Update on clinical biomarkers in the diagnosis of tuberculosis
DOI:
https://doi.org/10.62305/biosana.v5i3.653Keywords:
mycobacterium tuberculosis; pulmonary tuberculosis; diagnosis; biomarkersAbstract
Tuberculosis remains one of the leading causes of morbidity and mortality from infectious diseases worldwide. Although it is a preventable condition, timely diagnosis continues to be a major public health challenge, particularly in developing countries. This review is based on a descriptive and retrospective analysis of bibliographic sources. An meticulous literature review was conducted using databases such as PubMed, Scielo, Scopus, BVS, ScienceDirect, and epidemiological bulletins from the Ministry of Public Health of Ecuador. The article provides a comparative analysis between conventional laboratory diagnostic methods and the the usefulness and reliability of biomarkers derived from both the host and the pathogen. In response to current diagnostic limitations, omics-based approaches such as proteomics, transcriptomics, and metabolomics have emerged as promising alternatives for identifying diagnostic biomarkers in accessible biological fluids such as blood, serum, plasma, and urine. It is concluded that the detection of multiple biomarkers, including metabolites, microRNAs, lncRNA, and proteins, shows promising potential for achieving a minimally invasive diagnosis. However, further research is needed to confirm and validate relevant biosignatures in clinical practice.
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References
World Health Organization. 2024 Global tuberculosis report [Internet]. Geneva; 2024 [cited 2025 Jun 4]. Available from: https://www.who.int/publications/i/item/9789240101531
Castro-Rodriguez B, León-Ordóñez K, Franco-Sotomayor G, Benítez-Medina JM, Jiménez-Pizarro N, Cárdenas-Franco G, et al. Population structure of Mycobacterium tuberculosis in El Oro: A first insight into Ecuador-Peru tuberculosis transmission. J Infect Public Health [Internet]. 2024 Mar 1 [cited 2025 Jun 9];17(3):527–34. Available from: https://www.sciencedirect.com/science/article/pii/S1876034124000212
Boldi MO, Denis-Lessard J, Neziri R, Brouillet R, von-Garnier C, Chavez V, et al. Performance of microbiological tests for tuberculosis diagnostic according to the type of respiratory specimen: A 10-year retrospective study. Front Cell Infect Microbiol. 2023;13.
Cho Y, Park Y, Sim B, Kim J, Lee H, Cho SN, et al. Identification of serum biomarkers for active pulmonary tuberculosis using a targeted metabolomics approach. Sci Rep. 2020;10(1).
Schiff HF, Walker NF, Ugarte-Gil C, Tebruegge M, Manousopoulou A, Garbis SD, et al. Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. JCI Insight [Internet]. 2024;9(8). Available from: https://pubmed.ncbi.nlm.nih.gov/38512356/
Oreskovic A, Panpradist N, Marangu D, William Ngwane M, Magcaba ZP, Ngcobo S, et al. Diagnosing pulmonary tuberculosis by using sequence-specific purification of urine cell-free dna. J Clin Microbiol. 2021;59(8).
Pedersen JL, Barry SE, Bokil NJ, Ellis M, Yang YR, Guan G, et al. High sensitivity and specificity of a 5-analyte protein and microRNA biosignature for identification of active tuberculosis. Clin Transl Immunology. 2021;10(6).
