Risk Assessment of Tuberculosis in Contacts by IFN-γ Release Assays. A Tuberculosis Network European Trials Group Study

Abstract

Tuberculosis rarely developed among contacts, and preventive chemotherapy effectively reduced the tuberculosis risk among IGRA-positive contacts. Although the negative predictive value of IGRAs is high, the risk for the development of tuberculosis is poorly predicted by these assays.

Numbers needed to treat to prevent tuberculosis

“…While we respect the views of the authors that the targets may appear too ambitious, we believe that, if the scientific community stay focussed on innovative approaches that can translate into scalable and effective interventions, we could reap the benefits of such interventions within the space of the next two decades [2]. Figure 1 shows the trend in TB incidence into the future, should current efforts to control TB -including the treatment of latent Mycobacterium tuberculosis infection (LTBI) -be intensified and boosted by new techniques and approaches.…”

“…Notably, as incident cases of tuberculosis were mainly HIV positive, the number of HIV-infected persons with a positive test needed to treat was lower (range 14.0-25.5) and tuberculosis cases were only found in patients with ongoing viral replication [3]. It should be emphasised that incident tuberculosis cases also occurred in individuals with negative test results [2,3,5], especially among patients with HIV infection. In patients with chronic renal failure (n=270) or rheumatoid arthritis (n=199), stem cell (n=103) or solid organ transplant recipients (n=197) [3], and healthcare workers (n>15 000) [6][7][8], the number of individuals with LTBI needed to treat to prevent one case could not be calculated because no tuberculosis cases occurred during 2 years of follow up in these cohorts…”

“…More recently, it has become evident that the risk of the development of tuberculosis among patient groups classically considered at risk is highly variable, and is not necessarily associated with the results of immunodiagnostic testing by the TST or IGRAs [2][3][4][5]. More detailed knowledge of groups at actual risk of tuberculosis and on immunodiagnostic test performance in these risk groups may provide better guidance for physicians on priorities for targeting tuberculosis testing and LTBI treatment in low-incidence countries.…”

“…Although not selected by a systematic approach, we made use of the fact that several studies with large sample sizes from low-incidence countries of tuberculosis were recently published from three major groups classically considered at risk for progression. In these studies, tuberculosis contacts [2,4,5], immunocompromised hosts [3] and healthcare workers [6][7][8] were evaluated for LTBI and subsequent progression. We have calculated the number needed to treat to prevent one case of tuberculosis (table 1), and found that the number needed to treat was very similar across three studies evaluating 1579, 5020 and 4774 tuberculosis contacts, respectively, with a positive TST or IGRA, ranging from 30 to 37 [2,4,5] (table 1).…”

“…In these studies, tuberculosis contacts [2,4,5], immunocompromised hosts [3] and healthcare workers [6][7][8] were evaluated for LTBI and subsequent progression. We have calculated the number needed to treat to prevent one case of tuberculosis (table 1), and found that the number needed to treat was very similar across three studies evaluating 1579, 5020 and 4774 tuberculosis contacts, respectively, with a positive TST or IGRA, ranging from 30 to 37 [2,4,5] (table 1). In immunocompromised individuals with a positive test (n=1537) [3], the number needed to treat to prevent a case was higher and ranged from approximately 50 to 80 (table 1).…”