Epidemiologic Investigation Epi-Ready Epidemiologic Investigation Module 6

Module Objectives By the end of this module, participants will be able to evaluate the epidemiologic approaches used in an effective foodborne outbreak response. Recognize the various methods used to gather information during an investigation. Describe the measures of association calculated during an epidemiologic investigation. Explain the concept of statistical significance as it relates to measures of association.

The Epidemiologic Investigator Conducts Surveillance Activities Identifies and Interviews Cases Generates Hypothesis and Case Definitions Identifies Comparison Groups (Controls) Conducts Analytic Studies

Cross-Disciplinary Activities Environmental Investigator Focus Environmental Assessment Activity Product Tracing Laboratory Identify Appropriate Clinical Samples for Collection and Analysis

Case Definition Uniform criteria employed to define a case Based on the best available information at the time Subject to change Will include: Person Place Time Clinical Criteria

Building a Case Definition Person: Attended a bar-b-que on July 4th Place: Great Bear Wilderness Club Time: Illness onset July 6th or later Clinical Criteria: Anyone with diarrheal illness (3 or more loose stools in the past 24 hours) A case associated with this outbreak is a person attending a Bar-B-Que on July 4th at the Great Bear Wilderness Club with diarrheal illness with onset July 6th or later.

Case Finding Guest Lists Coordination Between Response Team Credit Card Receipts Loyalty Card Information Media Releases On-line Complaints

Hypothesis Generation A suggested explanation of what is making people sick Ongoing process subject to change Testing hypothesis may require a multidisciplinary approach Food and environmental surface laboratory analysis Product tracing activities by environmental health Additional epidemiologic investigation activities Hypothesis-generating questionnaires

Hypothesis-Generating Questionnaires Consumption of foods from a standard list Meals consumed during the time of likely exposure Food shopping habits Travel during the time of likely exposure Consumption of food away from the home Restaurant Events Likely exposure period

Challenges of Hypothesis Generation Poor recall due to time lag from onset of illness to interview Ingredient-level contaminated food (stealth food items) Foods with high consumption rates Foods not disclosed due to their sensitive nature (illegal substances) Interview fatigue of the interviewer and interviewee

Supportive Tools for Hypothesis Generation and Testing

Interpretation of Gathered Information Line Lists Epi Curves Spot Maps

Activity Working in pairs or in your table group, answer the questions in the participant manual. This activity should take no more than 5 minutes.

Epi Curves Visually depicts the time element associated with illness onset May provide a pattern of onsets that can lead to better understanding of how the illness was contracted Point Source Continuous Common Source Propagated

Point Source Outbreak Exposure to same source over brief time Cases rise rapidly to a peak and fall off gradually Majority of cases within one incubation period Exposure

Continuous Common Source Outbreak Exposure to same source over a prolonged time Epidemic curve usually rises gradually Curve may flatten Recall

Propagated Outbreak Spread from person to person Often the series will have progressively taller peaks Peaks one incubation period apart

Spot Maps Distribution of Cases Reveals Clues Regarding the Source of the Outbreak Over broad area: commercial product with wide distribution Clustering: locally sold product, point source, or person-to-person spread Concentrated areas with outliers: travel to affected area or importation of product ** Bars represent cases

Epidemiologic Studies-Understanding Association Case Series Cohort Study Case-Control Study Case-Case Comparison

Case Series Detailed Examination of Cases No Comparison Group Supported by Other Disciplines

Multistate Outbreak of Salmonella Enteritidis Using shopper card information, it was determined that 7 of 9 cases bought Turkish pine nuts from chain store the week before onset of illness Background rate: <1% of all shoppers bought Turkish pine nuts at store in previous six months Lab testing identified outbreak strain of S. Enteritidis in pine nuts/pesto from store. Strain was indistinguishable to the clinical isolates Store and producer voluntarily recalled pine nuts

Cohort Study Analytic Study in a Well-defined Group (Cohort) Compares Attack Rates of People Exposed Against People That Were Not Exposed to a Certain Food Cohort Ate Food Illness No Illness Did Not Eat Food

Attack Rates Is the Incidence of Disease in a Group of People (Cohort) Food-specific Attack Rates are calculated in the following manner: Attack Rate Number of ill that consumed the food item Total number that consumed the food Item 100 ? 10 ill persons consumed the salad 20 persons consumed the salad 100

Attack Rate Table Ate the Food Did Not Eat the Food Foods Served   Ate the Food Did Not Eat the Food Foods Served ill (a) Not ill (b) Attack Rate ill (c) Not ill (d) Chicken Salad 12 18 40% 10 50% Hamburger 20 7 74% 3 23% Baked Beans 55% 8 44% Veggie Burger 2 20% 22 5 81% Iced Tea 31 61% 6 54%

Relative Risk Measure of association for a cohort study Answers: “How much more likely is it for people who ate the food to become ill than people who did not eat the food?” Relative Risk attack rate among exposed attack rate among unexposed

Interpreting Relative Risk Close to 1.0: risk of disease is similar among people eating and not eating the food  food not associated with illness Greater than 1.0: risk of disease is higher among people eating the food than people not eating the food  food could be risk factor Less than 1.0: risk of disease is lower among people eating the food than people not eating the food  food could be “inversely associated with” Magnitude of Relative Risk reflects strength of association between eating food and illness.

