TB diagnostics: Current pipeline, new developments and unmet needs

One of the biggest barriers for TB control is the lack of tools and strategies to diagnose TB quickly and accurately, such that TB transmission can be reduced. In the past few years, the new diagnostics pipeline for TB has rapidly expanded, and there have been several new policies and guidelines on TB diagnostics. For active TB diagnosis and rapid diagnosis of drug resistance, the most important recent breakthrough has been the Xpert® MTB/RIF, a completely automated, cartridge-based molecular assay. Currently, efforts are underway to scale-up the Xpert MTB/RIF technology in high TB burden countries, but there are several barriers to scale-up, including high cost, limited laboratory capacity, widespread abuse of suboptimal and inaccurate tests and lack of adequate regulation in many high TB burden countries. Currently available serological (antibody-detection) tests for TB have failed and the WHO has issued a negative policy recommendation against their use. However, further research is needed to develop a simple, rapid, inexpensive point-of-care test for TB disease. Newer tests, the IFN-γ release assays, have recently emerged for LTBI diagnosis. These tests are highly specific and most helpful for latent TB infection screening in bacillus Calmette-Guérin (BCG)-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple BCG vaccinations are given. A growing number of studies show that both the IFN-γ release assays and tuberculin skin test have limited prognostic value. There is a need for a highly predictive biomarker or combination of biomarkers and risk factors that will allow accurate prediction of the subgroup of latently infected individuals that are at highest risk of progression to disease. Overall, major advances have been made in TB diagnostics product and policy development. However, products and policies by themselves do not guarantee scale-up or impact. The biggest challenge now is translation of policy into practice, to save lives and reduce TB incidence.