1. FDA Response to Foodborne Disease Outbreaks Elisa L. Elliot, Ph.D. Microbiologist U.S. Food and Drug Administration Center for Food Safety and Applied Nutrition Office of Food Defense, Communication and Emergency Response Emergency Coordination and Response Team

2. FDA Response to Foodborne Outbreaks FDA actively works to prevent and to respond to food-related threats that can come from biological, chemical or radiological agents. Whether contamination is unintentional or deliberate there is a need to Make a public health decision Often with limited information In a very short timeframe and Implement the appropriate level of response with respect to the emerging incident.

3. Investigation and coordination in multi- state outbreaks Investigation and coordination in multi- state outbreaks Review epidemiological, lab and environmental data Review epidemiological, lab and environmental data Laboratory analysis and assistance Laboratory analysis and assistance Alert consumers Alert consumers Establishment inspections Establishment inspections Tracebacks of implicated foods Tracebacks of implicated foods What is FDA’s Role?

4. Ensure removal, if possible, of implicated foods from commerce Ensure removal, if possible, of implicated foods from commerce Monitor recalls Monitor recalls Farm investigations Farm investigations Other appropriate regulatory actions Other appropriate regulatory actions Evaluate data to identify trends and develop policy, guidance, or regulations to prevent future outbreaks Evaluate data to identify trends and develop policy, guidance, or regulations to prevent future outbreaks What is FDA’s Role?

5. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Recovery Recovery Foodborne Outbreak Investigation

6. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Recovery Recovery Foodborne Outbreak Investigation

7. FDA Plans Crisis Management Plan Crisis Management Plan Emergency Response Plan (ERP) Emergency Response Plan (ERP) BSE ERP BSE ERP Chemical and Biological ERP Chemical and Biological ERP Pandemic Influenza ERP Pandemic Influenza ERP Radiological ERP Radiological ERP

8. Plan and guidance on emergencies affecting FDA- regulated products: food defense food defense food safety and food safety and cosmetics safety emergencies cosmetics safety emergencies

9. Interaction During a Foodborne Outbreak Emergency Interaction During a Foodborne Outbreak Emergency FDA Office of Regulatory Affairs CFSAN FDA Office of Crisis Management–Office of Emergency Operations* (EOC) CDC USDA * FDA’s hub for all emergency response activities States

10. Contacting the FDA Office of Emergency Operations (OEO) 301-443-1240 (24-hour line) E-mail: emergency.operations@fda.gov emergency.operations@fda.gov The FDA OEO serves as the Agency’s focal point for all emergency response activities seven days a week, 24 hours a day. The FDA OEO serves as the Agency’s focal point for all emergency response activities seven days a week, 24 hours a day. Note: CORE (Coordinated Outbreak Response and Evaluation) Network is a new team at FDA starting today, July 18, and will coordinate and respond to new foodborne outbreaks. Note: CORE (Coordinated Outbreak Response and Evaluation) Network is a new team at FDA starting today, July 18, and will coordinate and respond to new foodborne outbreaks.

11. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Recovery Recovery Foodborne Outbreak Investigation

12. Foodborne Outbreak Surveillance Why do we conduct surveillance and outbreak investigations? Why do we conduct surveillance and outbreak investigations? Prevent additional illnesses Prevent additional illnesses Identify causes / trends to prevent future illnesses Identify causes / trends to prevent future illnesses

13. Foodborne Disease Surveillance About 48 million people (1 in 6 Americans) get sick, 128,000 are hospitalized, and 3,000 die each year from foodborne diseases, according to recent FoodNet and other data from the Centers for Disease Control and Prevention (Scallen et al., Dec. 2010). About 48 million people (1 in 6 Americans) get sick, 128,000 are hospitalized, and 3,000 die each year from foodborne diseases, according to recent FoodNet and other data from the Centers for Disease Control and Prevention (Scallen et al., Dec. 2010). This is a significant public health burden that is largely preventable. This is a significant public health burden that is largely preventable.

