Using Genotype Data to Detect Outbreaks

Tambi Shaw, MPH, ChiefOutbreak Prevention and Control Section

Tuberculosis Control BranchCalifornia Department of Public Health

October 22, 2010

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Overview • California’s progress towards universal

genotyping

• TB Control Branch’s (TBCB’s) genotype cluster surveillance methods, limitations, and potential benefits

• Steps to take if we notify you about a concerning genotype cluster

• Next steps

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Percent of Culture-Confirmed TB Cases Genotyped, California and US,

2005–2009

52%

60%

84% 82%78%

61%64%

79% 80% 82%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

2005 2006 2007 2008 2009

Year

% G

en

oty

ped

CA US

2015 CDC Goal 94%

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Genotype Cluster Surveillance

Goal: To identify undetected TB outbreaks and stimulate public health investigation and action

• Is it recent transmission?• How worried are we about it? • Is it amenable to intervention?

Data Source: TB surveillance (RVCT) and genotype datasets matched by name and birth date

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Methods (1)

Epidemiologist runs an algorithm based upon “triggers” to flag genotype clusters:

– Growth: Spike of cases in a genotype cluster over a period of time

– Location: Genotype cluster in one county

– New clusters: With ≥ 3 cases in past 12 months

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Methods (2) Outbreak Response Team (ORT) assesses and

categorizes flagged clusters using surveillance data; assessment is subjective

• Person– Demographics and risk factors?

• Place– Where else is the genotype?– Genotype common or rare?– Jurisdictions involved?

• Time– Recent cases? – Cluster growth?

Categories:

1) Very concerning; probable outbreak

2) Somewhat concerning; possible outbreak

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Methods (3)• ORT notifies LHDs about high priority clusters

– Genotype Cluster Surveillance Form; case line list– ORT and LA County meet monthly to review clusters

• Genotype clusters assigned to ORT staff for follow-up with LHDs

• ORT staff available upon request to provide:– Consultation– Tools: chart abstraction instrument, patient questionnaire– Support for interjurisdictional coordination/communication– Record searches to aid investigations – Onsite field assistance (typically reserved for very concerning

clusters only)

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LHD Role

• Critically review ORT’s assessment of the genotype cluster

• Communicate with ORT if you think our assessment is off-target

• If you agree with the assessment, initiate genotype cluster investigation

• Ask for ORT help if you need and want it

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Genotype Cluster Form TBCB describes: • Reasons for concern • Level of concern • Characteristics of cluster• Geographic distribution of

genotype

****************************************

LHD asked to assess: • Is this is an outbreak? Is it

contained?• Where did transmission occur? • Prior local knowledge of

cluster? • Did notification of cluster lead to

action? • Need support from TBCB?

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Very Concerning Cluster: CA_0408 Rx Start Age Sex LHD Race/Eth Country Site

Sputum Smear

Sputum Culture

Cav CXR Risks

Drug R?

60’s Male FRESNO Hispanic USA Pulm Neg Pos No Not Emp, ND

3/2009 30’s Male FRESNOHispanic

Mexico Pulm Pos Pos Yes Mig Work No

1/2009 20’s Male FRESNOHispanic

Mexico Pulm Pos Pos YesAlc, NIDU, Mig Work  No

11/2007 20’s Male FRESNOHispanic

Mexico Pulm Pos Pos No Mig Work No

9/2006 40’s Male FRESNOHispanic

Mexico Pulm Pos Pos Yes Alc  No

11/2005 30’s Male FRESNOHispanic

Mexico Pulm Pos Pos Yes

Homeless, NIDU, Mig

Work  No

• Person: All Hispanic men; most migrant farm workers from Mexico aged 20s to 40s; no drug resistance; 5/6 smear positive

• Place: Only cases in the US with this genotype are in Fresno County; 5/6 patients lived in same city within 2 sq mile area

• Time: 3 cases in 2009; 3 cases 2005-2007

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Genotype Cluster Investigation Challenges

“I hate this genotype cluster!” -- Epidemiologist

Challenges often similar to the CI challenges that resulted in the cluster of concern: • Patients unable or unwilling to provide contact information• Lengthy infectious periods• Transmission in congregate settings with transient populations • Staffing resource constraints

