Anatomy of an Outbreak · Anatomy of an Outbreak Kirk Smith, DVM, MS, PhD Supervisor, Foodborne,...

Anatomy of an Outbreak

Kirk Smith, DVM, MS, PhD

Supervisor, Foodborne, Vectorborne, and Supervisor, Foodborne, Vectorborne, and

Zoonotic Diseases Unit

Acute Disease Investigation and Control Section

Minnesota Department of Health

[email protected]

Office phone: 651-201-5240

Some Recent Notable Multi-state

Foodborne Outbreaks of Salmonellosis

PCA peanut butter

•691 cases

•46 states

Cake Mix

• 25 cases

• 9 states

Hot peppers

•1,442 cases

•44 states

Peter Pan

peanut butter

•714 cases

•48 states

2005 2006 2007 2008

Pot pies

•401 cases

•42 states

Tomatoes

•183 cases

•21 states

Veggie Booty

•70 cases

•23 states

Diseases Reportable to the Minnesota Department of Health

Botulism (Clostridium botulinum)

Campylobacteriosis (Campylobacter sp.)*

Cholera (Vibrio cholerae)*

Cryptosporidiosis (Cryptosporidium sp.)

Enteric Escherichia coli infection (E. coli O157:H7 and other

pathogenic E. coli from gastrointestinal infections)*

FOODBORNE AND WATERBORNE DISEASES

Giardiasis (Giardia lamblia)

Hemolytic uremic syndrome

Listeriosis (Listeria monocytogenes)*

Salmonellosis, including typhoid (Salmonella sp.)*

Shigellosis (Shigella sp.)*

Toxoplasmosis

Yersiniosis (Yersinia sp.)*

* Submit isolates or clinical materials to the Minnesota Department of Health

Submission of

isolate to public

health lab

Becomes ill

Confirmation/

serotyping,

PFGE subtyping

Person eats

contaminated food

Goes to doctor, stool

sample collected

2 - 3 days

1 - 7 days

(incubation) 2 - 4 days

health lab

Report of case

to public health

PFGE subtyping

Interview

Lab and epi

data

combined

Stool sample

positive

2 - 5 days 1 - 5 days

Reportable Bacterial Enteric

Pathogen Surveillance in Minnesota

• Isolates must be submitted to the Minnesota

Department of Health

• Real-time pulsed-field gel electrophoresis • Real-time pulsed-field gel electrophoresis

(PFGE) subtyping of all isolates

• Routine, real-time interviews of all cases

Molten agarose

Pulsed-Field Gel Electrophoresis (PFGE)

Lysis

Enzyme digestion (XbaI)

BacteriaDNA

1.5 hours

Enzyme digestion (XbaI)Pulse electrophoresis

18 hours

1.5 hours

The National Molecular Subtyping Network for

Foodborne Disease Surveillance

Area LabsArea Labs

National Database

FoodNet Sites

FDA, USDA Lab

PulseNet Laboratory NetworkPulseNet Laboratory Network

PulseNet National

Databases (CDC)

PulseNet National

Databases (CDC)Participating LabsParticipating Labs PFGE PatternsPFGE Patterns

Local

Databases

Bacterial Isolate Flow from Clinical Labs

to Public Health Labs

• Completeness and timeliness of isolate

submission to public health labs, and

timeliness of serotyping/PFGE subtyping

at public health labs, determines the at public health labs, determines the

sensitivity of outbreak detection

– i.e., need this for optimal detection of

outbreaks (local and multistate) caused

by Salmonella, E. coli O157:H7

Minnesota Surveillance Philosophy

• Interview all cases, ASAP

• Collect details on specific exposures

– Restaurant, grocery store names

– Brand names

– Open-ended food histories

• Investigation of all PFGE clusters

– Intensity/resource expenditure depends

on the exact nature of the cluster

– Follow leads aggressively

Standard Questionnaire for

Salmonella, E. coli O157 cases

Minnesota Surveillance Philosophy

• Interview all cases, ASAP

• Collect details on specific exposures

– Restaurant, grocery store names

– Brand names

– Open-ended food histories

• Investigation of all PFGE clusters

– Intensity/resource expenditure depends

on the exact nature of the cluster

– Follow leads aggressively

Response for PFGE Clusters

• Minimum: Compare case interviews

• Maximum: Case-control study

• Food Testing: Before, during, or after case

control studycontrol study

• “Informational” product tracing

Minnesota Approach to Investigation

of PFGE Clusters:

