1. National Tuberculosis Genotyping Service
Patrick K. Moonan, DrPH, MPH
Surveillance, Epidemiology, and Outbreak Investigation
Division of Tuberculosis Elimination
Northeast TB Controllers
Princeton, NJ
October 24, 2006

2. National Genotyping Service

3. Richmond, CA
Lansing, MI
CDC – Atlanta, GA

4. National Genotyping Service
Began in January, 2004
CDC contracts with 2 reference laboratories
Genotype up to 5,000 isolates/lab/year
Genotype at least 1 isolate for each new culture-positive case of TB

5. National Genotyping Service
Acquiring Isolates
Genotyping Isolates
Analysis & Distribution
Public Health and Clinical Laboratories
Contract Reference Laboratories
State and Local TB Programs

6. Isolate and Data Flow Other Labs CDC isolates & data Genotyping Lab
results
CDC’s contract with the genotyping laboratories requires that the laboratories genotype all of the eligible isolates by PCR tests and report results for at least 90% of isolates to the TB programs within 10 working days of receipt of the isolates.
These rapid turnaround times assume a steady flow of isolates to the laboratory. Although we expect that these projected turnaround times will be met most of the time, there are several reasons for possible delays. The MIRU automated sequencer is limited to 24 isolates in each run; if a genotyping laboratory receives large batches at one time, there will be a delay in reporting some of the results. Technical difficulties (e.g., instrument failure) may also cause delays.
Under certain circumstances, the TB program can request that the genotyping laboratories perform IS6110-based RFLP analysis on isolates that match by both spoligotyping and MIRU analysis. CDC’s contract stipulates that the genotyping laboratories will report RFLP results for 90% of isolates within 15 working days from the date of the RFLP analysis request.
In almost all instances, these turnaround times are fast enough to ensure that there will be no need for TB programs to prioritize requests, even for investigations of outbreaks or false-positive cultures.
State Lab
TB Program
patient names

7. How are we doing?
As of October 20, 22,257 isolates have been submitted for typing
2 Quarterly Reports have been distributed
CDC Webpage is under construction
Future home for:
Genotyping education materials
Quarterly reports
National Database Interface (Kansas Model)
During the presentation,
I will define an outbreak and a cluster and what is the difference between an epidemiologic cluster and a genotype cluster
I will also discuss and provide examples from recently conducted investigations where genotyping helped:
Confirm or rule-out recent transmission of TB
Detect unsuspected transmission of M tuberculosis or
Helped prioritize cluster of outbreak-related cases whose contacts needed to be screened and followed up during outbreak investigations

10. How are we doing?
34 of 53 (64.2%) participating programs have submitted updated RVCT linking variables through 6/30/2006
Aberration detection program has been developed to identify outbreak from a national perspective

12. How are we doing?
34 of 53 (64.2%) participating programs have submitted updated RVCT linking variables through 6/30/2006
Aberration detection program has been developed to identify outbreaks from a national perspective

13. Geography and Genotyping

14. Number of isolates as of 10/31/2005 n = 46 IN = 65.2% of isolates 9 30 1 1 1 2 1 4 1 3 1 2 6 1 6 1 1 1
Number of isolates as of 10/31/2005
n = 46
IN = 65.2% of isolates
(Note: 1 case in Florida matches on spoligotype and is missing MIRU but is linked epidemiologically)
Spoligo:
MIRU:

15. Net gain in clustered isolates 10/31/2005 to 10/01/2006 4 3 3 1 1 1 4 2 2 +1 +4 1 +1 +6 1 2 1 1 +1 +1 1 6 1 6 1 1 +2
Net gain in clustered isolates
10/31/2005 to 10/01/2006
Spoligo:
MIRU:

16. Geography and Genotyping7
Number of Indiana isolates as of 10/01/2006 (n = 36)
County A (n = 25)
69.5% of state total
40.3% of national total
County B (n = 7)
all six cases are linked epidemiologically to County A cases
Other Counties
No clear epidemiologic link has been identified to these cases through interviews and records review of County A and B cases 25 2 1 1

17. Preliminary Analyses NTGS 2004 – 2005

18. Non-duplicates with RVCT
Figure 1. Derivation of genotype isolates
17,653 Isolates
(Jan 1, 2004 to Jun 30, 2006)
7,000 (39.6%)
Incomplete genotyping results, duplicate results or missing RVCT
10,653 Isolates
Non-duplicates with RVCT
323 (3.0%)
Non-matching RVCT
During the presentation,
I will define an outbreak and a cluster and what is the difference between an epidemiologic cluster and a genotype cluster
I will also discuss and provide examples from recently conducted investigations where genotyping helped:
Confirm or rule-out recent transmission of TB
Detect unsuspected transmission of M tuberculosis or
Helped prioritize cluster of outbreak-related cases whose contacts needed to be screened and followed up during outbreak investigations
10,330 Isolates
Included in analysis

19. NTGS Preliminary Analyses
6,706 (64.9%) clustered isolates
1,974 clusters
Median of 3 members
Range: 2 – 687
Key characteristics for clustering

20. NTGS Preliminary Analyses
6,706 (64.9%) clustered isolates
1,974 clusters
Median of 3 members
Range: 2 – 687
Key characteristics for clustering

21. NTGS Preliminary Analyses
6,706 (64.9%) clustered isolates
1,974 clusters
Median of 3 members
Range: 2 – 687
Key characteristics for clustering

22. NTGS Preliminary Analyses
181 MDR-TB isolates in database
100 (55.2%) clustered (within state)
OR = 1.41 (95% CL 1.05, 1.89)
1,183 Mono-resistant TB isolates in database
579 (48.9%) clustered (within state)
OR = 1.10 (95% CL 0.97, 1.24)

23. Tell us how we can do better
During the presentation,
I will define an outbreak and a cluster and what is the difference between an epidemiologic cluster and a genotype cluster
I will also discuss and provide examples from recently conducted investigations where genotyping helped:
Confirm or rule-out recent transmission of TB
Detect unsuspected transmission of M tuberculosis or
Helped prioritize cluster of outbreak-related cases whose contacts needed to be screened and followed up during outbreak investigations