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National Center for Emerging and Zoonotic Infectious Diseases

Food Safety: Better outbreak investigations can make


the food supply safer

National Press Foundation


St. Louis, Missouri
September 15, 2019
Robert Tauxe, MD, MPH, Director
Division of Foodborne, Waterborne, and Environmental Diseases
National Center for Emerging and Zoonotic Infectious Diseases
Centers for Disease Control and Prevention
Selected 2018 Multi-state Outbreaks
1946 Atlanta 2012 Bldg 24 opens

How does CDC protect the health


of the public with expert science?
 Public health surveillance: Monitoring frequency of particular
illnesses in the population (reported by doctors and clinical
laboratories)
 Investigation: Find causes and sources of illness and outbreaks

 Prevention: Develop, assess and improve methods and strategies

 Communication: Inform public, press, partners and decision makers

 Education: Train next generation of public health workers


What does CDC do in food
safety?

 Conduct national surveillance for infections often transmitted by food

 Investigate and control outbreaks to stop them and prevent future illness

 Drive illness prevention policy with data, analyses, and partnerships

 Support state and local health departments, regulatory agencies, and other
partners to fulfill their primary roles in food safety

 Innovate by applying advanced technologies to improve public health actions


Surveillance and investigation are multi-partner efforts
 Caregivers, clinical labs, and patients themselves
– Make the diagnoses, and report the specific illnesses
– Patients participate in interviews
 State and local health departments: epi, lab, and food safety officials
– Receive reports of specific diseases
– Interview people
– Subtype pathogens in the public health labs
– Traceback, assess and control within state events
 CDC is lead national public health agency (non-regulatory)
– National disease surveillance and multistate outbreak detection
– Epidemiologic investigation
 FDA (most foods) and USDA/FSIS (meat and poultry) are regulatory agencies
– Trace suspected foods back to source
– Assess production and processing facilities
 Industry, assisting with traceback, assessment, recalls, and prevention measures
Foodborne disease prevention involves many partners
 Many points for:
– Contamination
– Control
– Prevention
 At each step, public health has
partners in prevention
 Industry efforts, regulation,
inspection, and enforcement,
and food microbiologists
Health burden of infection from contaminated foods
 Each year, 48 million people become sick
(1 in 6 Americans), 128,000 are
hospitalized, and 3,000 die

 ~ 800 foodborne outbreaks are reported


annually

 Major pathogens: $3 billion in health-


related costs each year

Scallan et al (2011) EID 17: 7-15, 16-22.


Food source attribution: Proportion of illnesses and
deaths attributed to food categories
 2013: Estimates based on analysis of 4,589
outbreaks reported 1998 – 2008

 Produce was the dominant source for illnesses

 Meat and poultry was the dominant source for


fatal illnesses

 Online Supplement Table 4 provides


percentages for each pathogen and food type

Painter et al (2013) EID 19: 407-415


Using surveillance to target interventions
IFSAC Attribution: Salmonella infections for 2016

https://www.cdc.gov/foodsafety/ifsac/annual-reports.html
The changing landscape of foodborne infections
 Food industry has become more centralized

 Food sourcing is going global

 Rising consumer demand for food that is less processed

 Rising demand for local, small scale and “natural”

 Emerging pathogens and unsuspected food hazards

 Better surveillance means that we detect more dispersed outbreaks


Improving prevention of foodborne diseases
 Reduce the chance that food gets contaminated with pathogens
 Make food production and processing safer
– on farms, ranches, orchards
– in packing plants, slaughter houses, food factories
– in restaurants and private kitchens
– in other countries as well as in the US
 Target specific points in production to improve control
 Expect new problems to emerge as landscape of food production changes
 Cycle of continuous adjustment and improvement
 Outbreak investigations important way to learn of new problems
Outbreaks of foodborne infection are opportunities to
learn how to improve prevention
 Something goes awry somewhere on the food chain