Dynamic Cluster Investigation Model

Case #1 Case #2 Case #3 Case #4

Dynamic Cluster Investigation - Pot Pies

4

10/4

afternoon

1

Initial trawling questionnaire interview date

9/10

2

9/27

3

10/3

night

PP

Consumed

Banquet PP“trawling”

questionaire

Re-interviewed cases about frozen foods and pot pies

10/4

morning

10/4

evening

Exposure

added

Team Diarrhea

Fall 2007

Epidemiologic Follow-up of Cases

• Determines the likelihood of identifying

the source of an outbreak

Epidemiologic Data are Dirty

• Not all exposed people get sick

• Some people get sick without being

exposed

• Not all “exposed people” are really • Not all “exposed people” are really

exposed

• Not all “unexposed people” are really

unexposed

• Not all sick people are really sick

Presentations of Outbreaks due to

Commercially Distributed Food Items

• Cases in community, no obvious common

exposure

– Retail food (grocery stores)– Retail food (grocery stores)

• Cases occur among patrons of restaurant(s)

• Cases clustered in institution(s)

• Any combination of above three

Dole Prepackaged Salad O157 Outbreak

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

Outbreak Investigation - Methods

September 28–29, 2005

• Additional O157 isolates received and

subtyped by PFGE

– 7 isolates demonstrated outbreak PFGE – 7 isolates demonstrated outbreak PFGE

subtype

• Supplemental interview form created

• Case-control study initiated

– Age-matched community controls

recruited through sequential digit dialing

anchored on case’s telephone number

Case-Control Study Results

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

Any lettuce 9/10 17/26 3.5 0.5–25.0

9/10

Prepackaged

lettuce salad 10/26 8.4 1.2–59.6

0.17

0.01

* OR = odds ratio† CI = confidence interval

9/10lettuce salad 10/26 8.4 1.2–59.6

Brand A

prepackaged

lettuce salad 9/10 5/23

0.01

0.00210.1 1.5–67.3

E. coli O157:H7 Cases Associated with

Brand A Prepackaged Lettuce by Date of

lllness Onset

Number of Cases 7

Date of Onset

2005

15 16 17 18 19 20 21 22 23 24 25

Number of Cases

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

September October

Initial cluster of 3 isolates

among MN residents identified.

Case-control study initiated.

Case-control study implicated Brand A salad.

E. coli O157:H7 Cases Associated with

Brand A Prepackaged Lettuce(n=26)

Number of Cases 7

Minnesota

Additional states

Date of Onset

2005

15 16 17 18 19 20 21 22 23 24 25

Number of Cases

26 27 28 29 30 1 2 3 414

1

2

3

4

5

6

September October

WI

WI

OR



• Cases in community, no obvious

common exposure


• Cases occur among patrons of

restaurant(s)



Salmonella Saintpaul Patron Cases Associated

with Restaurant A by Date of Isolate Receipt in

MDH Laboratory, June 2008

Number of Cases

5

6

7 Two cases name

Restaurant A

June

Date of Isolate Receipt

Number of Cases

23 24 25 26 27 28 29 30 1 2 3 422

2

3

4

1

Restaurant A Outbreak

June 30, 2008

• MDH and Ramsey County staff visited

restaurant

– Interviewed management and employees– Interviewed management and employees

– Collected invoices for ingredients used in

dishes consumed by cases

– Requested credit card receipts from same

time period

– Obtained copies of menu

Salmonella Saintpaul Patron Cases Associated

with Restaurant A by Date of Isolate Receipt in

MDH Laboratory, June 2008

Number of Cases

5

6

7 Second case names

Restaurant A

Visit restaurant

June

Date of Isolate Receipt

Number of Cases

23 24 25 26 27 28 29 30 1 2 3 422

2

3

4

1

Initial case-control

study/traceback

results to CDC

Univariate and Multivariate Results of

Minnesota Case-Control study

Ingredient

No. cases

exposed/total OR p aOR p

Red salsa 13/18 14.7 <0.001 Not significant

Avocado salsa 14/19 7.5 <0.001 Not significant

Mexican

garnish

17/19 69 <0.001 Not significant

Red peppers 17/19 43 <0.001 Not significant

Cilantro 18/19 21.4 <0.001 Not significant

Fresh

tomatoes

6/19 0.5 0.2 Not significant

Jalapenos 17/19 69 <0.001 62 <0.001



• Cases in community, no obvious

common exposure


• Cases occur among patrons of

restaurant(s)



December 3, 2008

1st 11 cases in MN

Institutional link,

Implication of PB

S. Typhimurium Investigation, 2008-2009

November 17-24, 2008

– MDH received 3 outbreak isolates

Early December

– Leading hypothesis in national – Leading hypothesis in national

investigation was chicken

• Restaurant-associated outbreak in

another state with three PFGE patterns

� Ultimately shown to be a “red herring”

