1. TB Surveillance Using QuantiFERON® -TB Gold Is it measuring up?
Dr. David Marder, MD, MPH
Medical Director of University Health Service
University of Illinois Medical Center Chicago

2. Areas of Concern Estimated 10-15 million persons in U.S. infected
with M. tuberculosis (60-90 M worldwide)
Roughly 2-3 million deaths per year (worldwide)
Drug-resistant cases reported in almost every state
Without intervention, about 10% will develop
TB disease at some point in life

3. Problems with TST… Poor inter-reader reliability
9 mm (negative) vs. 10mm (positive)?
False-positives/specificity
NTM infection
Prior BCG
Poor positive-predictive value in low prevalence populations (like US)
Cost/time of patient visits
Unread tests
Sensitivity?
Reaction wanes over time
Lack of gold standard

4. • TB specific antigen, Nil &Mitogen tubes
TB and the 21st Century; Introducing QuantiFERON® TB Gold ‘‘In-Tube’”
In the field:
• TB specific antigen, Nil &Mitogen tubes
• Blood collected directly into tubes
In the lab:
• ELISA for detection of
IFN gamma IFN-

5. TB-Specific antigens (ESAT-6, CFP-10, TB7.7)
Absent from BCG
Absent from most NTM
Produced as synthetic peptides
Only stimulate T-cells in infected people

6. Species specificity of QFTTM TB Antigens
Tuberculosis
Complex
ESAT-6
CFP-10
TB7.7
Environmental
strains
M tuberculosis +
M abcessus -
M africanum
M avium
M bovis
M branderi
M celatum
BCG substrain
M chelonae
gothenburg
M fortuitum
moreau
M gordonii
tice
M intracellulare
tokyo
M kansasii
danish
M malmoense
glaxo
M marinum
montreal
M oenavense
pasteur
M scrofulaceum
M smegmatis
M szulgai
M terrae
M vaccae
M xenopi 6

7. QuantiFERON®-TB GOLD Offers fundamental advantages over the TST:
Single Patient Visit
100% results, No need to follow up on negatives
Contacts, Homeless, Jail inmates
Unaffected by BCG and NTM
Highly specific test
Reduces false positives
Better detection of active TB
Increased sensitivity for active TB

8. QuantiFERON®-TB GOLD Also: Objective and controlled test
Reduces subjectivity in TB diagnosis
Simple diagnostic cut-off
Straight forward positive/negative interpretation
Eliminates 2 step testing
No ‘booster’ effects
Faster turn-around, results in hours
Results are electronic (computer generated reports)

9. QuantiFERON®-TB GOLD Advantages (cont.)
Reduces unnecessary CXR and prophylaxis
Reliable detection of post exposure LTBI
Not subject to reader bias

10. QuantiFERON ® TB-Gold Implementation at UICMC
First Brought up at TB Sub-Committee Meeting
Multidisciplinary approach involving Pulmonary, Infection Control, Employee Health, Infection Disease, Laboratory and Environmental Health and Safety Department
Review of the Literature

11. University Health Service at UICMC QuantiFERON ® TB-GOLD Pilot Program
University Health Services (UHS) began exploring the new gamma-interferon assay in June 2005 as an alternative to the PPD skin test for screening Health Care Workers.
With the University of Illinois Medical Center Chicago (UIMCC) laboratory, a pilot project began in August 2005.
Full implementation of the Quantiferon surveillance program in January 2006.

12. Moving forward w/ Pilot Study
Support from Hospital Administration
Support from the Lab and Phlebotomy staff to assist w/ blood collection and turn around time on results
Recruitment of employee’s
Positive PPD group
Negative PPD group

13. PILOT SUBJECTS
79 health care workers were recruited for the pilot program from the following 3 groups:
TST negative
TST positive/BCG negative
TST positive/BCG positive

14. PILOT RESULTS
25 out of 37 (68%) of previous TST positive were Quantiferon negative.
In the BCG group alone, 11 (65%) were TST positive and Quantiferon negative.
The decrease in positive TB tests will increase the number of employees who can affectively be screened for TB in the future with Quantiferon as opposed to the monitoring of symptoms by questionnaire as done in the past.

15. PILOT RESULTS
TST -
TST +
TST +/BCG
QFT + 6
QFT - 42 14 11

16. We Did It! The Illinois Department of Public Health changes
Tuberculosis screening law
 Control of Tuberculosis Code
(77 Ill. Adm. Code 696)
Illinois Register Citation: 32 Ill. Reg. 4010
Date Published: March 14, 2008
Effective Date: February 29, 2008
The current rules on tuberculosis (TB) cover the screening, treatment, testing, management and reporting requirements for persons with active or suspected of TB, having TB disease or latent TB infection (LTBI). The rules previously required the use of the Mantoux tuberculin skin test (TST) as the only test approved for screening for LTBI. The amendment allows the use of a newly developed FDA-approved blood test for the detection of patients with active TB disease or LTBI. The amendment only adds the use of the new FDA approved blood test as an approved test for screening patients and does not remove the TST as an approved test for screening.

17. UIMCC TB Control Plan
IDPH - Tuberculosis Prevention and Exposure Control Plan, Section 7, Employee Surveillance: Previously only TST approved.
IC Committee approved changes to the policy to include “…the current screening methodology which may include PPD, QuantiFERON-TB Gold, and any other approved /newly developed test…” November 2005.
At this time QuantiFERON TB-Gold is the recommended form of testing for all Medical Center employees.

