Foodborne Disease Outbreak
Investigation Team Training:
Module 5 – Epidemiologic
Investigation
Epidemiologic investigation
1
Module Learning Objectives
At the end of this module, you will be able to
1. Compare a case series, a cohort study, and a
case-control study.
2. Interpret the measure of association for a
cohort and a case-control study.
3. Explain what is meant by the term “statistically
significant.”
4. Identify potential problem areas in the conduct
of an epidemiologic study which might impact
the findings.
Epidemiologic investigation > Learning objectives
2
Epidemiologic Activities
• Perform descriptive epidemiology
• Conduct hypothesis-generating interviews
• Undertake analytic studies
– Case series
– Cohort studies
– Case-control studies
Epidemiologic investigation
3
Case Series
• Examination of a series of cases associated with
an outbreak
• Collection of detailed information on foods eaten
by cases (and other exposures)
• Common foods (or other exposures) among
cases suggestive of source of outbreak
Ate food
Cases
Did not eat food
Epidemiologic investigation > Case series
Population
at risk
4
Outbreak of Salmonella Enteriditis
• Multistate outbreak of Salmonella Enteritidis
• Using shopper card information, it was
determined that 7 of 9 cases bought Turkish pine
nuts from chain store in week before illness
• Background rate: <1% of all shoppers bought
Turkish pine nuts at store in previous six months
• Laboratory testing identified outbreak strain of
S. Enteritidis in pine nuts
and pesto from store
• Store and producer
voluntarily recall pine nuts
Epidemiologic investigation > Case series
5
The Need for a Comparison Group
• Commonalities among cases:
– Reflective of population at large?
– A chance happening?
– Related to some unknown factor that is the
true source of the outbreak? (confounders)
• Comparison (control) group needed to put
findings into perspective
Epidemiologic investigation > Case series
6
Cohort Study
• Well-defined group in which outbreak occurs
• Compare attack rates among people who ate and
did not eat certain food(s)
• Higher attack rates among people eating a food
(compared to those not eating it) suggest the
food might be associated with illness
Illness
Ate food
Well defined
group
No illness
Illness
Did not eat food
No illness
Epidemiologic investigation > Cohort studies
7
Outbreak of Salmonellosis at Hospital X
• Over 200 cases of salmonellosis occurred
among nurses (a well-defined group) at
Hospital X following the Nurse’s Appreciation
Day Luncheon
• Cohort study of nurses at hospital
– 736 nurses and nursing students responded
– 195 (34%) of 571 persons who attended
luncheon became ill
– 8 (5%) of 165 persons
who did not attend
luncheon became ill
Epidemiologic investigation > Cohort studies
8
Relative Risk (RR)
• Measure of association for a cohort study
• Compares proportion of people who ate the
food who became ill with the proportion of
people did not eat the food who became ill
relative
attack rate among exposed
=
risk
attack rate among unexposed
• Answers the question “How much more likely is
it for people who ate the food to become ill than
people not eating the food?”
Epidemiologic investigation > Cohort studies
9
Relative Risk
• Close to 1.0 = risk of disease is similar among
people eating and not eating the food  food
not associated with illness
• Greater than 1.0 = risk of disease is higher
among people eating the food than people not
eating the food  food could be risk factor
• Less than 1.0 = risk of disease is lower among
people eating the food than people not eating
the food  food could be “protective factor”
• Magnitude reflects strength of association
between eating food and illness.
Epidemiologic investigation > Cohort studies
10
Outbreak of Salmonellosis at Hospital X
Returning to the outbreak of salmonellosis:
• 195 (34%) of 571 attending luncheon became ill
• 8 (5%) of 165 not attending luncheon became ill
relative
attack rate (attended)
=
=
risk
attack rate (did not attend)
34%
= 6.8
5%
A relative risk of 6.8 means that people who
attended the luncheon were almost 7 times
more likely to become ill than those who did
not attend. Attending the luncheon might be a
risk factor for salmonellosis in this outbreak.
Epidemiologic investigation > Cohort studies
11
Class Question

