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M ltiM lti St t Cl t D t ti d P i iti tiSt t Cl t D t ti d P i iti tiMultiMulti--State Cluster Detection and Prioritization: State Cluster Detection and Prioritization: National Level Epi PerspectiveNational Level Epi Perspective
September 23, 2009
Ian Williams PhD, MSChief, OutbreakNet Team
Enteric Diseases Epidemiology BranchDivision of Foodborne, Bacterial and Mycotic Diseases
National Center for Zoonotic Vectorborne & Enteric DiseasesNational Center for Zoonotic, Vectorborne, & Enteric DiseasesCenters for Disease Control and Prevention
The findings and conclusions in this presentation are those of the author and do not g pnecessarily represent the views of the Centers for Disease Control and Prevention
Flow of PulseNet Cluster Identification and Flow of PulseNet Cluster Identification and Evaluation at CDCEvaluation at CDC
Submission of PFGE patterns by state to CDC PulseNet
Cluster identification by CDC PulseNety
Epidemiologic e al ation of cl ster b EDEBEpidemiologic evaluation of cluster by EDEB
When does CDC engage state health department partners and initiate a multistate outbreak investigation?
Basic Challenge in Cluster EvaluationBasic Challenge in Cluster Evaluationgg
• In a resource limited environment whichIn a resource limited environment, which clusters should be given highest priority for further evaluation and investigation?further evaluation and investigation?– CDC perspective
• Possibly related cases in several statesPossibly related cases in several states• Which clusters hold a higher potential to detect
common source of infection• When should state health departments be engaged
to initiate active investigation?St t d l l h lth d t t ti– State and local health department perspective• How many cases in my state?
H f d d?• How many of my resources needed?
The State Perspective: Foodborne Disease Outbreaks by The State Perspective: Foodborne Disease Outbreaks by Reporting Source, Connecticut, 2004Reporting Source, Connecticut, 2004--20062006
50%
60%
40%
50%
t bre
aks
Most outbreaks reported via citizen report
20%
30%
nt o
f Out
10%
20%
Per
cen
0%CitizenReport
MedicalProfessional
PFGE Surveillance CDC/OtherState Inquiryp q y
Source of Report
The CDC Perspective: Clusters by Reporting Source, 2008 (n=175)
Percent of Clusters
75%80%
Most clusters reported via PulseNet
50%
60%
70% Most clusters reported via PulseNet
30%
40%
50%
14%
3% 2% 2%10%
20%
30%
3% 2% 2% 1% 1% 0.6% 0.6%0%
PulseNet State Regulatoryagency
FBOListserv
Other Lab Media Epi-X Internationalagency
Source of Report
The CDC Perspective: Status of PulseNet PFGE Pattern Submissions and ClustersPFGE Pattern Submissions and Clusters
Identified by PulseNet by year, 1996 - 2008
70,000 350
50,000
60,000
250
300Total PFGE patterns submitted to PulseNet
Clusters identified by PulseNet
Clusters PulseNet sends to CDC epis
NuE
patte
rns
40,000 200
Clusters PulseNet sends to CDC epis
umber of clus
mbe
r of P
FGE
20,000
30,000
100
150
stersNum
10,000 50
01996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
0Year
Year
Average Weekly Number* of Clusters CDC OutbreakNet Team Followed by Month and Pathogen, February, 2008 – August**, 2009
35
25
30 Salmonella
E. coli
Listeria
20
25
Median for all pathogens = 23 (range 10 to 39)
15
10
0
5
0Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug*
2008 2009* Number per week averaged over a month period
** Includes data through August 11
*
Which Multistate Clusters Should be Given Hi h t P i it f F th E l ti ?Highest Priority for Further Evaluation?
• The large number of clusters identified by PulseNetThe large number of clusters identified by PulseNet currently precludes active investigation of every one – CDC capacity issuesp y
• Cluster investigations last weeks and can require many people
– State and local health department capacity issues• How much effort should be expended to interview cases when state
has only a few cases?
