Intent of the workshop

1. Intent of the workshop • To give a functional understanding of epidemiology and it’s relevance to food safety • To discuss the current and the future uses of epidemiology by FSIS • To give you an understanding of the cascade of events that will lead to and result in, if/when you are subjected to an epi/epi-related investigation

2. Epi/Epi related investigation • Swat Teams • In-Depth Verification (IDV) Teams • Epidemiological Team • Expanded IDV • ?????????? • It is for your own good

3. Events leading to an investigation • Linkage of illnesses to food produced in a given plant: • Linkage by epidemiology • Linkage by epi and PFGE • Frequent isolation of a pathogen from products linked to a plant • Failing the Second/third Salmonella set • Rumors and innuendo

4. What is Epidemiology • Study of occurrence of diseases in population • Epidemiology of infectious disease • Person, place, time, infectious agent, vehicle of infection, sources of the infectious agents • Who • What • Where • When • How

5. Epi investigation example • In our last epi-workshop we had 100 participants. Two to five days after the workshop, 18 of the participants called and reported a sever gastrointestinal illness. The workshop faculty contacted the rest of the participants and identified 12 more cases. Based on their phone interviews of the cases and the rest of the participants the epi-investigation team determined that the cause of the outbreak was one of the items served at the lunch buffet at the workshop. Each of the participants were asked to fill out an epidemiological questionnaire.

6. Epi investigation example cont. • Refer to the Epi Example handout, identify the source of the outbreak and calculate the following parameters: • Incidence Rate • Mortality Rate • Relative Risk • Odds Ratio • Outline a trace back study

7. Foodborne OutbreaksI. Identification • Epidemiologists in at least one State Health Department notice an increase in number of cases for a reportable disease (week 1-2), or a cluster of isolates will be identified by genetic fingerprinting by one of the state health department laboratories (the PulseNet), or other subtyping methods. • Patients are interviewed and their food history is taken (week 2-3) • On the basis of the epidemiological data, exposure to a common source is determined (Week 2-4)

8. Foodborne OutbreaksI. Identification Cont. • The CDC, FDA and USDA are notified • A case control study is conducted to determine the relative risk and odds ratio for each of the possible sources of the outbreak (Week 3-4) • All clinical microbial isolates from the recent cases are subtyped; the results will be used in conjunction with the epidemiological data to determine the outbreak cluster, and identify the source (Week 3-5) • After the source is identified, the company is notified, and public announcements are made • (Week 3-5)

9. Foodborne OutbreaksII. USDA, CDC, FDA On-Site Investigation • A team of USDA and/or state health department and/or the CDC investigators will visit the plant to conduct source tracking and investigate the “How” and “Why” of the outbreak • The team will take samples (shelf-life, new products and environmental) and scrutinize production records and manufacturing practices

10. Foodborne OutbreaksII. USDA, CDC, FDA On-Site Investigation Cont. • On the basis of the findings, a theory will be formulated as to the “How” and “Why” of the outbreak (Week 4-6) • The recall may be expanded based on the findings of the group • During this investigative phase, communication between the Company and the Feds will be at its maximum level • The CDC will publish their report on the outbreak (Week 20- )

11. Problems with epidemiological investigation of foodborne outbreaks • Most investigations are conducted properly • Too slow to be beneficial to food industry • Less shoe leather epidemiology • More high tech • Over reliance on genetic fingerprinting data • Chasing high profile pathogens • Rush to conclusions in the absence of evidence • Scheduling the execution before the trial • Many outbreaks go undetected

12. Who are epidemiologists • Epidemiology of infectious diseases as applied to foodborne outbreaks is a simple and elegant science • MS or Ph.D. in epidemiology • BS, MS, Ph.D., MD, DVM, and training (formal or informal) in epidemiology • The knowledge of the food industry and food processing depends on the individual's personal or professional background, it is often lacking

13. Assumptions made by most epidemiologists • Until proven otherwise, for a given pathogen, the universe of possibilities for sources of the outbreak are the ones that have most frequently been associated with the previous outbreaks • For a given disease, in the absence of an increase in baseline numbers there is no outbreak

14. Tools used in epidemiological investigations: Data gathering and analysis • Investigations are conducted at local levels • Communications with health care providers • Reportable diseases • Active management of infectious disease reports, watch for increase in number of cases • Patient interviews, phone, epi questionnaire

15. Epi tools cont.: Data • Gather exposure histories • Look for common exposures • Formulate a hypothesis • Case control studies • Testing samples • Use of laboratory data

16. Epi tools: Laboratory data • Clinical labs: testing patient samples • Food labs (private, county, state, federal): testing food and environmental samples • State Health Departments: reference labs to verify the isolates • State Health Department: PFGE analysis as a part of the PulseNet • Use of Molecular Epidemiology

17. Molecular Epidemiology • Application of the principles and methods of molecular biology immunochemistry, microbial population genetics, and epidemiology to the identification and tracking of outbreak clones.

