Blood test levels predict who develops symptomatic tuberculosis
Frahm Nicole and colleagues found higher QuantiFERON® TB-Gold Plus IFN γ levels, especially TB2, were linked to later symptomatic tuberculosis in high-burden settings.
Tuberculosis (TB) remains a major global health problem, and a key challenge for prevention is identifying people who are most likely to progress from infection to symptomatic disease. Predictive biomarkers that flag that risk could help focus preventive treatment and follow-up where it will do the most good. In an exploratory analysis reported by Frahm Nicole and colleagues, researchers examined whether quantitative results from a widely used immune test could serve that role. They analyzed baseline Interferon-Gamma (IFNγ) concentrations measured by QuantiFERON® TB-Gold Plus (QFT-Plus), which reports two antigen-stimulated values called TB1 and TB2. The study included 5,259 participants recruited from TB-endemic regions and followed them for a median of 525 days. Participants were grouped as controls (no TB), suspected TB (clinical suspicion without microbiologic confirmation), laboratory-confirmed TB, and a stringent case definition requiring ≥2 positive microbiologic tests. The goal was to test whether higher QFT-Plus IFNγ concentrations at study entry were associated with later progression to symptomatic tuberculosis.
The investigators looked at baseline TB1 and TB2 IFNγ concentrations in relation to subsequent TB outcomes. In the full cohort, TB2 IFNγ concentrations at baseline were significantly higher than in controls among participants who went on to develop suspected TB (p=0.01), laboratory-confirmed TB (p=0.01), and those meeting the stringent case definition (p<0.0001). When the analysis was limited to IGRA+ participants, baseline TB2 concentrations remained significantly higher than controls for suspected (p=0.01) and laboratory-confirmed (p=0.02) groups. Associations with baseline TB1 IFNγ concentrations were observed for participants meeting the stringent case definition within the full cohort (p=0.009). For the subset meeting the stringent definition, TB2 concentrations produced an area under the Receiver Operating Characteristic curve of 0.84, with a sensitivity of 80% and specificity of 78%. The authors noted that these quantitative QFT-Plus IFNγ results, particularly TB2, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers.
These findings suggest that quantitative IFNγ measurements from an existing test, QuantiFERON® TB-Gold Plus, could help identify people at higher risk of progressing to symptomatic TB in high-burden settings. The stronger signal from the TB2 antigen tube, and the performance seen in the stringent case group, indicate that reporting numeric IFNγ concentrations rather than only a positive/negative result may add useful prognostic information. Because the study was conducted across TB-endemic regions and included over five thousand participants followed for a median of roughly a year and a half, the results provide an encouraging signal that a tool already used in many settings could be repurposed to support biomarker-based stratification in TB clinical research. While described as an exploratory analysis, the study authors conclude that quantitative QFT-Plus results may support targeted prevention efforts and the design of trials that aim to prevent progression to symptomatic tuberculosis.
Using numeric IFNγ results from QuantiFERON® TB-Gold Plus could help target preventive therapy to people most likely to develop symptomatic TB. This approach may improve efficiency of TB control programs and focus resources where they are likely to prevent disease.
Author: Justine Sunshine