Looking only at the nurses who attended the
Nurse’s Appreciation Day Luncheon
• 14 (18%) of 78 eating tuna salad became ill
• 172 (40%) of 431 not eating tuna salad became
ill
• Relative risk = 0.45
What does this relative risk mean?
Answer: Persons eating tuna salad sandwiches
were half as likely to develop illness as those
not eating tuna salad sandwiches. Eating tuna
salad could be “protective” in this outbreak.
Epidemiologic investigation > Cohort studies
12
Case-Control Study
• Cases (people with illness) and controls (people
with no illness)
• Compare foods eaten by cases and controls
• Foods more commonly eaten by cases than
controls might be associated with illness
Ate food
Did not eat food
Cases
Population
at risk
Ate food
Controls
Did not eat food
Epidemiologic investigation > Case-control studies
13
Outbreak of Botulism in Vancouver, B.C.
• 36 cases of botulism among patrons of
Restaurant X
• Case-control study undertaken
– 20 (91%) of 22 cases ate beef dip sandwich
– 3 (14%) of 22 controls ate beef dip sandwich
Epidemiologic investigation > Case-control studies
14
Odds Ratio (OR)
• Measure of association for a case-control study
• Compares odds of cases having eaten a certain
food to odds of controls having eaten the food
odds of eating food among cases
odds ratio =
odds of eating food among controls
• Answers the question “How much higher is the
odds of eating the food among cases than
controls?”
Epidemiologic investigation > Case-control studies
15
Odds Ratio
• Close to 1.0 = odds of eating food is similar
among cases and controls  no association
between food and illness
• Greater than 1.0 = odds of eating food among
cases is higher than among controls  food
could be risk factor
• Less than 1.0 = odds of eating food among
cases is lower than among controls  food
could be “protective factor”
• Magnitude reflects strength of association
between illness and eating the food.
Epidemiologic investigation > Case-control studies
16
Outbreak of Botulism in Vancouver, B.C.
Returning to the outbreak of botulism:
• 20 of 22 cases ate beef dip sandwich (2 didn’t)
• 3 of 22 controls ate beef dip sandwich (19 didn’t)
odds of eating food (cases)
20/2
odds ratio =
=
odds of eating food (controls)
3/19
odds ratio = 63
An odds ratio of 63 means that the odds that
cases ate the beef dip sandwich was 63 times
higher than the odds among controls. Eating
the beef dip sandwich might be a risk factor
for botulism in this outbreak.
Epidemiologic investigation > Case-control studies
17
Class Question

• Outbreak of cyclosporiasis in New Jersey not
associated with particular event/establishment
• Case-control study undertaken
– 21 (70%) of 30 cases ate raspberries
– 4 (7%) of 60 controls ate raspberries
– Odds ratio = 32.7
What does this odds ratio mean?
Answer: Odds of eating raspberries is 33 times
higher among cases than controls. Eating raspberries could be a risk factor for cyclosporiasis.
The association between raspberries and illness
is strong.
Epidemiologic investigation > Case-control studies
18
When to Do Which Type of Study?
• Case series – when the number of cases is
small (less than five) and no controls are
available
• Cohort study – when investigators can easily
identify the population at risk (i.e., outbreak
has occurred in a well-defined group) and the
population at risk can be enumerated
• Case-control study – when the population at
risk (i.e., people potentially exposed to source
of outbreak) is unknown or cannot be
enumerated or the illness is rare
Epidemiologic investigation
19
Summary
Enroll
Analysis
Case
Cohort
Series
Study
People with People in a welldefined group who
disease
ate and did not eat
certain foods
Ate food or Developed
disease or not
not
Relative risk
None
Measure of
association
When to use Small
number of
cases
Epidemiologic investigation
Population at risk
• Easily identified
• Can be
enumerated
Case-control
Study
People with
and without
disease
Ate food or not
Odds ratio
• Population at
risk unknown
• Rare disease
20
Role of Chance
Epidemiologic investigation
21
Role of Chance
• Things do just happen by coincidence!
• Odds ratios and relative risks are estimates
• Observed results could be due to chance alone
• Role of chance explored through
– p-value
– Confidence interval (CI)
Epidemiologic investigation > Statistical significance
22
p-value
• Probability that findings due to chance alone
• Ranges from 0 to 1 (0% to 100%)
– Closer to 1.0 (100%)  high probability
findings due to chance
– Closer to 0.0 (0%)  low probability
findings due to chance
• Example:
p-value = 0.02
finding occurred by chance 2 in 100 times
Epidemiologic investigation > Statistical significance
23
p-value
• If p-value smaller than predetermined value
 considered “statistically significant”
Example:
If cut-off for statistical significance is 0.05
p-value = 0.02  statistically significant
• Cut-off for statistical significance set by
investigator (usually 0.05 meaning the
finding could have occurred by chance alone
5 in 100 times)
Epidemiologic investigation > Statistical significance
24
Confidence Intervals (CI)
• Range of values for the measure of association
that are consistent with study findings
• Has specified probability (e.g., 95%) of
including “true value” for the measure of
association
• Example:
odds ratio = 5.2
95% CI = 4.0 – 6.1
[
4.0
]
5.2
6.1
Epidemiologic investigation > Statistical significance
25
Confidence Intervals (CI)

