1. 2004 Public Health Training and Information Network (PHTIN) Series

2. Site Sign-in Sheet Please mail or fax your site’s sign-in sheet to: Linda White NC Office of Public Health Preparedness and Response Cooper Building 1902 Mail Service Center Raleigh, NC 27699 FAX: (919) 715 - 2246

3. Outbreak Investigation Methods From Mystery to Mastery

5. 2004 PHTIN Training Development Team Jennifer Horney, MPH - Director, Training and Education, NCCPHP Pia MacDonald, PhD, MPH - Director, NCCPHP Amy Nelson, PhD Penny Padgett, PhD, MPH Sarah Pfau, MPH Amy Sayle, PhD, MPH Michelle Torok, MPH, Doctoral Candidate Drew Voetsch, MPH, Doctoral Candidate Aaron Wendelboe, MSPH, Doctoral student

6. Future PHTIN Sessions August 17 th..........“Interviewing Techniques” September 14 th.......“Designing Questionnaires” October 12 th......... “Analyzing Data” December 14 th....... “Risk Communication” Each session will be on a Tuesday from 10:00 am - 12:00 pm (with time for discussion)

7. Session I – VI Slides After the airing of each session, NCCPHP will post PHTIN Outbreak Investigation Methods series slides on the following two web sites: NCCPHP Training web site: http://www.sph.unc.edu/nccphp/training/index.html North Carolina Division of Public Health, Office of Public Health Preparedness and Response http://www.epi.state.nc.us/epi/phpr/

8. Session II “Study Design”

9. Today’s Presenters Michelle Torok, MPH Graduate Research Assistant and Doctoral Candidate, NCCPHP Amy Sayle, PhD, MPH Mellon Writing Fellow, Duke University Mary Crabtree Workplace Safety Manager, Department of Environment, Health, and Safety, UNC Chapel Hill Sarah Pfau, MPH Moderator

10. “Study Design” Learning Objectives Upon completion of this session, you will: Understand what an analytic study contributes to an epidemiological outbreak investigation Understand the differences in methodology between cohort and case-control study designs Understand how to select cases and controls in a case-control study design

11. “Study Design” Learning Objectives (cont’d.) Be able to describe the advantages and disadvantages of alternative forms of questionnaire administration in an outbreak investigation Know how to interpret odds ratios from case-control study data and risk ratios from cohort study data Be able to describe short- and long-term control measures that might be implemented in a food borne illness outbreak investigation Understand how to implement long-term control measures such as policy change at an institutional or community level

12. Session I Review

13. Detected an outbreak of gastroenteritis at a university in Texas, based on a March 11 complaint from a student Conducted: –active case finding –chart reviews –hypothesis generating interviews 75 cases detected by March 12

14. Session I Review (cont’d.) Collected stool specimens –All negative for bacterial pathogens –Assume viral pathogen Earliest date of exposure was March 5 Conducted interviews with 7 of the earliest cases (all students) –Only commonality was 6 of 7 reported eating at deli bar of main campus cafeteria

15. Session I Review (cont’d.) Developed a leading hypothesis with the main campus cafeteria as the suspect –No source food identified Interviewed 30 of 31 cafeteria staff members –Staff member who declined interview worked at deli bar* * Today’s session includes a follow up investigation with this staff member

16. Session I Review (cont’d.) Closed deli bar on March 12 th based on: –Link between 6 out of 7 interviewed cases and a common food source –Several unsanitary food handling practices identified via an environmental health investigation

17. Basic Steps of an Outbreak Investigation 1.Verify the diagnosis and confirm the outbreak 2.Define a case and conduct case finding 3.Tabulate and orient data: time, place, person 4.Take immediate control measures 5.Formulate and test hypothesis 6.Plan and execute additional studies 7.Implement and evaluate control measures 8.Communicate findings

18. Next Step: Analytic Study Test current hypothesis: “Main campus cafeteria / deli bar is source of infection” What do we know? What do we suspect? What can we “prove”?