 A group of people become ill with the same illness after eating the same food

 More cases of an illness occur than expected

 As a result of eating a particular contaminated food

 It is not always food. Infection can spread by other routes (e.g. water, animal
contact, person-to-person)
Investigating an Outbreak
 Detect that an outbreak may be happening

 Develop a hypothesis about how transmission occurred

 Test the hypothesis – 3 lines of investigation


– Epidemiological investigation
– Trace suspect foods back to source
– Microbiological investigation
 Control and halt the outbreak

 Learn and take steps to prevent the next one


Three lines of investigation help solve outbreaks
 Epidemiological data:
– Do the ill people share a particular exposure in common?
– Is it more frequent among them that we would expect?

 Traceback and environmental assessment data:


– Does the suspect food come from one single source?
– Does the distribution of the suspect food match the cases?
– Can assessment of production explain how contamination occurred?

 Microbiological data:
– Is there a single strain or group of strains?
– Can the organism be found in the suspect food or environment?

 It takes at least two lines of information to solve an outbreak


 Improving methods we use for all three
Patient level Public health surveillance of intestinal
infections in the United States
“I feel sick, so I am going to
the doctor ”

“Probably a virus, but lets


send a sample to the lab”

“This is an infection with


Campylobacter bacteria”
Patient level Public health surveillance of intestinal
infections in the United States
“I’m glad to know what it is”

“Campylobacter”, eh? We can treat that,


and we need to report it to the local
health department”

“I will test it for antibiotic resistance”


Campylobacter infections
 1.3 million illnesses, 13,000 hospitalizations, and 120
deaths annually in the U.S.

 Acquired from different sources


– bird and cattle reservoirs
– poultry, raw milk, animal contact, surface water

 Causes diarrheal illness in humans


– bloody and non-bloody diarrhea
– Guillain Barré Syndrome (1/1000 cases)
– can be treated with antibiotics
Patient level Public health surveillance of intestinal
infections in the United States
Local/State Health
“Hello Joe – hope you are
Department Level
feeling better

“May we ask you some


questions, please? We want
to learn how you might have
caught this Campylobacter”

“We’ve gotten a lot of reports


like this recently”
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Surveillance sounds the alarm

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Reported Campylobacter infections, Alaska, 2000-2008
Cases mostly in South-central Alaska, around
Anchorage

Mat-Su Valley

Anchorage

Kenai
Peninsula
Initial investigation: describing the outbreak
(Who, where, when?)
 45 cases of Campylobacter infection diagnosed between Aug 1– Sept 10, 2008
– Age range; 1-79 years, median 47
– Female: 51%; White: 85%, Alaska Native: 10%
– Anchorage resident: 73%
 Illness features:
– 93% diarrhea
– 87% abdominal cramps
– 22% bloody diarrhea
 In initial interviews, some mentioned eating fresh raw peas

Gardner 2011 Clin Infect Dis 53:26-32


Testing the hypothesis
Epidemiologic investigation and traceback
Case-control study using systematic interviews:
 67% of persons with Campylobacter ate raw peas in the week before they
got sick, compared to
 17% of healthy controls interviewed
 Probability of observing that difference by chance is less than 1 in 1000. (p<
0.001)

 Suspect food traced back to source:


– Peas all came from one pea farm
– there is only one pea farm in Alaska
– in business for years
The implicated food vehicle

Directions: Patients said:

“TO PROCESS” “Ate ‘em raw,


Blanching in straight out of the
boiling water  bag”
Pea harvesting operation
Combine harvesting
machine with wash
tank (no chlorine in
water)
Sandhill Crane (Grus canadensis)
Testing the hypothesis (cont’d)
Microbiological findings
 Campylobacter identified in samples from
– patients
– peas in packages and in field
– Sandhill Crane poop
 Molecular “fingerprint” typing: variety of matching “fingerprints”
found in strains from
– patients
– peas
– cranes