14. Centers for Disease Control and Prevention SAFER HEALTHIER PEOPLE

15. Foodborne Outbreak Surveillance Federal involvement by the Centers for Disease Control and Prevention (CDC) Federal involvement by the Centers for Disease Control and Prevention (CDC) National reportable disease National reportable disease Multi-state outbreaks Multi-state outbreaks Unusual pathogens Unusual pathogens Unusual vehicles Unusual vehicles

16. Foodborne Outbreak Surveillance Formal Surveillance Systems Formal Surveillance Systems National Notifiable Disease Surveillance System National Notifiable Disease Surveillance System NORS National Outbreak Reporting System NORS National Outbreak Reporting System (formerly eFORS -- electronic Foodborne Outbreak Reporting System) PulseNet PulseNet FoodNet FoodNet EHS-Net EHS-Net Who’s involved? Who’s involved? Local and state public health and environmental health officials, laboratories, and the Feds - CDC, FDA, USDA, EPA Local and state public health and environmental health officials, laboratories, and the Feds - CDC, FDA, USDA, EPA

17. Foodborne Outbreak Surveillance Pulsed Field Gel Electrophoresis (PFGE) Patient 1 Patient 2 Bacteria in food “Genetic fingerprint”

18. Foodborne Outbreak Surveillance What is the Role of PulseNet? Detect foodborne disease case clusters by pulsed- field gel electrophoresis (PFGE) Detect foodborne disease case clusters by pulsed- field gel electrophoresis (PFGE) Facilitate early identification of common source outbreaks Facilitate early identification of common source outbreaks Assist epidemiologists in investigating outbreaks Assist epidemiologists in investigating outbreaks Separate outbreak-associated cases from other sporadic cases Separate outbreak-associated cases from other sporadic cases Assist in rapidly identifying the source of outbreaks Assist in rapidly identifying the source of outbreaks Act as a rapid and effective means of communication between public health laboratories Act as a rapid and effective means of communication between public health laboratories

19. EHS-Net --Environmental health specialists who collaborate with epidemiologists and laboratory scientists to identify and prevent environmental factors contributing to foodborne and waterborne illness and disease outbreaks.

20. Foodborne Disease and Outbreak Surveillance Local / State Response Local / State Response Physicians Physicians Local Health Departments Local Health Departments State Health Departments State Health Departments

21. Foodborne Outbreak Surveillance Informal Surveillance Systems Informal Surveillance Systems Network of public health officials, laboratorians, and healthcare professionals Network of public health officials, laboratorians, and healthcare professionals Report to each other unusual numbers of cases, unusual vehicles or agents Report to each other unusual numbers of cases, unusual vehicles or agents

22. Exposure in the general population Person becomes ill Person seeks care Specimen obtained Culture confirmed case Reported to Health Department/CDC Lab tests for organisms Surveillance and Reporting

23. Why does it take so long?

24. Surveillance - Outbreak Detection “ Is an outbreak occurring?” Ongoing collection, analysis and dissemination of information Ongoing collection, analysis and dissemination of information Monitor changes in disease frequency Monitor changes in disease frequency Establish background levels of specific diseases in a community Establish background levels of specific diseases in a community by time, place, and or person Association by time, place, and or person

25. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Foodborne Outbreak Investigation

26. Foodborne Outbreak Investigations – States and Local Epidemiological Investigation Steps Epidemiological Investigation Steps Verify diagnosis - Case interviews and laboratory confirmation Verify diagnosis - Case interviews and laboratory confirmation Range of onset of systems - Epi curve Range of onset of systems - Epi curve Case definition Case definition Epi associations Epi associations Time, place, person associations Time, place, person associations Has an outbreak occurred Has an outbreak occurred Hypotheses generation Hypotheses generation

27. Epi curve: E. coli O157:H7 outbreak associated with fresh bagged spinach CDC MMWR Dispatch 9/26, 2006 / 55(Dispatch);1-2

28. Epidemiological Associations Implicating a food vehicle Implicating a food vehicle It’s not magic, but is based on statistical calculations using data from case questionnaires It’s not magic, but is based on statistical calculations using data from case questionnaires Food-specific attack rates Food-specific attack rates Stratified analysis Stratified analysis Multivariate analysis Multivariate analysis Case-control studies Case-control studies

29. Foodborne Outbreak Investigations Federal food regulatory agency involvement (FDA and or USDA) Federal food regulatory agency involvement (FDA and or USDA) Interstate commerce of food Interstate commerce of food Outbreaks associated with the same food in multiple states Outbreaks associated with the same food in multiple states Sporadic cases of unusual pathogens / serotypes linked by PFGE Sporadic cases of unusual pathogens / serotypes linked by PFGE

