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

CDC Guidelines for Use of QuantiFERON®-TB Gold Test

Philip LoBue, MD

Centers for Disease Control and Prevention

Division of Tuberculosis Elimination

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

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

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

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• Reviewed published and unpublished data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

Recommendations for Use of QFT-G

• 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

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

Follow up of Positive QFT-G

• 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

Follow up of Negative QFT-G

The majority of healthy adults who have negative QFT-G results are unlikely to

have M. tuberculosis infection and do not require further evaluation

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

Follow up of Indeterminate QFT-G

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

Contact Investigations

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

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

Serial Testing (e.g., Healthcare Workers)

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

Future Research Needs

• 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

• 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)

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