Making the Causal Link: Investigating Foodborne Disease Outbreaks

William D. Marler, Esq.

Defense Research Institute

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(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

Ill person

Specimen collection

Pathway of a Foodborne Illness Investigation

Health Care Provider

Organism identified

Ill person

Organism identified

Specimen collection

Pathway of a Foodborne Illness Investigation

Health Care Provider

Epidemiologic investigation

Public Health Laboratory

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.

Ill person

Organism identified

Specimen collection

Pathway of a Foodborne Illness Investigation

Health Care Provider

Epidemiologic investigation

Public Health Laboratory

Environmental investigation

Product Trace BackPRODUCT RECALL

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

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

• Symptoms• Incubation• Duration• Food History• Medical Attention• Suspected source• Others Ill

Real-time interviewing with a broad-based exposure questionnaire

Pulsed Field Gel Electrophoresis (PFGE)

• 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

A Powerful Outbreak Detection Tool

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?

E. coli O157:H7 Outbreak, Minnesota, September 2005

Team Diarrhea

Thanks to MN DOH for use of the following slides!

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

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

Initial cluster of 3 isolates among MN residents identified.

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

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

Initial cluster of 3 isolates among MN residents identified.

Case-control study initiated.

Case-Control Study Results

Exposure Cases Controls p-valueMatched OR*95% CI†

*OR = odds ratio† CI = confidence interval

Any lettuce9/10 17/26 3.5 0.5–25.0

9/10Prepackaged lettuce salad 10/26 8.4 1.2–59.6

Dole prepackaged lettuce salad9/10 5/23

0.17

0.01

0.00210.1 1.5–67.3

E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

Initial cluster of 3 isolates among MN residents identified.

Case-control study initiated.

Case-control study implicated Dole salad.

E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

Initial cluster of 3 isolates among MN residents identified.

Case-control study initiated.

Case-control study implicated Dole salad.

CDC, FDA notified.

E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

Initial cluster of 3 isolates among MN residents identified.

Case-control study initiated.

Case-control study implicated Dole salad.

CDC, FDA notified.

Minnesota

Additional states

Date of Onset 2005

15 16 17 18 19 20 21 22 23 24 25

Num

ber

of

Case

s

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

7

September October

WI

WI

OR

E. coli O157:H7 Cases Associated with Dole Prepackaged Lettuce (N=26)

Shared common "Best if Used By” Date and production code

Dole Classic Romaine Salad Recovered from Case-Households

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

SourceInitial Minnesota Case-patient

Classic RomaineBag #2

Classic RomaineBag #1

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 SalmonellaPatterns Submitted 5,37629,168Clusters Identified 67 176Multi-state Clusters 36 152Epi Investigation 19 30Vehicle Implicated 4 8Regulatory Activity 4 8

Questions?