Biomarkers in Diagnosis of Tuberculosis

cocukgogus-4-3-2023-kapak

Ece OCAKa , Gökçen KARTAL ÖZTÜRKa , Figen GÜLENa

aEge University Faculty of Medicine, Department of Pediatric Chest Diseases, İzmir, Türkiye

ABSTRACT
Tuberculosis (TB) is a preventable and curable infectious disease that remains a serious public health problem, mainly due to inadequate diagnosis and treatment. Efforts have focused on discovering new biomarkers with higher efficiency and accuracy for TB diagnosis, derived from an easily accessed sample. Limitations of promising TB biomarker studies in children are lack of validation in different populations, small sample sizes, and typically Mycobacterium tuberculosis (Mtb)-negative pulmonary TB. WHO recommendations are; Mtb PCR tests (Xpert MTB/RIF, Xpert MTB/RIF Ultra, Truenat®) to diagnose active tuberculosis disease (ATB) and artificial-intelligence-based computeraided detection to screen pulmonary TB for all children; and lipoarabinomannan to diagnose ATB and CRP to screen ATB for HIV-positive children. Here we described most of the recent advances in research of biomarkers (Mtb PCR, lipoarabinomannan, Mtb-spesific proteins, cytokine response, transcriptomics, proteomics, metabolomics, miRNA, Mtb-specific CD4+ and CD8+ T cells) for the diagnosis of ATB, latent tuberculosis infection and treatment response.
Keywords: Tuberculosis; biomarkers; child

Referanslar

  1. Bagcchi S. WHO's Global Tuberculosis Report 2022. The Lancet Microbe. 2023;4(1):e20. [Crossref]  [PubMed]
  2. Goletti D, Petruccioli E, Joosten SA, Ottenhoff THM. Tuberculosis Biomarkers: From Diagnosis to Protection. Infect Dis Rep. 2016;8(2):6568. [Crossref]  [PubMed]  [PMC]
  3. World Health Organization. (2014). High priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting, 28-29 April 2014, Geneva, Switzerland: World Health Organization
  4. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95. [Crossref]  [PubMed]
  5. Goletti D, Lee MR, Wang JY, Walter N, Ottenhoff THM. Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease. Respirology. 2018;23(5):455-66. [Crossref]  [PubMed]
  6. Wallis RS, Peppard T. Early Biomarkers and Regulatory Innovation in Multidrug-Resistant Tuberculosis. Clin Infect Dis. 2015;61Suppl 3:S160-S3. [Crossref]  [PubMed]
  7. Dorman SE, Schumacher SG, Alland D, Nabeta P, Armstrong DT, King B, et al. Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect Dis. 2018;18(1):76-84. [Crossref]  [PubMed]
  8. Nogueira BMF, Krishnan S, Barreto-Duarte B, Araújo-Pereira M, Queiroz ATL, Ellner JJ, et al. Diagnostic biomarkers for active tuberculosis: progress and challenges. EMBO Mol Med. 2022;14(12):e14088. [Crossref]  [PubMed]  [PMC]
  9. Molecular assays intended as initial tests for the diagnosis of pulmonary and extrapulmonary TB and rifampicin resistance in adults and children: rapid communication. Policy update. Geneva: World Health Organization; 2020. World Health Organization. Published 2020. (cited: August 2023. [Link]
  10. Flores J, Cancino JC, Chavez-Galan L. Lipoarabinomannan as a Point-of-Care Assay for Diagnosis of Tuberculosis: How Far Are We to Use It? Front Microbiol. 2021;12:638047. [Crossref]  [PubMed]  [PMC]
  11. Bjerrum S, Schiller I, Dendukuri N, Kohli M, Nathavitharana RR, Zwerling AA, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019;10(10):CD011420. [Crossref]  [PubMed]  [PMC]
  12. Sigal GB, Pinter A, Lowary TL, Kawasaki M, Li A, Mathew A, et al. A Novel Sensitive Immunoassay Targeting the 5-Methylthio-d-Xylofuranose-Lipoarabinomannan Epitope Meets the WHO's Performance Target for Tuberculosis Diagnosis. J Clin Microbiol. 2018;56(12). [Crossref]  [PubMed]  [PMC]
