Combining GBP5 Gene Expression and Adenosine Deaminase To Improve Diagnosis Of Tuberculosis


Principal Investigator 
Dr Le Hong Van 

2023 – 2024

This project aims to develop a more affordable yet effective diagnostic test for TB diagnosis.

Tuberculosis (TB) remains the leading cause of death among single infectious diseases. Early diagnosis is crucial in reducing the burden of this widespread and deadly disease. However, in 2021, more than four million cases went undiagnosed, which increases disease transmission and worsens outcomes.

Biomarkers have been rigorously searched to provide an alternative approach for TB diagnosis: non-sputum-based tests. Adenosine deaminase (ADA) and Interferon-gamma (IFN-γ) are among the most studied and widely used biomarkers in biological fluids. Pleural fluid ADA is more widely used than IFN-γ in clinical practice, especially in low-middle income countries where TB is prevalent, because it is cheaper, easier to use and not inferior to IFN-γ in terms of diagnostic performance. Despite the diagnostic potential, ADA is not on the list of tests endorsed by the World Health Organization. The approach of detecting TB based on the specific host response is urgently needed yet lacking.


  1. Develop a multiplex qPCR test for measuring 3-gene signature in blood samples 
  2. Evaluate and compare the performance of 3-gene signature and standalone GBP5 gene expression in diagnosing different forms of TB: pulmonary TB, pediatric TB, pleural TB effusion and TB meningitis.
  3. Evaluate the performance of combining GBP5 gene expression and ADA. 


ADA levels will be measured in blood and biological fluids, including pleural fluid and CSF. Three-gene expressions will be assessed in blood samples.

Descriptive statistics will be used to describe the study population. Definite TB is defined by microbiological and histopathological evidence. The 3-gene signature (namely TB scores) will be calculated following the published methodology. We evaluated the diagnostic performance of a 3-gene signature, standalone gene GBP5 and ADA in distinguishing TB from other symptom-like infections based on the receiver operating characteristic (ROC) curves and the area under the curve (AUC).   

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