Factors Contributing to

Foodborne Disease Outbreaks

FDSN 505
October 5, 2020

Catherine Rolfe, Ph.D. Candidate

Food Science and Nutrition
 Overview

• Foodborne Illness Definitions

• Factors Associated with Foodborne Illness
• Illnesses and Outbreak Investigations
• Consequences of Foodborne Illness
 What is Foodborne Illness?

• Usually infectious or toxic in nature and

caused by bacteria, viruses, parasites
or chemical substances entering the
body through contaminated food or
water.
- World Health Organization
 Foodborne Illness
• Infection  enteropathogenic agent
– Bacteria, viruses
– Ex: Listeriosis, Hepatitis A infection

• Intoxication  preformed toxin

– Biological toxins (microbial, plant, animal), chemical
– Ex: Staphylococcal food poisoning, Mycotoxin poisoning

• Toxicoinfection  Toxins produced within the intestines

– Ex: Bacillus cereus gastroenteritis, Cholera

• Allergenic reaction  normal food components

– Immuoglubin E (IgE) mediated and Non-IgE mediated
– Ex: Tree nuts, peanut, shellfish, wheat
Ray et al
 Foodborne Illness

• Infectious Dose: number of pathogen cells

needed to be ingested to cause illness
– HepA and Norovirus  10-100 virus particles
– Salmonella  strain specific, 101 – 109 CFU

• Incubation Period: time between exposure

to pathogen and appearance of symptoms
– Norovirus  12 – 48h
– HepA  15 – 50 days
– Salmonella  6h – 48h
– Campylobacter  2 – 5 days
FDA - Foodborne Illness-Causing Organisms in the U.S.
From Massimo Pacilli, Chicago Dept.
Public Health, 2016
 Foodborne Illness

• Several factors may be involved in the high

incidence caused by pathogenic bacteria:
– Found in raw food materials of animal & plant origin
– Present in food environments
– Grow very effectively in different foods
– Survive conditions used for processing

Salmonella C. perfringens Campylobacter Staph. aureus

Causative agents involved in ~30% of the
outbreaks are not known.
Ray et al
Factors Associated with Foodborne Illness

• Nature of Pathogen • Time/Location

• Food Type • Human Factors
• Place of Consumption • Ways of Exposure

CDC estimates that each year

48 million people get sick from
a foodborne illness, 128,000
are hospitalized, and 3,000 die.
 Nature of Pathogen

• Disease may involve:

– gastrointestinal symptoms
– neurological symptoms
– invasive / systemic disease
– Sequelae
(condition resulting from prior disease)

• Illness may be fatal

–Especially in susceptible groups of people
 Nature of Pathogen

• Virulence or Pathogenicity  capacity of a

pathogen to cause disease in a host

• Characterized by:
– Pathogen Infectivity
– Host Resistance
– Disease Severity
• No complications
• Complications with need for hospitalization
– Ability to cause death
 Nature of Pathogen

• Virulence can be measured via LD50 (Lethal

Dose 50) and ID50 (Infectious Dose 50), which
is the dose required to kill or infect 50% of the
test population

• Morbidity  condition of being diseased, or to the

amount of disease within a population

• Mortality  death rate, number of deaths in a certain

population
Infectious dose 50 (ID50), a measure of infectivity
 Infectious dose 50 (ID50) and Lethal Dose 50 (LD50)

Levi Clancy

 Pathogen A is highly infectious and readily causes

disease, but does not efficiently kill the host.

 Pathogen B is not as infectious but readily causes death

if and when infection is established.
 Nature of Pathogen

• Resulting disease is influenced by:

– Degree of virulence of the pathogen
– How many pathogen cells consumed Severity of Illness:

High
Minor Severe
Virulence of
Pathogen

Low
Few Many

Number of Organisms Consumed

 Predominant Food Types

• Certain food types implicated more repeatedly

with foodborne disease
– Presence of pathogen in raw materials in higher frequency
– Ability of pathogen to grow advantageously in food product
– Greater chance of failure in quality control in specific
environment
– Higher possibility of contaminating finished product by food
handlers