30. FDA Foodborne Outbreak Response FDA review and evaluation of the preliminary epidemiological evidence, assessing the public health implications, and determining the extent of CFSAN involvement based on the evidence available. FDA review and evaluation of the preliminary epidemiological evidence, assessing the public health implications, and determining the extent of CFSAN involvement based on the evidence available. A food or foods may have been epidemiologically associated as “suspect” in causing illness, the food(s) or cases were likely to have traveled interstate, and clinical laboratory testing has isolated an agent. A food or foods may have been epidemiologically associated as “suspect” in causing illness, the food(s) or cases were likely to have traveled interstate, and clinical laboratory testing has isolated an agent. The laboratory data may include subtyping, such as speciation, pulsed-field gel electrophoresis (PFGE) analysis, or phage typing. The laboratory data may include subtyping, such as speciation, pulsed-field gel electrophoresis (PFGE) analysis, or phage typing.

31. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Foodborne Outbreak Investigation

32. Foodborne Outbreak Investigations: Lab testing Laboratory investigation Laboratory investigation Clinical samples Clinical samples Food samples Food samples Environmental samples Environmental samples Match clinical results to food product and or environmental results Match clinical results to food product and or environmental results

33. Lab Results: Connections to a Common Source Genus (Salmonella) Genus (Salmonella) Subtyping Subtyping Serotype - Salmonella Poona, S. Enteritidis, S. Newport Serotype - Salmonella Poona, S. Enteritidis, S. Newport PFGE - DNA fingerprint PFGE - DNA fingerprint MLVA - Multiple-Locus Variable number tandem repeat Analysis –molecular typing using naturally occurring variation in the number of tandem repeated DNA sequences found in many different loci in the genome of a variety of organisms. MLVA - Multiple-Locus Variable number tandem repeat Analysis –molecular typing using naturally occurring variation in the number of tandem repeated DNA sequences found in many different loci in the genome of a variety of organisms. Antibiotic resistance pattern Antibiotic resistance pattern Gene sequencing - PCR Gene sequencing - PCR

34. PFGE Patterns of E. coli O157:H7 Isolates from Lettuce Source Initial Case-patient Bag #2 Bag #1

35. FDA Foodborne Outbreak Response A CFSAN epidemiologist reviews summary epidemiological and laboratory (and environmental if available) evidence and renders a decision of support for an association or not. A CFSAN epidemiologist reviews summary epidemiological and laboratory (and environmental if available) evidence and renders a decision of support for an association or not. If epidemiologically supported and scientifically plausible, and there is no evidence of on-site contamination at the point of purchase, then CFSAN will conduct a situational assessment. If epidemiologically supported and scientifically plausible, and there is no evidence of on-site contamination at the point of purchase, then CFSAN will conduct a situational assessment. A response strategy will be formulated by CFSAN in cooperation with the FDA Office of Emergency Operations and OEO and Office of Regulatory Affairs (HQ and field). A response strategy will be formulated by CFSAN in cooperation with the FDA Office of Emergency Operations and OEO and Office of Regulatory Affairs (HQ and field).

36. FDA Foodborne Outbreak Response Risk management – control the product and limit exposure Risk management – control the product and limit exposure Conducting a traceback investigation Conducting a traceback investigation Voluntary market withdrawal or recall by manufacturer or distributor Voluntary market withdrawal or recall by manufacturer or distributor Request state embargo Request state embargo FDA requested recall, seizure, administrative detention, import alert, or other FDA regulatory action FDA requested recall, seizure, administrative detention, import alert, or other FDA regulatory action Risk communication Risk communication Warning consumers Warning consumers Notifying state and federal regulatory agencies, other federal agencies, and industry Notifying state and federal regulatory agencies, other federal agencies, and industry Providing guidance to industry Providing guidance to industry