Kwan 2014, Appl Env Microbiol 80:4540-4546


Campylobacter illness from fresh peas
Control and prevention efforts
In all: 98 cases identified
5 hospitalized, 1 with Guillain-Barré Syndrome
 Sept 2008: Harvest halted and peas removed from shelves
 Outbreak promptly stopped

 2009: Scare-cranes, and also


– Larger label recommending washing and blanching,
– Chlorine in water wash tank for harvested peas
– Harvest resumed that year – no spike in cases
 Through 2018: No recurrence
What was learned
 First time Campylobacter and fresh raw produce linked
– Epidemiology – very strong
– Traceback – incontrovertible
– Laboratory – isolates from people, food, birds matched
 Spread from avian reservoir to food
 Prevented by chlorinating washtank water on the farm
 General implications for any fresh produce eaten raw
 New requirements for produce in Food Safety Modernization Act regulation (Oct
31 2015)
A large outbreak in one place may be obvious

Local surveillance will


detect this event
An outbreak with cases dispersed in many places is
difficult to detect, unless

 We test bacteria from all the cases, and


 We find they are infected with the same bacterial strain
 We learn by interview they shared an exposure
The spectrum of foodborne disease outbreaks
 Local outbreak  Dispersed outbreak
– Many cases in one place – A few cases in each of many
– Detected by affected group jurisdictions
themselves – Detected by lab-based subtype
– Local investigation surveillance
– Local food handling error – Multi-state investigation
– Local solution – Industrial contamination event
– Broad implications

Multistate outbreaks point to contamination early in


production of widely distributed foods
Detecting a dispersed outbreak is like finding a needle
in a haystack

Would a magnet help?


PulseNet 1996-2019: National network for molecular
surveillance of bacterial enteric infections
Hundreds of clusters/year

 Standard lab method


 Results in CDC database
 All participants can view

87 labs participate:
 All state heath departments
 City health departments
 FDA laboratories
 FSIS laboratories

50,000 bacteria/year from


Now changing method to whole genome  ill people
sequencing = Next generation PulseNet (with  foods
FDA, USDA, NIH) on July 15, 2019  animals
PulseNet data analysis: Searching for clusters

 PulseNet staff search for clusters of similar


patterns

 When a cluster is identified, they report it


to epidemiologists

 All participants can look at PulseNet


database

Cluster of infections with same pattern


Is there a single source?
Public health surveillance of intestinal infections in
Patient level
the United States
Local/State Health
“Hello Joe – hope you are
Department Level
feeling better

“May we ask you some


questions, please? We want
to learn how you might have
caught this Salmonella”

“This is a rare type of


Salmonella. We don’t see this
type very often. Let’s check
the PulseNet database.”
Public health surveillance of intestinal infections in
Patient level
the United States
Local/State Health National
Department Level Level=CDC
“In the last week, we have reports of
several people in our state with the
same infection. We are starting to
investigate them.”

“We have seen a Salmonella with the same


fingerprint recently. It also looks like there
are cases in other states that have the same
rare fingerprint. Maybe this is bigger than
just one state.”
Public health surveillance of intestinal infections in
Patient level
the United States
Local/State Health National
Department Level Level=CDC
“We’ll hold a conference call with all
the states that have cases. Let us
know on the call if your initial
interviews give any clues.”

“We usually get about 10 of these per year


in the US. Now we have 20 reported to
PulseNet in the last week around the country
– concerning.”
Multistate foodborne outbreaks reported to CDC
1973-2010
25
PulseNet begins
Cost-benefit analysis
20
• 270,000 fewer illnesses/yr
• $507 M/yr saved
15
• ROI = 70/1
Scharff 2016 Am J Prev Med
10

