Interferon-Gamma Release Assays Preferred for Latent TB

Interferon-gamma release assays (IGRAs) are significantly better than tuberculin skin tests (TST) at predicting progression from latent tuberculosis (TB).

In order to avoid unnecessary treatment, mass therapy of latent TB infection depends above all on the availability and use of adequate screening tests that more accurately predict progression from latent tuberculosis infection (LTBI) to active tuberculosis than the TST does.

Scientists at the Medical School Hanover (Germany) carried out a meta-analysis to qualitatively evaluate the positive predictive value (PPV) and negative predictive value (NPV) for progression of commercial and “in-house” IGRAs and the TST for persons not receiving preventive treatment. The respective IGRA studies were pooled using both a fixed and a random effect model. In all, 1,225 subjects were tested by "in house" IGRAs, 5,194 by commercial IGRAs and 8,479 by TST.

The pooled PPV for progression for all studies using commercial IGRAs was 2.7%, which was statistically significant compared with 1.5% for the TST.

PPV increased to 6.8% for the IGRAs and 2.4% for the TST when only high-risk groups were considered. Pooled values of NPV for progression for both IGRAs and the TST were very high at 99.7% and 99.4%, although significantly higher for IGRAs.

Five studies included in the metaanalysis utilized “in-house” tests; seven used the T-SPOT.TB ELISPOT (Oxford Immunotec Ltd.; Abingdon, UK); four used the QuantiFERON-TB Gold (QFT-G) and 14 used its successor the QuantiFERON-TB Gold In-Tube (QFT-IT), both products of Cellestis Ltd., (Chadstone, Australia). QFT-IT uses whole blood and produces a result within 16 hours and T-SPOT processes peripheral blood mononuclear cells within eight hours measuring the number of interferon-gamma producing cells.

Roland Diel, MD, MPH, the lead authors of the study said, "This is also highly important for tuberculosis control programs, because a test with a high negative predictive value means that therapy for latent tuberculosis can be limited to test-positive contacts without the danger of overlooking some who are truly infected but undetected by the tests."

The authors concluded that progression rates for commercial IGRA blood tests are remarkably higher than those for the TST, but remain low in absolute numbers. The data suggests that IGRAs provide significant benefits over the TST, but that the use of IGRAs, and testing for LTBI in general, should be targeted at high-risk groups. The study was published online on April 5 2012 in the journal Chest.

Related Links:
Medical School Hanover
Oxford Immunotec Ltd.
Cellestis Ltd.