Detecting and Investigating Foodborne Outbreaks Ian Williams PhD, MS Chief, Outbreak Response and...

Detecting and Investigating Foodborne Outbreaks

Ian Williams PhD, MSChief, Outbreak Response and Prevention BranchCenters for Disease Control and Prevention, USA

Dubai, February 2014

Objectives

At the end of this lecture, you will be able to:Describe how outbreaks are detectedExplain the steps in investigating an outbreakIdentify the necessary collaborators for an outbreak investigation, including epidemiologists, laboratorians, environmental health specialists, among others

Last meal bias: A common problem

• When people develop an enteric (diarrheal) illness that might be caused by food, most people think the last meal they ate is what made them sick• This is not true in most instances, especially for bacterial

pathogens (like salmonella)

• In a outbreak that is suspected to be related to food, it is important to understand and follow certain steps in the investigation• Requires collaboration between laboratorians,

epidemiologists, and environmental health specialists

Successful outbreak investigation depends on collaboration


Experts on surveillanceand investigating illness

in humans

Experts on testing samples from humans

and food

Experts on food preparation

and food production

What is an outbreak?

The occurrence of cases of an illness clearly in excess of the normal expectancy

Where you work,

how are outbreaks detected?

Laboratory confirmed cases are the tip of the iceberg

Lab-confirmed case reported

Laboratory-based

surveillance

Laboratory-based

surveillance

Pyramid (iceberg) of laboratory-based surveillance

Person has symptoms

Person goes to doctor

Doctor requests sample

Sample submitted to lab

Lab identifies pathogen

Lab-confirmed case reported

Public complaints

Syndromicsurveillance

Outbreak detection and interventions

can occur at all levels

Is it an outbreak?

Causes of an increased number of casesArtificial increase

Change in lab methods Change in reporting Data entry errors

Real increase Increased population size Change in population characteristics Random variation Outbreak

Why investigate foodborne outbreaks?

• Immediate goal: prevent more illnesses from this outbreak

• Longer-term goals– identify pathogens that often cause outbreaks– identify food vehicles that often cause outbreaks– Identify common settings and contributing factors– identify gaps in the food safety systemto take action to prevent future outbreaks

and illnesses

Steps in investigating an outbreak

1. Detect the outbreak and assemble a team2. Gather descriptive information 3. Generate hypotheses4. Test hypotheses 5. Determine how and where contamination occurred6. Prevent more illnesses7. Communicate

Step 1. Detect the outbreak and assemble a team

Ways outbreaks are detected informal reports, e.g., physician, ill persons, clinical

laboratory notifiable disease surveillance laboratory-based surveillance subtyping results, e.g.,

• Salmonella serotyping• antibiotic resistance pattern• pulsed-field gel electrophoresis (PFGE)• phage typing

Step 1: Detect the outbreak and assemble a team

Types of foodborne outbreaks

Traditional Scenario Cases clustered in time and

space Common meal or event Result of food handling

error

New Scenario Seemingly unlinked cases Widely distributed foods Foods with

long shelf-life, or ready-to-eat, orthat require no or little consumer handling


Traditional scenario “point source” foodborne outbreak

New scenario “ongoing exposure” foodborne outbreak

E. coli O157 outbreak

Step 6: Prevent more Illnesses

Example: United States, 2009

On May 19, PulseNet identified 17 human Escherichia coli O157 isolates with a particular pulsed-field gel electrophoresis (PFGE) pattern uploaded in May

On average, 6 to 7 isolates with this pattern uploaded each month


Shiga toxin-producing E. coli O157

Causes diarrhea, often bloody can be severe in children and elderly hemolytic uremic syndrome (HUS) is a complication

• causes kidney failure

• Usual food vehicles: ground beef, leafy greens, unpasteurized milk


Assemble a team

Contact key groups local, regional, national laboratory, epidemiology, health inspectors, food

regulators, communicators, clinicians, others Determine responsibilities

collect and analyze data implement control measures communicate


Step 2: Gather descriptive information

2a: Determine the etiology2b: Describe the outbreak by time, place, and person2c: Write a case definition2d: Look for more cases

The order of these steps can vary depending on the investigation

2a: Determine the etiology

If the outbreak was detected by public complaint or syndromic surveillance, determine the etiology use symptoms, incubation period, etc, to

determine possible etiologies decide which lab tests are needed (eg, bacterial

stool culture) collect specimens from ill persons and test them

Step 2: Gather descriptive information. Step 2a: Determine the etiology

Food testing does not determine the etiology

Collect food samples for laboratory testing IF preliminary data points to certain foods epidemiologists, food regulatory authorities, and

laboratorians discuss and then decide appropriate tests on food

be aware of limitations of food testing

Do not expect to learn the etiology from laboratory testing of food! Do not delay investigation awaiting tests on food!


