OpiniãoAs explained in Chapter 1, TB infection is a state that is characterized by persistent immune response to stimulation by Mtb antigens with no evidence of clinically manifest TB disease (1). Initially, the TST was the only tool available for TB infection detection.
The identification of genes in the Mtb genome that are absent from M. bovis BCG and most NTM has supported the development of more specific and sensitive tests for the detection of Mtb. The M. bovis BCG has 16-gene deletions, including the region of difference 1 (RD-1) that encodes for ESAT-6 and CFP-10, both of which are strong targets of the cellular immune response in patients with Mtb infection. In such people, sensitized memory or effector T-cells produce IFN-γ in response to these antigens, allowing a biological basis for T-cell-based tests such as IGRAs.
In 2011, WHO issued recommendations on the use of IGRAs for the diagnosis of TB infection. In 2018, WHO updated the recommendations to stipulate that the TST or IGRAs (or both) can be used for TB infection.
Among the WHO-recommended tests (i.e. the TST and IGRAs), the TST has some disadvantages, in that it has relatively low specificity in those with recent BCG vaccination and immunosuppressed individuals (e.g. People with HIV), requires two clinic visits and is only valid if the results are read within the suggested time frame. In contrast, IGRAs measure T-cell release of IFN-γ following stimulation by ESAT-6 and CFP-10 (antigens that are specific to Mtb). Unlike the TST, IGRAs are not affected by prior BCG vaccination or by infection with NTM (with a few exceptions), but IGRA platforms are more expensive to run, requiring specialized facilities and trained personnel. Thus, the TST is the most commonly used test for TB infection globally; however, recent global shortages of the TST have underscored the need for alternatives.