis (Keat, 1983; Johnsen, 1983; Hannu, 2002). A retrospective study carried out in Finland found that 7.4% (45/609) of laboratory-confirmed campylobacteriosis cases fulfilled the criteria for ReA (Hannu, 2002), which is similar to that found by another study: 8.1% (3/37) (Johnsen, 1983). A further study reported a 2.6% (9 of 350) frequency of ReA in patients contacting a municipal health centre following an outbreak of C. jejuni (Hannu, 2004) and 16% of laboratory-confirmed cases self-reported having had ReA (Locht & Krogfeld, 2002), although self-reporting might be prone to overestimation (Hannu, 2002). Other studies including clinical testing report a 2.8% and a 2.4% risk of developing rheumatological symptoms (Rees, 2004; Kosunen, 1980). In order to account for the large uncertainty, the risk of developing ReA from all symptomatic cases is 1.7% (0.73–4.4%) (Kemmeren, 2006).

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

Irritable Bowel Syndrome (IBS)

In a recent literature review, 8.8% (7.2–10.4%) of symptomatic campylobacteriosis symptomatic cases were considered at risk of developing IBS, irrespective of age and gender; the duration 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 campylobacteriosis outcome tree in our study.

Guillain-Barré syndrome (GBS)

GBS is a neurological disease frequently preceded by an acute infectious illness, mainly upper respiratory infections and gastrointestinal infections. The functional status of patients with GBS is scored on a seven-point disability scale (F-score), ranking from 0 (healthy) to 6 (death). GBS-patients with an F-score at nadir of < 3 (able to walk unaided at nadir) are considered to be mildly affected. GBS patients with an F-score of ≥ 3 (unable to walk unaided at nadir) are considered to be severely affected (van Koningsveld, 2001). Paralysis from GBS is generally reversible over time, but some patients are bedridden for life and others die prematurely.

Incidence is estimated at 0.8–2.0 or 0.4–4 cases per 100 000 persons year (van Koningsveld, 2001; Mc Grogan, 2009; Hughes & Rees, 1997) in Europe and North America. A systematic review of the literature and metanalysis estimated an age-specific GBS rate per 100 000 person years of exp[-12.0771 + 0.01813(age in years)] × 100 000 (Sejvar, 2011).

Studies show that 14–36% of GBS patients previously had a Campylobacter infection (Jacobs, 1998); 33–50% of GBS patients had increased levels of Campylobacter spp. (Mishu, 1993). A more recent systematic literature review estimated that 31% of the 2 502 GBS cases studied were attributable to Campylobacter infection (Poropatich, 2010).

Research has found that about 0.022% of laboratory-confirmed campylobacteriosis cases would develop GBS (13/57,425) (Ternhag, 2008), resulting for all symptomatic cases in a 0.0015% risk of developing GBS; in Sweden one GBS case per 3 285 Campylobacter jejuni infections (95% C.I.: 1.729 – 7.210) resulting in a risk of 0.03% (McCarthy & Giesecke, 2001); in the USA one per 1 058 campylobacteriosis cases (0.09% risk; Allos, 1997). Studies estimating the burden of campylobacteriosis assumed a 0.075% and 0.023% risk of developing GBS (Mangen, 2004 and 2005; Cressy & Lake, 2007). Given the large diversity found in the literature, the risk of developing GBS following a symptomatic Campylobacter infection is set to 0.0015–0.09%.

Males were more commonly affected by GBS in almost all studies (Sedano, 1994; Hughes & Rees, 1997; Nachamkin, 1998; Nagpal, 1999; van Koningsveld, 2000; Sejvar, 2011). However, these differences might be based on environmental factors as well as biological factors (van Koningsveld, 2000) and therefore it is difficult to speculate about the origin of this gender difference and the cause and determinants of GBS and therefore we do not distinguish in risk between genders.

Havelaar et al. (Havelaar 2000 a,b) estimated the proportion of mild and severe GBS cases after Campylobacter infections to be 17% and 83%, respectively. Age plays a role (van Koningsveld et al., 2000; Sejvar et al., 2011), we therefore assume that the age-group-specific distribution of the risk of developing a mild GBS is 17% and a severe GBS is 83% – see Table 4 and 5 (Havelaar 2000a, b). A total of 69% of mild GBS cases are under the age of 50, whereas for severe GBS cases this is only 48%.

The clinical course of GBS is highly variable. Very limited information is available for mildly affected patients. About 50% of the patients recover fully after six months, and the others have an F-score of 1. Most will recover after one year and the remainder will only suffer from minor symptoms (Havelaar, 2000a). We therefore assumed that mild cases will recover fully after one year.