Minnesota S. Typhimurium Investigation

December 10-19, 2008

• MDH received 8 additional outbreak isolates

• All chicken for first 4 cases traced back -

source did not converge with other state’s source did not converge with other state’s

investigation or with each other

• First 8 interviewed cases reported eating

peanut butter

– Suspicious, but not enough evidence to

implicate one product, or even peanut butter

overall, as the vehicle


December 22, 2008

• Medical director of LTCF (LTCF A) in

northern MN reports confirmed

Salmonella infections in 3 residentsSalmonella infections in 3 residents

• Specimens from 2 other residents pending

– All five cases confirmed with outbreak

strain of S. Typhimurium

• Outbreak cases identified in other

institutions


• LTCF A, LTCF B, elementary school all

purchased food from a common

distributor in Fargo, North Dakota

• Only food common to the 3 institutions • Only food common to the 3 institutions

was King Nut Creamy Peanut Butter

• Open tub of King Nut peanut butter

collected from LTCF A by Minnesota

Department of Agriculture on January 5

Cases

12

14

16

18

20

22

Cases of Salmonella Typhimurium, by Week of Specimen

Collection, Minnesota, June -September, 1995

Week

June July Aug Sept

Cases

0

2

4

6

8

10

Cases

12

14

16

18

20

22

PFGE Subtype Restaurant A

PFGE Subtype Restaurant B

PFGE Subtype Restaurant C

Other PFGE Subtypes

PFGE Subtype Patterns of Salmonella Typhimurium, by Week of Specimen

Collection, Minnesota, June -September, 1995

June July Aug Sept

Cases

0

2

4

6

8

10

Week

Selected Enteric Pathogens Reported to MDH, 1996-2008

800

1000

1200

Number of Cases

Campylobacter

Salmonella

0

200

400

600

1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008

Year

Number of Cases

E. coli O157:H7

Cryptosporidium

Shigella

1 confirmed case of salmonellosis =

38 actual cases

Interview Options

• In person, telephone, mail, e-

mail, web-based

• Rate-limiting step in most

outbreak investigations is outbreak investigations is

number of interviewers available

to conduct interviews

– staff epidemiologist or sanitarian

– public health nurses and other

professionals

– Team Diarrhea

Examine Descriptive Epidemiology

• Age, gender distribution of cases can

give clues to vehicle

– e.g., predominately female, median age in

30’s suggests a produce item like lettuce, 30’s suggests a produce item like lettuce,

tomatoes, or sprouts

– e.g., predominately school-aged children,

young adults often associated with vehicles

like ice cream, microwaveable chicken

products, etc.

Generate and Test Hypotheses

• Analytic study designed to test

hypothesis

– study design based on study questions,

resources, and target populationresources, and target population

– regardless of form of study, intent is to

determine whether given exposure led to

the occurrence of the disease.

Comparison Groups

• Gathering/event (e.g., wedding reception)

– non-ill attendees

• Restaurant

– well-meal companions, credit card names– well-meal companions, credit card names

• Cluster of bacterial cases identified through routine surveillance

– age-matched controls obtained through sequential digit dialing using case’s telephone prefix

– Friends, neighboring households

– Population surveys

Analytical Study – Need More than

Just a Statistical Association

• A true exposure should account for

high proportion of cases (although in

some outbreaks there can be multiple

vehicles)vehicles)

• Biologic plausibility

– right incubation, plausible vehicle, etc.

• Distribution of cases vs. distribution of

food

• Converging tracebacks

Analytic Study Problems

•Background rate of consumption is

high

– chicken, eggs

•Risk is diffuse – product used in

dozens of products

•Food is “cryptic” or eaten as an

ingredient

– e.g., spices

•Not enough interviews completed

Sub-Cluster Analyses

• In large outbreaks, there may be sub-clusters

of epi-linked cases

– e.g., multiple cases at a restaurant, – e.g., multiple cases at a restaurant,

nursing homes, or school

•Look for common suppliers and food items

•Specific analytical studies in these settings

Why Epidemiologic Links May Not be

Identified for Cases in a Cluster

• Cases have imperfect recall

• Cases may not know they were • Cases may not know they were

exposed

Secondary

transmission





• Case did not consume product but

may have handled it or was exposed

through cross-contaminationthrough cross-contamination



• Common exposures could be

difficult to link

– Lack of specific brand information from – Lack of specific brand information from

patient on a common commodity (e.g.,

eggs, chicken)

– Traceback inadequacies

• Establishment record-keeping

• Resources available

• There isn’t a common source for all of

the cases (or any of them)

– Stable, endemic strains of various bacteria



– Stable, endemic strains of various bacteria

are present in the animal population

• e.g., E. coli O157 PFGE subtype associated with

Jack-in-the-Box outbreak is still identified in

Minnesota each year

Daily Report from MDH Lab to

EpiCultures Confirmed Yesterday

Daily Report from MDH Lab to Epi

Cultures Confirmed or Subtyped in the Past 30 Days

Anatomy of an Outbreak · Anatomy of an Outbreak Kirk Smith, DVM, MS, PhD Supervisor, Foodborne,...

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