19. What do we know? We know… –75 cases reported by March 12 – all were students who lived on campus –All of cases sampled (n=7) reported eating at the main campus cafeteria 6 of 7 at the deli bar –No illness among off-campus students, faculty, or community members

20. What do we suspect? We suspect the main cafeteria is the source of infection We also suspect the deli bar, in particular, may be the outbreak source

21. What can we “prove”? Can we “prove” it? –Need to conduct an analytic study –Need a testable hypothesis

22. What hypothesis will be tested? Main cafeteria vs. other dining halls? Within the main cafeteria: –Deli bar vs. grill? –Salad bar vs. hot entrée? Food item vs. food handler at deli bar?

23. Our Hypothesis A viral infection spread by food(s) or beverage(s) served at the university’s main cafeteria between March 5 and 10

24. Source Population Students (12,000) 2400 on campus 2000 meal plan Town residents (39,000)

25. Which Study Design? Cohort or case-control?

26. Cohort Study

27. Definition of a Cohort In Epidemiology, “Any designated group of individuals who are followed or traced over a period of time.” - Last, JM. A Dictionary of Epidemiology, 3 rd ed. New York: Oxford University Press, 1995

28. Cohort Study Types A cohort study analyzes an exposure / disease relationship within the entire cohort. Prospective –The Framingham Study Retrospective –Usually used in outbreak investigations

29. Cohort Study Design Exposed Not Exposed Develop Do Not Disease Develop Disease Disease

30. Cohort Study Steps in a Cohort Study: 1.Identify Cohort 2.Administer Questionnaire 3.Analyze Data

31. Cohort Study Step 1 – Identify cohort –Entire student body (n=12,000) –On-campus students (n=2400) –On campus students with meal plan who mainly ate at cafeteria (n=2000) –Sick students (n=75)  Do not select cohort so that either everyone is exposed or everyone is diseased

32. Cohort Study Step 2 – Administer questionnaire –Step 2a – Determine exposure status Main cafeteria Deli bar Food item –Step 2b – Determine disease status Importance of well-defined case definition

33. Cohort Study Example Dartmouth University: 698 (13.8%) of 5060 students had conjunctivitis in spring 2002 To identify risk factors... –web-based questionnaire set up –E-mail sent to 3682 undergraduates –No data entry-rapid analysis 1832 (50%) responded An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae. N Engl J Med. 2003;348 (12):1112-21.

34. Cohort Study Step 3 – Analyze data IllNot IllTotal ExposedABA+B UnexposedCDC+D Risk Ratio[A/(A+B)] [C/(C+D)]

35. Interpreting a Risk Ratio The risk ratio is the ratio of the risk of disease in exposed individuals to the risk of disease in unexposed individuals RR=1.0 = no association between exposure and disease RR>1.0 = positive association RR<1.0 = negative association

36. Interpreting a Risk Ratio Example: Outbreak of conjunctivitis at Dartmouth College RR = 2.5 Disease = Conjunctivitis Exposure = Attended a fraternity / sorority party “Students who attended a fraternity or sorority party had 2.5 times the risk of having conjunctivitis compared to students who did not attend a fraternity or sorority party”

37. Cohort Study Preferred study design when: –Members of cohort are easily identifiable –Members of a cohort are easily accessible –Exposure is rare –There may be multiple diseases involved

38. Cohort Study Example Recent norovirus outbreaks on cruise ships Attempt to interview all passengers Collect food history information MMWR: December 13, 2002 / 51(49);1112-1115

39. Cohort Study Examples Shigellosis among swimmers in a Georgia park – Used park registry to identify park visitors Iwamoto M, Hlady G, Jeter M et al. Shigellosis among Swimmers in a Freshwater Lake-Georgia, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004. Whirlpools and Methicillin-Resistant Staphylococcus aureus –Occurred on a college football team Begier EM, Barrett FK, Mshar PA et al. Body Shaving, Whirlpools, and Football: An Out break of Methicillin-Resistant Staphylococcus aureus Cutaneous Infections in a College Football Team-Connecticut, 2003. Presented at the 53 rd Annual Epidemic Intelligence Service Conference. Atlanta, GA. April, 2004.