 Animal origin (meat, fish, eggs, dairy…)

 Fruit and vegetables (soil and handling)
 Consumer trends (ex: increase in fish consumption)
 Likely from
methods used
during
preparation

Salmonella involved in large proportions  animals are carriers of Salmonella in digestive tracts
Ray et al
 Predominant Places of Consumption

• High proportions of food served

within short period of time

• High number of people involved

with handling

 Improper cooling of foods

 cross-contamination
 Lack of proper sanitation

Ray et al
 Influence of Time/Location
‫منتشر‬
• Outbreaks more prevalent in Summer months
– May  September
– Raw and processed products exposed to increased outside temperatures
during transportation, display in retail stores, food establishments, home,
etc…
– Picnics and outdoor eating more common

• Incidence of outbreak lower in developed countries

– Socioeconomic factors and climatic conditions

• Within US, states with more incidents include those with:

– Higher populations, large numbers of industry, warm climates, and greater
number of people traveling
 Human Factors
• Resulting disease depends on the host defenses, pathogen must
elude host defenses of upper GI tract to reach intestines
– Mouth
– Esophagus
– Stomach acidity
• Approx. pH 1.5 – 3.5
– Small and large intestines
• Normal microbiota  “Gut Microbiome”
– Out-compete for living space
– Release factors with antibacterial activity
» bacteriocins, colicins

• Immune system of GI Tract

– Gut-associated lymphoid tissue (GALT)
– T cells, plasma cells, mast cells, dendritic cells,
macrophages, antibodies (IgA)
Goering, R. V., et al. Mims’ Medical Microbiology. 2013.
 Human Factors
• Resulting disease depends on the host:
– Everyone is susceptible, but some are more susceptible
– YOUNG, OLD, PREGNANT, IMMUNO-COMPROMISED

< 5 years Immature Immune System

Age
> 50 – 60 years Failing Immune System

Pregnant Altered Immunity

Immuno-compromised: chemo- or
radiation therapy, organ transplant, Inadequate Immune System
Special AIDS, leukemia, etc…
Populations
Taking Antibiotics Normal Flora Disrupted

Taking Antacids Stomach Acidity Neutralized

NC State, Safe plates

 Ways of Exposure

• Pathogens in raw or undercooked foods

– Pre-harvest contamination:
• Fields & manure
• Contaminated water
• Vectors
– Wild animals: birds, deer, rodents, insects…
– Domesticated animals: cows, pigs, chickens…
 Ways of Exposure

• Pathogens in processed foods

– Post-harvest contamination
• Cross-contamination during processing
– Contaminated facility environment

• Process failure
– Inadequate cooking, preservatives, packaging

• Pathogen growth in food

– Improper holding temperatures
 “temperature abuse”
 Ways of Exposure
• Humans as agents of infection
– Fecal-oral route
– Improper handling and preparation
 Foodborne Illness Outbreaks - Definitions

• Case: one person having illness after

eating a food

• Outbreak: more than one person having

a similar illness after eating the same
food

• Cluster: larger number of cases than

expected in a time and location
Agencies Involved in Investigating and Controlling
Foodborne Illness Outbreaks

• Local and State Public Health Departments

– Illness surveillance  know how many to expect in a
given time and place
– Report to federal agencies

• Federal Agencies:
– National illness surveillance and investigations 
• Centers for Disease Control and Prevention (CDC)
– Regulatory agencies:
• U.S. Department of Agriculture (meat & poultry)
• U.S. Food and Drug Administration (other foods)
What Happens in an Outbreak Investigation?

1. Detecting the outbreak

2. Finding the likely source

3. Controlling the outbreak

 Ways of Detecting a Possible Outbreak

• Physician suspects foodborne illness and submits

sample to clinical lab, or group of people report
illnesses to local health department

• CDC gets reports - National Outbreak Reporting

System

• Lab analysis indicates similar types of pathogen

isolated

• Disease reporting is higher than expected

CDC - National Outbreak Reporting System
Search foodborne outbreak data by:
• Year: 1998 - 2017 https://wwwn.cdc.gov/norsdashboard/
• State or multi-state
• Food or ingredient
• Water
• Location type
• Pathogen

Get:
• Number of illnesses
• Hospitalizations
• Deaths
Timeline for Salmonellosis Outbreak

The time from the beginning

of the person’s illness to the
confirmation that he or she
was part of an outbreak is
typically about 2 - 4 weeks.

