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Cohort Studies for Outbreak Investigations

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Title: Cohort Studies for Outbreak Investigations


1
Cohort Studies for Outbreak Investigations
2
Goals
  • 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.

3
Quick 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

4
Establishing 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

5
Establishing 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

6
Conducting 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

7
Conducting 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

8
Analyzing 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)

9
Analyzing 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)

10
Analyzing 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

11
Analyzing 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)
12
Analyzing 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)

13
Practice 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

14
Practice Calculating Risk
  • The overall risk of illness among children
  • ill 27 0.44 44
  • total children 61

15
Practice 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

16
Practice 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
17
Practice 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 ill 

18
Practice 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
19
Practice 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

20
Practice 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

21
Practice 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

22
Practice 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

23
Practice 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)

24
Example 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

25
Example 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)

26
Example 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)

27
Example 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)

28
Example 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)

29
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. 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.

30
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.
    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.

31
References
  • 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.
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