Tobin EH, Tristram D. Tuberculosis Overview. StatPearls [Internet]. 2024 Dec 22 [cited 2025 Jun 4]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK441916/
Ramirez-Vélez JL, Ortiz--Mera DL, Lucas-Parrales EN. Prevalencia y prevención de la tuberculosis pulmonar en poblaciones Latinoamericanas. MQRInvestigar [Internet]. 2023 Aug 12 [cited 2025 Jun 9];7(3):2144–57. Available from: https://www.investigarmqr.com/ojs/index.php/mqr/article/view/560
Garzon-Chavez D, Garcia-Bereguiain MA, Mora-Pinargote C, Granda-Pardo JC, Leon-Benitez M, Franco-Sotomayor G, et al. Population structure and genetic diversity of Mycobacterium tuberculosis in Ecuador. Sci Rep [Internet]. 2020 Dec 1 [cited 2025 Jun 9];10(1):6237. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7148308/
Ministerio de Salud Pública. Análisis Indicadores priorizados de la Estrategia Fin de la TB [Internet]. 2022 [cited 2025 Jun 4]. Available from: https://www.salud.gob.ec/wp-content/uploads/2023/10/Reporte-de-TB-2019-2022-vd-signed-signed-signed-signed-signed.pdf
Ministerio de Salud Pública. GACETAS TUBERCULOSIS – Ministerio de Salud Pública [Internet]. [cited 2025 Jun 9]. Available from: https://www.salud.gob.ec/gacetas-tuberculosis/
Ge P, Lei Z, Yu Y, Lu Z, Qiang L, Chai Q, et al. M. tuberculosis PknG manipulates host autophagy flux to promote pathogen intracellular survival. Autophagy [Internet]. 2021 [cited 2025 Jun 10];18(3):576. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9037497/
Tapia-Sequeiros G, Hueda-Zavaleta M, Gómez de la Torre JC, Hernandez-Vargas A, Barletta-Carrillo C, Flores C, et al. Rendimiento diagnóstico de las técnicas de tinción Ziehl-Neelsen y Auramina-Rodamina en la detección de tuberculosis pulmonar y extrapulmonar. Rev Peru Med Exp Salud Publica [Internet]. 2025 Jun 9 [cited 2025 Jun 11];42(1):37–45. Available from: https://rpmesp.ins.gob.pe/index.php/rpmesp/article/view/14062
Chen WC, Chang CC, Lin YE. Pulmonary Tuberculosis Diagnosis Using an Intelligent Microscopy Scanner and Image Recognition Model for Improved Acid-Fast Bacilli Detection in Smears. Microorganisms 2024, Vol 12, Page 1734 [Internet]. 2024 Aug 22 [cited 2025 Jun 4];12(8):1734. Available from: https://www.mdpi.com/2076-2607/12/8/1734/htm
Hueda-Zavaleta M, Gomez-de-la-Torre J, Barletta-Carrillo C, Flores-Flores C, Piscoche-Botello N, Miranda-Visalot C, et al. Diagnostic accuracy of Xpert MTB/RIF and Xpert ultra tests in pulmonary and extrapulmonary tuberculosis compared to Löwenstein-Jensen culture. Clin Epidemiol Glob Health [Internet]. 2024 Sep 1 [cited 2025 Jun 10];29:101730. Available from: https://www.sciencedirect.com/science/article/pii/S2213398424002264#sec4
Maharjan B, Thapa J, Shah DK, Shrestha B, Avsar K, Suzuki Y, et al. Comparison of Xpert MTB/RIF to Microscopy and Culture for the Diagnosis of Tuberculosis in a Referral Laboratory in Nepal. Jpn J Infect Dis. 2021 Nov 22;74(6):517–21.
Phetsuksiri B, Klayut W, Rudeeaneksin J, Srisungngam S, Bunchoo S, Toonkomdang S, et al. The performance of an in-house loop-mediated isothermal amplification for the rapid detection of mycobacterium tuberculosis in sputum samples in comparison with xpert MTB/RIF, microscopy and culture. Rev Inst Med Trop Sao Paulo. 2020;62.
Lyu L, Li Z, Pan L, Jia H, Sun Q, Liu Q, et al. Evaluation of digital PCR assay in detection of M.tuberculosis IS6110 and IS1081 in tuberculosis patients plasma. BMC Infect Dis [Internet]. 2020 Sep 7 [cited 2025 Jun 12];20(1):657. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7487892/
Estévez O, Anibarro L, Garet E, Pallares Á, Barcia L, Calviño L, et al. An RNA-seq Based Machine Learning Approach Identifies Latent Tuberculosis Patients With an Active Tuberculosis Profile. Front Immunol. 2020;11.
Li G, Feng Z, Song H, Wang Y, Zhu L, Li Y. Long non-coding RNA expression in PBMCs of patients with active pulmonary tuberculosis. Front Microbiol. 2023;14.
