Transcript Slide 1

Cohort Studies for
Outbreak Investigations
Goals
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Describe the basic steps of conducting a
cohort study.
Discuss how to calculate measures of
disease and disease association.
Practice conducting basic analysis for an
example outbreak.
Provide examples of recent outbreak
investigations that have used the cohort
study design.
Quick Review of Cohort
Studies
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Useful when:
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Defined population at risk for developing disease
of interest
Possible to interview all members or
representative sample of the cohort
Usually retrospective because exposure and
enough cases to signal an outbreak have
already occurred
Aim is to determine what exposures occurred
in the past to cause cases of disease
Establishing the Cohort
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Choose cohort members based on characteristics that
assume exposure has occurred
Unexposed group must be similar to the exposed
group in all respects except the exposure
Using groups that have other differences may lead to
“confounding”
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Cannot know whether difference in disease outcome due to
exposure or the other differences
Establishing the Cohort
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Or identify a population group and then determine
whether they were exposed
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People who happened to be at the same place at the same
time
Attendance at an event
Membership in a particular group
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Example: Athletes competing in the Eco-Challenge Sabah 2000
multi-sport race in Malaysia who developed illness after
exposure to the Segama River. (1)
People who all belong to the same group or attend
the same event are likely to be very similar to each
other—confounding may not be a major issue
Conducting the Investigation
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The exposure causing an outbreak is not
always known
Investigators measure number of plausible
exposures and evaluate each one
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People
People
People
People
who
who
who
who
did/did not
did/did not
did/did not
did/did not
eat at a restaurant
use swimming facilities
get ice from ice machine
eat potato salad at picnic
Conducting the Investigation
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Develop questionnaires and interview
members of the cohort
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Demographic information
Exposure to any potential risk factors for disease
Determine which cohort members meet the
case definition
Analyze information to determine whether
there is a relationship between exposure and
disease
Analyzing Data—Prevalence
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Prevalence = number of ill people
divided by the total population at risk
(the cohort) at a particular point in time
Often expressed as a percent
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Example: in 1993, the prevalence of chronic
fatigue syndrome among patients attending a
primary care physician was 3%. (2)
Analyzing Data—Risk
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Risk = probability of acquiring disease
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Risk = number of cases divided by total population
(cases and non-cases)
Can calculate risk in cohort because you know the
number of people at risk of developing disease
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Example: The risk of acquiring HIV from a blood transfusion
in the U.S. is approximately 0.0002% (3)
Cannot calculate risk in a case-control study because
includes only a sample of people at risk or may not know
number of people at risk
Also called attack rate
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Example: an influenza epidemic in a nursing home had an
attack rate of 83% (43 of 52 residents became ill) (4)
Analyzing Data—Risk Ratio
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Risk can be calculated separately for
exposed and unexposed groups
Known as risk ratio (RR) or relative risk:
the risk of one group relative to the risk
of another group
Risk Ratio = the risk in exposed group
divided by the risk in unexposed group
Analyzing Data—2x2 Table
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Risk and Risk Ratios: 2x2 table
Ill
Not Ill
Total
Risk
(Attack Rate)
Exposed
a
b
a+b
a/a+b
Not
Exposed
c
d
c+d
c/c+d
Risk Ratio= (a/a+b) /(c/c+d)
Analyzing Data—Risk Ratio
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To interpret RR, compare the value to 1
If risks in both groups are the same, RR will be 1,
indicating no association between the exposure and
the risk of disease
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If RR = 1, no association with disease
If RR > 1, exposure positively related to disease
If RR < 1, exposure inversely related to disease
Example: In an outbreak of histoplasmosis in a high school,
the risk ratio for students in classrooms near the courtyard
during rototilling was 1.3, meaning that the risk of illness for
students near the courtyard was 1.3 times the risk of illness
for students not near the courtyard. (5)
Practice Calculating Risk
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61 children who attended Daycare X taken to
the zoo, given boxed lunches
Over next few days, several children became
ill and 6 culture-confirmed with Salmonella
Enteritidis
Case defined as any child or adult attending
the Zoo Day trip of Daycare X presenting with
diarrhea, abdominal cramps, and/or fever
within 72 hours of the trip.
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27 children met case definition
Practice Calculating Risk
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The overall risk of illness among
children:
# ill
= 27 = 0.44 = 44%
total # children
61
Practice Calculating Risk
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All children and adults asked which
animal exhibits they visited, whether
they participated in the petting zoo,
what lunch and snack items they ate
Practice Calculating Risk
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Selected exposures from children
attending Daycare X Zoo Day
Exposure
Ill (n=27)
Not Ill (n=34)
Turkey sandwich
21
14
Fruit salad
10
30
Chips
13
17
Petting zoo
17
15
Practice Calculating Risk
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Many sick children ate turkey sandwich, so
let’s focus on that exposure:
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35 of the 61 children reported eating at least part
of turkey sandwich = EXPOSED group
26 children reported NOT eating any of the turkey
sandwich = UNEXPOSED group
21 of 35 exposed children became ill
6 of the 26 unexposed children became ill
Practice Calculating Risk
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2x2 table showing exposure to the
turkey sandwich by illness status
Exposure
Ill
Not Ill
Total
Turkey sandwich
21 (60%) 14 (40%) 35
No turkey sandwich 6 (23%)
20 (77%) 26
Total
34
27
61
Practice Calculating Risk
Calculate risk of illness among those exposed
to turkey:
# ill exposed
= 21 = 0.60 = 60%
total # exposed
35
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Calculate risk of illness among those NOT
exposed to turkey:
# ill unexposed
= 6 = 0.23 = 23%
total # unexposed
26
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Practice Calculating Risk
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Risk of illness among exposed = 60%
Risk of illness among unexposed = 23%
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Calculate risk ratio:
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risk among the exposed
risk among the unexposed
= 0.60 = 2.61
0.23
Practice Calculating Risk
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RR of 2.61 shows that the risk of
acquiring Salmonella among those who
ate turkey was 2.61 times the risk of
acquiring Salmonella among those who
did not eat turkey
Strength of association will be discussed
in future issue of FOCUS
Practice Calculating Risk
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If the turkey sandwich was responsible, why
were there cases among the not exposed?