0
Salmonella infections
 1.2 million illnesses, 23,000 hospitalizations, and 450
deaths annually in the U.S.
 Acquired from many different sources
– Animal reservoirs (mammals, birds, reptiles,
amphibians)
– Poultry, meat, fresh produce, eggs, raw milk
– Animal contact
 Causes diarrheal illness in humans
– blood stream infections
– severe focal infections
 Many serotypes: Enteritidis, Typhimurium, and Newport
are most common
Complex multi-strain outbreak, from a surprising source:
Kratom and six serotypes of Salmonella
Public Products
warned recalled
 Feb 16, 2018: 28 ill with Salmonella I 4,5,12,:b:- in 20 states
 8 (73%) of 11 consumed kratom in various forms
 Leaf of Mitragyna speciosa shrub in SE Asia (coffee family)
 Purchased at small retail locations, or over the internet
 52% of kratom samples yielded Salmonella
 I 4,5,12,b:-, Heidelberg, Javiana, Weltevreden, Okatie, Thompson
 85 different “fingerprint” patterns

 199 infections in 41 states, 50 hospitalized


 Cases go back to January 2017
 Public warned on February 20, 2018
 1 brand recalled on March 10, 2018
 By May 24, 8 more brands recalled, and investigation ended
 Kratom still for sale on the web (Illegal in 6 states)
Kratom and six serotypes of Salmonella
Lessons learned
 Remarkable frequency and diversity of contamination
 Remarkable diversity of brands, suppliers
 Internet sourcing and marketing
 Many suppliers, sources in several SE Asian countries
 Source(s) of contamination unknown
By ThorPorre - Own work, CC BY 3.0,
https://commons.wikimedia.org/w/index.php?curid=25187129

 Revealed by inquiring broadly about herbal agents, dietary supplements


 No “industry safety standard”
 Regulatory status unclear
 Difficult to control.
 Principle control measure for now is warning the public
What was learned?
 Dispersed outbreak traced to an imported plant product used in many ways
(a novel source of salmonellosis)

 Long shelf life product – recalls and warnings are important

 Press has been a major partner to warn the public

 Quality control steps appear to be missing in processing in SE Asia

 “Foreign Supplier Verification” rules in Food Safety Modernization Act would


apply if this is determined to be a food
Incidence of diagnosed cases, by pathogen — FoodNet, 2018
 Active surveillance since 1996, in Emerging Infections Program
 Collaboration among CDC, 10 FoodNet sites, FDA, USDA/FSIS
 8 infections often spread through food
 Reliable and up-to-date data on illness trends
E. coli O157 Campylobacter
Confirmed
only

Healthy People
2020 Goals:

25-50%
Listeria Salmonella reductions
from 2007-
2009 baseline
If detecting a dispersed
outbreak is like finding a
needle in the haystack,

would a bigger
magnet help?
Reading and comparing bacterial DNA sequences
Big data meets microbiology
 In 15 years, cost and speed of sequencing DNA from a bacterium
has dropped from $100,000s and a year to $100 and hours

 Reading and interpreting the whole genome sequence is faster


and more automated

 3M base pairs = 1800 pages of text (2 x Moby Dick)

 Comparing alleles and sequences provides much greater


precision than PFGE to say:
– Strains are closely related (and thus may have same source)
– Strains are not closely related, (and can be excluded from
What happens if we investigation)
use this new – Strains from ill people are closely related to strains from
technology in suspect foods or environment (a clue to the source)
PulseNet?
2013 Pilot project:
Does WGS technology improve listeriosis surveillance?
 Since 1998, State public health laboratories have used PFGE in the
PulseNet network for Listeria monocytogenes

 In 2013, collaborative multiagency effort began sequencing


isolates of Listeria as part of routine surveillance
– Clinical isolates at CDC (~800/year),
– Food isolates at FDA, USDA
– WGS data stored at NIH National Center for Bioinformatics
Information

 State health departments interviewed all listeriosis cases

 Coordination with Canada, UK, France, Denmark, Australia


http://www.hhs.gov/idealab/projects-item/whole-genome-sequencing-future-of-food-safety/
Surveillance based on DNA Sequencing: Solving
10
more foodborne listeriosis outbreaks
9
Year before WGS
8
Year 1 WGS
Year 2 WGS
7 Year 3 WGS