Case counts during an

outbreak investigation are
therefore always preliminary
and must be interpreted
within this context.
Types of Data in Outbreak Investigations

1. Epidemiologic Data
– Geographic distribution of illnesses
– Time periods when people got sick
– Clusters of sick people who ate at same restaurant,
shopped at same grocery store, attended same
event, etc…
2. Traceback Data
3. Laboratory Testing Data
 Epidemiological Investigation
Local, State, CDC Investigators
• Who became ill, and what are the
characteristics of this person?
– Age, sex, occupation, etc…
• When did the person become ill?
• What foods, beverages, or meals are
suspected?
• Where did the ill person eat or purchase these
foods and when did they consume them?
 Epidemiological Curve: Timeline of an Outbreak
Example: E. coli O104:H4 – sprouts in EU (2011)

EHEC – enterohemorrhagic E. coli, illness

HUS – hemolytic uremic syndrome
Cases Deaths
EHEC 3167 16
HUS 908 34

> 3000 cases in 2 months

Frank, C. et al. 2011. Epidemic profile of Shiga-toxin-producing Escherichia coli

O104:H4 outbreak in Germany. N Engl J Med 365:1771–1780.
Epidemiological Curve: Timeline of an Outbreak
Example: Listeria monocytogenes - ricotta salata cheese (2012)

22 cases, 2 deaths
over 6 months in 14 states
Types of Data in Outbreak Investigations

1. Epidemiologic Data
2. Traceback Data
– Identifying a common point of contamination
– Reviewing records collected from restaurants
and/or stores where sick people ate or shopped
– Finding food safety risks in relevant restaurants,
stores, facilities, farms, etc…
3. Laboratory Testing Data
Traceback and Controlling the Outbreak

CDC
 Traceback Example:
Salmonella Bareilly and Salmonella Nchanga
Infections Associated with a Raw Scraped Ground
Tuna Product - United States, 2012

Raw Scraped Ground Tuna

425 cases over 5 months,

55 hospitalizations, 0 deaths
28 States involved
Timeline of Events: Multistate Outbreak of Salmonella
Bareilly and Salmonella Nchanga Infections Associated with a
Raw Scraped Ground Tuna Product - United States, 2012

April 26, 2012: FDA announced finding the

outbreak strains of Salmonella Bareilly and
Salmonella Nchanga in unopened packages of
yellowfin tuna product imported from Moon
Marine USA Corporation.
Traceback Example - Raw Scraped Ground Tuna Distribution of contaminated tuna
Product - United States, 2012 outlined in red
Types of Data in Outbreak Investigations

1. Epidemiologic Data
2. Traceback Data
3. Laboratory Testing Data
– Pathogen that caused illness found in:
• Patient samples
• Food item collected from sick person’s home, in
a retail location, or in a food production facility
– Same DNA fingerprint linking pathogen in sick
people and food or food production facility
Pathogen Genotyping - “DNA Fingerprinting”

Pulsed Field Gel Electrophoresis (PFGE)

Patient isolate = Food isolate

CDC PulseNet:
National Molecular Subtyping Network
(Established 1996)
 CDC PulseNet National Molecular Subtyping Network:
How It Works

• State or local public health department enters

DNA fingerprint pattern into electronic
database

• Pattern is sent to CDC and filed in PulseNet

computer

• Software compares DNA fingerprints from

many samples in the database

• If patterns from different clinical isolates

match, the PulseNet Team notifies all network
labs of a possible foodborne outbreak
 When PFGE was not good enough:
e.g., Salmonella Enteritidis in Shell Eggs – 2010
• Could not distinguish strains by PFGE
• May – Nov: 3,578 total illnesses reported
• Outbreak estimate: 1,939 illnesses

