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Hyla Middle
School Science

Making the Causal
Link: Investigating
Foodborne Disease
Outbreaks

William D. Marler, Esq.
CDC Estimates of Foodborne Illness


               • 48 million cases of
                 foodborne illness annually

               • 125,000 hospitalizations

               • 3,000 deaths
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
Notifiable/Reportable Diseases


  •   Reporting authorized by Congress in 1878

  •   Nationally Reportable Diseases
      - 1993 (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
Pathway of a Foodborne Illness
Investigation
Pathway of a Foodborne Illness
Investigation




                          If there are more ill
                        persons than expected,
                        an OUTBREAK might be
                               underway.
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.
Pathway of a Foodborne Illness
Investigation
Typical Steps of an Outbreak
Investigation
•   Verify the diagnosis
•   Establish that an outbreak is occurring
•   Define and identify cases
•   Orient the data in terms of person, place,
    and time
•   Develop and test the hypotheses
•   Case Control Study
•   Refine the hypotheses and carry out additional
    studies
•   Implement control and prevention measures
•   Report findings
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
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
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
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
Questions to Consider in Assessing
PFGE Clusters
• How common is the
  PFGE 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?
E. coli O157:H7 Outbreak,
 Minnesota, September 2005




 Thanks to MN DOH “Team D” for use of the following slides!
Team Diarrhea
Outbreak Detection

 September 27, 2005
 • Three O157 isolates with indistinguishable
   PFGE patterns identified by Minnesota Public
   Health Laboratory
 • PFGE pattern new in Minnesota,
   rare in United States
   – 0.35% of patterns in National Database
 • Patients reported eating prepackaged salad;
   no other potential common exposures evident
E. coli O157:H7 Cases Associated
with Dole Prepackaged Lettuce


                  7
Number of Cases




                  6
                  5
                  4
                  3
                  2                      Initial cluster of 3 isolates
                                         among MN residents
                  1                      identified.

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1   2   3   4

                                            September                        October
                                                      Date of Onset 2005
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
E. coli O157:H7 Cases Associated
with Dole Prepackaged Lettuce


                  7
Number of Cases




                  6
                  5
                  4
                                           Case-control study initiated.
                  3
                  2                      Initial cluster of 3 isolates
                                         among MN residents
                  1                      identified.

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1   2   3   4

                                            September                        October
                                                      Date of Onset 2005
Case-Control Study Results


Exposure        Cases Controls Matched OR*   95% CI† p-value

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        10.1      1.5–67.3   0.002


*OR = odds ratio
†
  CI = confidence interval
E. coli O157:H7 Cases Associated
with Dole Prepackaged Lettuce



                  7
Number of Cases




                  6
                  5                   Case-control study implicated Dole salad.

                  4
                                            Case-control study initiated.
                  3
                  2                       Initial cluster of 3 isolates
                                          among MN residents
                  1                       identified.

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1        2   3   4

                                             September                            October
                                                       Date of Onset 2005
E. coli O157:H7 Cases Associated
with Dole Prepackaged Lettuce
                                                                  CDC, FDA notified.




                  7
Number of Cases




                  6
                  5                   Case-control study implicated Dole salad.

                  4
                                            Case-control study initiated.
                  3
                  2                       Initial cluster of 3 isolates
                                          among MN residents
                  1                       identified.

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1             2   3   4

                                             September                                 October
                                                       Date of Onset 2005
E. coli O157:H7 Cases Associated
with Dole Prepackaged Lettuce
                                                                  CDC, FDA notified.




                  7
Number of Cases




                  6
                  5                   Case-control study implicated Dole salad.

                  4
                                            Case-control study initiated.
                  3
                  2                       Initial cluster of 3 isolates
                                          among MN residents
                  1                       identified.

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1             2   3   4

                                             September                                 October
                                                       Date of Onset 2005
E. coli O157:H7 Cases Associated with
Dole Prepackaged Lettuce (N=26)

                                                                     Minnesota
                                                                     Additional states
Number of Cases




                  7
                  6
                  5              OR
                  4
                  3
                  2                          WI

                  1                               WI

                      14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1    2   3   4

                                 September                                   October
                                              Date of Onset 2005
Dole Classic Romaine Salad Recovered
from Case-Households
 Shared common "Best if Used By”
 Date and production code
Product Traceback




  • Single processing plant (Soledad, CA)
  • Production Date of September 7, 2005
  • Lettuce harvested from any 1 of 7 fields
PFGE Patterns of E. coli O157:H7
Isolates from Lettuce

                              Source
                              Initial Minnesota
                              Case-patient


                              Classic Romaine
                              Bag #1

                              Classic Romaine
                              Bag #2
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
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
Questions?

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2011 Hyla Middle School Science Talk

  • 1. Hyla Middle School Science Making the Causal Link: Investigating Foodborne Disease Outbreaks William 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 - 1993 (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
  • 6. Pathway of a Foodborne Illness Investigation If there are more ill persons than expected, an OUTBREAK might be underway.
  • 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
  • 9. Typical Steps of an Outbreak Investigation • Verify the diagnosis • Establish that an outbreak is occurring • Define and identify cases • Orient the data in terms of person, place, and time • Develop and test the hypotheses • Case Control Study • 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 the PFGE 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 “Team D” for use of the following slides! Team Diarrhea
  • 16. Outbreak Detection September 27, 2005 • Three O157 isolates with indistinguishable PFGE patterns identified by Minnesota Public Health Laboratory • PFGE pattern new in Minnesota, rare in United States – 0.35% of patterns in National Database • Patients reported eating prepackaged salad; no other potential common exposures evident
  • 17. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce 7 Number of Cases 6 5 4 3 2 Initial cluster of 3 isolates among MN residents 1 identified. 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 18. 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
  • 19.
  • 20. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce 7 Number of Cases 6 5 4 Case-control study initiated. 3 2 Initial cluster of 3 isolates among MN residents 1 identified. 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 21. Case-Control Study Results Exposure Cases Controls Matched OR* 95% CI† p-value 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 10.1 1.5–67.3 0.002 *OR = odds ratio † CI = confidence interval
  • 22. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce 7 Number of Cases 6 5 Case-control study implicated Dole salad. 4 Case-control study initiated. 3 2 Initial cluster of 3 isolates among MN residents 1 identified. 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 23. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce CDC, FDA notified. 7 Number of Cases 6 5 Case-control study implicated Dole salad. 4 Case-control study initiated. 3 2 Initial cluster of 3 isolates among MN residents 1 identified. 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 24. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce CDC, FDA notified. 7 Number of Cases 6 5 Case-control study implicated Dole salad. 4 Case-control study initiated. 3 2 Initial cluster of 3 isolates among MN residents 1 identified. 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 25. E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce (N=26) Minnesota Additional states Number of Cases 7 6 5 OR 4 3 2 WI 1 WI 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 September October Date of Onset 2005
  • 26. Dole Classic Romaine Salad Recovered from Case-Households Shared common "Best if Used By” Date and production code
  • 27. Product Traceback • Single processing plant (Soledad, CA) • Production Date of September 7, 2005 • Lettuce harvested from any 1 of 7 fields
  • 28. PFGE Patterns of E. coli O157:H7 Isolates from Lettuce Source Initial Minnesota Case-patient Classic Romaine Bag #1 Classic Romaine Bag #2
  • 29. 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
  • 30. 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