Cohort Studies for Outbreak Investigations

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Cohort Studies for Outbreak Investigations
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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.

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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

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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

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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

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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

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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

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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)

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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)

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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

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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)
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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)

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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

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Practice Calculating Risk

• The overall risk of illness among children
• ill 27 0.44 44
• total children 61

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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

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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
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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 

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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
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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

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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

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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

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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

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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)

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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

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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)

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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)

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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)

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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)

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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.

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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.

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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.