Using Genotype Data to Detect Outbreaks Tambi Shaw, MPH, Chief Outbreak Prevention and Control Section Tuberculosis Control Branch California Department of Public Health October 22, 2010

2 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

3 Percent of Culture-Confirmed TB Cases Genotyped, California and US, 2005–2009

4 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

5 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

6 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

7 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)

8 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

9 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?

10 Very Concerning Cluster: CA_0408 Rx StartAgeSexLHDRace/EthCountrySite Sputum Smear Sputum Culture Cav CXRRisks Drug R? 60’sMaleFRESNOHispanicUSAPulmNegPosNoNot Emp,ND 3/200930’sMaleFRESNO Hispanic MexicoPulmPos YesMig WorkNo 1/200920’sMaleFRESNO Hispanic MexicoPulmPos Yes Alc, NIDU, Mig Work No 11/200720’sMaleFRESNO Hispanic MexicoPulmPos NoMig WorkNo 9/200640’sMaleFRESNO Hispanic MexicoPulmPos YesAlc No 11/200530’sMaleFRESNO Hispanic MexicoPulmPos 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

11 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

12 Somewhat Concerning Cluster: CA_0969 Rx StartAgeSexLHDRace/EthCountrySite Sputum Smear Sputum Cx Cav CXRRisks Drug R 10/200930’sFVenturaWhiteUSAPulmUnk NoHCW S- resist 6/200930’sM Los AngelesWhiteUSAPleuralNeg No Alc, NIDU S- resist 6/2009<5FVenturaWhiteUSAPulmND No Strep- sens 3/200930’sFVenturaHispUSAPulmNegPosNo Strep not done 2/200860’sM Los AngelesHispMexicoMiliaryPos 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

13 Genotype Cluster Investigation Steps Existing Data New Data

14 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

15 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

16 Acknowledgments Fresno County TB Control Los Angeles TB Control Santa Clara County TB Control Ventura County TB Control Martin Cilnis Pennan Barry Kacy Hornor CDPH Microbial Diseases Lab Other local health departments in California CDC’s TB Molecular Epidemiology Team CDC’s National TB Genotyping Service

17 Contacts Martin Cilnis (510) Tambi Shaw (510)

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

19 Genotyping Resources (2) Guidance for investigating genotype clusters (from the CDC TB genotyping guide): hap6/6_Apply_6_Cluster.htm hap6/6_Apply_6_Cluster.htm

20 Genotyping Resources (2) CDC TB genotyping website: – CDC TB genotyping guide: – htmhttp:// htm TB genotyping in California: – ormsTBCB.aspxhttp:// ormsTBCB.aspx

21 Genotyping Resources (3) Laboratories and testing in California: – ing.aspxhttp:// ing.aspx Resources for LHDs on CA TB Control Branch website: – sLHDsTBCB.aspxhttp:// sLHDsTBCB.aspx