Talk to lab!

False negative tests of food

Why might the lab not identify the etiologic agent in a food that caused the outbreak?


Why the laboratory may not find the etiologic agent in food

Collection reasons sample was improperly collected or transported the actual food that caused illness was not sampled

Food reasons all the food that caused illness was consumed only some parts of the food were contaminated the etiologic agent did not survive in the food

Lab reasons the laboratory does not test for the agent the lab test is not sensitive enough to detect the agent there is no lab test for the agent


Talk to lab!

False positive tests of food

Why might lab identify a pathogen in a food that did not cause the outbreak?


False positive tests on food

The lab may identify a pathogen that did not cause the outbreak

Food reasons foods may be contaminated with pathogens

unrelated to the outbreak especially true for raw meat and poultry

Lab reasons: false positive results, errors

In most diarrheal outbreaks, you will learn more by collecting specimens from ill people than from food


Step 2b: Describe outbreak by time, place, person

When did the illnesses occur? Where did illnesses occur? Who was affected?

age, sex symptoms and signs number ill, hospitalized, died

Step 2: Gather descriptive information. Step 2b: Describe by time, place, person

Step 2b: Describe outbreak by time, place, person

When did the illnesses occur? Where did illnesses occur? Who was affected?

age, sex what were the symptoms and signs? % hospitalized % died

Make a map


Draw an epidemic curve

Summarize in a table

Epi curve made at start of investigation


Map made at start of investigation


Table of patient characteristics


Characteristic n (%)*

Age < 19 years 50 (66)

Female 53 (71)

Median age (range): 15 years (2 – 65 years)

2c: Write a case definition

Components: illness, pathogen, time, place Case types: possible, probable, confirmed

Step 2: Gather descriptive information. Step 2c: Write a case definition

Include the lab in the discussion

Example: Confirmed case definition, US outbreak of E. coli O157 infections

E. coli O157 infection, and PFGE pattern indistinguishable from outbreak

strain, and multi-locus variable-number tandem repeat

analysis (MLVA) pattern indistinguishable from outbreak strain pattern and

illness began (or isolation date if date illness began is not available) on or after March 1, 2009


Talk to lab!

Some outbreaks also have definitions for probable and possible cases

What is MLVA?

DNA sequence-based subtyping technique During outbreak investigations

PFGE alone might not differentiate between outbreak-associated and unrelated cases

adding MLVA information can help


2d: Look for more cases

Purpose of case finding treat ill persons prevent secondary cases determine location and magnitude of outbreak find clues about source

Why does finding more cases increase the likelihood of a successful investigation?

Step 2: Gather descriptive information. Step 2d: Look for more cases

What can you do to find more cases?

2d: Ways to look for more cases

Request information from health care providers Review calls to health department from ill persons Request information from clinical laboratories Review notifiable disease reports to health department Contact nearby health departments to see if they have

similar illnesses Assure strong communication between epidemiology and

laboratory groups In special circumstances, request information directly

from the public, via the media

Step 2: Gather descriptive information. Step 2d: Look for more cases

3: Generate hypotheses

Promptly, thoroughly interview some cases to identify common exposures eliminate uncommon exposures

Alternative interview methods one investigator conducts open-ended interviews

with 5-10 ill persons, or one or more investigators conduct interviews with

some ill persons using a detailed “hypothesis-generating” questionnaire

Example: US outbreak of E. coli O157 infections

First, used “hypothesis-generating” questionnaire to interview cases

several epidemiologists did interviews

Step 3: Generate hypotheses

Possible vehiclesground beefstrawberriesice cream

Unlikely vehiclesspinachunpasteurized dairyanimal contact

Findings (no strong hypothesis emerged):

Example: US outbreak of E. coli O157 Infections

Then, they tried a different approach One investigator interviewed 5 people with

recent illness from one state (Washington) open-ended, conversational interviews

conducted during June 13 - 16 asked about exposures during week before

illness


Open-ended interview results

What patients reported:5 of 5 ate ground beef 3 of 5 ate strawberries 5 of 5 ate raw cookie dough4 of 5 ate Brand X raw cookie dough

On June 16, presented these data to investigation groupMaryland, Iowa, Illinois, and Minnesota reported that patients they interviewed also ate raw cookie dough!