40. Question & Answer Opportunity

41. Case Control Study

42. Case-Control Study Design Exposed Not Exposed Disease No Disease “CASES” “CONTROLS”

43. Cohort versus Case-Control Study

44. Case-Control Study Steps in a Case-Control Study: 1.Identify the source population 2.Establish a case definition and select cases 3.Select controls 4.Analyze data

45. Case-Control Study Step 1 - Identify source population Represents the population that gives rise to the cases; is similar to a cohort study In the Texas case study, the source population is: all students who live on- campus

46. Case-Control Study Step 2 – Establish a case definition and select cases A standard set of criteria for deciding disease status –Clinical criteria, time, place, and person

47. Case Study Case Definition Study Hypothesis A viral infection spread by food(s) or beverage(s) served at the university’s main cafeteria between March 5 and 10 Case definition Vomiting or diarrhea (≥3 loose bowel movements during a 24-hour period) Onset on or after March 5, 1998 On-campus student seen at an emergency room or the Student Health Center

48. Case-Control Study Step 3 – Select Controls Represent source population –On-campus students in Texas case study Collect same exposure information as for cases

49. Case-Control Study Step 3 – Select Controls (cont’d.) Sources of controls –Random sample –Friends

50. Case-Control Study CasesControls ExposedAB UnexposedCD Odds Ratio(A/C)/(B/D)=(A*D)/(B*C) Step 4 – Analyze Data

51. Interpreting an OR The odds ratio is interpreted in the same way as a risk ratio: OR=1.0 = no association between exposure and disease OR>1.0 = positive association OR<1.0 = negative association

52. Interpreting an OR Example: Hepatitis A outbreak investigation OR = 12.0 Disease = Hepatitis A Exposure = Eating at restaurant X in April 2003 “Among those with Hepatitis A, the odds of having eaten at restaurant X in April, 2003 is 12 times greater among the cases than among the controls.”

53. Case-Control Study Preferred study design when: –Identifying or accessing the entire cohort would be cost prohibitive or too time consuming –Disease of interest is rare –There are multiple exposures

54. Cohort versus Case-Control

56. Question & Answer Opportunity

57. Activity 1 Choose a study design to investigate the source of the Texas outbreak Completion time: 5 minutes

58. Activity 1 Will you conduct a cohort study or a case- control study? List 2 reasons for your choice. Recall the TX Case Study scenario: Source population = 2,400 on-campus students 75 cases of illness reported by March 12 Hypothesis: Viral infection spread by food(s) or beverage(s) served at the university’s main cafeteria between March 5 and 10

59. Activity 1 Answer The TX investigators decided to conduct a case-control study. The disease is rare (only 3% are cases) Interested in a single disease Exposure of interest (eating in main cafeteria) is common

60. Matching in Case-Control Studies

61. Makes one or more case and control attributes similar (e.g., age, gender, residence) An unmatched study design is usually preferred

62. Matching: Points to Consider More complex data analysis required Inability to assess role of matching factor on disease status –Do not match on exposure factor Potential for over-matching

63. Texas Dept. of Health Study Design Matched case-control study conducted among students at the university CASESCONTROLS Ill students who could be reached in the dorm room Roommates who had not become ill

64. Hypothesis Testing Results Texas case study: –Eating at the main cafeteria was not associated with illness –Eating lunch at the deli bar on March 9 or March 10 appeared to be associated with illness Individual food items could not be evaluated Conduct a larger, unmatched case-control study to identify high risk items or practices at deli bar

65. Hypothesis Testing: Validity of Results Selection / participation bias –Only 29 of 75 cases interviewed Not enough information on deli bar Matching on a risk factor –Can’t evaluate person-to-person transmission

66. 5 Minute Break

67. Refine Hypothesis: Update TX Case Definition On-campus student with vomiting or diarrhea (≥3 loose bowel movements during a 24-hour period) Onset of disease on or after March 5, 1998 Member of the university meal plan

68. Test the Refined Hypothesis: Case-Control Study 40 cases were randomly selected from those reported to TDH by a local emergency room or the Student Health Center 160 controls who did not have nausea, vomiting, or diarrhea since March 5 were randomly selected from the university meal plan list

69. Questionnaire Administration

70. Questionnaire Administration Options 1.Interviewer administered A.Face to face interview B.Telephone interview 2.Self-administered A.Mail-out B.Email C.Web-based

