I have no known conflicts of interest to disclose

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

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

3. Background

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

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-basedrestriction fragment length polymorphism analysis (RFLP) pattern and spacer oligonucleotide type (spoligotype) result • 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 Steps in a routine cluster investigation, New York City Collect and analyze existing data Generatefinal report Assign cluster Develop cluster questionnaire Communicate with case managers Develop transmissionhypotheses Re-interview patient Communicate results * When indicated, intervention(s) are developed to stop transmission

9. Cluster investigation • Epidemiological links are categorized as possible, probable or definite POSSIBLE (weakest) DEFINITE (strongest) EPIDEMIOLOGIC LINK • 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 • 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

10. Results

11. 29 cases 54 recently diagnosed 121 cases Number of cluster cases counted by year and drug resistance, January 1, 1995 - July 1, 2001 (n=150) Drug susceptible Other-drug-resistant Universal genotyping Multidrug-resistant Number of Cases Year

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

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

14. MIRU-12 results among cluster cases and corresponding PCR type* (n=78) * PCR type: CDC definition of complete genotype using spoligotype and MIRU-12 results

15. Select epidemiologic links identified for recently-diagnosed cluster cases 1990 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 Same person Probable epidemiologic link Possible epidemiologic link 2003 2005 2007 2009 2011

16. Select epidemiologic links identified for recently-diagnosed cluster cases by MIRU-12 and drug susceptibility results 1990 S S MIRU-12 pattern: M 223325153323 224325153324 224325153323 S NA NA I 224325143323 224325183325 224325163323 S 224325153314 224325153322 No MIRU-12 Definite link Probable link Possible link S S 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 R 2003 S S S M 2005 S S S M M S I I S S S M M S S S M S S I,P 2007 S I I S S I I S 2009 S I R S S S P S S S 2011

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 • Co-authors: Janelle A. Anderson, Bianca R. Perri, Shama D. Ahuja • Cluster investigators: A. Regner, R. Espinoza, R. Fernandez, J. Abdelwahab, J. Park, M. Macaraig • 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