Associations Between QuantiFERON-TB Gold Plus IFN γ Concentrations and Progression to Symptomatic Tuberculosis in Global High-Burden TB Settings
Year: 2026
Type: preprint
Abstract: Introduction Predictive biomarkers for symptomatic tuberculosis (TB) progression would transform targeted prevention efforts. Although interferon-gamma release assays (IGRAs), including QuantiFERON® TB-Gold Plus (QFT-Plus), have been studied for this purpose, systematic evaluation of the QFT-Plus TB1 and TB2 Interferon-Gamma (IFNγ) concentrations remains limited, particularly in high-burden TB settings. Methods Baseline TB1 and TB2 IFNγ concentrations from 5,259 participants in TB-endemic regions were analyzed in relation to subsequent TB outcomes over a median of 525 days follow-up. Participants were categorized as controls (no TB), suspected TB (no microbiological confirmation), or laboratory-confirmed TB, including a subset meeting a stringent case definition (≥2 positive microbiologic tests). Associations between baseline IFNγ concentrations and progression to symptomatic TB were assessed. Results In the full cohort (IGRA+/-participants), baseline TB2 IFNγ concentrations were significantly higher compared to controls among participants who developed suspected TB (p=0.01), laboratory-confirmed TB (p=0.01), or met the stringent case definition (p<0.0001). In IGRA+ participants, baseline TB2 concentrations were significantly higher than controls in suspected (p=0.01) and laboratory-confirmed (p=0.02) groups. Associations with baseline TB1 IFNγ concentrations and TB progression were observed for participants meeting the stringent case definition within the full cohort (p=0.009). Among stringent definition cases, TB2 concentrations achieved an area under the Receiver Operating Characteristic curve of 0.84, with a sensitivity of 80% and specificity of 78%. Conclusions Quantitative IFNγ concentrations from QFT-Plus, particularly TB2, were associated with progression to symptomatic TB, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers, and may support biomarker-based stratification in TB clinical research. Summary In an exploratory analysis from a global tuberculosis (TB) epidemiology study, higher QuantiFERON-TB Gold Plus IFNγ concentrations were associated with progression to symptomatic TB and met WHO predictive biomarker thresholds, supporting their potential value for risk stratification in TB research.
Authors: Justine Sunshine, Michael Shaffer, Linda L. Han, Deepali Gaikwad, Amelia A. Houana, Maria Tarcela Gler, Sri Rezeki Hadinegoro, Willem A. Hanekom, Javier R. Lama, Monde Muyoyeta, Sissy Musala, Videlis Nduba, Valeria C. Rolla, Tapash Roy, Jayne S. Sutherland, Celso Khosa, Anne Wajja, Timothy M. Walker, Amy Cinar, Alexander C. Schmidt, Alemnew F. Dagnew, Nicole Frahm, TBV02-E01 Study Group
Institutions: Manhiça Health Research Centre, University of Indonesia, Africa Health Research Institute, Asociación Civil Impacta Salud y Educación, Centre for Infectious Disease Research in Zambia, Kenya Medical Research Institute, Fundação Oswaldo Cruz, Institut de Recherche pour le Développement, MRC Unit the Gambia, Medical Research Council, Eduardo Mondlane University, Liverpool School of Tropical Medicine, Instituto Nacional de Saúde, London School of Hygiene & Tropical Medicine, MRC/UVRI & LSHTM Uganda Research Unit, Uganda Virus Research Institute, University of Oxford, Oxford University Clinical Research Unit
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7127436522