anatomy of an outbreak
DESCRIPTION
Anatomy of an Outbreak. Kirk Smith, DVM, MS, PhD Supervisor, Foodborne, Vectorborne, and Zoonotic Diseases Unit Acute Disease Investigation and Control Section Minnesota Department of Health. [email protected] Office phone: 651-201-5240. - PowerPoint PPT PresentationTRANSCRIPT
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Anatomy of an Outbreak
Kirk Smith, DVM, MS, PhD
Supervisor, Foodborne, Vectorborne, and Zoonotic Diseases Unit
Acute Disease Investigation and Control Section
Minnesota Department of Health
[email protected] phone: 651-201-5240
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Some Recent Notable Multi-state Foodborne Outbreaks of Salmonellosis
2005 2006 2007 2008
Pot pies•401 cases•42 states
PCA peanut butter•691 cases•46 states
Cake Mix• 25 cases• 9 states
Tomatoes•183 cases•21 states
Hot peppers•1,442 cases•44 states
Veggie Booty•70 cases•23 states
Peter Pan peanut butter•714 cases•48 states
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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)*
Giardiasis (Giardia lamblia)
Hemolytic uremic syndrome
Listeriosis (Listeria monocytogenes)*
Salmonellosis, including typhoid (Salmonella sp.)*
Shigellosis (Shigella sp.)*
Toxoplasmosis
Yersiniosis (Yersinia sp.)*
FOODBORNE AND WATERBORNE DISEASES
* Submit isolates or clinical materials to the Minnesota Department of Health
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Submission of isolate to public
health lab
Report of case to public health
Becomes ill
Confirmation/ serotyping,
PFGE subtyping
Interview
Lab and epi data
combined
Person eats contaminated food
Stool sample positive
Goes to doctor, stool sample collected
2 - 3 days
1 - 7 days (incubation)
2 - 5 days 1 - 5 days
2 - 4 days
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Reportable Bacterial Enteric Pathogen Surveillance in Minnesota
• Isolates must be submitted to the Minnesota Department of Health
• Real-time pulsed-field gel electrophoresis (PFGE) subtyping of all isolates
• Routine, real-time interviews of all cases
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Molten agarose
Pulsed-Field Gel Electrophoresis (PFGE)
Lysis
Enzyme digestion (XbaI)
Bacteria
Pulse electrophoresis
DNA
18 hours
1.5 hours
1.5 hours
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The National Molecular Subtyping Network for Foodborne Disease Surveillance
Area Labs
National
Database
FoodNet Sites
FDA, USDA Lab
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PulseNet Laboratory NetworkPulseNet Laboratory Network
Local Databases
PulseNet National
Databases (CDC)
PulseNet National
Databases (CDC)
Participating LabsParticipating Labs PFGE PatternsPFGE Patterns
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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 sensitivity of outbreak detection
– i.e., need this for optimal detection of outbreaks (local and multistate) caused by Salmonella, E. coli O157:H7
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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
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Standard Questionnaire for Salmonella, E. coli O157 cases
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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
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Response for PFGE Clusters
• Minimum: Compare case interviews
• Maximum: Case-control study
• Food Testing: Before, during, or after case control study
• “Informational” product tracing
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Minnesota Approach to Investigation of PFGE Clusters:
Dynamic Cluster Investigation Model
Case #1 Case #2 Case #3 Case #4
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Dynamic Cluster Investigation - Pot Pies
Consumed Banquet PP
4
10/4afternoon
“trawling” questionaire
1
Initial trawling questionnaire interview date
9/10
2
9/27
3
10/3night
Re-interviewed cases about frozen foods and pot pies
10/4morning
10/4evening
PP
Exposure
added
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Team Diarrhea Fall 2007
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Epidemiologic Follow-up of Cases
• Determines the likelihood of identifying the source of an outbreak
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Epidemiologic Data are Dirty
• Not all exposed people get sick
• Some people get sick without being exposed
• Not all “exposed people” are really exposed
• Not all “unexposed people” are really unexposed
• Not all sick people are really sick
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Presentations of Outbreaks due to Commercially Distributed Food Items
• Cases in community, no obvious common exposure
– Retail food (grocery stores)
• Cases occur among patrons of restaurant(s)
• Cases clustered in institution(s)
• Any combination of above three
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Presentations of Outbreaks due to Commercially Distributed Food Items
• Cases in community, no obvious common exposure
– Retail food (grocery stores)
• Cases occur among patrons of restaurant(s)
• Cases clustered in institution(s)
• Any combination of above three
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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
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Outbreak Investigation - Methods
September 28–29, 2005
• Additional O157 isolates received and subtyped by 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
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Case-Control Study Results
Exposure Cases Controls p-valueMatched OR* 95% CI†
Any lettuce 9/10 17/26 3.5 0.5–25.0
* OR = odds ratio† CI = confidence interval
9/10Prepackaged lettuce salad 10/26 8.4 1.2–59.6
Brand A prepackaged lettuce salad 9/10 5/23
0.17
0.01
0.00210.1 1.5–67.3
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E. coli O157:H7 Cases Associated with Brand A Prepackaged Lettuce by Date of
lllness Onset
Date of Onset2005
15 16 17 18 19 20 21 22 23 24 25
Nu
mb
er o
f C
ases
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 Brand A salad.
