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Background <p>Accurate 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.</p> Methods <p>In 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.</p> Results <p>Here 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.</p> Conclusions <p>The 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.</p>

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Combining ADA, IFN-γ, and IL-6 as host biomarkers enhances diagnosis of paucibacillary and extrapulmonary tuberculosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月8日

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  • Zhan Qiu Mao,
  • Jia Mao,
  • Huilie Zheng,
  • Qian Zhong Liu,
  • Xiao Mei Tang,
  • Qi Long Zhang

摘要

Background

Accurate 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.

Methods

In 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.

Results

Here 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.

Conclusions

The 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.