18. Basic Assumptions • Clonal population Structure • Clones stable within the outbreak window • Most outbreaks involve a single clone • Enough diversity at the species level that outbreak clones can be differentiated from each other and from sporadic cases

19. Reality • There could be more than one clone involved in an outbreak • A clone can present from multiple sources • In the absence of epidemiological linkage a molecular match does not have epidemiological significance

20. Clonality • Result of asexual reproduction • When a number of strains isolated at different times, from different sources, and different places have have identical phenotypic and genotypic characteristics that the only logical conclusion is that they are of clonal descent.

21. Clonality cont. • Clonality is impacted by time • There is a statistical likelihood of clonality • True clonality vs. perception of clonality • Perception of clonality a function of methodology

22. METHODS • Phenotypic: biotyping, serotyping, antimicrobial sensitivity, phage typing, fatty acid profiles • Genotypic methods: Plasmid profiles, restriction fragment length polymorphism based methods, ribotyping, PFGE, MRF, PCR based methods, DNA sequencing

23. Phenotype Based Methods Antimicrobial Sensitivity Isozyme Analyses Fatty Acid Analysis Biotyping Phagetyping Less Sensitive More Sensitive MRF DNA* Sequencing IS Element Subtyping PFGE Ribotyping Plasmid Pattern PCR Based Methods Genotype Based Methods The sensitivity continuum of some of the widely used subtyping methods. Phenotypic based methods (methods based on the expression of phenotypes) are at the less sensitive domain of the continuum while genotypic based methods constitute the more sensitive end of the spectrum. *The level of sensitivity depends upon the choice of gene(s) and the size of fragment(s) sequenced.

32. Limitations of genetic fingerprinting data • A two way sward • Genetic fingerprinting is not a substitute for epidemiology and/or common sense • Accurate subtyping of microbes is not an easy task, the use of multiple subtyping methods, and a high level of training for the interpretation of the data • Mistakes have been made in subtyping and application of subtyping data

33. Bases for epidemiological linkage of a food producer and an outbreak • Direct evidence: Very high relative risk and odds ratio, and isolation of the pathogen with exact genetic fingerprints from unopened packages of the product or from the production line • Circumstantial evidence: low to moderate relative risk and odds ratio, either no isolates from the plant or the products, or isolates which are genetically related but are not identical (human Vs. monkey)

34. Recall public notification • Are to be done when the source of the outbreak are positively identified, and there are reasons to believe that the contaminated batch of the product is still available in the market • Examples: a good and a bad recall • Done properly it will reduce your exposures • A not so voluntary recall: When you are approached to do so, in the absence of compelling evidence, you are left with very little choice

35. Resources needed when a plant is implicated in an outbreak • Same as the resources that need to be in place before it happens • A proactive approach is more cost effective • A crisis prevention/management team composed of: in-house QAQC team, production managers, physical plant management, industrial hygienist, sanitarian, public affair and legal counsel, lead by a person with authority to make decisions on the spot • The team can be augmented by outside consultants and advisors from trade associations

36. How to get outside help • Best resource are other companies that have been in similar situations and have survived the process; the trick is to find one! • Trade associations

37. Crisis management team • Ideally the team should have a clear mandate and goals • Ideally the team will work with investigative bodies (SHD, CDC, USDA, FDA) in a collaborative manner • Some of the SHDs are more open and cooperative than others, they do a good job of keeping the companies informed • Unfortunately this is not the norm • Of the federal agencies USDA is the most accessible as far as sharing the available information

38. Crisis management goals • Fact finding: Is this our outbreak, if yes: how to help the effected individuals, how to contain the outbreak, how to resolve the underlying problem(s), how to minimize the impact on our customers, how to manage our employee’s moral, how to respond to media inquiries, how to respond to consumer inquiries, how to respond to document request, how to manage the recall, how to deal with our vendors, how to deal with our insurance providers, legal issues, potential criminal charges, implications for our brand names implicated, implications for our other brand names, etc., etc.