71. Face-to-Face Interview Pros –Higher response rate –Can have more complex skip patterns –More accurate recording of responses Cons –Costly –Potential for interviewer bias –Less anonymous than self-administered –Participants less inclined to be honest

72. Telephone Interview Pros –Similar advantages as face-to-face, but less costly –Quicker access to participants Cons –Similar disadvantages as face-to-face –Unable to capture important visual information (e.g. Rash, working conditions)

73. Self-administered Questionnaire Pros –More anonymous –May collect more honest responses –Data collection takes less personnel time –Less expensive

74. Self-administered Questionnaire Cons –Questionnaire must be simple –Lower response rate –Waiting time to collect completed questionnaires –Potentially more errors in recording responses

75. Activity 2 Choose a method of questionnaire administration for the TX Case Study Completion time: 5 minutes

76. Activity 2 Special Considerations When choosing a method of questionnaire administration, keep in mind that: 1.You plan to contact 40 cases and 160 controls 2.Spring break is March 13-23. Today is March 13.

77. Questionnaire Administration Options Choose a method below for the TX case study. List 2 reasons for your choice. 1.Interviewer-administered A.Face-to-face interview B.Telephone interview 2.Self-administered A.Mail-out B.Email C.Web-based

78. Activity 2 Answer The TX investigators decided to administer the questionnaire by telephone. Need for fast responses; subjects likely to be out of town Desire for accurate information, high response Anonymity not likely to be an issue Take measures to avoid interviewer bias

79. Test the Refined Hypothesis: Conduct Case-Control Study Texas study questionnaire administered by telephone March 15 - 23 –Called students at dormitory room or their home telephone number as recorded in university records –Follow-up phone calls were made to students, when possible or necessary

80. Test the Refined Hypothesis: Carry out Case-Control 36 cases and 144 controls were enrolled Cases included in the study were similar to all cases with respect to gender, age, year in college, and date of onset

81. Test the Refined Hypothesis: Case-Control Results ExposureOdds Ratio Salad Bar Lunch, Mar 90.8 Salad Bar Dinner, Mar 91.1 Deli Bar Lunch, Mar 911.1 Deli Bar Dinner, Mar 97.1 Deli Bar Lunch, Mar 105.7 28 (78%) of the 36 cases reported eating at the deli bar during at least one of the implicated meals.

82. Test the Refined Hypothesis: Case-Control Results* ExposureOdds Ratio American Cheese3.40 Swiss Cheese0.61 Ham1.50 Turkey0.95 Mayonnaise3.10 * Only participants reporting eating at deli bar during Mar 9-10 included

83. Interpretation of Analysis Results What do we know? What do we suspect? What can we “prove”?

84. What do we know? We know that 125 cases of vomiting or diarrhea have been reported – all students We know the cases were more likely to have eaten at the deli bar Mar 9 – Mar 10 We know the pathogen is not bacterial

85. What do we suspect? We suspect that cases were more likely to have eaten ham, mayonnaise, and American cheese, but results were not statistically significant We suspect the pathogen is viral We suspect the food was contaminated by cafeteria staff

86. What can we “prove”? We have “proven” the source came from the deli bar We will probably never “prove” which food was the source We may yet “prove” the pathogen is viral We may yet “prove” the food was contaminated by cafeteria staff

87. Interpretation of Analysis Results What questions do we still have? –Lab results for viral pathogen –Missing food handler who worked at deli bar

88. Texas Case Study: Additional Investigations

89. Additional Investigations: Environmental Sampling Results Water and ice samples obtained from the cafeteria on March 12 were negative for fecal coliforms Stool cultures and rectal swabs from the 23 food handlers were negative for bacteria

90. Additional Investigations: The Missing Food Handler The staff member who initially refused to be interviewed worked primarily at the deli bar She finally agreed to be interviewed on March 23, and reported slicing ham on March 9 for use at the deli bar during lunch and dinner that day and lunch on March 10 –Prepared and served sandwiches for March 9 and 10 meals –Wore gloves while slicing ham and while serving at the deli bar

91. Additional Investigations: The Missing Food Handler Denied any gastrointestinal illness during the outbreak period Reported her infant had been sick with watery diarrhea since March 7 Had not thought that hand washing was an important activity because she wore gloves during food preparation and serving

