Objective: To assess aptamer-based assays for diagnosing latent tuberculosis infection (LTBI).
Methods: Literature from Medline, ScienceDirect, and Scopus, covering publications from January 1, 2012, to December 31, 2023, was examined. This review evaluates different aptamers, biomarkers, sample types, sample sizes, reference assays, and the assays’ sensitivity and specificity. By using the Quality Assessment of Diagnostic Accuracy Studies 2, the risk of bias in each study was evaluated.
Results: Aptamer-based assays generally showed a sensitivity of 90% (95% CI: 75%-100%) and specificity of 90% (95% CI: 50%-100%), where optical aptasensor showed the highest sensitivity and specificity at 100%. Serum samples were frequently used to enhance antigen detectability, improving the assay’s performance. Meanwhile, HspX was the most studied biomarker, followed by MPT64, and IFN-γ.
Conclusions: Aptamer-based assays could be reliable alternatives to current LTBI detection methods, but further research is needed to validate their clinical efficacy.
Author Information
Conflict of interest statement
The authors declare that there is no conflict of interest.
Funding
This research was supported by Higher Institution Centre of Excellence (HICoE) Grant (A305-KR-AKH002-0000000278-K134) from the Ministry of Higher Education, Malaysia.
Data availability statement
The data supporting the findings of this study are available from the corresponding author upon request.
Authors’ contributions
SY conducted the experimental studies, performed data acquisition and analysis, and prepared the manuscript. NFMZ defined the intellectual content of the study and conducted literature search. MHY was involved in defining the intellectual content, and contributed in editing and reviewing the manuscript. KS carried out both data analysis and statistical analysis. KMFM led the conceptualization and study design, supervised manuscript editing and review, and served as the guarantor of the study. All authors have read and approved the final manuscript.
Publisher’s note
The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
| [1] |
Tuberculosis. [Online]Available from: https://www.who.int/news-room/fact-sheets/detail/tuberculosis [Accessed on 4 April, 2024].
|
| [2] |
Arumugam J, De Silva S. Disseminated tuberculosis presenting as meningitis and spondylodiscitis in an immunocompetent adult. Asian Pac J Trop Med 2023; 16(6): 284-286.
|
| [3] |
Ikrama IH, Zakou AT, Lamini NJ, Osanga C, Dogara AN, Wakili LY, et al. Tuberculosis in Nasarawa State, Nigeria: A three-year retrospective study. One Health Bull 2024; 4; 2. doi: 10.4103/ohbl.ohbl_31_23.
|
| [4] |
Salgame P, Geadas C, Collins L, Jones-López E, Ellner JJ. Latent tuberculosis infection - Revisiting and revising concepts. Tuberculosis 2015; 95(4): 373-384.
|
| [5] |
Houben RMGJ, Dodd PJ. The global burden of latent tuberculosis infection: A re-estimation using mathematical modelling. PLoS Med 2016; 13(10): e1002152.
|
| [6] |
Kik SV, Denkinger CM, Chedore P, Pai M. Replacing smear microscopy for the diagnosis of tuberculosis: What is the market potential? Eur Respir J 2014; 43(6): 1793-1796.
|
| [7] |
Huang Y, Ai L, Wang X, Sun Z, Wang F. Review and updates on the diagnosis of tuberculosis. J Clin Med 2022; 11(19): 5826.
|
| [8] |
Acharya B, Acharya A, Gautam S, Ghimire SP, Mishra G, Parajuli N, et al. Advances in diagnosis of tuberculosis: An update into molecular diagnosis of Mycobacterium tuberculosis. Mol Biol Rep 2020; 47(5): 4065-4075.
|
| [9] |
Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, Oxlade O, et al. Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev 2014; 27(1): 3-20.
|
| [10] |
Ku TH, Zhang T, Luo H, Yen TM, Chen PW, Han Y, et al. Nucleic acid aptamers: An emerging tool for biotechnology and biomedical sensing. Sensors (Basel) 2015; 15(7): 16281-16313.
|
| [11] |
Mascini M, Palchetti I, Tombelli S. Nucleic acid and peptide aptamers: Fundamentals and bioanalytical aspects. Angew Chem Int Ed 2012; 51(6): 1316-1332.
|
| [12] |
Elskens JP, Elskens JM, Madder A. Chemical modification of aptamers for increased binding affinity in diagnostic applications: Current status and future prospects. Int J Mol Sci 2020; 21(12): 4522.