Raw cookie dough documented in notes from first interview

Finally, a hypothesis!

Raw cookie dough as a vehicle? some questioned biological plausibility never before linked to E. coli outbreak

Based on epidemiologic evidence, raw cookie dough became a leading hypothesis



1. Detect the outbreak and assemble a team2. Gather descriptive information3. Generate hypotheses4. Test hypotheses 5. Determine how and where contamination occurred6. Prevent more illnesses7. Communicate

Step 4: Test hypotheses

4a: Gather data relevant to the hypothesis 4b: Design a study 4c: Analyze the study

Do a study only after you have a strong hypothesis!

Step 4a. Gather data relevant to the hypothesis

Discuss possible steps with food safety agencies For point source outbreaks, restaurant inspection history, etc. For dispersed outbreaks, product distribution

• what regions of country, which stores• could the product come from one factory?

Consider collecting data from patients information on food packages leftover food

Step 4: Test hypothesis. Step 4a: Gather data relevant to hypothesis

Step 4b: Design a study

Basic strategy: compare exposures of ill and well persons

Two standard methods Cohort study

• illness in a defined group• interview everyone possible

Case-control study• interview ill persons and similar well persons (controls)

Both methods use a standard questionnaire• use hypothesis to decide what questions to ask

Step 4: Test hypotheses. Step 4b: Design a study

Step 4b: Design a study

Comparison groups to consider persons who attended the event the ill persons

attended persons from the same community as the ill

persons persons previously interviewed in surveys of food

consumption in the general population persons with illness caused by the same pathogen

who are not part of the outbreak persons with illness caused by a different pathogen

Step 4: Test hypotheses. Step 4b: Design a study

Step 4c: Analyze the study

Determine whether each exposure (food, water, etc.) is associated with illness calculate the appropriate measure of effect for the

study design (relative risk, odds ratio) determine the statistical significance of results

(95% confidence intervals, p-values) interpret results in light of the power of the study

if the study is too small, findings may not be statistically significant

Step 4: Test hypotheses. Step 4c: Analyze the study

Example: US outbreak of E. coli O157 infections

Hypothesis: Raw cookie dough was the source Study design: case-control study

controls from health department databases of persons with other enteric illnesses

controls matched 1:1 on age, sex, and state of residence

questionnaire asked about 20 food items, including raw cookie dough, ground beef, and strawberries


Results: US outbreak of E. coli O157 Infections

94% (33/36) of cases but only 11% (4/37) controls ate raw cookie dough

matched odds ratio = 42.8 • 95% confidence interval 7.6 – ∞• p < 0.0001

No other exposure associated with illness


Other evidence implicating raw cookie dough

93% of patients who ate raw cookie dough ate Brand X

Brand X made by Company X, which produced only ~40% of U.S. market share of cookie dough

No cases in Canada Company X did not ship Brand X to Canada


Really? Raw cookie dough?

We learned that, although cookie dough is sold to be baked,

some people, especially young girls, love to eat it raw!


1. Detect the outbreak and assemble a team2. Gather descriptive information3. Generate hypotheses4. Test hypotheses 5. Determine how and where contamination occurred6. Prevent more illnesses7. Communicate

Step 5: Determine how and where contamination occurred

Obtain details about implicated food When and where prepared? Where purchased, brand, lot number Contaminated in the kitchen?

• cross-contamination by a food handler?• inadequate cooking?

Contaminated before the kitchen?• at the processing plant?• on the farm?