Attack Rate Table with Relative Risks   Ate the Food Did Not Eat the Food Foods Served ill (a) Not ill (b) Attack Rate ill (c) Not ill (d) Relative Risk Chicken Salad 12 18 40% 10 50% 0.80 Hamburger 20 7 74% 3 23% 3.21 Baked Beans 55% 8 44% 1.23 Veggie Burger 2 20% 22 5 81% 0.25 Iced Tea 31 61% 6 54% 1.13

Case-Control Study Cases (people with illness) and controls (people with no illness) Compare foods eaten by cases and controls Foods more commonly eaten by cases than controls might be associated with illness Ate Food Did Not Eat Food Controls Population at Risk Cases

Odds Ratio Measure of association for a case-control study Answers: “How much higher is the odds of eating the food among cases than controls?” odds of eating food among cases odds of eating food among controls odds ratio =

Botulism Outbreak In Vancouver B.C. 36 cases of botulism among patrons of Restaurant X Case-control study undertaken 20 (91%) of 22 cases ate beef dip sandwich 3 (14%) of 22 controls ate beef dip sandwich

Determining the Odds Ratio 20 of 22 cases ate beef dip sandwich (2 didn’t) 3 of 22 controls ate beef dip sandwich (19 didn’t) An odds ratio of 63 means the odds that cases ate the beef dip sandwich was 63 times higher than the odds among controls. Eating the beef dip sandwich might be a risk factor for botulism in this outbreak. odds of eating food (cases) 20/2 odds of eating food (controls) 3/19 odds ratio = odds ratio = 63

Interpreting Odds Ratios Close to 1.0: odds of eating food is similar among cases and controls  no association between food and illness Greater than 1.0: odds of eating food among cases is higher than among controls  food could be risk factor Less than 1.0: odds of eating food among cases is lower than among controls  food could be “inversely associated ” Magnitude reflects strength of association between illness and eating the food.

Case-Case Study Design Yields odds ratio similar to case-control studies depending on risk factors under investigation May eliminate the need to match controls Reduces selection and recall bias Saves valuable resources as case-patients are interviewed as part of an effective surveillance program

Choosing a Study Design Case series – when the number of cases is small (generally less than five) and no controls are available Cohort study – when investigators can easily identify the population at risk (i.e., outbreak has occurred in a well-defined group) and the population at risk can be enumerated Case-control study – when the population at risk (people potentially exposed to source of outbreak) is unknown or cannot be enumerated or the illness is rare

Statistical Significance Odds ratios and relative risks are estimates Observed results could be due to chance alone Role of chance explored through Confidence interval (CI) p-value

Confidence Intervals Range of values for the measure of association that are consistent with study findings Has specified probability of including “true value” for the measure of association. Generally a probability of 95% is used. Positive association when range of values are greater than 1.0 Inverse association when range of values between 0 and 1.0 Ranges that include 1.0 are not significant!

Confidence Intervals of the Cohort Study   Ate the Food Did Not Eat the Food Confidence Interval Foods Served ill (a) Not ill (b) Attack Rate ill (c) Not ill (d) Relative Risk Lower Limit Upper Limit Chicken Salad 12 18 40% 10 50% 0.80 0.43 1.48 Hamburger 20 7 74% 3 23% 3.21 1.16 8.88 Baked Beans 55% 8 44% 1.23 0.64 2.33 Veggie Burger 2 20% 22 5 81% 0.25 0.07 0.86 Iced Tea 31 61% 6 54% 1.13 0.65 1.96

P-Value Probability that findings due to chance alone Ranges from 0 to 1.0 (0% to 100%) Closer to 1.0 (100%)  high probability the findings are due to chance Closer to 0.0 (0%)  low probability the findings are due to chance p-value = 0.02 Interpretation: the probability of the finding occurred by chance is 2 in 100 times

P-Values Calculated for Attack Rate Table   Ate the Food Did Not Eat the Food Foods Served ill (a) Not ill (b) Attack Rate ill (c) Not ill (d) Relative Risk p-value Chicken Salad 12 18 40% 10 50% 0.80 0.48 Hamburger 20 7 74% 3 23% 3.21 0.002 Baked Beans 55% 8 44% 1.23 0.53 Veggie Burger 2 20% 22 5 81% 0.25 0.0005 Iced Tea 31 61% 6 54% 1.13 0.65

Summary Recognize the various methods use to gather information during an investigation Describe the measures of association calculated during an investigation Explain the concept of statistical significance as it relates to measures of association

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