CDC Guidelines for Use of QuantiFERON

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CDC Guidelines for Use of QuantiFERON-TB Gold
Test

• Philip LoBue, MD
• Centers for Disease Control and Prevention
• Division of Tuberculosis Elimination

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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

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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

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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/mmwrht
  ml/maj_guide.htm

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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• Reviewed published and unpublished data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

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Recommendations for Use of QFT-G
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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

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

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Follow up of Negative QFT-G
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The majority of healthy adults who have negative
QFT-G results are unlikely to have M.
tuberculosis infection and do not require further
evaluation
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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 lt17 years

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Follow up of Indeterminate QFT-G
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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

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Contact Investigations
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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
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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

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Serial Testing (e.g., Healthcare Workers)
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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

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Future Research Needs
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• 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

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• 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)

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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