• CDC OutbreakNet Team triages each cluster; either• CDC OutbreakNet Team triages each cluster; either– CDC monitors, but states not contacted, or– CDC contacts states to begin hypothesis generation– CDC contacts states to begin hypothesis generation
Some Features Considered in Triaging Clusters
• PathogenS it (b t li E li O157 S l ll )– Severity (botulism v. E. coli O157 v. Salmonella)
• Number of deaths or hospitalizations
– Frequency of serotype or PFGE patternFrequency of serotype or PFGE pattern• Distribution over time• Geographic distribution
• Person, place and time– “Momentum”: the number of ill over time versus baseline– Gender and age distribution – Geographic distribution by case residence
• Matches to non-human isolates in Pulsenet or VetNet• State has already developed a strong hypothesis• External interest
Status of Every Cluster Reviewed at Least Weekly to Determine Which Ones Should Have Furtherto Determine Which Ones Should Have Further
Evaluation and Investigation
• Spectrum of cluster investigations– CDC monitoring, but states not contacted– CDC contacted states, hypothesis generation
ongoingA l ti id i l i t d– Analytic epidemiologic study planned/underway/completed by state/local partner, CDC involved but not in leading roleCDC involved but not in leading role
– CDC assumes active role in leading multistate investigation, analytic epidemiologic studyinvestigation, analytic epidemiologic study planned/underway/completed
– CDC Emergency Operations Center activated to g y passist in multistate investigation
Flow of PulseNet Cluster Identification d E l ti t CDCand Evaluation at CDC
Submission of PFGE patterns by state to CDC PulseNet
Cluster identification by CDC PulseNety
Epidemiologic evaluation of cluster by EDEBEpidemiologic evaluation of cluster by EDEB
C t t t t t b i h th i tiContact states to begin hypothesis generation
Status of PulseNet PFGE pattern submissions and cl ster in estigations b ear 1996 2008cluster investigations by year, 1996 - 2008
60,000
70,000
300
350
Total PFGE patterns submissions to PulseNet
50,000 250
p
Clusters identified by PulseNet
Clusters PulseNet sends to CDC epis
Clusters CDC refers to state epis
E pa
ttern
sN
u
30,000
40,000
150
200
mbe
r of P
FGEum
ber of clus
20,000
,
100
Num
sters
0
10,000
0
50
01996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
0
YearYear
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonellaInfections Associated with Peanut Butter and Peanut ButterInfections Associated with Peanut Butter and Peanut Butter--
Containing ProductsContaining Products United States 2008United States 2008 20092009Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium infections (13 cases in 12 states), CDC begins monitoring for additional reports of cases with same DNA fingerprint
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium
November 24, 2008November 24, 2008CDC PulseNet identifies second multistate cluster of Salmonellayp
infections (13 cases in 12 states), CDC begins monitoring for additional reports of cases with same DNA fingerprint
multistate cluster of Salmonella Typhimurium infections (27 cases in 14 states)
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium
November 24, 2008November 24, 2008CDC PulseNet identifies second multistate cluster of Salmonella
November 25, 2008November 25, 2008CDC contacts states to begin
id i l i t fyp
infections (13 cases in 12 states), CDC begins monitoring for additional reports of cases with same DNA fingerprint
cluster of Salmonella Typhimurium infections (27 cases in 14 states)
epidemiologic assessment of first Salmonella Typhimurium cluster (35 cases in 16 states)
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 24, 2008November 24, 2008CDC PulseNet identifies second multistate cluster of Salmonella Typhimurium infections (27 cases in 14 states)
November 25, 2008November 25, 2008CDC contacts states to begin epidemiologic assessment of first Salmonella Typhimurium cluster (35 December 2, 2008December 2, 2008
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium infections (13 cases in 12 states), CDC begins monitoring for additional reports of cases with same DNA fingerprint
yp (cases in 16 states) CDC contacts states to begin
epidemiologic assessment of second Salmonella Typhimurium cluster (41 cases in 17 states)of cases with same DNA fingerprint ( )
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 24, 2008November 24, 2008CDC PulseNet identifies second multistate cluster of Salmonella Typhimurium infections (27 cases in 14 states)
November 25, 2008November 25, 2008CDC contacts states to begin epidemiologic assessment of first
