Title: Cohort Studies for Outbreak Investigations
1Cohort Studies for Outbreak Investigations
2Goals
- 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.
3Quick Review of Cohort Studies
- Useful when
- 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
4Establishing the Cohort
- 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 - Cannot know whether difference in disease outcome
due to exposure or the other differences
5Establishing the Cohort
- Or identify a population group and then determine
whether they were exposed - People who happened to be at the same place at
the same time - Attendance at an event
- Membership in a particular group
- 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 otherconfounding may not be a major issue
6Conducting the Investigation
- The exposure causing an outbreak is not always
known - Investigators measure number of plausible
exposures and evaluate each one - People who did/did not eat at a restaurant
- People who did/did not use swimming facilities
- People who did/did not get ice from ice machine
- People who did/did not eat potato salad at picnic
7Conducting the Investigation
- Develop questionnaires and interview members of
the cohort - 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
8Analyzing DataPrevalence
- 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
- Example in 1993, the prevalence of chronic
fatigue syndrome among patients attending a
primary care physician was 3. (2)
9Analyzing DataRisk
- Risk probability of acquiring disease
- Example The risk of acquiring HIV from a blood
transfusion in the U.S. is approximately 0.0002
(3) - 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 - 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
- Example an influenza epidemic in a nursing home
had an attack rate of 83 (43 of 52 residents
became ill) (4)
10Analyzing DataRisk Ratio
- 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
11Analyzing Data2x2 Table
- Risk and Risk Ratios 2x2 table
  Ill  Not Ill  Total Risk (Attack Rate)
Exposed a b ab a/ab
Not Exposed c d cd c/cd
Risk Ratio (a/ab) /(c/cd) Risk Ratio (a/ab) /(c/cd) Risk Ratio (a/ab) /(c/cd) Risk Ratio (a/ab) /(c/cd) Risk Ratio (a/ab) /(c/cd)
12Analyzing DataRisk Ratio
- 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 - If RR 1, no association with disease
- If RR gt 1, exposure positively related to
disease - If RR lt 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)
13Practice Calculating Risk
- 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. - 27 children met case definition
14Practice Calculating Risk
- The overall risk of illness among children
-
- ill 27 0.44 44
- total children 61
15Practice Calculating Risk
- All children and adults asked which animal
exhibits they visited, whether they participated
in the petting zoo, what lunch and snack items
they ate
16Practice Calculating Risk
- Selected exposures from children attending
Daycare X Zoo Day
Exposure Ill (n27) Not Ill (n34)
Turkey sandwich 21 14
Fruit salad 10 30
Chips 13 17
Petting zoo 17 15
17Practice Calculating Risk
- Many sick children ate turkey sandwich, so lets
focus on that exposure - 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 illÂ
18Practice Calculating Risk
- 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 27 34 61
19Practice Calculating Risk
- Calculate risk of illness among those exposed to
turkey - ill exposed 21 0.60 60
- total exposed 35
- Calculate risk of illness among those NOT exposed
to turkey - ill unexposed 6 0.23 23
- total unexposed 26
20Practice Calculating Risk
- Risk of illness among exposed 60
- Risk of illness among unexposed 23
- Calculate risk ratio
- risk among the exposed 0.60 2.61
- risk among the unexposed 0.23
21Practice Calculating Risk
- 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
22Practice Calculating Risk
- If the turkey sandwich was responsible, why were
there cases among the not exposed? - 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
23Practice Calculating Risk
- So have you found the culprit?
- 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)
24Example Cohort Study Gastroenteritis at a
tourist resort
- July 2000 outbreak of gastroenteritis at tourist
resort in southern Italy (6) - Illness identified in 344 people, including 69
staff members - Retrospective cohort study performed to assess
risk factors associated with illness in staff
members
25Example Cohort Study Gastroenteritis at a
tourist resort
- July 2000 outbreak of gastroenteritis at a
tourist resort in southern Italy (6) - Illness identified in 344 people, inlcuding 69
staff members - Retrospective cohort study among staff
- 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 (RR1.8) and consuming drinks with ice
(RR1.8)
26Example Cohort Study Foodborne outbreak at a
restaurant
- December 2000-January 2001 health authorities in
southwest Germany contacted by ill persons about
gastroenteritis symptoms (7) - 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 - 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 (RR5)
27Example Cohort Study Gastroenteritis on a cruise
ship
- 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 - 189 passengers in cohort, 132 interviewed, 22 met
case definition (attack rate 17) - Attack rate for persons who ate oysters 29 (14
of 48)
28Example Cohort Study MRSA outbreak on football
team
- 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
- 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)
29References
- 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. 20015021-24. - 2. Bates D, Schmitt W, Buchwald D, et al.
Prevalence of fatigue and chronic fatigue
syndrome in a primary care practice. Arch Intern
Med. 19931532759-2765. - 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.
30References
- 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.
19961(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 23909-914. - 6. Boccia D, Tozzi AE, Cotter B, et al.
Waterborne outbreak of Norwalk-like virus
gastroenteritis at a tourist resort, Italy. Emerg
Infec Dis. 20028563-568.
31References
- 7. Doller PC, Dietrich K, Filipp N, et al.
Cyclosporiasis outbreak in Germany associated
with the consumption of salad. Emerg Infec Dis.
20028992-994. - 8. McLaughlin JB, DePaola A, Bopp CA, et al.
Outbreak of Vibrio parahaemolyticus
gastroenteritis associated with Alaskan oysters.
N Engl J Med. 20053531463-1470. - 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.
2004391446-1453.