  13. Li Z, Tong X, Liu S, Yue J, Fan H. The Value of FujiLAM in the Diagnosis of Tuberculosis: A Systematic Review and Meta-Analysis. Front Public Health. 2021;9:757133. [Crossref]  [PubMed]  [PMC]
  14. Nicol MP, Schumacher SG, Workman L, Broger T, Baard C, Prins M, et al. Accuracy of a Novel Urine Test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan, for the Diagnosis of Pulmonary Tuberculosis in Children. Clin Infect Dis. 2021;72(9):e280-e8. [Crossref]  [PubMed]  [PMC]
  15. Bulterys MA, Wagner B, Redard-Jacot M, Suresh A, Pollock NR, Moreau E, et al. Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update. J Clin Med Res. 2019;9(1). [Crossref]  [PubMed]  [PMC]
  16. Kashyap RS, Rajan AN, Ramteke SS, Agrawal VS, Kelkar SS, Purohit HJ, et al. Diagnosis of tuberculosis in an Indian population by an indirect ELISA protocol based on detection of Antigen 85 complex: a prospective cohort study. BMC Infect Dis. 2007;7:74. [Crossref]  [PubMed]  [PMC]
  17. Carranza C, Pedraza-Sanchez S, de Oyarzabal-Mendez E, Torres M. Diagnosis for Latent Tuberculosis Infection: New Alternatives. Front Immunol. 2020;11:2006. [Crossref]  [PubMed]  [PMC]
  18. Meier NR, Jacobsen M, Ottenhoff THM, Ritz N. A Systematic Review on Novel Mycobacterium tuberculosis Antigens and Their Discriminatory Potential for the Diagnosis of Latent and Active Tuberculosis. Front Immunol. 2018;9:2476. [Crossref]  [PubMed]  [PMC]
  19. Liu C, Zhao Z, Fan J, Lyon CJ, Wu HJ, Nedelkov D, et al. Quantification of circulating Mycobacterium tuberculosis antigen peptides allows rapid diagnosis of active disease and treatment monitoring. Proc Natl Acad Sci U S A. 2017;114(15):3969-74. [Crossref]  [PubMed]  [PMC]
  20. Aggerbeck H, Giemza R, Joshi P, Tingskov PN, Hoff ST, Boyle J, et al. Randomised clinical trial investigating the specificity of a novel skin test (C-Tb) for diagnosis of M. tuberculosis infection. PLoS One. 2013;8(5):e64215. [Crossref]  [PubMed]  [PMC]
  21. Zetola NM, Modongo C, Matsiri O, Tamuhla T, Mbongwe B, Matlhagela K, et al. Diagnosis of pulmonary tuberculosis and assessment of treatment response through analyses of volatile compound patterns in exhaled breath samples. J Infect. 2017;74(4):367-76. [Crossref]  [PubMed]  [PMC]
  22. Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK, Natividad MPR, et al. Breath biomarkers of active pulmonary tuberculosis. Tuberculosis . 2010;90(2):145-51. [Crossref]  [PubMed]
  23. Steingart KR, Flores LL, Dendukuri N, Schiller I, Laal S, Ramsay A, et al. Commercial serological tests for the diagnosis of active pulmonary and extrapulmonary tuberculosis: an updated systematic review and meta-analysis. PLoS Med. 2011;8(8):e1001062. [Crossref]  [PubMed]  [PMC]
  24. Commercial serodiagnostic tests for diagnosis of tuberculosis: policy statement. World Health Organization. Published February 15, 2011. (cited: August 2023). [Link]
  25. Perley CC, Frahm M, Click EM, Dobos KM, Ferrari G, Stout JE, et al. The human antibody response to the surface of Mycobacterium tuberculosis. PLoS One. 2014;9(2):e98938. [Crossref]  [PubMed]  [PMC]
  26. Yong YK, Tan HY, Saeidi A, Wong WF, Vignesh R, Velu V, et al. Immune Biomarkers for Diagnosis and Treatment Monitoring of Tuberculosis: Current Developments and Future Prospects. Front Microbiol. 2019;10:2789. [Crossref]  [PubMed]  [PMC]
  27. MacLean E, Broger T, Yerlikaya S, Fernandez-Carballo BL, Pai M, Denkinger CM. A systematic review of biomarkers to detect active tuberculosis. Nat Microbiol. 2019;4(5):748-58. [Crossref]  [PubMed]
  28. Chegou NN, Sutherland JS, Malherbe S, Crampin AC, Corstjens PLAM, Geluk A, et al. Diagnostic performance of a seven-marker serum protein biosignature for the diagnosis of active TB disease in African primary healthcare clinic attendees with signs and symptoms suggestive of TB. Thorax. 2016;71(9):785-94. [Crossref]  [PubMed]
