Epidem iol ogy
EUROPEAN PROGRAMME FOR
INTERVENTION EPIDEMIOLOGY TRAINING
Mahon, Spain, 26 September – 15 October 2005
Tiramisu is good for you! Beer too!
Exercise
Case study based on an investigation conducted by Anja Hauri
FETP / EPIET fellow, Robert Koch Institute, Berlin, 2001
Case study prepared by Alain Moren, EPIET
EPIET 2004. Major revision: 2005
1
Objectives
At the end if the case study, participants should be able to:



State hypothesis to be tested in a food borne outbreak
Sort out the respective roles of several incriminated food items
Select an appropriate control group among several options
2
Introduction: A school graduation ceremony where everything should have gone well
On 26 June 1998 the St Sebastian High School in Stegen, Germany, celebrated the
graduation from school by organising a party to which 250 to 350 participants were expected.
Attendants included graduates from St Sebastian High School, their families and friends,
teachers, 12th grade students and some graduates from the nearby Marie-Curie school of
Kirchzarten.
A self service party buffet was supplied by a commercial caterer from Freiburg.
Food was prepared the day of the party and transported in a refrigerated van to the school.
Festivities started with a dinner buffet open from 8.30 pm and followed by a dessert buffet
offered from 10 pm. The party and the buffet extended late during the night and alcoholic
beverages were quite popular. All agreed it was a party to be remembered.
The alert
On 2nd July 1998, the Freiburg Health office of the Federal Council Office of BreisgauHochschwarzwald reported to the Robert Koch Institute (RKI) in Berlin the occurrence of
many cases of gastroenteritis following the graduation party described above. More than 100
cases were suspected among participants and some of them were admitted to nearby
hospitals. Sick people suffered from fever, nausea, diarrhoea and vomiting lasting for several
days. Most believed that the tiramisu consumed at dinner was responsible for their illness.
Salmonella Enteritidis was isolated from 19 stool samples.
The Freiburg health office sent a team to investigate the kitchen of the caterer. Food
preparation procedures were reviewed. Food samples, except tiramisu (none was left over),
were sent to the laboratory of Freiburg University. Microbiological analyses were performed
on samples of the following: brown chocolate mousse, caramel cream, remoulade sauce,
yoghurt dill sauce, and 10 raw eggs.
The Freiburg health office requested help from the RKI in the investigation to assess the
magnitude of the outbreak and identify potential vehicle(s) and risk factors for transmission in
order to better control the outbreak.
Cases were defined as any person attending the party at St Sebastian High School who
suffered from diarrhoea (>= 3 loose stool for 24 hours) between 27 June and 6 July 1998; or
who suffered from at least three of the following symptoms: vomiting, fever>= 38.5 ° C,
nausea, abdominal pain, headache.
Students from both schools attending the party were asked through phone interviews to
provide names of persons who attended the party.
Overall 291 responded to enquiries and 103 cases were identified (Attack rate = 35%).
Among these cases, 84 received medical treatment and four were admitted to hospitals.
Attack rates by age group were 36.6% for persons < 20 years, 32.1% for persons 20 to 29
years, and 36.8% for persons older than 29 years.
3
Most cases occurred between 27 and 29 June with an early peak from June 27, 0 am until
June 28, 6 am.
Figure 1
Cases of gastroenteritis by time of onset among attendees
of a high school graduation ceremony (n=104), Germany, June 1998
Dessert-Buffet
Number of cases
20
One case
15
10
5
0
1
Ju 2
ne
0
12
1.
Ju
ly
0
12
2.
Ju
ly
0
3. 12
Ju
ly
0
12
4.
Ju
ly
0
12
5.
Ju
ly
0
12
6.
Ju
ly
0
12
30
.
Ju
ne
0
12
29
.
Ju
ne
0
12
28
.
Ju
ne
27
.
26
.
Ju
ne
0
12
0
Day/Month/Time in 6-hour-intervalls
Q1. Summarise the above information and formulate hypotheses to be tested.
4
The shape of the epidemic curve, the attendance to a single event (a buffet) pointed towards
a food borne outbreak related to a point common source of infection.
