ArticleCommunications medicine2026
Combining ADA, IFN-γ, and IL-6 as host biomarkers enhances diagnosis of paucibacillary and extrapulmonary tuberculosis.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
6 authors.
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Abstract
backgroundAccurate diagnosis of paucibacillary and extrapulmonary tuberculosis remains a major global challenge, as conventional pathogen-focused methods often lack sensitivity. This study aimed to evaluate whether combining host-derived immune biomarkers could improve diagnostic accuracy.
methodsIn a retrospective diagnostic accuracy study of 605 participants, nucleic acid amplification tests served as the reference standard. We assessed the performance of adenosine deaminase, interferon-gamma, and interleukin-6 individually and in combination using receiver operating characteristic analysis. Serial (rule-in) and parallel (rule-out) testing algorithms were compared to define strategies for confirmation or exclusion of disease.
resultsHere we show that while interferon-gamma was the strongest single discriminator, combinations of biomarkers significantly outperform any single marker. The dual-panel of interferon-gamma and interleukin-6 achieves the highest overall accuracy. Serial testing of adenosine deaminase and interferon-gamma maximizes specificity to 97.4% (95% CI: 95.6-98.7%), providing a reliable rule-in tool. Conversely, parallel testing of all three biomarkers achieves 94.9% (95% CI: 95.6-98.7%)sensitivity, enabling an effective rule-out strategy.
conclusionsThe integration of complementary host biomarkers overcomes the inherent limitations of single analyte tests. By enabling adaptable, context-specific algorithms tailored for either high-specificity confirmation or high-sensitivity screening, this approach provides a scalable and cost-effective diagnostic approach, tailored for resource-constrained settings.
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