Food regulatory authorities, environmental health specialists, epidemiologists, laboratorians (as needed) should discuss all findings


Trace the contamination back as far as possible Talk to owners and employees Examine invoices Ensure that the inspection of facilities is directed

at understanding the outbreak (that is, not like a routine inspection) look for unrecognized problems in procedures use epidemiologic information to guide facility

investigation


Product testing State public health laboratories tested open packages

from homes and unopened packages from stores FDA tested finished product retained by Company X


Cookie dough culture results

157 packages from stores: negative 2 packages from patient homes:

non-O157 Shiga toxin-producing E. coli Unopened package retained by Company X:

E. coli O157 PFGE and MLVA patterns were different from

outbreak strain


Cookie dough ingredients


Food facility inspections

Food and Drug Administration (FDA) inspected Plant X and flour supplier

E. coli O157 not isolated from cookie dough plant environment cookie dough production line

Non-O157 Shiga toxin-producing E. coli isolated from flour mill


Step 6: Prevent more illnesses

Institute short-term prevention Institute long-term prevention

What questions remain unanswered? What technological, regulatory, or human

behavior changes would prevent future illnesses from this food?

Evaluate effectiveness of prevention measures

Short-term prevention

Product recall On June 18, CDC and FDA informed Company X

about investigation

On June 19, Company X recalled all refrigerated cookie dough products 47 flavors 3.6 million packages

Photo: Bill Keene, Oregon Department of HealthStep 6: Prevent more Illnesses

Short-term prevention

E. coli O157 Infections, by Week of Onset of Illness, March 1—July 31, 2009 (n=70)*

*Onset date missing for 7 cases.


Long-term prevention

Company made a new label with more visible warning

Before Recall After Recall

Photos courtesy of Bill Keene, Oregon Department of HealthStep 6: Prevent more Illnesses


After the outbreak was long over, Plant X continued to test product on January 13, 2010, 2 samples of finished raw

cookie dough tested positive for E. coli O157 none had been shipped

Company X switched to heat-treated flour


Step 7: Communicate

Needed throughout all steps! During investigation

among all investigators, e.g., lab, epi, regulators with stakeholders, e.g., press, health care providers,

industry After investigation

present findings at meetings write a report make practical recommendations

Report essential information to national outbreak surveillance

Step 7: Communicate


http://www.cdc.gov/ecoli/2009/0630.html Clin Infect Dis. (2011) doi: 10.1093/cid/cir831

Step 7: Communicate

Steps in investigating an outbreak1. Detect the outbreak and assemble a team2. Gather descriptive information

a. determine etiology b. describe the outbreak by time, place, and person c. write a case definition d. conduct surveillance for more cases

3. Generate hypotheses4. Test hypotheses

a. gather data relevant to the hypothesisb. design a study

c. analyze the study5. Determine how and where contamination occurred6. Prevent more illnesses7. Communicate

Final thoughts

Most outbreaks are local Most information about foodborne illness comes from

investigation of local outbreaks Investigation of local outbreaks can lead to identification of

widespread problems and result in widespread improvements

Widespread outbreaks Demonstrate the power of subtyping combined with the

epidemiologic method When solved, can result in widespread improvements

Finding a local cluster that is part of a widespread outbreak increases the chance of solving the widespread outbreak

Food commodities implicated in US outbreaks, 1998-2010 (n=3565)

Objectives

At the end of this lecture, you will be able to:Describe how outbreaks are detectedExplain the steps in investigating an outbreakIdentify the necessary collaborators for an outbreak investigation, including epidemiologists, laboratorians, environmental health specialists, among others

Acknowledgements: E. coli and cookie dough investigation

Arizona

California

Colorado

Connecticut

Delaware

Georgia

Hawaii

Iowa

Illinois

Kentucky

Ohio

Oklahoma

Oregon

Pennsylvania

South Carolina

The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention

Virginia Department of AgricultureMinnesota Department of AgricultureFood and Drug Administration

USDA Food Safety Inspection Service

Enteric Diseases Laboratory BranchEnteric Diseases Epidemiology BranchOutbreak Reponse and Prevention Branch

State and local health departmentsMassachusettsMarylandMaine

Minnesota

Missouri

Montana

North Caroline

New Hampshire

New Jersey

Nevada

New York

Texas

Utah

Virginia

Washington

Wisconsin

Karen NeilKathryn MacDonaldCarlota MedusKirk SmithBill KeeneNicole ComstockEija Hyytia-TreesGerry Gomez

Patricia LafonMike HumphrysSteven StroikaGwen EwaldMark SotirJack GuzewichBonnie KisslerPatricia Griffin

Special Thanks

Thank [email protected]

The findings and conclusions in this presentation are those of the author and do not necessarily represent the views of the Centers for Disease Control and Prevention

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