A blood test that measures the tuberculosis-specific protein ESAT-6 could provide clinical laboratories with a new way to identify active pulmonary tuberculosis (TB) in patients who cannot produce sputum, according to research presented at the 2026 Association for Diagnostics & Laboratory Medicine (ADLM) Annual Meeting.
Although sputum-based testing remains the standard approach for diagnosing TB, collecting adequate samples can be difficult, particularly in patients with early disease or a low bacterial burden. Those delays may postpone treatment and increase opportunities for transmission. The investigators evaluated whether circulating levels of ESAT-6, a protein secreted by Mycobacterium tuberculosis, could serve as a blood-based marker for active disease.
The case-control study included 217 participants with active pulmonary TB or a range of comparison conditions, including latent TB infection, exposure without infection, lung cancer, other mycobacterial lung disease, and healthy controls. Using a quantitative immunoassay, researchers found that blood ESAT-6 levels distinguished patients with active TB from those without the disease and increased progressively across the spectrum from TB exposure to latent infection and active disease.
Unlike many blood tests that measure the body's immune response, ESAT-6 is produced directly by the TB bacterium. That distinction could make it a more specific indicator of active infection rather than prior exposure. In the study, the marker outperformed two commonly used blood-based inflammatory measures and maintained strong diagnostic performance even in culture-negative cases.
The findings point to a potential role for ESAT-6 testing as a triage tool rather than a replacement for conventional microbiological methods. Sputum culture would still be required to confirm infection and determine drug susceptibility, but a rapid blood test could help prioritize patients for further investigation when sputum collection is not possible or results are delayed.
The authors caution that the current study was retrospective, meaning participants' disease status was already known. A prospective clinical study is planned to determine whether the assay performs as well in routine practice before it can be considered for broader diagnostic use.
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