ArticleThe Journal of infectious diseases2026
Host Plasma Protein Biomarkers for Tuberculosis Disease Screening in Febrile Adults in Tanzania.
Article in The Journal of infectious diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHost circulating biomarkers may enhance access to tuberculosis (TB) diagnostics in low-resource settings. We sought to identify host plasma proteins that differentiate TB disease from other infectious causes of fever.
methodsThis secondary analysis of a prospective cohort included outpatients ≥18 years old in urban Tanzania presenting with ≤7 days of fever. Fourteen plasma proteins reflecting endothelial and immunoregulatory pathways were evaluated against a composite reference standard including sputum Xpert MTB/RIF, urine lipoarabinomannan, and/or chest radiography. Multivariable models assessed proteins and symptoms associated with TB diagnosis.
resultsOf 507 participants, 40 (7.9%) had TB disease and 467 (92.1%) had other causes of fever. Eight proteins were significantly elevated (P < .05) in people with TB. Regression modeling identified a 4-protein biosignature (soluble triggering receptor expressed on myeloid cells 1 [sTREM-1], chitinase 3-like protein 1, soluble tumor necrosis factor receptor 1, and C-reactive protein) with a cross-validated median area under the receiver operating characteristic curve (AUC) of 0.81 (2.5th-97.5th percentiles, 0.65-0.93), sensitivity of 80.0% (41.4%-100%), and specificity of 65.5% (54.2%-76.6%); however, discrimination was lower in people living with human immunodeficiency virus (AUC, 0.71 [95% confidence interval, .61-.81]). Classification and regression tree analysis yielded a simplified algorithm incorporating cough and sTREM-1, with a cross-validated AUC of 0.79 (95% confidence interval, .69-.88), sensitivity of 77.5% (61.6%-89.2%), and specificity of 84.2% (80.5%-87.4%); this approach may be more pragmatic for low-resource settings.
conclusionsThis exploratory analysis identified a parsimonious biosignature and biomarker-based algorithm for TB evaluation among febrile adults in a high-burden setting. With further development, host protein-based assays may enhance TB case detection in resource-limited settings.
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