37. FDA Foodborne Outbreak Response Regulatory Action-Domestic Product: Regulatory Action-Domestic Product: If epi evidence implicates a domestic product or imported product in domestic commerce, CFSAN may recommend that the manufacturer If epi evidence implicates a domestic product or imported product in domestic commerce, CFSAN may recommend that the manufacturer voluntarily hold the product, voluntarily hold the product, withdraw the product from the market, withdraw the product from the market, conduct a recall, conduct a recall, suggest that the firm issue a press release. suggest that the firm issue a press release. FDA may request the state to embargo the product. FDA may request the state to embargo the product. FDA may take regulatory action, such as seizure. FDA may take regulatory action, such as seizure. New! Mandatory Recall: The Food Safety Modernization Act (FSMA) provides FDA with authority to issue a mandatory recall when a company fails to voluntarily recall unsafe food after being asked to by FDA. New! Mandatory Recall: The Food Safety Modernization Act (FSMA) provides FDA with authority to issue a mandatory recall when a company fails to voluntarily recall unsafe food after being asked to by FDA.

38. FDA Foodborne Outbreak Response Regulatory Action—Imported Product Regulatory Action—Imported Product If epi evidence has implicated an imported product, CFSAN may recommend an Import Alert or Bulletin. Administrative detention may also be considered. If epi evidence has implicated an imported product, CFSAN may recommend an Import Alert or Bulletin. Administrative detention may also be considered. If epi evidence is supported by environmental or product lab findings, then If epi evidence is supported by environmental or product lab findings, then FDA may issue an Import Alert FDA may issue an Import Alert Screening criteria for imports may be adjusted. Screening criteria for imports may be adjusted.

39. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Foodborne Outbreak Investigation

40. Environmental Investigation – State / Local Environmental Investigation – State / Local Food preparation review Food preparation review Interview food workers Interview food workers Determine if time, temperature abuse or cross-contamination occurred Determine if time, temperature abuse or cross-contamination occurred Collect samples Collect samples

41. Foodborne Outbreak Investigation Environmental Investigation – Federal Environmental Investigation – Federal Traceback Traceback Source investigations along distribution chain Source investigations along distribution chain identify common denominator identify common denominator i.e., processors, packers, farms i.e., processors, packers, farms

42. Foodborne Outbreak Investigation Environmental investigation is led by the state or local regulatory agency. Information provided to FDA should include Information provided to FDA should include Summary epidemiological data suggesting an association to a CFSAN regulated product Summary epidemiological data suggesting an association to a CFSAN regulated product Clinical laboratory data Clinical laboratory data Environmental investigational reports Environmental investigational reports Results of environmental or product testing conducted by state or local agencies Results of environmental or product testing conducted by state or local agencies

43. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Packinghouse / farm investigation Packinghouse / farm investigation Recovery Recovery Foodborne Outbreak Investigation

44. Record collection Record collection Production lot Production lot Distribution Distribution Bills of lading Bills of lading Invoices Invoices Record review Record review Quantities Quantities Lot numbers Lot numbers Ship and receipt dates Ship and receipt dates

46. Example of Traceback Steps First date of illness onset = Nov 27 First date of illness onset = Nov 27 Shipment of lettuce lasts 2-3 days at restaurant Shipment of lettuce lasts 2-3 days at restaurant What shipments to concentrate on? FDA determined that shipments between November 24 and 25 had highest probability of contamination FDA determined that shipments between November 24 and 25 had highest probability of contamination Records identified 2 farms as probable sources of lettuce in CA Records identified 2 farms as probable sources of lettuce in CA

47. Traceback Flow Diagram Example POS Distributors Packers POS Distributors Packers Farms

49. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Origin or Packinghouse/farm investigation Origin or Packinghouse/farm investigation Recovery Recovery Foodborne Outbreak Investigation

50. Produce: Sources and Spread of Contamination – Trend Analysis Multiple Modes Of Contamination Multiple Modes Of Contamination Soil Soil Water Water Workers Workers Animals Animals

51. Microbial Quality of Water PONDS CROP SPRAY WASH WELLS IRRIGATION

52. Potential Sources of Contamination

54. Pig feces in a spinach field Pig tracks across a spinach field v Potential Sources of Contamination

56. Foodborne Outbreak Data Gathering Outbreak data include – epidemiology, environmental findings, laboratory analytical data Outbreak data include – epidemiology, environmental findings, laboratory analytical data Tracebacks Tracebacks Firm investigations Firm investigations Farm Investigations Farm Investigations Laboratory data Laboratory data Produce surveillance assignments Produce surveillance assignments Firm and farm investigations Firm and farm investigations Environmental investigations critical Environmental investigations critical