18. Pre-Employment Screening
At the time of employment, all UIMCC employees including those with a history for BCG vaccine shall receive a tuberculosis screening test, such as QuantiFERON® -TB Gold (QFT-G), or any other approved test.

19. Pre-Employment Cont.
All employees that have a positive tuberculosis screening test will be referred for a chest x-ray and medical evaluation. The employee shall be provided with documentation of his/her test results and instructed to consult with a personal physician regarding prophylactic therapy. A positive tuberculosis screening test will not affect employment status unless active TB disease is present

20. Annual Surveillance
All employees employed by UIC Medical Center and all those employed elsewhere that have patient contact shall have repeat tuberculosis screening test (annually or semi-annually in accordance with their unit or department schedule).

21. An overview of UIMCC’s first year of QuantiFERON® testing

22. 2006 RESULTS A total of 4643 QuantiFERON tests were completed in 2006.
4313 Negative (92.9%)
140 Positive (3.0%)
190 Indeterminate (4.1%)

23. 2006 RESULTS
A subset of the previous TST positive received QFT of the 505 were QFT negative (72%).

24. Cost Evaluation Considerations Is QFT Cost Effective?
Amount of collection time
Supplies
Cost of test
Laboratory support, time and cost
Nurse time

25. Other Possible Cost Evaluation Considerations
Cost of medication and associated side effects
Convenience for employees
Employee time away from work
# of visits to employee health
Failure of ppd reads

26. PROGRAM REVIEW ANALYSIS
A cost benefit analysis was done in September.
It showed considerable savings to the Medical Center, especially when the outreach lab did several thousand tests.
This analysis did not take into account the lost time Health Care Workers incur when utilizing the TST.
In 2006, there were 2,000 less visits to UHS since the program transitioned to the Quantiferon testing.

27. PPD vs. QFT Cost Analysis Low end pricing
Year Number of skin tests low end price Annual cost
Year $41       $205,    
Number of QFTs               
Year $25       $125,000.00
Cost Savings $ 80,000.00/yr.
* Statistics are extracted from the CDC Lambert Paper. All numbers are on the conservative side.
             

28. PPD vs. QFT Cost Analysis National Average
Year Number of skin tests Nat'l avg. price   Annual
Year $100       $500,000.00
Number of QFTs    
Year $25       $125,000.00
Cost Savings $ 375,000.00/yr.

29. CONVERSIONS & REVERSIONS
Wobble effect – results may wobble around the 0.35 cutoff when tested serially. This can give results of positive one time and then negative next or visa versa.
This variation occurs more with positive results than negative.

30. QuantiFERON® TB-Gold “In Tube” Test Validation
EVOLIS
QFTB-G
TOTAL
POS
IND
NEG 23 2 22 47 1 8
340
350 25 10
363
398

31. QFT - IT tests done at UIC 8/08 to 8/09
Total number of QTBGI tests done at UIC - 7,688
Total number of positives - 612
Total number of indeterminates - 155
Total number of Negatives - 6,921

32. Discordant results with QFT - Gold
Total number of new positives that are on raw data sheet during this time: 88
47 of the 88 cases had a positive PPD history, negative QTBG gold history and presently are positive In-tube at initial and repeat testing.
Total from this number that went from 1st time positive and then negative at repeat testing: 24
13 from this number had a positive PPD history
11 from this number had a negative PPD history

33. Higher sensitivity seen with QuantiFERON® TB-Gold “In Tube”
A.R. PPD positive in past.
QFT-2G: ESAT-6 CFP-10
Neg 3/6/
Pos 9/14/
Neg 3/21/
QTBG IN-TUBE TB-Ag
Pos 9/4/
Pos 10/30/

34. Interpreting Results
A general overview of the guidelines used at UICMC
Must recognize some results (very small number, <1% at UICMC) must be reviewed in more detail on case by case basis
Successful interpretation may involve collaboration between Employee Health Services, Laboratory, Infection Control, and/or Cellesitis; as well as, detail history from the employee

35. Interpreting Results
Negative – exposure to M. tuberculosis is unlikely
Positive – exposure to M. tuberculosis is likely
Indeterminate – results are inconclusive. Not a positive test.

36. QFT negative regardless of PPD history
Cleared for employment
QFT positive w/ negative PPD
Repeat the QFT immediately and do TB Questionnaire
Positive
Chest X-ray
Referral to PCP for evaluation
Future testing to be determined
Negative – Annual or semi-annual Surveillance depending on department
Notify lab to get raw data

37. Indeterminate Results at Pre-Employment Screening
Repeat QFT at time of annual or semi-annual testing
Certain percentage of the population (very small number) are repeatedly Indeterminate
Continue Surveillance on these employees
Remember Indeterminate results are NOT positive results

38. Final Thought
Cut the Cord!

39. REFERENCES http://www.cdc.gov/nchstp/tb/default.htm
Guidelines for Using QuantiFERON-TB Gold Test for detecting Mycobacterium tuberculosis Infection, United States, MMWR December 16, 2005; 54.
Guidelines for the Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005, MMWR December 30, 2005;54.

40. QUESTIONS