A highly sensitive blood test that detects a protein released directly by Mycobacterium tuberculosis may offer a fast, accurate way to identify active pulmonary tuberculosis (TB), particularly in patients who cannot produce sputum or have early-stage disease, according to research presented July 28 at the 2026 Association for Diagnostics & Laboratory Medicine (ADLM) Annual Scientific Meeting.
The findings suggest that measuring circulating levels of the bacterial protein 6-kDa early secreted antigenic target (ESAT-6) could help clinicians identify patients who need further testing and treatment sooner, potentially reducing transmission of one of the world’s deadliest infectious diseases.
“Every week of delay in diagnosing TB matters—so early identification may allow treatment to begin sooner and potentially reduce transmission,” said lead investigator Sheng-Wei Pan, MD, of Taipei Veterans General Hospital in Taiwan.
Tuberculosis is typically diagnosed by analyzing sputum samples, but many patients—particularly those with early disease or a low bacterial burden—are unable to produce sputum when they first seek medical attention. That limitation has fueled the search for accurate blood-based diagnostic tools.
In the case-control study, investigators measured plasma ESAT-6 concentrations in 213 participants, including 83 patients with active pulmonary TB and 130 controls. The control group included patients with nontuberculous mycobacterial lung disease, lung cancer, latent TB infection, TB-exposed individuals without latent infection, and healthy volunteers.
Patients with active pulmonary TB had significantly higher ESAT-6 levels than every control group. Median plasma concentrations reached 113.6 ng/mL in active TB, compared with 73.0 ng/mL in latent TB infection and 49.8 ng/mL in TB-exposed individuals without latent infection. The researchers observed a clear stepwise increase in ESAT-6 levels across the spectrum of TB infection.
The biomarker also demonstrated excellent diagnostic performance. Receiver operating characteristic analysis yielded an area under the curve (AUC) of 0.976. Using an optimized cutoff of 95 ng/mL, the blood test achieved 95.2% sensitivity and 90.8% specificity for identifying active pulmonary TB. The assay also outperformed commonly used blood markers, including the monocyte-to-lymphocyte ratio and C-reactive protein, and maintained strong performance in clinically important subgroups, including patients with culture-negative TB.
“The novelty of our study lies in the highly sensitive quantification of circulating ESAT-6,” Pan said.
Unlike inflammatory biomarkers that measure the body’s immune response to infection, ESAT-6 is produced directly by the TB bacteria, which investigators believe contributes to its ability to distinguish active disease from latent infection and other lung disorders.
Because the study compared patients whose diagnoses were already known, the researchers caution that prospective clinical studies are needed to confirm the test’s real-world performance.
If validated, ESAT-6 could serve as a valuable laboratory-based triage tool alongside conventional sputum testing, helping clinicians identify patients with active TB sooner while awaiting confirmatory cultures and drug susceptibility testing.