|
| [13] |
Zhou J, Rossi J. Aptamers as targeted therapeutics: Current potential and challenges. Nat Rev Drug Discov 2017; 16(3): 181-202.
|
| [14] |
Taneja V, Goel M, Shankar U, Kumar A, Khilnani GC, Prasad HK, et al. An aptamer linked immobilized sorbent assay (ALISA) to detect circulatory IFN-α an inflammatory protein among tuberculosis patients. ACS Comb Sci 2020; 22(11): 656-666.
|
| [15] |
Thakur H, Kaur N, Sabherwal P, Sareen D, Prabhakar N. Aptamer based voltammetric biosensor for the detection of Mycobacterium tuberculosis antigen MPT64. Microchim Acta 2017; 184(7): 1915-1922.
|
| [16] |
Thakur H, Kaur N, Sareen D, Prabhakar N. Electrochemical determination of M. tuberculosis antigen based on poly(3,4-ethylenedioxythiophene) and functionalized carbon nanotubes hybrid platform. Talanta 2017; 171: 115-123.
|
| [17] |
Chuang PC, Liao PC, Chen YF. Enhancing the sensitivity of localized surface plasmon resonance (LSPR) biosensors using nanorods and DNA aptamers. Plasmo Bio Med XII 2015; 9340.
|
| [18] |
De Groote MA, Higgins M, Hraha T, Wall K, Wilson ML, Sterling DG, et al. Highly multiplexed proteomic analysis of quantiferon supernatants to identify biomarkers of latent tuberculosis infection. J Clin Microbiol 2017; 55(2): 391-402.
|
| [19] |
Kim HJ, Jang CH. Liquid crystal-based aptasensor for the detection of interferon-γ and its application in the diagnosis of tuberculosis using human blood. Sens Actuators B Chem 2019; 282: 574-579.
|
| [20] |
Kumari P, Lavania S, Tyagi S, Dhiman A, Rath D, Anthwal D, et al. A novel aptamer-based test for the rapid and accurate diagnosis of pleural tuberculosis. Anal Biochem 2019; 564-565: 80-87.
|
| [21] |
Li L, Liu Z, Zhang H, Yue W, Li CW, Yi CA. Point-of-need enzyme linked aptamer assay for Mycobacterium tuberculosis detection using a smartphone. Sens Actuators B Chem 2018; 254: 337-346.
|
| [22] |
Sypabekova M, Dukenbayev K, Tsepke A, Akisheva A, Oralbayev N, Kanayeva D. An aptasensor for the detection of Mycobacterium tuberculosis secreted immunogenic protein MPT64 in clinical samples towards tuberculosis detection. Sci Rep 2019; 9(1): 16273.
|
| [23] |
Lavania S, Das R, Dhiman A, Myneedu VP, Verma A, Singh N, et al. Aptamer-based TB antigen tests for the rapid diagnosis of pulmonary tuberculosis: Potential utility in screening for tuberculosis. ACS Infect Dis 2018; 4(12): 1718-1726.
|
| [24] |
Tang XL, Zhou YX, Wu SM, Pan Q, Xia B, Zhang XL. CFP10 and ESAT6 aptamers as effective mycobacterial antigen diagnostic reagents. J Infect 2014; 69(6): 569-580.
|
| [25] |
Chen P, Peng W, Qu R, He Y, Liu T, Huang J, et al. Fluorescence aptasensor of tuberculosis interferon-γ in clinical samples regulated by steric hindrance and selective identification. Anal Chem 2022; 94(25): 9122-9129.
|
| [26] |
Dhiman A, Haldar S, Mishra SK, Sharma N, Bansal A, Ahmad Y, et al. Generation and application of DNA aptamers against HspX for accurate diagnosis of tuberculous meningitis. Tuberculosis 2018; 112: 27-36.
|
| [27] |
Tang XL, Wu SM, Xie Y, Song N, Guan Q, Yuan C, et al. Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis. J Infect 2016; 72(5): 573-586.
|
| [28] |
Rotherham LS, Maserumule C, Dheda K, Theron J, Khati M. Selection and application of ssDNA aptamers to detect active TB from sputum samples. PLoS One 2012; 7(10): e46862.
|
| [29] |
Das R, Dhiman A, Mishra SK, Haldar S, Sharma N, Bansal A, et al. Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis. Int JNanomed 2019; 14: 2103-2113.
