Use of interferon-y (‎inteferon-gama)‎ release assays (‎IGRAs)‎ in tuberculosis control in low- and middle-income settings

Overview

Research over the past decade has resulted in the development of two commercial interferon-gamma release assays (IGRAs). Both assays work on the principle that the T-cells of an individual who have acquired TB infection will respond to re-stimulation with M. tuberculosis-specific antigens by secreting interferongamma. The QuantiFERON-TB Gold (QFT-G, Cellestis, Australia) and the newer generation QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis, Australia) are whole-blood based enzyme-linked immunosorbent assays (ELISA) measuring the amount of IFN- produced in response to three M. tuberculosis antigens (QFT-G: ESAT-6 and CFP-10; QFT-GIT: ESAT-6, CFP-10 and TB7.7). In contrast, the enzyme-linked immunospot (ELISPOT)-based T-SPOT.TB (Oxford Immunotec) measures the number of peripheral mononuclear cells that produce INF-y after stimulation with ESAT-6 and CFP-10.

In recent years, IGRAs have become widely endorsed in high-income countries for diagnosis of latent TB infection (LTBI) and several guidelines (albeit equivocal) on their use have been issued. Currently, there are no guidelines for their use in high TB- and HIV-burden settings, typically found in low-and middle-income countries, where IGRA use are being marketed and promoted, especially in the private sector. Systematic reviews have suggested that IGRA performance differs in high- versus low TB and HIV incidence settings, with relatively lower sensitivity in high-burden settings. The majority of IGRA studies have been performed in high-income countries and mere extrapolation to low- and middle-income settings with high background TB infection rates is not appropriate. The WHO Stop TB Department has therefore commissioned systematic reviews on the use of IGRAs in low- and middle-income settings, in pre-defined target groups, with funding support from the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) and TREAT-TB/The Union.