December 2, 2008December 2, 2008CDC contacts states to begin epidemiologic assessment of second Salmonella Typhimurium cluster (41
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium infections (13 cases in 12 states), CDC begins monitoring for additional reports of cases with same DNA fingerprint
Salmonella Typhimurium cluster (35 cases in 16 states)
Salmonella Typhimurium cluster (41 cases in 17 states)
December 4, 2008Both clusters followed with
of cases with same DNA fingerprint parallel assessments
Cluster Evaluation Example: Multistate Outbreak of Cluster Evaluation Example: Multistate Outbreak of SalmonellaSalmonella Infections Associated with Infections Associated with Peanut Butter and Peanut ButterPeanut Butter and Peanut Butter--Containing Products Containing Products ------ United States, 2008United States, 2008----20092009
November 24, 2008November 24, 2008CDC PulseNet identifies second multistate cluster of Salmonella Typhimurium infections (27 cases
D b 2 2008D b 2 2008
November 25, 2008 to January 2, 2009November 25, 2008 to January 2, 2009Detailed questionnaires collected on ~90 cases
November 10, 2008November 10, 2008CDC PulseNet identifies first multistate cluster of Salmonella Typhimurium infections (13 cases in 12 states), CDC begins monitoring for additional
yp (in 14 states)
November 25, 2008November 25, 2008CDC contacts states to begin epidemiologic assessment of first Salmonella Typhimurium cluster (35 cases in 16 states)
December 2, 2008December 2, 2008CDC contacts states to begin epidemiologic assessment of second Salmonella Typhimurium cluster (41 cases in 17 states)
December 4, 2008Both clusters followed with parallel assessments), g g
reports of cases with same DNA fingerprintBoth clusters followed with parallel assessments
Generating HypothesesGenerating Hypothesesg yg y• If we know the pathogen, consider
– Reservoir– Biology
Hi t f i tb k– History of previous outbreaks• Also consider past outbreaks in the electronic Foodborne Outbreak
Reporting System (eFORS)/National Outbreak Reporting System (NORS)
– “Seasonality” (e.g.: Chicks at Easter)
– Past case-control studies of sporadic casesPast case control studies of sporadic cases– Isolates from animals and foods– History of food product recalls by regulatory agenciesHistory of food product recalls by regulatory agencies
• Evaluate current cases with respect to person, place, and timeand time
Hypothesis-Generating Interviewsyp g
• Typically need 10 to 20 completed interviews• Strategies include
– Interviews with structured questionnaire with many food q yitems on it: “trolling, trawling, or shotgun”
– Intensive open-ended interviews about everything that went into patient’s mouth in the last 5 days
• In-depth interview with people in their homes, including refrigerator, pantryrefrigerator, pantry
– Some combination of the two– Best if all done the same wayBest if all done the same way
• Process may need to be iterativeA food product is not the source of all outbreaks!• A food product is not the source of all outbreaks!
“H th i G ti ” T b k“Hypothesis-Generating” Tracebacks
• Data on product distribution production can be critical in development of hypothesis– Evaluate potential sources
• Ways to obtain this informationWays to obtain this information– State Departments of Agriculture– Regulatory agenciesRegulatory agencies
• Involvement before a product has been implicated can pose unique problem for some agenciesp q p g
Challenges to Conducting Initial Multistate H th i G ti I t iHypothesis-Generating Interviews
• Many states do not routinely interview cases– Some only do a brief interview
• No standard national initial hypothesis-generating interview form or data collection systemform or data collection system– New questionnaire is developed for each new multistate cluster
investigation• Can take several days to weeks to agree upon elements for a common formCan take several days to weeks to agree upon elements for a common form
for initial interviews• Interviews with initial hypothesis-generating questionnaire may occur weeks
after illness onset
• Interviews often conducted by a variety of people in a variety of states – Limited ability to build hypotheses using the method of sequentialLimited ability to build hypotheses using the method of sequential,
iterative interviews of patients
• Need to refine questionnaire if no hypothesis emergesWhen do you discontinue investigation or scale back effort if a– When do you discontinue investigation or scale back effort if a hypothesis does not emerge?