Number of Listeria outbreaks Median number of cases per


solved Listeria investigation
Jackson 2016. Clin Infect Dis 63:380-6
Listeria and raw milk, 2014-2016
 November 2015: FDA collected raw milk
sample at a raw milk conference in CA
 January 2016: Listeria isolated from raw milk,
WGS matched 2 infections from 2014
 Patients in FL and CA
 Mean age 77: both hospitalized, 1 died
 PFGE: Two different patterns
 WGS: Extremely close: Within 2 SNPs

 Both drank raw milk


 One reported to get milk online from same
PA farm that FDA had sampled
 Source of other unclear
 PA farm sold milk interstate over the web
 Private membership organization
 March 18, 2016: CDC warned public
www.cdc.gov/listeria/outbreaks/
Foods implicated in listeriosis outbreaks since 2013 in
the United States (in the WGS era)
 Expected foods: Found as a result of
– Raw milk multi-state investigations
– Soft cheeses
Contamination often
– Mung bean sprouts occurred at the packing shed or processing
– (Not processed meats) facility
 Novel foods:
– Caramel-dipped apples Most investigations started with ill people. A
few started with finding Listeria in a food,
– Ice cream
that matched strains from patients who ate
– Packaged leafy green salads that food
– Stone fruits (nectarines)
– Frozen raw vegetables
 New efforts in food industry now to reduce
contamination with listeriosis
Value added by using whole genome sequencing
 Close genetic similarity means greater confidence that a group of infections may share a
common origin, so investigations are more focused
– Better determination of which cases to interview, which to not include
• Combines different PFGE patterns that were actually closely related
• Splits up some common PFGE patterns into more tightly related groups
– Compares strains from foods, animals, and production environments
– Like PFGE in the 1990’s, will be detecting even more clusters, including small ones
– Defines the “clades” of concern that are emerging, persisting or expanding

 Empowers epidemiologists, rather than replacing them


– Still need to find out what patients ate, that others did not
– Still need to trace foods to their sources
Greek: “Klados”
Greater confidence in linking patterns
Recurring clade: MDR E. coli O157:H7 and Romaine lettuce
 Large outbreak in spring of 2018, linked to Romaine
 Began as restaurant-associated outbreak in New Jersey Investigation Public Warning
Begins
 Rapidly expanded, linked to Romaine lettuce within 8 days
 87% said they ate Romaine lettuce, far more than baseline
 Traced to up to ~ 23 fields, across span of ~ 50 miles
in Yuma Growing area
 Largest O157 outbreak in last decade
 Ended after repeated warnings, end of harvest

 210 cases, 36 states, 96 hospitalized, 27 HUS, 5 deaths


 WGS defined two main clades
 Largest clade has a history:
– Mid 2017: 11 cases, Lake Wildwood in California
– Late 2017: 17 cases, salad suspected in Midwest
 Need heightened surveillance, prevention actions and
research
Thanks to Matt Wise, CDC
WGS is making investigations more powerful
 2018: E. coli O157 infections and Romaine
Lettuce - Yuma Growing Area
 WGS linked together 22 different PFGE patterns
into 2 main clades
 Contamination on up to two dozen farms was
related, reflecting widespread contamination
 E. coli O157 isolated from the irrigation canal
water matched the outbreak clades
 This outbreak is linked with events in preceding
year - the strain is persisting in the environment!

