1. Endemic or Outbreak? Differentiating recent transmission of an historic tuberculosis strain in New York City IUATLD-NAR 16 th Annual Meeting February 23-25, 2012 Jeanne Sullivan Meissner, MPH New York City Department of Health and Mental Hygiene Bureau of Tuberculosis Control

2. I have no known conflicts of interest to disclose Funding source: New York City Tuberculosis Control Program funds Disclosure statements

3. Background

4. Number of Cases Rate/100,000 *Rates since 2000 are based on population estimates. Tuberculosis cases and rates, New York City 1980-2010* 1991: Selective genotyping begins in NYC 2001: Universal genotyping implemented

5. A tuberculosis (TB) strain first detected in New York City (NYC) in 1995 has continued to cause disease through 2011 Recently-diagnosed cases with this strain were investigated to identify epidemiologic links and assess recent transmission

6. Methods

7. Cluster investigation NYC TB cluster: two or more cases with matching IS6110-based restriction fragment length polymorphism analysis (RFLP) pattern and spacer oligonucleotide type (spoligotype) result o 12-loci mycobacterial interspersed repetitive-unit variable- number tandem repeat analysis (MIRU-12) results were obtained for cluster cases counted since January 1, 2004 Cluster cases are routinely investigated to identify epidemiologic links and develop transmission hypotheses Recently-diagnosed cases for this investigation: Cluster cases counted between Jan 1, 2006 - Jul 1, 2011

8. Cluster investigation Assign cluster Communicate with case managers Collect and analyze existing data Develop transmission hypotheses Generate final report Develop cluster questionnaire Re-interview patient Communicate results Steps in a routine cluster investigation, New York City * When indicated, intervention(s) are developed to stop transmission

9. EPIDEMIOLOGIC LINK POSSIBLE (weakest) POSSIBLE Cases live/spend time in area within approximately 0.5 miles of each other (regardless of infectious period) Cases have similar social environment (e.g., similar social networks) PROBABLE Cases frequent same location during same date range, exclusive of infectious period of either case DEFINITE Cases name each other as contacts Cases share common contact without naming each other Cases frequent same location during infectious period of at least one of the cases Cluster investigation DEFINITE (strongest) Epidemiological links are categorized as possible, probable or definite

10. Results

11. Year Number of Cases Drug susceptible Other-drug-resistant Multidrug-resistant Universal genotyping 29 cases121 cases Number of cluster cases counted by year and drug resistance, January 1, 1995 - July 1, 2001 (n=150) 54 recently diagnosed

12. Among all cluster cases (n=149*): o 62% male o Median age: 45 (Range: 16-95) o 76% US-born 78% of foreign-born in US >5 years when diagnosed o 37% HIV-positive (125 cases with known HIV status) Among cases counted since 2001 (n=120*): o 20% known history of homelessness o 28% known history of drug use o 23% known history of incarceration o Cases commonly had more than one of above Patient characteristics * One individual was a counted cluster case in two different years. This individual’s patient characteristics were only counted once

13. RFLP Spoligotype: o Octal Code: 777776777760601 2-band RFLP pattern All cluster cases counted since January 1, 2004 (n=78) have MIRU-12 results o 19 MIRU-12 patterns  11 unique patterns Genotyping

14. MIRU-12 results among cluster cases and corresponding PCR type* (n=78) MIRU-12 patternNumber of cases Corresponding PCR type* 22432515332339PCR00015 2243251433238PCR00160 2243251533254PCR00062 2343251533234PCR02232 2243251532234PCR00061 2243251533243PCR00017 2243251533143PCR00573 2243251533222PCR00027 Other unique patterns11N/A * PCR type: CDC definition of complete genotype using spoligotype and MIRU-12 results

15. Select epidemiologic links identified for recently-diagnosed cluster cases 2011 1990 2009 2007 2005 2003 Recently diagnosed cluster case Cluster case; not recently diagnosed NYC case with incomplete genotype; same RFLP NYC case; no genotype information available Definite epidemiologic link Probable epidemiologic link Possible epidemiologic link Same person

16. Select epidemiologic links identified for recently-diagnosed cluster cases by MIRU-12 and drug susceptibility results 2011 1990 2009 2007 2005 2003 R M M R I I II II I S SSS S S S SS S M SS S S S S S S S S S M I S S S SS S I,P NA S S S M M M S S P Drug susceptibility: S: Drug-susceptible I: Isoniazid-resistant R: Rifampin-resistant M: Multidrug-resistant NA: No results available I,P: Isoniazid- and pyrazinamide-resistant P: Pyrazinamide-resistant 224325153323 224325143323 224325153314 224325163323 224325153324 224325153322 223325153323 224325183325 MIRU-12 pattern: Definite linkPossible linkProbable link No MIRU-12

17. Conclusions

18. Transmission of this endemic TB strain is ongoing in NYC, while disease among remotely-infected persons continues Identification of multiple links across different years and patient characteristics highlights the difficulty of differentiating recent transmission of endemic TB strains Common characteristics, activities and geographic locations among cases suggest social networks and community transmission Implications of epidemiologic links across different MIRU-12 results warrants further investigation New genotyping and investigative tools may help further differentiate large, endemic clusters such as this one

19. Acknowledgements NYC Department of Health and Mental Hygiene, Bureau of Tuberculosis Control staff o Co-authors: Janelle A. Anderson, Bianca R. Perri, Shama D. Ahuja o Cluster investigators: A. Regner, R. Espinoza, R. Fernandez, J. Abdelwahab, J. Park, M. Macaraig o Clinic and field staff Lab partners: NYC Public Health Lab, New York State Wadsworth Center, Public Health Research Institute New Jersey Department of Health New York State Department of Health Centers for Disease Control and Prevention