Endemic or Outbreak? Differentiating recent transmission of an historic

tuberculosis strain in New York City

IUATLD-NAR 16th Annual MeetingFebruary 23-25, 2012

Jeanne Sullivan Meissner, MPHNew York City Department of Health and Mental Hygiene

Bureau of Tuberculosis Control

• I have no known conflicts of interest to disclose

• Funding source: New York City Tuberculosis Control Program funds

Disclosure statements

Background

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10Year

0

10

20

30

40

50

60Case Rate

# Cases

N

umb

er o

f C

ases

R

ate/1

00,000

*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

• 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

Methods

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

Cluster investigation

Assign cluster

Communicate with case managers

Collect and analyze

existing data

Develop transmissionhypotheses

Generatefinal report

Develop cluster questionnaire

Re-interviewpatient

Communicate results

Steps in a routine cluster investigation, New York City

* When indicated, intervention(s) are developed to stop transmission

EPIDEMIOLOGIC LINKPOSSIBLE(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

Results

Year

Num

ber

of

Cas

es

Drug susceptible

Other-drug-resistant

Multidrug-resistant

Un

ive

rsa

l g

en

oty

pin

g

29 cases 121 cases

Number of cluster cases counted by year and drug resistance, January 1, 1995 - July 1, 2001 (n=150)

54 recently diagnosed

• 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

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

MIRU-12 results among cluster cases and corresponding PCR type* (n=78)

MIRU-12 pattern Number of casesCorresponding

PCR type*

224325153323 39 PCR00015

224325143323 8 PCR00160

224325153325 4 PCR00062

234325153323 4 PCR02232

224325153223 4 PCR00061

224325153324 3 PCR00017

224325153314 3 PCR00573

224325153322 2 PCR00027

Other unique patterns 11 N/A

* PCR type: CDC definition of complete genotype using spoligotype and MIRU-12 results

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

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

I I

I I

I

S

S S S

S

S

S

S S

S

M S S

S

S

S

S

S

S

S

S

SM

I

S

S

S

S S

S

I,P

NANA

S

SS

M

M

M

S

S

P

Drug susceptibility: S: Drug-susceptible I: Isoniazid-resistant R: Rifampin-resistant M: Multidrug-resistant NA: No results availableI,P: Isoniazid- and pyrazinamide-resistant P: Pyrazinamide-resistant

224325153323

224325143323

224325153314

224325163323

224325153324

224325153322

223325153323

224325183325

MIRU-12 pattern:

Definite link Possible linkProbable link

No MIRU-12

Conclusions

• 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

Acknowledgements

• NYC Department of Health and Mental Hygiene, Bureau of Tuberculosis Control staffo 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