Common PFGE fingerprint

 Could not determine which cases

were outbreak-related
CDC
 Using Genomics to Identify Food Contamination:
Whole Genome Sequencing (WGS)

• Most accurate, high-resolution sub-typing method

– Replaces PFGE as primary molecular characterization

• Shows relatedness between strains or identity of isolates

– Focuses on environmental and food isolates to be a large reference
datable for clinical samples

• Public software and analysis tool available to industry

 GenomeTrakr Database

• Each genomic sequence includes:

• Species
• Geographic location
• Date of isolation/collector
• Isolation source (food product, environmental…) Adapted from Eric Stevens, FDA,
WGS Symposia 2019
 Current WGS Methodology
1. Isolate bacterial genome and break it up into many small fragments
2. Sequence the fragments using Short or Long-Read Sequencing Technology
3. Assemble the thousands to millions of sequenced reads back into the entire
genomic sequence of the isolate
4. Find genetic differences between isolates (SNPs)
5. Use SNPs to create a phylogenetic tree to inform genetic relatedness of
foodborne isolates

PFGE Tree
WGS Tree

Adapted from Eric Stevens,

FDA, WGS Symposia 2019
FDA GenomeTrakr
Total Number of Sequences in the GenomeTrakr Database

FDA GenomeTrakr
PulseNet and GenomeTrakr Working Together

From Eric Stevens, FDA,

WGS Symposia 2019
NCBI’s Pathogen
Detection Portal
 Special Detection Challenges:
Viruses and Parasites

• Enrichment culture not available

• Molecular detection using PCR
– Sample preparation critical
• Elution  separation  concentration
– No correlation to infectivity

Detection of viable pathogen or

fragment of pathogen’s DNA?
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter

Jan – Apr 2017

32 Cases
12 Hospitalizations
(9 HUS)
0 Deaths

12 States
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter

Epidemiological Data
25/32 cases interviewed reported:
• Eating I.M. Healthy SoyNut butter at home (19)

• Attending childcare centers or other facility that

served I.M. Healthy SoyNut Butter or I.M. Healthy
granola coated with SoyNut Butter (6)
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter

Traceback Data
Dixie Dew Products, Inc., Erlanger KY
• Sole manufacturer of I.M. Healthy SoyNut
Butter products

Distributors  private labels of products

• ProSports Clubs, Bellevue WA
• SoyNut Butter Co, Glenview IL
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter

Laboratory Testing Data

Clinical Samples
• E. coli O157:H7 isolated from patient samples
• PulseNet PFGE patterns identify possible links
• WGS data confirm strain relatedness

Food Samples
• E. coli O157:H7 isolated from I.M. Healthy SoyNut
Butter
• opened containers  patient homes
• unopened containers  retail stores
• WGS data confirm strain relatedness to clinical
samples
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter
Controlling the Outbreak

Outbreak revealed to firm:

• Mar 2  FDA/CDC notification call
• Mar 3  FDA demand for records

Product recalls issued:

• Mar 4  15-oz jars; individual cups; 4-lb tubs
• Mar 7 
• All varieties: original, chunky, honey, unsweetened,
chocolate
• Granola products: original, apple, blueberry, raisin, cranberry
• Mar 10  Dixie Diner’s Club Carb Not Beanit
Butter
• Mar 24  20/20 LifeStyles Yogurt Peanut Crunch
bars
 Outbreak Investigation Case Study:
E. coli O157:H7 - I.M. Healthy SoyNut Butter
Controlling the Outbreak

Dixie Dew facility inspection:

• Mar 3 – 15  Insanitary conditions:

 Product leftover in kettle after production run

overnight or weekend, no subsequent kill step
 Product cooking with uncalibrated thermometer
 Processing / packaging rooms coated with product
build-up, standing water, filth
 Leaking pipes dripping into production equipment
 Fly, rodent, mold infestation
 Inadequate employee hygiene facilities
 Others

• Mar 30  Facility registration suspended

Cyclospora Infections Linked to Salad Mix and Cilantro
Jun – Aug 2013

25 states involved:

