We investigated host-derived biomarkers that were previously identified in QuantiFERON supernatants, in a large pan-African study. We recruited individuals presenting with symptoms of pulmonary TB at seven peripheral healthcare facilities in six African countries, prior to assessment for TB disease. We then evaluated the concentrations of 12 biomarkers in stored QuantiFERON supernatants using the Luminex platform. Based on laboratory, clinical and radiological findings and a pre-established algorithm, participants were classified as TB disease or other respiratory diseases(ORD). Of the 514 individuals included in the study, 179(34.8%) had TB disease, 274(51.5%) had ORD and 61(11.5%) had an uncertain diagnosis. A biosignature comprising unstimulated IFN-γ, MIP-1β, TGF-α and antigen-specific levels of TGF-α and VEGF, identified on a training sample set (n = 311), validated by diagnosing TB disease in the test set (n = 134) with an AUC of 0.81(95% CI, 0.76–0.86), corresponding to a sensitivity of 64.2%(95% CI, 49.7–76.5%) and specificity of 82.7%(95% CI, 72.4–89.9%). Host biomarkers detected in QuantiFERON supernatants can contribute to the diagnosis of active TB disease amongst people presenting with symptoms requiring investigation for TB disease, regardless of HIV status or ethnicity in Africa.

Background: In the search for fast, simple and better ways for diagnosis of tuberculosis (TB), there is need to discover and evaluate new biomarkers that are found in samples other than sputum to determine their effectiveness. This study examined the utility of saliva vis-a-vis serum by evaluating levels of biomarkers found in saliva and serum from TB suspects. Methods: Study enrolled tuberculosis suspects. Sputum MGIT was used as the gold standard for active TB. Quantiferon gold-In tube assay was done to identify exposure to Mycobacterium tuberculosis (M.tb). Multiplex assay was run for 10 markers using a 10 plex customized kit from Bio-Rad Laboratories.Results: There was a significant difference between saliva and serum marker levels. Saliva had significantly higher levels of GM-CSF and VEGF. Serum had higher levels of MIP-1a, b, TNF-a, G-CSF and IFN-g. Serum levels of IL-6, VEGF and TNF-a were significantly different between participants with active TB disease and those with other respiratory diseases.

A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance.

No abstract