If confidence interval includes 1.0  not
statistically significant
Example: 95% CI = 0.8 – 4.2
[
0.8
]
1.0
4.2
If confidence interval does not include 1.0 
statistically significant
Example: 95% CI = 1.8 – 4.2
[
1.0 1.8
]
4.2
Epidemiologic investigation > Statistical significance
26
Class Question
• An outbreak of Salmonella Typhi in Tajikistan
• Case-control study undertaken
• Exposures in 30 days before illness for cases (or
before interview for controls)
• Results analyzed using a p-value of 0.05 as the
cut-off for statistical significance
Epidemiologic investigation > Statistical significance
27

Class Question
Which odds ratios are statistically significant?
Exposure
Eating street
vendor food
Eating apples
Drinking untreated water
Odds
ratio p-value
95% CI
Statistically
significant
1.5
0.3
0.9−5.6
No
0.2
0.03
0.04−0.9
Yes
9.6
0.0005
2.7−34
Yes
Odds ratio for drinking
eating apples
food
untreated
from
less
street
than
tap water
vendor
1.0 suggesting
is greater
possible
than
1.0 suggesting
protective factor.
could be
possible
p-value
risk
risk factor.
factor.
< 0.05p-value
But
andp-value
<
> 0.05
confidence
0.05
and
and
confidence
confidence
interval does
interval
interval
not include
does
includes
not1.0.
includes
1.0.
Finding
Finding
1.0.
is
is likely to
unlikely
Finding
unlikely
to be
be due
due
toto
to
bechance.
chance.
due to chance.
Epidemiologic investigation > Statistical significance
28
Statistical Significance
• Means chance is an unlikely (though not
impossible) explanation for observed association
• Does not mean cause and effect or indicate
“public health significance”
• Is affected by size of study (the more subjects
included in a study, the smaller the p-value will
be regardless of the measure of association)
Epidemiologic investigation > Statistical significance
29
No Statistically Significant Findings?
• Too few study subjects
• Did not ask about food or other exposure that
led to outbreak
• Multiple contaminated food items
• Everyone ate the contaminated food
• Problems with study
Epidemiologic investigation > Statistical significance
30
Potential Study Problem Areas
• Investigator “beliefs” about the cause of the
outbreak (investigator bias)
• Study participation (selection bias)
• Accuracy of information on development of
illness or foods eaten (information bias)
• Quality of study (investigator error)
Epidemiologic investigation > Study problems
31
Group Exercise
Work in groups by table.
1. Read the brief description of a study that was
undertaken following at outbreak associated
with an office potluck.
2. Circle any red flags that make you concerned
about the study conduct or its findings?
3. Do you agree with the investigator about the
cause of the outbreak?
Be prepared to share your
thoughts with the class.
Time: 10 minutes
Epidemiologic investigation
32
Group Exercise (cont’d)
A holiday potluck luncheon was held on December
22 at the headquarters of a private business.
Submarine sandwiches were purchased from a
local deli. Staff members and their spouses were
invited and asked to bring a side dish.
Over 120 persons attended the luncheon. About
40 side dishes were brought
.by attendees. Staff and
spouses socialized, ate,
and drank most of the
afternoon. The office was
then closed for the holidays.
Epidemiologic investigation
33
Class Question (cont’d)