92. Additional Investigations: Viral Testing Of 18 fresh stool specimens sent to CDC, 9 (50%) had evidence of Norwalk-like virus (NLV) by reverse transcriptase polymerase chain reaction (RT-PCR) Of the four deli foods available from the implicated meals, only the March 9 ham sample was positive for the NLV RNA

93. Additional Investigations: Viral Testing NLV was also detected by RT-PCR in a stool sample from the ill infant of the food handler who prepared the deli sandwiches on March 9 The sequence of the amplified product was identical to those PCR products from the ill students and the deli ham

94. Texas Case Study Conclusions The evidence implicates the food handler as the source of the outbreak Diarrheal illness in the food handler’s child preceded the outbreak Food handler prepared ingredients and sandwiches served at the deli bar during the time that her child was ill

95. Texas Case Study Conclusions NLV was isolated from the child’s stool and was identical to that obtained from ill students and the deli ham The food handler was not necessarily ill or infected –May have transferred contamination directly from her ill infant

96. Control Measures

97. At this point in the investigation, you should consider short-term interventions for the control of the current outbreak. Long-term interventions which might prevent the spread of foodborne diseases at the cafeteria in the future should be considered and implemented after the situation is under control.

98. Activity 3: Identify potential control measures Completion time: 5 minutes

99. Activity 3 Part A: Please write down 2 suggested short- term control measures for the TX outbreak Part B: Please write down 2 suggested long- term control measures for the TX outbreak

100. Possible Short-Term Control Measures Throw away all leftover deli bar foods and ingredients Clean and disinfect all equipment and surfaces in the deli bar Require all food handlers to submit a stool specimen before allowing them to return to work? Quarantine or isolation a necessary consideration

101. Possible Long-Term Control Measures Education on proper food handling procedures including: –hand washing –hot-holding and cold-holding temperatures Develop a sick food handlers policy Consider institution’s responsibility to assure recommended policies and practices are followed

102. Control Measures: Follow Up The health department should monitor until a safe food handling system has been established

103. Control Measures: Follow Up A food safety specialist and / or sanitarian should return to the university cafeteria in one month and on a quarterly basis for at least the first year –Make sure no further disease is occurring –Assess the development and implementation of appropriate policies –Evaluate practice of good food handling procedures by employees –Assure ongoing oversight by / within the institution

104. Control Measures: Policy Change Develop actions or policies for the campus food service to prevent a recurrence by consulting with: –University administrators or their representatives –Supervisors in the cafeteria –Food handlers –Union representatives (if applicable) –Staff from the local health department

105. Control Measures Today’s Guest Expert Lecturer: Mary Crabtree Workplace Safety Manager, Department of Environment, Health, and Safety, UNC Chapel Hill

106. UNC Norovirus Outbreak ehs.unc.edu 962-5507

107. Objectives General Information UNC Norovirus Outbreak Actions taken within UNC Debriefing within UNC Attendance at NCSU’s debriefing Lessons Learned Recommendations for Other Institutions ehs.unc.edu 962-5507

108. General Information In January, EHS implemented a Hand Washing Campaign with Orange County Health Dept. Goal: To reduce overall risk of exposure to infectious diseases and food borne illnesses ehs.unc.edu 962-5507

109. General Information Carolina Dining Services: Two full dining facilities Four snack facilities Aramark: contractor for food services Serve 7,000 meals per day in full dining halls ehs.unc.edu 962-5507

110. UNC Norovirus Outbreak Cases Reported: On January 21, 2004, 66 students reported to Student Health Services Symptoms: nausea, vomiting, diarrhea, acute gastroenteritis ehs.unc.edu 962-5507

111. UNC Norovirus Outbreak ehs.unc.edu 962-5507 Data Sources: UNC Chapel Hill Student Health Services (“SHS”); UNC Chapel Hill Housing & Residential Education (“Not Seen”)

112. UNC Norovirus Outbreak Overall, ~250 students became ill during this outbreak. ehs.unc.edu 962-5507

113. UNC Norovirus Outbreak Orange County Health Department’s Finding (February 2, 2004): Outbreak from a single source Time limited Common environmental exposure 5x more likely in one location of dining hall 4x more likely if the student ate salad bar No point to a specific salad item No procedural problems found with the Dining Services ehs.unc.edu 962-5507