Using the updated list of attendants, a retrospective cohort study including all attendants to
the party (that could be reached) was conducted. All had received a standard questionnaire
asking for demographic information, signs, symptoms and duration, admission to hospital,
and food and beverages consumption at the party including amount consumed. Food specific
attack rates were computed for more than 50 food items and beverages. Only those strongly
associated to illness are shown in table I.
Q2
Food and beverage specific attack rates are shown in table I.
Identify potential vehicles and protective factors.
Interpret the results
Table I
Food specific attack rates among attendants at a high school
graduation ceremony, Germany, 26 June 1998, n=291
Eaten
Not eaten
Number
ill
Number
not ill
Attack
rate
(%)
Number Number
ill
not ill
Attack
rate
(%)
RR
95%CI
Tiramisu
94
27
77.7
7
158
4.2
18.5
8.8-38.0
Dark
Mousse au
Chocolat
76
37
67.3
26
148
14.9
4.8
3.1-6.6
White
Mousse au
Chocolat
49
23
68.1
49
156
23.9
2.8
2.1-3.8
Fruit Salad
46
25
64.8
53
159
25.0
2.6
1.9-3.5
Beer
30
74
28.8
67
95
41.4
0.7
0.6-1.0
Red Jelly
45
34
57
56
150
27
2.1
1.6-2.8
Vanilla
Sauce
28
21
57
72
160
31
1.8
1.4-2.5
5
Several food items seem to play a role in the occurrence of illness; tiramisu, dark and white
chocolate, fruit salad, red jelly and vanilla sauce. They can potentially explain up to
respectively (94, 76, 49, 46, 45 and 28 of the 103 cases). Consumption of beer seems to
play a protective role in the occurrence of gastroenteritis.
Q3
Can we conclude that we had a multi-vehicle outbreak?
How would you sort out the respective role of each food item?
Draw relevant dummy tables.
6
In order to study the independent role of the consumption of fruit salad, dark and white
chocolate, red jelly and vanilla sauce, the occurrence of gastroenteritis was studied among
the group of attendants who did not eat tiramisu (Table II).
Table II
Food specific attack rates among attendees who did not eat tiramisu,
high school graduation ceremony, Germany, 26 June 1998.
Eaten
Not eaten
Number
ill
Number
not ill
Attack
rate (%)
Number
ill
Number
not ill
Attack
rate (%)
RR
95%CI
Dark Mousse au
Chocolat
5
17
23
2
139
1
16.0
3.3-77.6
White Mousse au
Chocolat
4
13
24
3
141
2
11.3
2.8-46.3
Red Jelly
1
19
5
4
137
3
2.6
0.3-21.6
Vanilla sauce
1
13
7
4
141
3
2.6
0.3-21.6
Fruit salad
4
12
25
2
144
1
18.3
3.6-92.0
Q4
Interpret the results
7
Results presented in table II suggest that dark and white chocolate as well as fruit salad, red
jelly and vanilla sauce consumption may have contributed to illness (since RR are high even
among those who did not eat tiramisu). Such an association can be real (several
contaminated food items, use of a single spoon to serve portions) or due to another
unidentified confounding factor. Interpretation of results should also be cautious due to the
small number of cases involved in this stratified analysis.
8
Part two
In order to support the evidence that tiramisu was the main vehicle of the outbreak the
investigators decided to study if a dose effect was present. The amount of tiramisu
consumed was categorised as none, average or large.
Q4
Using the following table, decide if the rate of illness varies with the amount of
tiramisu consumed.
Table III Cases of gastroenteritis among attendants at a high school graduation ceremony by
amount of tiramisu consumed, Stegen, Germany, 1998
Tiramisu
Total
Cases
Large
Average
None
Unknown
56
65
158
12
50
44
7
2
Total
291
103
AR%
RR
9
Part three
From the crude analysis epidemiologists noticed that the occurrence of gastroenteritis was
lower among those attendants who had drunk beer. They decided to assess if beer had a
protective effect on occurrence of gastroenteritis.
Q5
How would you go about testing that hypothesis?
Q6
Develop any relevant table and calculate the relative risk. Interpret the results.