Ynés R. Ortega, Roxana Sanchez

Life Cycle of Cyclospora cayetanensis Clinical Microbiology Reviews Jan 2010, 23 (1) 218-234.
Cyclospora Infections Linked to Salad Mix and Cilantro
Jun – Aug 2013

Epidemiological Curve - 631 cases over 3 months

Cyclospora Infections Linked to Salad Mix and Cilantro
Jun – Aug 2013

• Restaurant investigations  Iowa and Nebraska

– Linked to bagged salad mix from one producer in Mexico

• Restaurant investigations – Texas

– Linked to salsa containing cilantro
– Not linked to lettuce

• Grocery store investigation – Texas

– Shopper cards reveal purchase of cilantro
– No other foods in common among cases
Cyclospora Infections Linked to Salad Mix and Cilantro
Jun – Aug 2013

Conclusion:
• There was more than one outbreak of
cyclosporiasis during Jun – Aug 2013

• Salad mix from producer in Mexico linked to

restaurant-associated illnesses in IA and NE

• Cilantro linked to many of the restaurant and

grocery store – associated illnesses in TX
 Repeated Cyclospora Outbreaks

2014: 304 cases in 3 months 2015: 546 cases in 4 months

cilantro - Puebla, Mexico cilantro - Puebla, Mexico

FDA – Aug. 2015:

• Detain cilantro from Puebla Mexico
• Exception “Green list” – 11 minimal requirements for good
agricultural and food safety practices

2016: 384 cases – vehicle uncertain

2017: 1,031 cases – vehicle uncertain
New Detection Method for Cyclospora in Salad Mix

• In 2015, FDA instructed Center

for Food Safety and Applied
Nutrition to develop a better
detection tool
 higher sensitivity of earlier method

– Multi-laboratory validation study, scientists

used the new method in different salad
components, such as basil, carrots,
cilantro, parsley, and raspberries

 Method was able to confirm July

2018 outbreak in Fresh Express
salad mix sold from McDonald’s
 Consequences of Foodborne Illness
Public Health
• Acute disease and progressions
• Gastrointestinal (e.g. norovirus - diarrhea, vomiting)
• Neurological (e.g. Clostridium botulinum - botulism)
• Invasive / Systemic (e.g. E. coli O157:H7 – Hemolytic Uremic
Syndrome)

• Sequelae: long-term effects

• e.g. Salmonella: reactive arthritis
• e.g. Campylobacter: Guillain-Barré syndrome

• Mortality
• e.g. Listeria monocytogenes: deaths, spontaneous abortions
 Consequences of Foodborne Illness
Economic
• Human
– Medical costs, lost productivity, sequelae, death
– 15 pathogens cost $15.5 billion annually in the U.S.

 Approx. 90% by 5 pathogens

‒ Salmonella - $3.6b
‒ Campylobacter - $1.9b
‒ Listeria monocytogenes - $2.8b
‒ Toxoplasma - $3.3b
‒ Norovirus - $2.3b

Most people with Salmonella infections recover,

however, deaths account for 89% of economic
burden
USDA, Economic Research Service
 Consequences of Foodborne Illness
Economic
• Industry
– Product recalls
– Loss of brand name/reputation
– Loss of product
– Company failure

Listeriosis , 2011 -
cantaloupes from Jensen Farms
147 cases, 33 deaths
Brothers Eric and Ryan Jensen pleaded guilty to six federal misdemeanors in
October 2013, including introducing adulterated food into interstate
commerce and criminal aiding and abetting. They were each sentenced to
five years probation and six months home detention, $150,000 in restitution
and 100 hours of community service. The farm operation filed for Chapter 11
bankruptcy. Food Safety News, 2015
 Consequences of Foodborne Illness
Legal
• Personal
– Executives of Peanut Corporation of America
• CEO Stewart Parnell  28 years in prison
• Other managers  3, 5, 6, and 20 years in prison

Peanut Corporation of America

2008 – 2009 salmonellosis outbreak
714 cases, 9 deaths
 Lecture Question…

Name the 3 types of data used in outbreak

investigations.