Mycobacterium tuberculosis (MTB) infection is acquired by inhalation of infectious aerosol particles coughed up by patients with active respiratory infection. Depending on the immune status, a wide range of clinical stages can occur: from primary infection (5 – 10 %) over latent tuberculosis infection (LTBI; 90 – 95%) to spontaneous clearance (unknown percentage) with or without priming memory response to tuberculosis (TB) antigens [1]. It is estimated that up to one quarter of the worldwide population is latently infected by MTB, with major geographical differences [2]. In LTBI, the patient's immune system can control the replication of the tubercle bacillus. The patient is not contagious, the sputum cultures remain negative, and no abnormalities are seen on the chest X-ray. However, when the immune system is no longer able to suppress the replication (due to physiological reasons or pharmacological interventions), clinical disease can develop as a consequence. The lifetime risk of TB reactivation in case of documented LTBI is estimated to be 5 – 15%, with the highest risk during the first five years after inoculation [1]. TB reactivation can be prevented, after exclusion of active TB, by means of LTBI treatment, with an efficacy ranging from 60 – 90% [3].

Because the annual incidence of active TB is less than 10 per 100 000 inhabitants, Belgium is classified as a low-incidence country according to the definition of the WHO [4]. Nevertheless, there is a geographic concentration in Belgium's large cities. To contribute to the global goal to reduce the incidence of TB in a cost-effective way [5], identification of asymptomatic carriers at greatest risk of reactivation and subsequent progression to active TB should be pursued. Additionally, the potential added value of treatment must be weighed against the potential drug-related adverse events. The Belgian guideline on the diagnosis and management of LTBI [6] strongly recommends systematic testing and treatment of LTBI in patients initiating immunosuppressive therapy. This risk group accounts for the main indication for screening in our regional hospitals with 921 (AZ Groeninge, Kortrijk) and 573 (AZ Maria Middelares, Ghent) beds.

Although there is no gold standard for the diagnosis of LTBI, there are currently two groups of diagnostic tests for LTBI screening: the in vivo tuberculin skin test (TST) and the in vitro interferon gamma release assays (IGRA). Both are based on the detection of memory T-cells that previously encountered MTB antigens, but these tests cannot distinguish between active TB disease and LTBI.

The TST was developed over 100 years ago and its use has been widespread ever since. It is an inexpensive test that uses a purified protein mixture with the aim to detect type IV delayed hypersensitivity skin reaction towards the tubercle bacillus. Well-known shortcomings of this test are the lack of sensitivity in immunocompromised individuals, the poor specificity in bacille Calmette-Guérin (BCG) vaccinated populations and cross-reactivity with non-tuberculous mycobacteria (NTM). In addition, the test also poses logistical challenges as two visits are required [7].

In contrast, the specificity of IGRA's is better because the in vitro immune response against MTB antigens is measured, which are not present in BCG or most NTM (i.e. early secretory antigenic target-6 and culture filtrate protein-10). Although not 100% sensitive either, IGRA's have a lower false negative rate compared to TST in patients treated with corticoids [8]. In turn, the disadvantages of IGRA's are the higher cost, the critical pre-analytical phase, and the need for a well-equipped laboratory. Until recently, there were two commercial IGRA tests available: the T-SPOT®.TB (Oxford Immunotech) and the QuantiFERON®-TB Gold-Plus (QFT®-Plus, QIAGEN). The T-SPOT®.TB counts the number of interferon gamma (IFN-γ) producing cells in antigen-stimulated peripheral blood mononuclear cells. The QFT®-Plus, on the other hand, measures the concentration of released IFN-γ from whole blood after in-tube antigen stimulation [7]. Based on the latter testing principle, a new assay was launched in the summer of 2021: TB-IGRA® on the VIDAS3 platform from bioMérieux. This fully automated test does not require batch analysis so this assay seems attractive for labs with less samples. Moreover, bioMérieux claims an enhanced automation, a better sensitivity on active TB, more valid results, minimal hands-on-time, shorter time to result, and higher cost-effectiveness compared with QTF®-Plus assay (package insert, version 2021-04). However to date, independent verifications of this assay are still lacking. Therefore, we compared the analytical performance of the TB-IGRA®assay on VIDAS3 in a predominantly low risk population in a low incidence area with the QFT®-Plus assay and evaluated the reproducibility.