Past and Present Approaches to Diagnosis of Active Pulmonary Tuberculosis

Abstract

Tuberculosis disease continues to contribute to the mortality burden globally. Due to the several shortcomings of the available diagnostic methods, tuberculosis disease continues to spread. The difficulty to obtain sputum among the very ill patients and the children also affects the quick diagnosis of tuberculosis disease. These challenges warrant investigating different sample types that can provide results in a short time. Highlighted in this review are the approved pulmonary tuberculosis diagnostic methods and ongoing research to improve its diagnosis. We used the PRISMA guidelines for systematic reviews to search for studies that met the selection criteria for this review. In this review we found out that enormous biosignature research is ongoing to identify host biomarkers that can be used as predictors of active PTB disease. On top of this, more research was also being done to improve already existing diagnostic tests. Host markers required more optimization for use in different settings given their varying sensitivity and specificity in PTB endemic and non-endemic settings.

Keywords: biomarkers; diagnosis; immune response; immunodiagnostic assay; tuberculosis.

Figure 1

PRISMA flow chart indicating the data extraction process. Adapted from Page et al. (14).

Figure 2

Blood transcriptomic markers predictive of active PTB. OAS, 2'-5'-Oligoadenylate Synthetase 1; IF, Interferon alpha-inducible protein 6; IFI, Interferon Gamma Inducible Protein; IRF, Interferon Regulatory Factor; IFIH, Interferon-induced helicase C domain-containing protein; IFIT, Interferon Induced Protein With Tetratricopeptide Repeats; IFITM, Interferon-induced transmembrane protein; GBP, guanylate-binding protein; STAT, signal transducer and activator of transcription; TAP, Transporter associated with Antigen Processing; SOCS, Suppressor of cytokine signaling; CXCL, C-X-C Motif Chemokine Ligand; FCGR, Low-affinity immunoglobulin gamma Fc region receptor; CD, Cluster of differentiation; LTF, Lactotransferrin; OSM, Oncostatin M; SERP-ING1, plasma protease C1 inhibitor; ICAM, Intercellular Adhesion Molecule; CHRM, Cholinergic Receptor Muscarinic; AMPH, Amphiphysin; SNX, Sorting Nexin; PIGC, Phosphatidylinositol N-acetylglucosaminyltransferase subunit C; TAS2R46, Taste 2 Receptor Member 46; HBD, Hemoglobin subunit delta; GLDC, Glycine Decarboxylase; ACOT, Acyl-CoA thioesterase; S100P, S100 Calcium Binding Protein P; STYXL, Serine/Threonine/Tyrosine Interacting Protein; IL, interleukin; BCL, B-cell lymphoma; CASP, cysteine-dependent aspartate-directed proteases; TGFB, transforming growth factor-beta; TGFBR, transforming growth factor-beta receptor; TNFRSFIB, tumor necrosis factor II receptor; SEC, Selenocysteine; NCAM, Neural Cell Adhesion Molecule; CCR, C-C Motif Chemokine Receptor; PTPRCv, protein tyrosine phosphatase receptor type C; GATA, Erythroid transcription factor. CTLA, Cytotoxic T-Lymphocyte Associated Protein; GNLY, Granulysin; TLR, Toll-like receptor; NLP, Nucleoplasmin-like protein; TIMP, tissue inhibitor of metalloproteinases; AREG, Amphiregulin; RAB, G-protein; BPI, Bactericidal Permeability Increasing Protein; TWIST, Twist-related protein; BLR, beta-lactam resistance protein; AIRE, Autoimmune regulator; MRC, Mannose Receptor C; Nod, nodulation; TAGAP, T-cell activation RhoGTPase activating protein; SPP, Signal Peptide Peptidase.