57. Emergency response plans Emergency response plans Disease surveillance Disease surveillance Epidemiological investigation Epidemiological investigation Laboratory analysis Laboratory analysis Environmental investigation and or establishment inspection Environmental investigation and or establishment inspection Traceback / trace forward Traceback / trace forward Origin or Packinghouse/farm investigation Origin or Packinghouse/farm investigation Recovery Recovery Foodborne Outbreak Investigation

58. Foodborne Outbreak Response: Recovery Communication to stakeholders that the type(s) of foods affected are now safe to consume Communication to stakeholders that the type(s) of foods affected are now safe to consume consumers consumers federal, state and local agencies federal, state and local agencies industry industry health care providers, if applicable health care providers, if applicable Investigational findings, laboratory analysis, and reporting Investigational findings, laboratory analysis, and reporting Investigations to identify source of contamination, which may include farm investigations Investigations to identify source of contamination, which may include farm investigations Compliance actions and/or recommendations initiated Compliance actions and/or recommendations initiated

59. The Long Term Public Health Impact of Outbreak Response What does FDA do after the outbreak/illness is over?

60. Foodborne Outbreak Response: Evaluation Foodborne Outbreak Response: Evaluation Improvements for preparedness Improvements for preparedness Improvements to emergency response plans and procedures Improvements to emergency response plans and procedures Interventions to better protect public health Interventions to better protect public health Improvements for communications Improvements for communications Best practices Best practices Recommendations to modify scientific and regulatory policy, laboratory and field operations, and research activities Recommendations to modify scientific and regulatory policy, laboratory and field operations, and research activities

61. Risk Management Approach Emergency: outbreak Develop policy Change existing Reduced # illness and outbreaks Stakeholders implement Identify contributing factors

62. A Framework for Reducing Foodborne Illness Through Prevention, Intervention and Response Production Preparation Transportation Retail Consumer Processing Regulations, Enforcement, and Guidance Consumption Distribution and Storage Illness ? Education Training Surveillance Research

63. Emergency response plans – at all levels Emergency response plans – at all levels Disease surveillance – States submit info to CDC Disease surveillance – States submit info to CDC Epidemiological investigation - Epidemiological investigation - States and CDC conduct epi investigation and FDA reviews Laboratory analysis - Laboratory analysis - Clinical (States and CDC), food and environmental (States and FDA) Environmental investigation and or establishment inspection – Environmental investigation and or establishment inspection – State, Local and FDA State, Local and FDA Traceback / trace forward – Traceback / trace forward – States, FDA and industry States, FDA and industry Packinghouse / farm investigation – State, FDA Packinghouse / farm investigation – State, FDA Recovery Recovery Foodborne Outbreak Investigation

64. Summary FDA depends on outbreak, traceback, and farm investigations to provide important information to guide response and set priorities. FDA depends on outbreak, traceback, and farm investigations to provide important information to guide response and set priorities. Resulting actions include changes in policy, development of guidance, targeted research, and regulatory action. Resulting actions include changes in policy, development of guidance, targeted research, and regulatory action. FDA continues to work with all stake- holders, including industry, government, and academia, to prevent contamination and outbreaks. FDA continues to work with all stake- holders, including industry, government, and academia, to prevent contamination and outbreaks.

65. Conclusions Foodborne disease surveillance and response comprises a network of physicians, local, State, and Federal public health officials, laboratory scientists, and others Foodborne disease surveillance and response comprises a network of physicians, local, State, and Federal public health officials, laboratory scientists, and others Investigations require critical thinking, scientific analysis, and risk- based approaches to real events Investigations require critical thinking, scientific analysis, and risk- based approaches to real events

66. Acknowledgments CFSAN Emergency Coordination and Response Team CFSAN Emergency Coordination and Response Team CFSAN Epidemiology Team CFSAN Epidemiology Team CAPT Thomas Hill for slides and photos of farm investigations CAPT Thomas Hill for slides and photos of farm investigations Office of Emergency Operations Office of Emergency Operations

67. Thank you!