39. Crisis management goals cont. • Is this our outbreak: If the linkage is based on circumstantial evidence then: • Aggressive auditing of the epidemiological investigation, and the laboratory data • Maintain open channels of communications w/FSIS • Let the science be your defense • You are entitled to the results of the investigations as they become available • Analyze the data and continue an active discussion with those involved in the investigation • This may come as a shock to them, the reaction ranges from indignation to respect

40. Crisis management goals cont. • Foodborne infectious disease outbreaks are easy to detect and document • Lack of clear evidence is the best indication that a company may not be involved in an outbreak • Some epidemiologists jump to conclusions in the absence of clear evidence and contrary to the scientific tradition • Till recently the FSIS had not taken action (issuance of NR, IDV, epi investigation, etc.) in the absence of a positive culture isolated from an unopened package of product by a sanctioned lab

41. Crisis management goals cont.Preparing for the swat/epi/idv team • Anywhere between the first week of the outbreak/recall to months after, the plant may be subjected to IDV/epi review • Any food production plant any day, anytime should be prepared for an unexpected visit • It is prudent for any production plant to undergo IDV audits • Aside from preparing in advance for such visits, have the crisis management team with appropriate experts and consultants be on site at the time of the IDV/epi review

42. The IDV/epi review team • The team will pour over all the available pertinent data regarding your production, HACCP, HACCP implementation, CCPs, NRs, intervention steps, laboratory data, shipping records, vendor and customer information, etc, etc, • They will conduct several inspections of the plant at different times • They will interview your personnel, and will consult with the USDA personnel at the plant and at the District Office • Some of the team members are USDA professionals with years of experience, and some have little experience with food production plants

43. IDV/epi review process • Notification of scheduled review, arrival • Initial interview: establish a partnership, negotiate your expectations, set milestones, ask for daily briefing • Have your expert/legal team onsite • Be cordial, be firm, be on your guards, it is a cross between a physical exam and tax audit for a middle aged person of some means (including high sugar and cholesterol) • They are there to find problems, and problems they will find, in a well run plant there should not be major problems, your experts should have identified and rectified all the problems beforehand

44. IDV/epi review process cont. • Sampling: The team should not have to sample. Sampling by the team could automatically put you on test and hold • Do not volunteer the resources • Daily progress meeting: Discuss their findings, involve your experts, correct the problems as they are found by either side (your consultants or the IDV team) • Ideally the team will present a balanced view of the production practices and the plant, they will identify areas for improvement, and make recommendations accordingly • If you disagree with their findings be prepared for immediate challenge at the agency or legal level

45. Possible outcomes of IDV/epi review • Recommendation for plant closure: Fight • Expanded recalls: In the absence of public health problems: Fight • Identification of minor issues and concerns: Within a month you will receive a report issued by the team, you will have a month to respond, correct all the problems that they have identified, or you have become aware of during your own audits, this is the main benefit of such reviews • Prepare and submit your response

46. Transition from crisis management to defense • After the first month or so the public interest in the outbreak will begin to decline • The epidemiological investigation will often continue for a prolonged period • The IDV/epi review may have ended by now • The official end of the investigation is issuance of the Epi Report by the SHD in charge or the CDC • While the public relations and the customer management issues will continue, the legal team will have to start with a large number of FOIA requests to appropriate agencies, continue with auditing the outbreak

47. Foodborne OutbreaksIII. The Press • In states which have cases, the outbreak will be the top story in the news media • The amount of media play at the national level will depend on the extent of the outbreak, and the organism involved • Patients, their families, relatives of the deceased, and current and former employees of the company will be interviewed • All inspection records, previous recalls, and health and safety violations will be publicized • On the basis of the Company’s testing data, a “Smoking Gun” will be created

48. Foodborne OutbreaksIV. Lawsuits: A) USDJ • There has been an increased tendency on the part of the USDJ, to bring criminal charges against the companies involved in large/high profile outbreaks • Criminal charges have been brought against Odwalla, Hudson and Sara Lee

49. Foodborne OutbreaksIV. Lawsuits: B) Class Action • One recent foodborne outbreak has resulted in a class action lawsuit representing the patients • Another major foodborne outbreak resulted in a CALS by franchise owners

50. Foodborne OutbreaksIV. Lawsuits: C) Individual • Large numbers of cases are filed • Some are unrelated to the outbreak • While a few law firms are experienced in the area of foodborne diseases, most law firms on both sides have no prior experience in this area • It is best if cases are settled as fast and as early as possible