1. Defense Research Institute Making the Causal Link: Investigating Foodborne Disease OutbreaksWilliam D. Marler, Esq.

2. CDC Estimates of Foodborne Illness 48 million cases of foodborne illness annually 125,000 hospitalizations 3,000 deaths

3. Estimates Differ From Actual Counts Annual E. coli O157 estimates 62,000 illnesses 1,800 hospitalizations 52 deaths But, only 2,621 E. coli 0157 cases were reported in 2005

4. Notifiable/Reportable Diseases Reporting authorized by Congress in 1878 Nationally Reportable Diseases(food or water borne origin)Botulism, Cryptosporidiosis, Cyclosporiasis, Giardiasis, Hemolytic Uremic Syndrome (post-diarrheal), Hepatitis A, Listeriosis, Salmonellosis, Shiga toxin producing Escherichia coli (STEC), Shigellosis, Trichinosis, Vibriosis http://www.cdc.gov/ncphi/disss/nndss/phs/infdis2008.htm

5. Pathway of a Foodborne Illness Investigation Health Care Provider Ill person Specimen collection Organism identified

6. Pathway of a Foodborne Illness Investigation Health Care Provider Ill person Specimen collection Public Health Laboratory Organism identified If there are more ill persons than expected, an OUTBREAK might be underway. Epidemiologic investigation

7. How Do We Know If There Is an Excess? Public Health Surveillance The ongoing collection, analysis, interpretation and dissemination of health data directed towards the control and prevention of diseases.

8. Pathway of a Foodborne Illness Investigation Health Care Provider Ill person Specimen collection Public Health Laboratory Organism identified Product Recall Epidemiologic investigation Environmental investigation Product Trace Back

9. Typical Steps of an Outbreak Investigation Establish that an outbreak is occurring Verify the diagnosis Define and identify cases Orient the data in terms of person, place, and time Develop and test the hypotheses Refine the hypotheses and carry out additional studies Implement control and prevention measures Report findings

10. A Word to the Wise! No mandatory list of how to proceed No set order of steps to take Investigation is dynamic: case definition, line listings, descriptive epidemiology, hypotheses can change Expect the unexpected

11. Investigative Partners Laboratory investigators Microbiologic diagnosis Virology/Parasitic Labs Molecular analysis Epidemiologic investigators Individual case interviews Outbreak investigation Cohort studies Case/control studies Environmental investigators Facility investigation Environmental sampling Product traceback

12. Epidemiology–Basic Tools of the Trade Real-time interviewing with a broad-based exposure questionnaire Symptoms Incubation Duration Food History Medical Attention Suspected source Others Ill

13. Pulsed Field Gel Electrophoresis (PFGE) A Powerful Outbreak Detection Tool Process separates chromosomal fragments of intact bacterial genomic DNA grown from patient isolate Results in 10 to 20 DNA fragments which distinguish bacterial strains Genetic relatedness among strains is based on similarities of the DNA patterns Outbreak strains are those that are epidemiologically linked AND genetically linked

14. Questions to Consider in Assessing PFGE Clusters How common is thePFGE subtype? How many cases are there? Over what time frame did cases occur? What is the geographic distribution of cases? What are the case demographics? Do any of the cases have a “red flag” exposure?

15. E. coli O157:H7 Outbreak, Minnesota, September 2005 Thanks to MN DOH for use of the following slides! Team Diarrhea

17. PFGE pattern new in Minnesota, rare in United States

18. 0.35% of patterns in National Database

20. Outbreak Investigation - Methods September 28–29, 2005 Additional O157 isolates received at the MDOH and subtyped by PFGE 7 isolates demonstrated outbreak PFGE subtype Supplemental interview form created Case-control study initiated

22. 7 6 5 Number of Cases 4 3 2 1 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 14 September October Date of Onset 2005 E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce Case-control study initiated. Initial cluster of 3 isolates among MN residents identified.

23. Case-Control Study Results Cases Exposure Controls p-value Matched OR* 95% CI† Any lettuce 9/10 17/26 3.5 0.5–25.0 0.17 Prepackaged lettuce salad 9/10 10/26 8.4 1.2–59.6 0.01 Dole prepackaged lettuce salad 9/10 5/23 0.002 10.1 1.5–67.3 *OR = odds ratio† CI = confidence interval

24. 7 6 5 Number of Cases 4 3 2 1 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 14 September October Date of Onset 2005 E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce Case-control study implicated Dole salad. Case-control study initiated. Initial cluster of 3 isolates among MN residents identified.

25. 7 6 5 Number of Cases 4 3 2 1 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 14 September October Date of Onset 2005 E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce CDC, FDA notified. Case-control study implicated Dole salad. Case-control study initiated. Initial cluster of 3 isolates among MN residents identified.

26. 7 6 5 Number of Cases 4 3 2 1 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 14 September October Date of Onset 2005 E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce CDC, FDA notified. Case-control study implicated Dole salad. Case-control study initiated. Initial cluster of 3 isolates among MN residents identified.

27. 7 6 Number of Cases OR 5 4 3 WI 2 WI 1 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 14 September October Date of Onset 2005 E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce (N=26) Minnesota Additional states

28. Dole Classic Romaine Salad Recovered from Case-Households Shared common "Best if Used By” Date and production code

29. Product Traceback Single processing plant (Soledad, CA) Production Date of September 7, 2005 Lettuce harvested from any 1 of 7 fields

30. PFGE Patterns of E. coli O157:H7 Isolates from Lettuce Source Initial Minnesota Case-patient Classic RomaineBag #1 Classic Romaine Bag #2

31. Why Epidemiologic Links May Not be Identified for Cases in a PFGE Cluster Cases have imperfect recall Common exposures can be difficult to link (e.g., eggs, chicken) Secondary transmission Cross-contamination exposure There isn’t a common source

32. CDC 2005 Cluster Investigations E. coli O157 Salmonella Patterns Submitted 5,376 29,168 Clusters Identified 67 176 Multi-state Clusters 36 152 Epi Investigation 19 30 Vehicle Implicated 4 8 Regulatory Activity 4 8

33. Questions?