Lack of evidence-based field-tested cluster investigation methods; lack of cluster investigation training resources

System’s time delays complicate investigation steps and reduce intervention opportunities

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Somewhat Concerning Cluster: CA_0969

Rx Start Age Sex LHD Race/Eth Country SiteSputum Smear

Sputum Cx

CavCXR Risks

Drug R

10/2009 30’s F Ventura White USA Pulm Unk Unk No HCWS-

resist

6/2009 30’s MLos

Angeles White USA Pleural Neg Neg NoAlc,

NIDUS-

resist

6/2009 <5 F Ventura White USA Pulm ND ND No  Strep-sens

3/2009 30’s F Ventura Hisp USA Pulm Neg Pos No  

Strep not

done

2/2008 60’s MLos

Angeles Hisp Mexico Miliary Pos Pos No   IS

• Time: 4 cases in 2009; 1 case in 2008

• Person: Most of the cases relatively young, including a child < 5 yo case; 3/5 female; 4/5 U.S.-born; strep resistance in 3 cases

• Place: Geographically concentrated in 2 adjacent counties; 3/5 cases in Ventura; genotype also found in 12 other states

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Genotype Cluster Investigation Steps

Existing Data

New Data

Staff Knowledge:- Epi-links already known?

- If no, can they be established through staff discussion?

Chart Reviews

Reinterviews

Outbreak or ECI

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Outbreak Detection by a LHD—Santa Clara County Example

Detection: Detected genotype cluster of 5 cases of Ethiopian/Eritrean ancestry detected, suspected an outbreak; notified ORT

Investigation: Confirmed 6 outbreak cases, including 2 children, epi-linked through family, church, and social networks

Outcomes: Identified and evaluated additional contacts and potential transmission sites; performed educational outreach; implemented system for routine review of genotype data

Advantage: LHD identified outbreak sooner than ORT

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Summary and Next Steps

• Analysis of genotype results is a promising tool for detecting outbreaks BUT more evaluation needed

• Genotype cluster investigations are new and challenging

• Incorporate use of CDC aberration detection methods and Task Order 26 findings

• Accelerate progress towards universal genotyping

• Expand implementation of CDC’s Genotyping Information Management System in 2011

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Acknowledgments

Fresno County TB ControlLos Angeles TB Control

Santa Clara County TB Control Ventura County TB Control

Martin CilnisPennan Barry Kacy Hornor

CDPH Microbial Diseases Lab

Other local health departments in CaliforniaCDC’s TB Molecular Epidemiology TeamCDC’s National TB Genotyping Service

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Contacts

Martin Cilnis(510) 620-3015martin.cilnis@cdph.ca.gov

Tambi Shaw(510) 620-3016tambi.shaw@cdph.ca.gov

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References

• Grant, J. “CDC Approach to Cluster Assessment.” PowerPoint presentation for Aberration Detection Working Group; 20 Sept. 2010.

• Cunningham, J; Shaw, T; Cilnis M; Barry P; Flood J; Watt J. Evaluation of a system for identifying previously unrecognized tuberculosis transmission using genotype data. Poster presented at CTCA Meeting; 5 May 2010.

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Genotyping Resources (2)

• Guidance for investigating genotype clusters (from the CDC TB genotyping guide): http://www.cdc.gov/tb/programs/genotyping/Chap6/6_Apply_6_Cluster.htm

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Genotyping Resources (2)

• CDC TB genotyping website:– http://www.cdc.gov/tb/programs/genotyping/

• CDC TB genotyping guide:– http://www.cdc.gov/tb/programs/genotyping/manual.

htm

• TB genotyping in California:– http://

www.cdph.ca.gov/programs/tb/Pages/TBSurvFormsTBCB.aspx

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Genotyping Resources (3)

• Laboratories and testing in California:– http://www.cdph.ca.gov/programs/tb/Pages/LabsTest

ing.aspx

• Resources for LHDs on CA TB Control Branch website:– http://

www.cdph.ca.gov/programs/tb/Pages/ResourcesLHDsTBCB.aspx