CDC Guidelines for Use of QuantiFERON ® -TB Gold Test

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 Methods for Developing Guidelines • Panel of expert consultants convened July 2005 • Reviewed published and unpublished data • In developing guidelines, CDC reviewed scientific evidence independently and considered opinion of consultants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. QFT-G can be used in all circumstances in which the TST is used, including • 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

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. A positive QFT-G should prompt the same health and medical interventions as a positive TST result • 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

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