The use of interferon-γ-based blood tests for the detection of latent tuberculosis infection

Abstract

As recently as 3 yrs ago, a colleague complained that after 100 yrs the only way to detect tuberculosis (TB) infection was still to measure “bumps on arms”. Now, at last, we have a genuine improved alternative: the ex vivo cellular interferon (IFN)-γ-based blood tests. The crucial questions we need to ask are how good they are at detecting infection with the TB bacterium and whether they are cost-effective? Unfortunately, determining the answers to these questions is not easy. The new ex vivo cellular IFN-γ assays (CIGAs) have been developed based on the release of IFN-γ from a patient’s T-cells when exposed to mycobacterial antigens. These novel assays rely on the principle that the genes encoding the secretory proteins early secretory antigenic target (ESAT)6/culture filtrate protein (CFP)10 are absent in the bacille Calmette–Guerin (BCG) vaccine strain and most environmental mycobacteria 1. Two commercial cellular immunological assays have been developed in which IFN-γ output from the patient’s whole blood or peripheral blood mononuclear cells are measured following treatment with ESAT6/CFP10 antigens 1. Different assay formats have been developed. One method relies on the relatively straightforward ELISA detection after a fixed volume of whole blood is incubated in a tube with ESAT6/CFP10 antigens (Quantiferon Gold; Cellestis Limited, Carnegie, Australia). The other method currently available commercially is the T-Spot.TB assay (Oxford Immunotec, Oxford, UK) based on the enzyme-linked immunospot (ELISPOT) principle. The methods appear to be both sensitive and specific. These assays have the potential to change the face of the diagnosis of latent TB infection (LTBI) and active TB at an early stage in the disease process. Their use is also likely to transform the screening of new migrants and other population groups. These tests require only a single blood sample without the repeat visit required for the tuberculin skin …