Biomarkers of Tuberculosis: A Research Roadmap

Abstract

Tuberculosis (TB) continues to represent a major public health problem worldwide. Prompt and accurate diagnosis and effective treatment are fundamental to reducing morbidity and mortality and curtailing spread of infection. Furthermore, tackling the large reservoir of latent infection is the cornerstone to TB control in many high income low TB incidence countries. However, our existing toolkit for prevention, diagnosis and treatment remains outdated and inadequate. Here, we discuss the key targets for biomarker research and discovery in TB and recent developments in the field. We focus on host biomarkers, in particular: correlates of vaccine efficacy and sterilizing immunity; biomarkers of latent TB infection, including diagnosis, risk of progression to active TB and response to treatment; and markers of active TB, including diagnosis, response to treatment and risk of relapse. Recent scientific and technological advances have contributed to significant recent progression in biomarker discovery. Although there are clear remaining paucities, continued efforts within scientific, translational and clinical studies are likely to yield a number of clinically useful biomarkers of TB in the foreseeable future.

QuantiFERON-TB performance enhanced by novel Mycobacterium tuberculosis-specific antigens

“…The addition of the novel peptides to the QFT resulted in a significant increase in the IFN-γ release in active TB, without altering specificity, and also in the BCG-vaccinated control population. This is consistent with previous data in the literature indicating that the addition of other non-RD1 proteins to QFT can result in an increase of the test performance [4,5], as also observed in the changes implemented in the QFT test versions [1].…”

“…One of the most significant developments in the diagnosis of tuberculosis (TB) infection has been the introduction of whole-blood based interferon-γ release assays (IGRAs) [1][2][3]. IGRAs, commercially available as QuantiFERON-TB Gold In-Tube test (QFT) (QIAGEN, Germantown, MD, USA) and T-SPOT.TB (Oxford Immunotec Ltd, Abingdon, UK), are based on the detection of a T-cell immune response towards RD1 antigens (ESAT-6 and CFP-10), with the addition of the TB7.7 antigen for the QFT only [1].…”

“…IGRAs, commercially available as QuantiFERON-TB Gold In-Tube test (QFT) (QIAGEN, Germantown, MD, USA) and T-SPOT.TB (Oxford Immunotec Ltd, Abingdon, UK), are based on the detection of a T-cell immune response towards RD1 antigens (ESAT-6 and CFP-10), with the addition of the TB7.7 antigen for the QFT only [1]. IGRAs are endowed with great specificity, as the antigens used are almost exclusively expressed by the Mycobacterium tuberculosis (MTB) complex, but not Mycobacterium bovis bacille Calmette-Guerin (BCG) [1][2][3]. However, the diagnostic sensitivity of IGRAs can be improved (75-85% in HIV-negative active TB patients) especially in countries with a high TB burden [3].…”

“…The development of rapid and sensitive diagnostic methods for active TB, latent TB infection and recent MTB infection is a key aspect of the TB control strategy [1][2][3]. The addition of the novel peptides to the QFT resulted in a significant increase in the IFN-γ release in active TB, without altering specificity, and also in the BCG-vaccinated control population.…”

“…The World Health Organization (WHO) has recently published a framework on tuberculosis (TB) elimination opening debates on elimination and multidrug-resistant (MDR)-TB [1,2]. The document highlights MDR-TB as a core area, emphasising the moral duty of preventing the selection of MDR-TB (by treating susceptible cases correctly with first-line drugs) and the necessary efforts to treat it when diagnosed.…”