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E. coli O157:H7 Cases Associated with Brand A Prepackaged Lettuce by Date of
lllness Onset
Date of Onset2005
15 16 17 18 19 20 21 22 23 24 25
Nu
mb
er o
f C
ases
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 Brand A salad.
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E. coli O157:H7 Cases Associated with Brand A Prepackaged Lettuce
(n=26)
Date of Onset2005
15 16 17 18 19 20 21 22 23 24 25
Nu
mb
er o
f C
ases
26 27 28 29 30 1 2 3 414
1
2
3
4
5
6
7
September October
WI
WI
Minnesota
Additional states
OR
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Presentations of Outbreaks due to Commercially Distributed Food Items
• Cases in community, no obvious common exposure
– Retail food (grocery stores)
• Cases occur among patrons of restaurant(s)
• Cases clustered in institution(s)
• Any combination of above three
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Salmonella Saintpaul Patron Cases Associated with Restaurant A by Date of Isolate Receipt in
MDH Laboratory, June 2008
JuneDate of Isolate Receipt
Nu
mb
er o
f C
ases
23 24 25 26 27 28 29 30 1 2 3 422
2
3
4
5
6
1
7 Two cases name Restaurant A
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Restaurant A Outbreak
June 30, 2008
• MDH and Ramsey County staff visited restaurant
– 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
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Salmonella Saintpaul Patron Cases Associated with Restaurant A by Date of Isolate Receipt in
MDH Laboratory, June 2008
JuneDate of Isolate Receipt
Nu
mb
er o
f C
ases
23 24 25 26 27 28 29 30 1 2 3 422
2
3
4
5
6
1
7 Second case names Restaurant A
Visit restaurant
Initial case-control study/traceback results to CDC
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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
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Presentations of Outbreaks due to Commercially Distributed Food Items
• Cases in community, no obvious common exposure
– Retail food (grocery stores)
• Cases occur among patrons of restaurant(s)
• Cases clustered in institution(s)
• Any combination of above three
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December 3, 2008
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1st 11 cases in MN
Institutional link,Implication of PB
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S. Typhimurium Investigation, 2008-2009
November 17-24, 2008
– MDH received 3 outbreak isolates
Early December
– Leading hypothesis in national investigation was chicken
• Restaurant-associated outbreak in another state with three PFGE patterns
Ultimately shown to be a “red herring”
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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 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
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Minnesota S. Typhimurium Investigation
December 22, 2008
• Medical director of LTCF (LTCF A) in northern MN reports confirmed Salmonella 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
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Minnesota S. Typhimurium Investigation
• LTCF A, LTCF B, elementary school all purchased food from a common distributor in Fargo, North Dakota
• 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
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Week
June July Aug Sept
Cas
es
0
2
4
6
8
10
12
14
16
18
20
22
Cases of Salmonella Typhimurium, by Week of Specimen Collection, Minnesota, June -September, 1995
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June July Aug Sept
Cas
es
0
2
4
6
8
10
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
Week
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Selected Enteric Pathogens Reported to MDH, 1996-2008
0
200
400
600
800
1000
1200
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
Nu
mb
er o
f C
ases
Campylobacter
Salmonella
E. coli O157:H7
Cryptosporidium
Shigella
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1 confirmed case of salmonellosis = 38 actual cases
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Interview Options
• In person, telephone, mail, e-mail, web-based
• Rate-limiting step in most outbreak investigations is number of interviewers available to conduct interviews
– staff epidemiologist or sanitarian
– public health nurses and other professionals
– Team Diarrhea
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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, tomatoes, or sprouts
– e.g., predominately school-aged children, young adults often associated with vehicles like ice cream, microwaveable chicken products, etc.
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Generate and Test Hypotheses
• Analytic study designed to test hypothesis
– study design based on study questions, resources, and target population
– regardless of form of study, intent is to determine whether given exposure led to the occurrence of the disease.
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Comparison Groups
• Gathering/event (e.g., wedding reception)– non-ill attendees
• Restaurant – 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
– Cases with similar (but not exact) illness
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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)
• Biologic plausibility
– right incubation, plausible vehicle, etc.
• Distribution of cases vs. distribution of food
• Converging tracebacks
• Explanation of outliers
• Watch out for co-linearity
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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
•Interviewer variability
•Confounding
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Sub-Cluster Analyses
• In large outbreaks, there may be sub-clusters of epi-linked cases
– e.g., multiple cases at a restaurant, nursing homes, or school
•Look for common suppliers and food items
•Specific analytical studies in these settings
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Why Epidemiologic Links May Not be Identified for Cases in a Cluster
• Cases have imperfect recall
• Cases may not know they were exposed
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Secondary
transmission
Why Epidemiologic Links May Not be Identified for Cases in a Cluster
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Why Epidemiologic Links May Not be Identified for Cases in a Cluster
• Case did not consume product but may have handled it or was exposed through cross-contamination
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Why Epidemiologic Links May Not be Identified for Cases in a Cluster
• Common exposures could be difficult to link
– Lack of specific brand information from patient on a common commodity (e.g., eggs, chicken)
– Traceback inadequacies
• Establishment record-keeping
• Resources available
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• There isn’t a common source for all of the cases (or any of them)
– 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
Why Epidemiologic Links May Not be Identified for Cases in a Cluster
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Daily Report from MDH Lab to Epi
Cultures Confirmed Yesterday
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Daily Report from MDH Lab to Epi
Cultures Confirmed or Subtyped in the Past 30 Days