There is a high heterogeneity among the severely-affected GBS patients: 60% of patients are reported to have an F-score of 4 when hospitalised, and approximately 20% of the patients had an F-score of 5 at nadir (Van der Meché, 1992). All patients recovered from intensive care, but after six months, 17% of them still had  an F-score of 3 or 4. In a follow-up study the residual symptoms were evaluated up to six years after onset (Bernsen, 1997): only 25% recovered fully, whereas 44% of patients continued to suffer from minor symptoms (F-score=1) and 31% had functional limitations (F-score 2-4). Given that there had been no significant improvement since the acute phase, we assume that 17–31% of severely affected GBS patients would have permanent sequelae; this risk is distributed by age groups, see Table 6 (Havelaar 2000 a;b).

The case fatality rate for GBS ranges from 2–5% (Havelaar, 2000a) to 3.4% in a retrospective study (Van Koningsveld, 2000). However, generally only the severe cases are at risk of dying, therefore the risk is only estimated for these cases (CFR/83% severe cases x 100): 4.1% (2.41–6.02). The case fatality rate is age-dependent (Havelaar, 2000a) and strictly linked to the risk of developing permanent disabilities due to GBS; therefore, we apply the same age-group distribution as the risk of dying, see Table 6).

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, GP)

(Complicated, hosp)

 

76%

23%

1%

 

Kemmeren, 2006; Kwong, 2012

Fatal cases following symptomatic infection

 

0.001–0.05%

Age dep. Table 3

Adak, 2002; Cressey & Lake, 2007; Mangen, 2005; Mead, 1999; TESSy 2009-2013

Reactive arthritis

 

1.7% (0.73–4.4%)

Kemmeren, 2006

Guillain-Barré syndrome
(Mild)

 

(Severe)

 

17%

Age dep. Table 4

83%

Age dep. Table 5

0.0015–0.09%

 

Allos, 1987; Ternhag, 2008; Havelaar 2000a, b

Fatal cases following severe GBS

 

4.1% (2.41–6.02%)

Age dep. Table 6

Koningsveld, 2001; Havelaar, 2000a

Assuming only severe cases are fatal

Permanent  disability following GBS

 

17–31%

Age dep. Table 6

Havelaar, 2000a, b

Assuming only severe cases

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, GP)

(Complicated, hosp)

 

 

0.073 (0.061–0.092)

0.149 (0.12–0.182)

0.239 (0.202–0.285)

 

 

Diarrhoea, mild

Diarrhoea, moderate

Diarrhoea, severe

 

 

0.009

0.027

0.039

Food Standard Agency, 2000; Mangen, 2004, 2005

Reactive arthritis

0.344 (0.3-0.391)

Musculoskeletal problems, generalized, moderate

0.131-0.608

Hannu, 2002; Kemmeren, 2006

 

 

 

 

 

Guillain-Barré syndrome

(Mild)

(Severe)

 

 

0.053 (0.042-0.064)

0.520 (0.465-0.581)

 

 

Motor impairment, moderate

Spinal cord lesion at neck level (treated)

 

 

1
1

Havelaar, 2000a, b

Permanent disability following GBS

0.421 (0.377-0.477)

Motor impairment, severe

Remaining life expectancy

Van der Meché, 1992; Bernsen, 1997

Table 3.  Age-group distribution of the case fatality rate (0.001–0.05%)

Age groups

%

0

0.54

1-4

1.09

5-9

3.26

10-14

1.63

15-19

0.54

20-24

4.35

25-29

5.98

30-34

1.63

35-39

3.26

40-44

3.80

45-49

3.80

50-54

5.43

55-59

5.98

60-64

5.98

65-69

8.15

70-74

6.52

75-79

11.96

80-84

11.96

>85

14.13

All ages

100.00

Table 4. Age distribution mild GBS

Age

%

0

0.63

01-04

5.02

05-09

2.51

10-14

1.25

15-19

6.27

20-24

6.90

25-29

10.04

30-34

9.41

35-39

9.41

40-44

8.78

45-49

8.78

50-54

5.17

55-59

4.82

60-64

4.13

65-69

5.51

70-74

5.17

75-79

4.13

80-84

0.69

85+

1.38

Total

100

Table 5. Age distribution – severe GBS

Age

%

0

0.44

01-04

3.49

05-09

1.75

10-14

0.87

15-19

4.36

20-24

4.80

25-29

6.98

30-34

6.55

35-39

6.55

40-44

6.11

45-49

6.11

50-54

8.67

55-59

8.09

60-64

6.93

65-69

9.24

70-74

8.67

75-79

6.93

80-84

1.16

85+

2.31

Total

100



Table 6.
Age distribution permanent GBS and case fatality rate

Age

%

0

0.00

01-04

0.00

05-09

0.00

10-14

0.00

15-19

0.00

20-24

1.56

25-29

1.56

30-34

1.56

35-39

1.56

40-44

2.08

45-49

2.08

50-54

2.08

55-59

6.25

60-64

6.25

65-69

6.25

70-74

18.75

75-79

25.00

80-84

18.75

85+

6.25

Total

100.00

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