|
| [30] |
Khabibullina NF, Kutuzova DM, Burmistrova IA, Lyadova IV. The biological and clinical aspects of a latent tuberculosis infection. Trop Med Infect Dis 2022; 7(3): 48.
|
| [31] |
Foster M, Hill PC, Setiabudiawan TP, Koeken VACM, Alisjahbana B, van Crevel R. BCG-induced protection against Mycobacterium tuberculosis infection: Evidence, mechanisms, and implications for next-generation vaccines. Immunol Rev 2021; 301(1): 122-144.
|
| [32] |
Ning Y, Hu J, Lu F. Aptamers used for biosensors and targeted therapy. Biomed Pharmacother 2020; 132:110902.
|
| [33] |
Cai R, Chen X, Zhang Y, Wang X, Zhou N. Systematic bio-fabrication of aptamers and their applications in engineering biology. Syst Microbiol Biomanuf 2023; 3(2): 223-245.
|
| [34] |
Kim DH, Seo JM, Shin KJ, Yang SG. Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy. Biomater Res 2021; 25(1): 42.
|
| [35] |
Chen Z, Liu H, Jain A, Zhang L, Liu C, Cheng K. Discovery of aptamer ligands for hepatic stellate cells using SELEX. Theranostics 2017; 7(12): 2982-2995.
|
| [36] |
Lavania M, Singh I, Turankar RP, Ahuja M, Pathak V, Sengupta U, et al. Molecular detection of multidrug-resistant Mycobacterium leprae from Indian leprosy patients. J Glob Antimicrob Resist 2018; 12: 214-219.
|
| [37] |
Yu Z, Han X, Li F, Tan X, Shi W, Fu C, et al. Lengthening the aptamer to hybridize with a stem-loop DNA assistant probe for the electrochemical detection of kanamycin with improved sensitivity. Anal Bioanal Chem 2020; 412(11): 2391-2397.
|
| [38] |
Carranza C, Pedraza-Sanchez S, de Oyarzabal-Mendez E, Torres M. Diagnosis for latent tuberculosis infection: New alternatives. Front Immunol 2020; 11:2006.
|
| [39] |
Castro-Garza J, García-Jacobo P, Rivera-Morales LG, Quinn FD, Barber J, Karls R, et al. Detection of anti-HspX antibodies and HspX protein in patient sera for the identification of recent latent infection by Mycobacterium tuberculosis. PLoS One 2017; 12(8): e0181714.
|
| [40] |
Cronan MR. In the thick of it: Formation of the tuberculous granuloma and its effects on host and therapeutic responses. Front Immunol 2022; 13:820134.
|
| [41] |
Shanmuganathan G, Orujyan D, Narinyan W, Poladian N, Dhama S, Parthasarathy A, et al. Role of interferons in Mycobacterium tuberculosis infection. Clin Pract 2022; 12(5): 788-796.
|
| [42] |
Suresh P, Biswas L, Prasad V, Kumar A, Sivadas S, Khan S, et al. BCG infection due to MPT64-negative strain: A diagnostic challenge. Am J Trop Med Hyg 2020; 103(3): 1072-1075.
|
| [43] |
Estévez O, Anibarro L, Garet E, Pallares Á, Pena A, Villaverde C, et al. Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection. PLoS One 2020; 15(7): e0235859.
|
| [44] |
Fihiruddin F, Inayati N, Jannah R, Unsunnidhal L, Kusumawati A. Expression and epitope prediction of MPT64 recombinant proteins from clinical isolates of Mycobacterium tuberculosis as immunoserodiagnostic candidates. Vet World 2022; 15(10): 2376-2383.
|
| [45] |
McNally E, Ross C, Gleeson LE. The tuberculous pleural effusion. Breathe 2023; 19(4): 230143.
|
| [46] |
Bethu R, Mittal HG, Sharma TK, Shulania A, Sharma N, Rangarajan S, et al. Rapid diagnosis of TB using aptamer-based assays for Mycobacterium tuberculosis antigens in children and adolescents. Lung India 2023; 40(5): 434-439.
|
| [47] |
Sedgwick P. What is publication bias in a meta-analysis? BMJ 2015; 351: h4419.
|
| [48] |
Imrey PB. Limitations of meta-analyses of studies with high heterogeneity. JAMA Netw Open 2020; 3(1): e1919325.
|