Abstract
Tuberculin skin testing (TST) and Interferon-gamma (IFNγ)release assays (IGRAs) are presently the only available assays for the detection of Mycobacterium tuberculosis infected individuals. IGRAs might progressively replace TST, as numerous published reports establish their higher specificity and similar sensitivity when tested in BCG vaccinated, immunocompetent individuals or in populations who may have been in contact with atypical mycobacteria. However, few published reports have commented on their role in TB diagnosis in immunocompromised individuals (HIV, immunosuppressive therapy, cancer…). It is the purpose of this report to review IGRAs published studies in HIV individuals in endemic and non endemic area for tuberculosis (TB). IGRAs were tested in the presence or absence of active TB but correlated to duration of exposure. In newly diagnosed active TB, IGRAs demonstrated a similar sensitivity to TST. In TB non infected individuals, TST and IGRAs also gave similar values when categorization of individuals was correlated to the risk of infection. A higher number of positive IGRAs was observed in individuals from TB endemic areas, in similar proportions to immunocompetent individuals. Comparison between the two IGRAs: QuantiFERON-TB Gold® (QF-TB, Cellestis, Australia) and T-SPOT-TB® (Oxford Immunotec, UK), and against TST, in the same HIV population demonstrates a higher sensitivity of T-SPOT-TB and TST than QF-TB. Indeterminate results, which correspond to the absence of a positive T-cell IFNγ response towards phytohemaglutinin (PHA), is a key point when comparing both IGRAs. This PHA control is indicative of the level of immunosuppression observed in the tested individual. QF-TB seems to present, in HIV populations, more indeterminate results than T-SPOT-TB. The calibration and/or concentration of PBMC on nitrocellulose membrane for the T-SPOT-TB, as compared to a whole blood assay, might explain this difference, with less indeterminate results with the T-SPOT-TB assay. Neither assay is able to differentiate active TB from latent TB infection (LTBI). Several laboratories have tried new antigenic epitopes to solve this issue. It is of importance that these studies need to be repeated on a larger scale by others to validate their results. Two blood assays might add information characterising the evolution from LTBI to active TB: either by losing protective immunity, as demonstrated by the whole blood killing assay, or by evaluating the kinetics of the antibodies synthesized against M. tuberculosis specific antigens. In conclusion, longitudinal studies are still needed to validate IGRAs and other assays and to define their respective predictive values.
Highlights
In most individuals infection with Mycobacterium tuberculosis is contained by the host’s immune defences and the infection remains latent [1,2]
The determinants for increased risk of progression from Latent Tuberculosis Infection (LTBI) to active TB disease are a recent infection with M. tuberculosis and several host-related factors, all of which seems to be associated with an impaired cell-mediated immune response [8]
Interferon-gamma (IFN) release assays (IGRAs) based on specific RD1 peptides have shown promising results for diagnosing LTBI in immunocompetent individuals, and in Human Immunodeficiency Virus (HIV)-infected persons at higher risk for development of active disease
Summary
In most individuals infection with Mycobacterium tuberculosis is contained by the host’s immune defences and the infection remains latent [1,2]. The determinants for increased risk of progression from LTBI to active TB disease are a recent infection with M. tuberculosis and several host-related factors, all of which seems to be associated with an impaired cell-mediated immune response [8] Among this high risk populations, individuals infected with the Human Immunodeficiency Virus (HIV) are the most prone to reactivate the persistent M. tuberculosis bacilli. New tests for diagnosing LTBI are warranted, and ideally such tests should have several characteristics: a high sensitivity in all populations at risk, and a high specificity, regardless of BCG vaccination or infection with environmental NTM It should be reliable, stable over time, and with objective criteria for a positive result.
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