You should use the following information:
Number of those who drank beer, ate tiramisu and developed illness
27
Number of those who drank beer, did not eat tiramisu and developed illness
3
Number of those who did not drink beer, ate tiramisu and developed illness
63
Number of those who did not drink beer, did not eat tiramisu and developed illness 4
Number who did not drink beer but ate tiramisu
75
Number who did not drink beer
162
Number who drank beer
104
Number who ate tiramisu
116
Number who did not eat tiramisu
150
Unknown consumption of beer or tiramisu
25
10
By stratifying the analysis on tiramisu consumption we can measure the potential protective
role of beer among those who ate tiramisu. The following tables show occurrence of
gastroenteritis according to beer and tiramisu consumption.
Table IV Cases of gastroenteritis among attendants at a high school graduation ceremony by
beer and tiramisu consumption, Stegen, Germany, 1998.
Tiramisu YES
Beer YES
Beer NO
Total
41
75
Cases
27
63
AR
65.9
84.0
RR
0.8
Reference
95% CI
0.6-1.0
Total
63
87
Cases
3
4
AR
4.8
4.6
RR
1.0
Reference
95% CI
0.2-4.5
Tiramisu NO
Beer YES
Beer NO
Q 7 Comment on the table above
11
It seems that consumption of beer may reduce the relative effect of tiramisu consumption on
occurrence of gastroenteritis. The RR differ (0.8 vs 1.0) in the two strata. Effect modification
may be present.
This association between beer consumption and occurrence of gastroenteritis is however not
confounded by Tiramisu consumption since the adjusted RR is 0.8 and the crude RR was 0.7
A similar stratification was conducted assessing dose response for tiramisu consumption
among beer drinkers and not.
Table V Cases of gastroenteritis among attendants at a high school graduation ceremony by
beer and amount of tiramisu consumption, Stegen, Germany, 1998.
Total
Cases
AR
RR
95% CI
__________________________________________________________________________
Tiramisu LARGE
Beer YES
Beer NO
19
34
17
30
89.5
88.2
1.0
0.8-1.2
Tiramisu AVERAGE
Beer YES
22
Beer NO
41
10
33
45.5
80.5
0.6
0.4-0.9
Tiramisu NONE
Beer YES
Beer NO
3
4
4.8
4.6
1.0
0.2-4.5
Q7
63
87
Comment on the results
12
After stratifying beer consumption on the amount of tiramisu consumed, it appears that beer
consumption reduces the relative effect of tiramisu on occurrence of gastroenteritis only
among those who have eaten a average amount of tiramisu. This is suggesting that, if the
amount of tiramisu is large, consumption of beer no longer reduces the risk of illness when
eating tiramisu.
13
Part four
During the investigation some epidemiologists considered that a lot of time and energy could
have been saved by doing a case control study instead of a retrospective cohort study. They
had proposed to do a case control study using the cases (here we will use the 101 cases for
whom information on tiramisu consumption is available) and 1 control per case.
Q8
How would you select controls?
14
In the following section of the case study we will illustrate the consequences of choosing
controls from the original cohort or from non cases.
Q9
Assuming you randomly select controls among non cases, and that controls
are representative of exposure among non cases, complete the following table:
Tiramisu
Cases
YES
94
NO
7
Total
101
Control
OR
95% CI
101
Q10 Assuming you randomly select control among attendants to the party and that
controls are representative of exposure in this group, complete the following table:
Tiramisu
Cases
YES
94
Control
OR
95% CI
NO
7
___________________________________________________________
Total
Q11
101
101
Discuss the results obtained using the different sets of controls
15
The crude RR obtained after comparing AR between those who ate and did not eat tiramisu
was 18.3 in the cohort study. The OR (76.9) obtained in the “case non-case” study (controls
selected from the non cases group) overestimate the RR, because consumption of tiramisu
is much lower (14.9 %) in the non cases group than in the entire source population (42.3%).
Since controls should be representative of exposure in the source population, we should
randomly select controls among the entire group attending the party rather than only among
non cases.
Anyhow the message is that when AR is high a cohort study is always preferred over any
type of case control study.
Q12
What other study design could have been chosen?
References
Rodriguez L and Kirkwood B: Case-control designs in the study of common diseases:
updates on the demise of the rare disease assumption and the choice of sampling scheme
for controls. Int J Epidemiol 1990; 19: 205-13
Rothman KJ: Epidemiology. An introduction. Oxford University Press2002. P 74ff
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