Some Future Options for Cluster pEvaluation and Hypothesis Generation• Development of analytic tools and processes to
evaluate which PulseNet clusters warrant more effort to investigate– Determine cluster characteristics that predict higher
potential to detect common source of infection• Development of standard national hypothesis-p yp
generating interview elements and data collection systemy
• Need for more capacity to conduct patient interviewsinterviews
A Gap in Multistate Outbreak Investigation Methods
• Limited resources for health departments to conduct interviewsinterviews– “Sporadic” illnesses (some may later be shown to be part of
outbreaks) • In many jurisdictions patients are not routinely interviewed to collect• In many jurisdictions, patients are not routinely interviewed to collect
information on exposures– Cluster and outbreak illnesses
• Interviews to probe possible sources may be delayed by otherInterviews to probe possible sources may be delayed by other priorities
• Re-interviews to collect product information may be delayed• Questionnaires often not standardized among states g• Information from questionnaires not put into standard database at all
States• Information on exposures usually not transmitted electronically to
CDCCDC
Contrast with PulseNet, in which lab information on every isolate is stored in a standard database at States, is rapidly transmitted to a national database at
CDC, and summary information is available to all participants
Our Vision: Our Vision: A National Multistate Foodborne Investigation NetworkA National Multistate Foodborne Investigation Networkgg
• Facilitate collection of exposure data from ill and well persons to help local State and federal epidemiologistspersons to help local, State, and federal epidemiologists more rapidly develop hypotheses and implicate vehicles
• Facilitate collection of specific product information p p(e.g., lot numbers) for traceback investigations
• More rapidly collate and analyze epidemiologic and product information from multiple states
• Routinely join epidemiologic and PulseNet dataI h li d d f d d id d• Improve the quality and speed of product data provided to regulatory agencies for traceback
• Share information in real time with regulatory agencies• Share information in real time with regulatory agencies
Shorten the time to pinpoint how p pand where contamination occurred!
OutbreakNet Sentinel SitesOutbreakNet Sentinel SitesOutbreakNet Sentinel SitesOutbreakNet Sentinel Sites
• Pilot program • Generate collaborative and innovative models to
improve epidemiologic capacity and the use of laboratory data in investigating enteric disease y g goutbreaks
• Three sites funded Summer, 2009Three sites funded Summer, 2009– WI, UT, NY City
Some Recent Large Multi-State Outbreaks of Foodborne Infections 2006-2009 (n=20)Foodborne Infections 2006 2009 (n 20)
2006 - E. coli O157 and bagged spinach 2006 - E. coli O157 and shredded lettuce (restaurant chain A)2006 - E. coli O157 and shredded lettuce (restaurant chain B)2006 - Botulism and commercial pasteurized carrot juice2006 - Salmonella and fresh tomatoes2007 E coli O157 and frozen pizza2007 - E. coli O157 and frozen pizza2007 - Salmonella and peanut butter 2007 - Salmonella and a vegetarian snack food 2007 - Salmonella and dry dog food2007 - Salmonella and dry dog food 2007 - Salmonella and microwaveable pot pies 2007 - Salmonella and dry puffed breakfast cereal 2007 - E. coli O157 and ground beef2007 E. coli O157 and ground beef2007 - Botulism and canned chili sauce2008 - Salmonella and cantaloupe2008 - E. coli O157 and ground beef 2008 - Salmonella and fresh produce items2009 - Salmonella and peanut butter containing foods2009 - Salmonella and imported white and black pepper2009 S l ll d lf lf t2009 - Salmonella and alfalfa sprouts2009 – E. coli O157 and prepackaged cookie dough
Some Recent Large Multi-State Outbreaks of Foodborne Infections 2006-2009 (n=20)Foodborne Infections 2006 2009 (n 20)
2006 - E. coli O157 and bagged spinach*2006 - E. coli O157 and shredded lettuce (restaurant chain A)2006 - E. coli O157 and shredded lettuce (restaurant chain B)2006 - Botulism and commercial pasteurized carrot juice*2006 - Salmonella and fresh tomatoes2007 E coli O157 and frozen pizza2007 - E. coli O157 and frozen pizza2007 - Salmonella and peanut butter*2007 - Salmonella and a vegetarian snack food*2007 - Salmonella and dry dog food*2007 - Salmonella and dry dog food2007 - Salmonella and microwaveable pot pies*2007 - Salmonella and dry puffed breakfast cereal*2007 - E. coli O157 and ground beef2007 E. coli O157 and ground beef2007 - Botulism and canned chili sauce*2008 - Salmonella and cantaloupe2008 - E. coli O157 and ground beef
*A “new” food vehicle *A “new” food vehicle in 12/20 outbreaksin 12/20 outbreaks
2008 - Salmonella and fresh produce items*2009 - Salmonella and peanut butter containing foods*2009 - Salmonella and imported white and black pepper*2009 S l ll d lf lf t2009 - Salmonella and alfalfa sprouts2009 – E. coli O157 and prepackaged cookie dough*
http://www.cdc.gov/foodborneoutbreaks/
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