1. CDC Guidelines for Use of QuantiFERON ® -TB Gold Test Philip LoBue, MD Centers for Disease Control and Prevention Division of Tuberculosis Elimination

2. Outline Background and purpose Where to find guidelines Methods for developing guidelines Recommendations for QFT-G use Guidance for follow up of –Positive test result –Negative test result –Indeterminate test result Special situations –Contact investigation –Serial testing (e.g., occupational) Future research needs Future guidelines

3. Background and Purpose QFT-G received final approval from FDA as an aid for diagnosing M. tuberculosis infection in May 2005 CDC statement (published December 2005) meant to provide interim guidance for use and interpretation of QFT-G

4. Where Can You Find the Guidelines? Print: Guidelines for Using the QuantiFERON®-TB Gold Test for Detecting Mycobacterium tuberculosis Infection, United States, MMWR, December 16, 2005 / Vol. 54 / No. RR-15, pp. 49-54. Internet: http://www.cdc.gov/nchstp/tb/pubs/mmwrhtml /maj_guide.htm

5. Methods for Developing Guidelines Panel of expert consultants convened July 2005 Reviewed published and unpublished data In developing guidelines, CDC reviewed scientific evidence independently and considered opinion of consultants

6. Recommendations for Use of QFT-G

7. Contact investigations Evaluation of recent immigrants who have had BCG vaccination TB screening of health-care workers and others undergoing serial evaluation for M. tuberculosis infection QFT-G can be used in all circumstances in which the TST is used, including

8. QFT-G usually can be used in place of (and usually not in addition to) the TST

9. Follow up of Positive QFT-G

10. No reason exists to follow a positive QFT-G with a TST Persons with a positive QFT-G result should be evaluated for TB disease before LTBI is diagnosed After TB has been excluded, treatment of LTBI should be considered A positive QFT-G should prompt the same health and medical interventions as a positive TST result

11. Follow up of Negative QFT-G

12. The majority of healthy adults who have negative QFT-G results are unlikely to have M. tuberculosis infection and do not require further evaluation

13. Cautions and Limitations As with a negative TST result, negative QFT-G results should not be used alone to exclude M. tuberculosis infection in persons with symptoms or signs suggestive of TB disease The performance of QFT-G has not been determined in persons who, because of impaired immune function (e.g., HIV infection), are at increased risk for M. tuberculosis infection progressing to TB disease As with a negative TST result, negative QFT-G results alone might not be sufficient to exclude M. tuberculosis infection in immunocompromised persons Limited published data document the performance of QFT-G in children aged <17 years

14. Follow up of Indeterminate QFT- G

15. An indeterminate QFT-G result does not provide useful information regarding the likelihood of M. tuberculosis infection Optimal follow up of persons with indeterminate QFT-G results has not been determined Options are to repeat QFT-G with a new blood sample, administer a TST, or do neither Decision should be based on pre-test likelihood of M. tuberculosis infection

16. Contact Investigations

17. For persons with recent contact to an infectious TB patient, negative QFT-G results should be confirmed with a repeat test 8-10 weeks after exposure (end of window period) as is recommended for a negative TST

18. When “window prophylaxis” has been started for high-risk contacts exposed to an infectious TB patient, a negative QFT-G result at the end of the window period should be interpreted in light of all other clinical and epidemiologic data A full course of LTBI treatment should be considered even with a negative result when the rate of M. tuberculosis transmission to other contacts is high or when a false-negative result is suspected because of an immunocompromising medical condition

19. Serial Testing (e.g., Healthcare Workers)

20. In situations with serial testing for M. tuberculosis infection (e.g., health-care workers), initial two- step testing (necessary for TST) is not necessary for QFT-G In contrast to TST, there is no boosting with QFT-G

21. Future Research Needs

22. Performance of QFT-G in young children Performance of QFT-G in persons with impaired immunity (e.g., HIV) Performance and practicality of QFT-G in substantial numbers of persons who undergo periodic screening Determination of subsequent incidence of TB disease after LTBI has been either diagnosed or excluded with QFT-G Length of time between exposure, establishment of infection, and emergence of a positive QFT-G test result

23. Economic evaluation and decision analysis comparing QFT-G with TST Changes in QFT-G results with therapy for TB disease and LTBI Ability of QFT-G to detect re-infection after treatment for LTBI and TB disease Performance of QFT-G in targeted testing programs (e.g., recent immigrants from high- incidence countries)

24. Future Guidelines Current guidelines will be modified or new guidelines developed as –Additional studies on QFT-G are published –New versions of QFT and other interferon- gamma release assays become available