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People (especially children) may have forgotten
that they ate the turkey sandwich
Cross-contamination may have occurred during
food preparation or while the children were eating
Secondary transmission could have occurred
between children at the daycare
Unexposed children could have become ill by
chance regardless of Zoo Day
Practice Calculating Risk
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So have you found the culprit?
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Even after we find an association between
an exposure and disease, we should
examine other potential exposures for
other significant associations
Next, we should attempt to find the source
of contamination (A future issue of FOCUS
will describe how to conduct a traceback
investigation)
Example Cohort Study:
Gastroenteritis at a tourist resort
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July 2000: outbreak of gastroenteritis at
tourist resort in southern Italy (6)
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Illness identified in 344 people, including
69 staff members
Retrospective cohort study performed
to assess risk factors associated with
illness in staff members
Example Cohort Study:
Gastroenteritis at a tourist resort
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July 2000: outbreak of gastroenteritis at a
tourist resort in southern Italy (6)
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Illness identified in 344 people, inlcuding 69 staff
members
Retrospective cohort study among staff
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Attack rate among staff = 38.1% (69 of 181);
highest in waiters, sports trainers, entertainers,
cleaning staff
Relative risks significant for exposure to beach
showers (RR=1.8) and consuming drinks with ice
(RR=1.8)
Example Cohort Study:
Foodborne outbreak at a restaurant
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December 2000-January 2001: health authorities
in southwest Germany contacted by ill persons
about gastroenteritis symptoms (7)
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Part of four independent parties who attended
luncheons at a particular restaurant
All 40 attendees at the four luncheons asked to
participate in a cohort study
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Of 30 persons who returned questionnaires, 26 met
clinical case definition; attack rate = 87%
Only food item with statistically significant association
with disease was a side salad (RR=5)
Example Cohort Study:
Gastroenteritis on a cruise ship
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July 2004: Alaska Department of Environmental
Conservation notified the Alaska Section of
Epidemiology of several cases of gastroenteritis
among passengers on a cruise ship in Prince William
Sound; additional report of laboratory-confirmed case
of Vibrio parahaemolyticus that started while on the
same ship (8)
Retrospective cohort study on passengers from four
July 2004 cruises on the same ship
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189 passengers in cohort, 132 interviewed, 22 met case
definition (attack rate = 17%)
Attack rate for persons who ate oysters = 29% (14 of 48)
Example Cohort Study:
MRSA outbreak on football team
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September 2003: Connecticut Department of
Public Health notified about cluster of
Methicillin-resistant Staphylococcus aureus
among members of a college football team (9)
Retrospective cohort study of the 2003 team
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90 of 100 players interviewed; 10 met case
definition (attack rate = 10%)
Highest risk among cornerback defensive backs
(RR = 17.5), wide receivers (RR = 11.7), players
with turf burns (RR = 7.2), players who reported
body shaving (RR = 6.1)
References
1. Centers for Disease Control and Prevention. Update:
outbreak of acute febrile illness among athletes
participating in Eco-Challenge Sabah 2000 — Borneo,
Malaysia, 2000. MMWR Morb Mortal Wkly Rep. 2001;50:2124.
2. Bates D, Schmitt W, Buchwald D, et al. Prevalence of fatigue
and chronic fatigue syndrome in a primary care practice.
Arch Intern Med. 1993;153:2759-2765.
3. Centers for Disease Control and Prevention. How safe is the
blood supply in the United States? Available at:
http://www.cdc.gov/hiv/pubs/faq/faq15.htm. Accessed
December 5, 2005.
References
4. Infuso A, Baron S, Fauveau H, et al. Value of influenza
vaccine during an outbreak of influenza A in a nursing
home, Pyrénées Atlantiques, France, November-December
1995. Euro Surveill. 1996;1(5):35-37.
5. Chamany S, Mirza SA, Fleming JW, et al. A large
histoplasmosis outbreak among high school students in
Indiana, 2001. Pediatr Inf Dis J. 2004; 23:909-914.
6. Boccia D, Tozzi AE, Cotter B, et al. Waterborne outbreak of
Norwalk-like virus gastroenteritis at a tourist resort, Italy.
Emerg Infec Dis. 2002;8:563-568.
References
7. Doller PC, Dietrich K, Filipp N, et al. Cyclosporiasis
outbreak in Germany associated with the consumption of
salad. Emerg Infec Dis. 2002;8:992-994.
8. McLaughlin JB, DePaola A, Bopp CA, et al. Outbreak of
Vibrio parahaemolyticus gastroenteritis associated with
Alaskan oysters. N Engl J Med. 2005;353:1463-1470.
9. Begier EM, Frenette K, Barrett NL, et al. A high-morbidity
outbreak of methicillin-resistant Staphylococcus aureus
among players on a college football team, facilitated by
cosmetic body shaving and turf burns. Clin Infect Dis.
2004;39:1446-1453.