Biomarkers to diagnose active and latent tuberculosis infection and monitor treatment regimen.
- Three biomarkers accurately distinguish active tuberculosis (TB) from latent TB infections with 100% specificity and greater than 96% sensitivity.
- Faster and more accurate test to monitor treatment response among active tuberculosis patients.
- Uses blood samples instead of sputum samples that are more difficult to obtain in some patient population.
Tuberculosis (TB) remains a serious global health problem with more than 9 million new cases and 1.5 million deaths annually. Current diagnostic tests rely on direct smear examination and culture of the respiratory samples. Smear tests fail to diagnose up to 66% of TB cases and culture tests of sputum for Mycobacterium tuberculosis take 4-6 weeks for results. There is an urgent need for reliable and inexpensive tools that can rapidly and accurately identify patients with active TB disease in order to begin treatment promptly. An effective diagnostic would also need to evaluate response to treatment. Because treatment regiments for patients with active and latent TB infections are different, an effective diagnostic test must also reliably distinguish individuals with active TB from those with a latent TB infection.
Although many tests, like host T cell-based tests, can diagnose Mycobacterium tuberculosis (Mtb), they fail to distinguish between active TB and latent TB infection. Emory inventors have identified three biomarkers that predict active TB and latent TB infection status. Expression of these biomarkers, CD38, HLA-DR and Ki-67, was significantly higher on Mtb-specific, IFN-y+ CD4 T cells in individuals with active TB compared to those with latent TB infection. They accurately distinguish active TB from latent TB infections with 100% specificity and higher than 96% sensitivity. In addition, these biomarkers show potential as a gauge of Mtb load in patients suggesting that they may serve as biomarkers of treatment response in patients undergoing anti-TB treatment as well as in clinical trials of new therapeutics.
The specificity and sensitivity of the three biomarkers have been proven in 25 patients with latent tuberculosis infection and 25 patients with active tuberculosis in a test cohort and validated in an independent cohort.
Publication: Adekambi et al. 2015. J Clin Invest March 30