Practice Alert

When, and when not, to use the interferon-gamma TB blood test

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Consider the following cases of patients needing testing for tuberculosis:

  1. A 55-year-old nurse returns to work after 10 years. Her pre-employment evaluation requires a test for tuberculosis.
  2. A 35-year-old woman has lupus. Her physician is considering placing her on prednisone and wants to know if she has latent TB infection.
  3. A homeless man presents to the clinic stating he has lost his TB medications that he has taken or the past 2 months. His diagnosis of TB was made in another city; he cannot remember its name. The physician wants to confirm the diagnosis of TB.
  4. A 5-year-old from Mexico with a history of BCG vaccination presents for a preschool health evaluation.
  5. A 35-year-old immigrant from Africa is pregnant and presents for prenatal care.

Patients 1 and 2 above are logical candidates for the newer interferon-gamma blood test to detect tuberculosis (TB). Patients 3, 4, and 5 are not; They should be evaluated with the conventional TB skin test.

The advantages and disadvantages of both kinds of testing are described in this review.

Is a better test at hand?

The TB skin test, using an intradermal injection of purified protein derivative, has been used to assist in the detection of active and latent TB for more than a century. However, this test has its problems: difficulty in accurately measuring and interpreting the reaction; low sensitivity in those with depressed cell-mediated immunity and those with early infections; lower specificity in those with a history of bacille Calmette-Guérin (BCG) vaccination and infection with other Mycobacteria; the need for 2 visits with-in 48 to 72 hours for test interpretation; and boosting of immune response caused by the TB skin test itself (see Boosting phenomena).

Those who work in TB control programs have sought better diagnostic tools. Two that are available today are the interferon-gamma blood tests QuantiFERON-TB (QFT) and QuantiFERON-TB GOLD (QFTG). The QFT and QFTG measure the release of interferon-gamma by sensitized lymphocytes when exposed to antigens of Mycobacterium tuberculosis.

The QFTG, licensed in 2004, is an improvement over the earlier QFT, licensed in 2001, which included antigens that M tuberculosis shares with other commonly encountered Mycobacteria. The QFTG is more specific to M tuberculosis, although it does cross-react with several relatively uncommon nontuberculous Mycobacteria. These tests have several advantages over the older skin test (TABLE 1).

Boosting phenomena

In those who have had prior Mycobacteria infections or BCG vaccine, cell-mediated immunity can wane and a TB skin test can therefore be negative. However, the skin test can boost the person’s immunity, and a second skin test can then be positive as a result of the immune boost. This can cause someone who is actually a reactor (someone who reacts positively to a skin test because of prior Mycobacteria infection) to look like a converter (someone who has a negative skin test at a recent point in time followed by a positive skin test, indicated recent infection with Mycobacteria). It is recommended that adults who have not had a skin test within 12 months and who will need repeated skin tests should receive a 2-step skin test on initial evaluation. A 2-step skin test involves an intitial test followed by a second one 1–2 weeks later.

TABLE 1
Advantages/disadvantages of the QFTG

Advantages of QFTG compared with the TB skin test
  • Improved sensitivity and specificity for latent TB infection
  • Unaffected by prior BCG vaccination
  • Only 1 patient visit required
  • No effect on repeat tests or on skin tests through immune boosting
  • Less subject to measurement bias and error
Disadvantages of QFTG
  • Phlebotomy required
  • May not be offered by all laboratories
  • Costs $80–$100 per test
  • Blood samples must be processed within 12 hours of collection

Factors to keep in mind when considering the QFT

In spite of the theoretical advantages of the QFT, research on its use is at an early stage. It can be considered a testing option for persons identified in TABLE 2. It may ultimately prove to be the test of choice for patients who have previously received a BCG vaccine, and in other instances where specificity is the predominant consideration. However, the Centers for Disease Control and Prevention (CDC) does not recommend it over a TB skin test in any situation.

Whether a skin test or QFTG is used, testing is recommended only for those at high risk of having latent TB infection and for those at high risk of developing active TB disease, if infected. Targeted testing along with treatment of active and latent TB remains the basis of TB control activities in the US.

When QFTG is unwarranted. The QFTG appears to be less sensitive than a TB skin test in those with symptoms of active TB, with the exception of those who are HIV-positive.1 In addition, the QFTG is not recommended for use with patients who are being treated for active TB. Current information is inadequate to recommend any QFTG use in children and pregnant women.

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