The office reopened on January 5.
At a managers’ meeting a week later (January 12),
several managers reported that they or their
spouses had become ill following the potluck.
Symptoms included predominantly nausea with
some vomiting. None had fever. None sought
medical care. The illnesses lasted less than a day.
Several managers thought
that the illness was due to
potato salad brought by
the boss’ wife.
Epidemiologic investigation
34
Class Question (cont’d)

An intern working with the company, who had
taken a course in epidemiology in college,
volunteered to do a cohort study. The intern sent
an email to all persons invited to the party asking:
Did you get sick after the office holiday potluck
held on December 22?
Did you eat the potato salad?
By January 20, responses had
been received from 30 people.
The intern analyzed the results
using Epi-Info.
Epidemiologic investigation
35
Class Question (cont’d)

The intern reported his findings to the boss:
Fourteen people who attended the potluck said they
had been ill. 15 said they had not been ill.
Ten of the 14 ill were managers or their spouses.
The 10 ill managers or spouses said they all had
eaten potato salad made by the boss’ wife.
The intern shared these calculations:
• 10 (64%) of 14 ill people ate potato salad.
• 4 (25%) of 16 well people ate potato salad.
odds ratio=10
p-value = 0.04
95% CI = 2.2-8.0
Epidemiologic investigation
36
Class Question (cont’d)
The intern reported to the boss that the outbreak
was caused by his wife’s potato salad and that he
was not surprised because it tasted terrible.
The intern was reassigned to the file storage
room in the basement.
Epidemiologic investigation
37
ALWAYS SCRUTINIZE
STUDY RESULTS!
Epidemiologic investigation > Study problems
38
Quick Quiz
Epidemiologic investigation
39
Quick Quiz
1. A case series includes a comparison group.
A. True
B. False
Epidemiologic investigation
40
Quick Quiz
2. What is the measure of association for a casecontrol study?
A. Odds ratio
B. Relative risk
C. p-value
D. Confidence interval
Epidemiologic investigation
41
Quick Quiz
3. In a cohort study, the relative risk for drinking
apple cider is 4.9. Which interpretation is
correct?
A. Apple cider is the cause of the outbreak.
B. People who drank apple cider were almost 5
times more likely to become ill than those
who did not.
C. Apple cider is protective.
D. The association between apple cider and
illness is statistically significant.
Epidemiologic investigation
42
Quick Quiz
4. Which of the following is a true statement about
the p-value?
A. The p-value cut-off for statistical significance
is always 0.05.
B. The p-value indicates the public health
significance of an association between a
food and an illness.
C. The p-value is not affected by study size.
D. A p-value of 0.05 means that there is a 5 in
100 probability that the observed association
between the food and illness is due to
chance alone.
Epidemiologic investigation
43
Quick Quiz
5. Only epidemiologists should interpret results
from epidemiologic studies.
A. True
B. False
Epidemiologic investigation
44

Relative Risk (Optional)
Ill
Ate food
a
Well
b
Did not eat food
c
d
TOTAL
(two-by-two
a+b
c+d
table)
attack rate(ate food) = a/(a + b)
attack rate(did not eat food) = c/(c+d)
relative
attack rate among those eating food
=
risk
attack rate among those not eating food
relative
risk
a/(a+b)
=
c/(c+d)
For more information, see Appendix on Calculating Measures
of Association
Epidemiologic investigation > Cohort studies
45

Odds Ratio (Optional)
Ate food
Did not eat food
TOTAL
Case
a
Control
b
c
d
a+c
b+d
(two-by-two
table)
odds ratio = odds of eating food (cases) =
odds of eating food (controls)
axd
odds ratio =
bxc
a/c
b/d
(cross product)
For more information, see Appendix on Calculating Measures
of Association
Epidemiologic investigation > Case-control studies
46