  29. Cannas A, Calvo L, Chiacchio T, Cuzzi G, Vanini V, Lauria FN, et al. IP-10 detection in urine is associated with lung diseases. BMC Infect Dis. 2010;10:333. [Crossref]  [PubMed]  [PMC]
  30. Whittaker E, Gordon A, Kampmann B. Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS One. 2008;3(12):e3901. [Crossref]  [PubMed]  [PMC]
  31. Jacobs R, Maasdorp E, Malherbe S, Loxton AG, Stanley K, van der Spuy G, et al. Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response. PLoS One. 2016;11(8):e0160546. [Crossref]  [PubMed]  [PMC]
  32. Berry MPR, Graham CM, McNab FW, Xu Z, Bloch SAA, Oni T, et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature. 2010;466(7309):973-7. [Crossref]  [PubMed]  [PMC]
  33. Zak DE, Penn-Nicholson A, Scriba TJ, Thompson E, Suliman S, Amon LM, et al. A blood RNA signature for tuberculosis disease risk: a prospective cohort study. Lancet. 2016;387(10035):2312-22. [Crossref]  [PubMed]
  34. Mendelsohn SC, Mbandi SK, Fiore-Gartland A, Penn-Nicholson A, Musvosvi M, Mulenga H, et al. Prospective multicentre head-to-head validation of host blood transcriptomic biomarkers for pulmonary tuberculosis by real-time PCR. Commun Med. 2022;2(1). [Crossref]  [PubMed]  [PMC]
  35. Scriba TJ, Fiore-Gartland A, Penn-Nicholson A, Mulenga H, Kimbung Mbandi S, Borate B, et al. Biomarker-guided tuberculosis preventive therapy (CORTIS): a randomised controlled trial. Lancet Infect Dis. 2021;21(3):354-65. [Crossref]  [PubMed]
  36. Sweeney TE, Braviak L, Tato CM, Khatri P. Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med. 2016;4(3):213-24. [Crossref]  [PubMed]
  37. Xpert MTB/RIF implementation manual: technical and operational "how-to"; practical considerations. World Health Organization 2014. Published 2014. (cited: August 2023). [Link]
  38. Sutherland JS, van der Spuy G, Gindeh A, Thuong NTT, Namuganga A, Owolabi O, et al. Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results. Clin Infect Dis. 2022;74(12):2136-41. [Crossref]  [PubMed]  [PMC]
  39. Weiner J 3rd, Parida SK, Maertzdorf J, Black GF, Repsilber D, Telaar A, et al. Biomarkers of inflammation, immunosuppression and stress with active disease are revealed by metabolomic profiling of tuberculosis patients. PLoS One. 2012;7(7):e40221. [Crossref]  [PubMed]  [PMC]
  40. 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):3825. [Crossref]  [PubMed]  [PMC]
  41. Dai Y, Shan W, Yang Q, Guo J, Zhai R, Tang X, et al. Biomarkers of iron metabolism facilitate clinical diagnosis in Mycobacterium tuberculosis infection. Thorax. 2019;74(12):1161-7. [Crossref]  [PubMed]  [PMC]
  42. Conde R, Laires R, Gonçalves LG, Rizvi A, Barroso C, Villar M, et al. Discovery of serum biomarkers for diagnosis of tuberculosis by NMR metabolomics including cross-validation with a second cohort. Biomed J. 2022;45(4):654-64. [Crossref]  [PubMed]  [PMC]
  43. Garay-Baquero DJ, White CH, Walker NF, Tebruegge M, Schiff HF, Ugarte-Gil C, et al. Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis. JCI Insight. 2020;5(18). [Crossref]  [PubMed]  [PMC]
  44. Mateos J, Estévez O, González-Fernández Á, Anibarro L, Pallarés Á, Reljic R, et al. Serum proteomics of active tuberculosis patients and contacts reveals unique processes activated during Mycobacterium tuberculosis infection. Sci Rep. 2020;10(1):3844. [Crossref]  [PubMed]  [PMC]
  45. De Groote MA, Sterling DG, Hraha T, Russell TM, Green LS, Wall K, et al. Discovery and Validation of a Six-Marker Serum Protein Signature for the Diagnosis of Active Pulmonary Tuberculosis. J Clin Microbiol. 2017;55(10):3057-71. [Crossref]  [PubMed]  [PMC]
  46. Sinigaglia A, Peta E, Riccetti S, Venkateswaran S, Manganelli R, Barzon L. Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers. Cells. 2020;9(10). [Crossref]  [PubMed]  [PMC]
