MltiMulti-St t Cl t D t ti d P i iti tiState Cluster ... · PDF fileMltiMulti-St t Cl t D t ti d P i iti tiState Cluster Detection and Prioritization: National Level Epi Perspective

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


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 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


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)


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)


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


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 ( )


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


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


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

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MltiMulti-St t Cl t D t ti d P i iti tiState Cluster ... · PDF fileMltiMulti-St t Cl t D t ti d P i iti tiState Cluster Detection and Prioritization: National Level Epi Perspective