 4/19/2019: Leafy Greens Marketing Agreement


Requires farmers to sanitize surface waters
sprayed onto leafy greens (for irrigation or
aerial applications)
Greater confidence in linking patterns
Emerging clade: MDR Salmonella Infantis and poultry
 2012: MDR strain first seen in travelers to Peru 200
 Rare ESBL resistance gene (strain defined by PFGE) Other
150
 Resistant/decreased susceptibility to 10 agents, Chicken
including Amp, Cipro, Ceftriaxone, and Tmp/Sxt 100 Human
 Difficult to treat with commonly used antibiotics 50
 First non travel-associated US case in 2014
0
 Increased rapidly in 2017-2018

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 Multiple PFGE types – all related by WGS


 Now represents 30% of all S Infantis in humans, 573 cases in 2018
 USDA/FSIS isolates: In chicken since 2013, rapid increase in 2017
 In 2018: 495 isolates from chicken, 53 isolates from turkey
 Met with National Chicken Council several times in last year, Jan 2019
 Preharvest investigations and interventions needed
Thanks to Louise Francois Watkins
Implementing whole genome sequencing as PulseNet
standard – 2017-2019
 2017-2019
– Built data infrastructure
– Expanded state lab and epi capacity
– Trained and certified staff in all states
– Partner with FDA labs, FSIS labs, and
NCBI at NIH Equipped, trained and certified
– PulseNet transition to WGS as of
July 15, 2019

 With WGS PulseNet expect more:


‒ Clusters that are truly genetically related
‒ Successful epidemiologic investigations
‒ Targets for prevention to be defined
Changing diagnostic methods impacts surveillance: culture-
independent diagnostic panels mean more tests, fewer isolates
 Since 2015, use of rapid multi-pathogen diagnostic panels increasing in clinical laboratories

 Can diagnose up to 22 different infections, with results available in hours

 More people are being tested for more pathogens, including some that could not be
routinely diagnosed before, but fewer are culture-confirmed.

 Tests do not yield a living bacterial isolate, unless the specimen that was positive is then
cultured for that organism. Access to the isolate is necessary for PulseNet subtyping

 Laboratories may decide not to perform these “reflex” cultures

 Clinical laboratories may send the positive specimens to the public health laboratories to
be cultured there
Future foodborne outbreaks more likely to be
 Dispersed in space: Multi-state, multi-national
 Dispersed in time: Multi-year duration
 Detected by sequence-based surveillance
 Detected as clades spreading around the world
 Associated with a broad array of foods, including fresh produce and
minimally processed foods
As microbiologic and diagnostic methods march
forward, what will keep us on the cutting edge?
 Whole genome sequencing currently can take two weeks to turn around and
requires an isolate
 Public health needs more advanced molecular diagnostic tools for direct use on
clinical specimens, to get sequence information in hours
 Clinical researchers are exploring metagenomic methods now
 Work at CDC has begun as well
 Current WGS databases are a bridge towards the post-isolate future

 5-10 years from now, we may have diagnosis and pathogen sequencing using
metagenomic methods at the bedside
Better foodborne disease prevention in the 21st century:
WGS is part of an evolving public health approach
 Whole genome sequence-based surveillance is an evolutionary step forward:
‒ More precise subtyping, combined with enhanced patient interviews and
traceback
‒ More outbreaks and sources detected and controlled
‒ More food safety gaps found and corrected
‒ Applicable to many other infections as well as the enteric ones
 Define broader clades of concern that emerge and persist
 Better target broader prevention strategies
 A bridge to the future when public health will have culture-independent tools
providing sequence information rapidly

 Long term effect: Helping industry, regulators, and consumers drive


down incidence of foodborne infections
Thank you

For more information, contact CDC


1-800-CDC-INFO (232-4636)
TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the
official position of the Centers for Disease Control and Prevention.
Visit Our Websites
 E. coli: www.cdc.gov/ecoli

 Salmonella: www.cdc.gov/salmonella

 Listeria: www.cdc.gov/listeria

 FoodNet: www.cdc.gov/foodnet

 PulseNet: www.cdc.gov/pulsenet

 Foodborne outbreaks: www.cdc.gov/foodsafety/outbreaks/index.html

 Foodborne burden of illness: www.cdc.gov/foodborneburden

 General Information About Foodborne Diseases:


– www.foodsafety.gov
– http://www.cdc.gov/vitalsigns/foodsafety/