  47. Sampath P, Periyasamy KM, Ranganathan UD, Bethunaickan R. Monocyte and Macrophage miRNA: Potent Biomarker and Target for Host-Directed Therapy for Tuberculosis. Front Immunol. 2021;12:667206. [Crossref]  [PubMed]  [PMC]
  48. Rozot V, Patrizia A, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, et al. Combined use of Mycobacterium tuberculosis-specific CD4 and CD8 T-cell responses is a powerful diagnostic tool of active tuberculosis. Clin Infect Dis. 2015;60(3):432-37. [Crossref]  [PubMed]  [PMC]
  49. Feruglio SL, Trøseid M, Damås JK, Kvale D, Dyrhol-Riise AM. Soluble markers of the Toll-like receptor 4 pathway differentiate between active and latent tuberculosis and are associated with treatment responses. PLoS One. 2013;8(7):e69896. [Crossref]  [PubMed]  [PMC]
  50. Portevin D, Moukambi F, Clowes P, Bauer A, Chachage M, Ntinginya NE, et al. Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study. Lancet Infect Dis. 2014;14(10):931-8. [Crossref]  [PubMed]
  51. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial. Lancet. 2013;381(9871):1021-8. [Crossref]  [PubMed]
  52. Fletcher HA, Snowden MA, Landry B, Rida W, Satti I, Harris SA, et al. T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nat Commun. 2016;7:11290. [Crossref]  [PubMed]  [PMC]
  53. Esmail H, Lai RP, Lesosky M, Wilkinson KA, Graham CM, Coussens AK, et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat Med. 2016;22(10):1090-3. [Crossref]  [PubMed]  [PMC]
  54. Fortún J, Martín-Dávila P, Gómez-Mampaso E, Vallejo A, Cuartero C, González-García A, et al. Extra-pulmonary tuberculosis: a biomarker analysis. Infection. 2014;42(4):649-54. [Crossref]  [PubMed]
  55. Kathamuthu GR, Kumar NP, Moideen K, Nair D, Banurekha VV, Sridhar R, et al. Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Are Potential Biomarkers of Pulmonary and Extra-Pulmonary Tuberculosis. Front Immunol. 2020;11:419. [Crossref]  [PubMed]  [PMC]
  56. Chegou NN, Sutherland JS, Namuganga AR, Corstjens PL, Geluk A, Gebremichael G, et al. Africa-wide evaluation of host biomarkers in QuantiFERON supernatants for the diagnosis of pulmonary tuberculosis. Sci Rep. 2018;8(1):2675. [Crossref]  [PubMed]  [PMC]
  57. Dhana A, Hamada Y, Kengne AP, Kerkhoff AD, Rangaka MX, Kredo T, et al. Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis. Lancet Infect Dis. 2022;22(4):507-18. [Crossref]  [PubMed]
  58. Doshi R, Falzon D, Thomas BV, Temesgen Z, Sadasivan L, Migliori GB, et al. Tuberculosis control, and the where and why of artificial intelligence. ERJ Open Res. 2017;3(2). [Crossref]  [PubMed]  [PMC]
  59. Kulkarni S, Jha S. Artificial Intelligence, Radiology, and Tuberculosis: A Review. Acad Radiol. 2020;27(1):71-5. [Crossref]  [PubMed]
  60. David PM, Onno J, Keshavjee S, Ahmad Khan F. Conditions required for the artificial-intelligence-based computer-aided detection of tuberculosis to attain its global health potential. Lancet Digit Health. 2022;4(10):e702-e4. [Crossref]  [PubMed]
  61. WHO Consolidated Guidelines on Tuberculosis: Module 2: Screening - Systematic Screening for Tuberculosis Disease. World Health Organization
  62. Balakrishnan V, Kherabi Y, Ramanathan G, Paul SA, Tiong CK. Machine learning approaches in diagnosing tuberculosis through biomarkers - A systematic review. Prog Biophys Mol Biol. 2023;179:16-25. [Crossref]  [PubMed]
  63. Albuquerque VVS, Kumar NP, Fukutani KF, Vasconcelos B, Arriaga MB, Silveira-Mattos PS, et al. Plasma levels of C-reactive protein, matrix metalloproteinase-7 and lipopolysaccharide-binding protein distinguish active pulmonary or extrapulmonary tuberculosis from uninfected controls in children. Cytokine. 2019;123:154773. [Crossref]  [PubMed]