Li Z Bin, Shi LY, Han YS, Chen J, Zhang SQ, Chen JX, et al. Pyridoxal phosphate, pyridoxamine phosphate, and folic acid based on ceRNA regulatory network as potential biomarkers for the diagnosis of pulmonary tuberculosis. Infection, Genetics and Evolution. 2022;99.
Zhang P, Zheng J, Han T, Ma J, Gnanashanmugam D, Li M, et al. A blood-based 3-gene signature score for therapeutic monitoring in patients with pulmonary tuberculosis. Tuberculosis [Internet]. 2024 Jul 1 [cited 2025 Jun 4];147:102521. Available from: https://www.sciencedirect.com/science/article/pii/S1472979224000477?via%3Dihub
Amin AG, De P, Graham B, Calderon RI, Franke MF, Chatterjee D. Urine lipoarabinomannan in HIV uninfected, smear negative, symptomatic TB patients: effective sample pretreatment for a sensitive immunoassay and mass spectrometry. Sci Rep. 2021;11(1).
Sun Y, Liao Y, Xiong N, He X, Zhang H, Chen X, et al. Amino Acid Profiling as A Screening and Prognostic Biomarker in Active Tuberculosis Patients. Clinica Chimica Acta. 2023;548.
Sun X, Liu K, Zhao Y, Zhang T. High miRNA-378 expression has high diagnostic values for pulmonary tuberculosis and predicts adverse outcomes. BMC Mol Cell Biol. 2022;23(1).
Bayaa R, Ndiaye MDB, Chedid C, Kokhreidze E, Tukvadze N, Banu S, et al. Multi-country evaluation of RISK6, a 6-gene blood transcriptomic signature, for tuberculosis diagnosis and treatment monitoring. Sci Rep. 2021;11(1).
Mesman AW, Calderon RI, Hauns L, Pollock NR, Mendoza M, Holmberg RC, et al. Detection of Mycobacterium tuberculosis transrenal DNA in urine samples among adults in Peru. Tuberculosis [Internet]. 2024 Sep 1 [cited 2025 Jun 17];148:102549. Available from: https://www.sciencedirect.com/science/article/pii/S1472979224000751?via%3Dihub
Wang X, Wu Z, Zeng J, Zhao Y, Zhang C, Yu M, et al. Untargeted metabolomics of pulmonary tuberculosis patient serum reveals potential prognostic markers of both latent infection and outcome. Front Public Health [Internet]. 2022 Nov 15 [cited 2025 Jun 17];10:962510. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9705731/
Viode A, van Zalm P, Smolen KK, Fatou B, Stevenson D, Jha M, et al. A simple, time- and cost-effective, high-throughput depletion strategy for deep plasma proteomics. Sci Adv [Internet]. 2023 Mar 29 [cited 2025 Jun 17];9(13). Available from: /doi/pdf/10.1126/sciadv.adf9717?download=true
Wu M, Liu Z, Zhang S. Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis. Innate Immun [Internet]. 2021 Jan 1 [cited 2025 Jun 17];28(1):11. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8841633/
Wu Z, Tan Q, Jia X, Wu H, Liang J, Wen W, et al. Single molecule measurements of microRNAs in the serum of patients with pulmonary tuberculosis. Front Immunol [Internet]. 2024;15:1418085. Available from: https://pubmed.ncbi.nlm.nih.gov/39286248/
Chen J, Wu L, Lv Y, Liu T, Guo W, Song J, et al. Screening of Long Non-coding RNAs Biomarkers for the Diagnosis of Tuberculosis and Preliminary Construction of a Clinical Diagnosis Model. Front Microbiol [Internet]. 2022 Mar 3 [cited 2025 Jun 17];13:774663. Available from: www.frontiersin.org
Hoa NB, Fajans M, Nguyen Van H, Vu Ngoc B, Nguyen Viet N, Nguyen Thi H, et al. Urine lipoarabinomannan concentrations among HIV-negative adults with pulmonary or extrapulmonary tuberculosis disease in Vietnam. Gupta RK, editor. PLOS Global Public Health [Internet]. 2024 Nov 6 [cited 2025 Jun 17];4(11):e0003891. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11540228/
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