114. Action Taken Within UNC Student Health Services Immediately notified Orange County Health Dept. Enacted Disaster Plan and notified EHS Assisted with Incident Communications Plan Posted “Student Illness Update” on websites ehs.unc.edu 962-5507

115. Action Taken within UNC Environment, Health, and Safety Established contact with entities that would be involved (i.e. Hskpg, UEOHC, Athletics, Housing & Residential Education) Coordinated Incident Communications Plan Prepared clean-up packets for Residential Halls Met with Housekeeping Zone Managers - Review Clean-up procedures - Identification of areas which students exhibit illness Discussed clean-up procedures with Athletics (Men’s Basketball Game January 24) ehs.unc.edu 962-5507

116. Action Taken within UNC ehs.unc.edu 962-5507

117. Action Taken within UNC Housing and Residential Education Distributed EHS clean-up kits to residential halls Assisted with Incident Communications Plan Prepared & distributed illness survey (for students who did not go to SHS for treatment) ehs.unc.edu 962-5507

118. Action Taken within UNC Carolina Dining and Aramark: Placed “Hand Wash” tents on dining tables Placed additional hand washing stations throughout dining halls Reviewed staff absenteeism records Fully assisted health investigators ehs.unc.edu 962-5507

119. Debriefing within UNC Debriefing was conducted on March 2 Parties involved: -Environment, Health & Safety -Student Health Services -Carolina Dining Services (including Aramark) -Housing & Residential Education -Housekeeping Services ehs.unc.edu 962-5507

120. Debriefing within UNC Reviewed OCHD Findings Effectiveness of Communications Involvement of Key Groups for decision making What if any other potential resources were needed - Further analysis by School of Public Health What other action can be taken to prevent / mitigate reoccurrence ehs.unc.edu 962-5507

121. Attendance at NCSU’s Debriefing Collaboration – What could we have done better? Paralleled UNC’s case After 6 th case at SHS, implemented survey Saw 410 students from Feb. 9 – Mar. 4 ehs.unc.edu 962-5507

122. Lessons Learned Initiate medical survey at the time of complaint (to complement the Health Department) Immediately review geographic data – who ate where and when Continue contingency planning with outside parties Implement a stronger Hand Washing Campaign ehs.unc.edu 962-5507

123. Recommendations for Other Institutions Establish emergency communication procedures Openly discuss contingency plans and responsibilities internally and with public health officials Conduct drills (i.e. table top) to identify needs Review Contracts of food service and establish a working partnership Implement stronger health campaigns Share Information ehs.unc.edu 962-5507

124. Question & Answer Opportunity

125. Session II Summary

126. An analytic study is used to test scientific hypotheses that may help support actions for specific control measures and to help prevent recurrence of problem. Risk ratios and odds ratios are used to assess an association between the exposure and illness. Risk and risk ratios can be directly calculated from cohort studies, but this design usually demands more resources.

127. Session II Summary Case-control studies, when conducted properly, are generally adequate and usually more efficient. A case definition with specific criteria helps you select your study population, as long as it does not include the hypothesis. Controls need to be representative of the source population, and not matched on the exposure factor if matching is used.

128. Session II Summary Interviewer administered questionnaires are generally higher quality, but more costly and time consuming. Self-administered questionnaires are generally more convenient but lower quality.

129. Session II Summary Short-term control measures help contain an outbreak. Long-term control measures help establish preventive measures and future spread of disease.

130. Next Session August 17th 10:00 a.m. - Noon Topic: “Interviewing Techniques”

131. Session II Slides Following this program, please visit one of the web sites below to access and download a copy of today’s slides: NCCPHP Training web site: http://www.sph.unc.edu/nccphp/training/index.html North Carolina Division of Public Health, Office of Public Health Preparedness and Response http://www.epi.state.nc.us/epi/phpr/

132. Site Sign-in Sheet Please mail or fax your site’s sign-in sheet to: Linda White NC Office of Public Health Preparedness and Response Cooper Building 1902 Mail Service Center Raleigh, NC 27699 FAX: (919) 715 - 2246