Comparative Analysis of Molecular Diagnostic Techniques for Pulmonary Tuberculosis: A Literature Review
Main Article Content
Pulmonary tuberculosis is a global health problem that requires early and precise diagnosis for effective control. In this literature review, we compare several molecular diagnostic techniques used in the detection of pulmonary tuberculosis, such as Polymerase Chain Reaction (PCR), Whole Genome Sequencing (WGS), and Next Generation Sequencing (NGS), as well as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based Diagnostic Techniques. Polymerase Chain Reaction stands out for its high sensitivity, although time-consuming and high operational costs. Meanwhile, whole genome sequencing and next generation sequencing have detailed tuberculosis (TB) strain identification capabilities but have high costs and limited availability. On the other hand, CRISPR-based diagnostic techniques offer speed and low cost but are still in the advanced stages of development. Challenges in implementing new techniques include technical barriers, logistics, and improving sensitivity and specificity. Suggestions for future research include the development of more effective, faster, and affordable techniques, especially in developing portable diagnostic tests for accessibility of pulmonary tuberculosis diagnosis in various regions.
Keywords:
Pulmonary tuberculosis
Molecular diagnostics
PCR
NGS
CRISPR
1. Glaziou P, Floyd K, Raviglione MC. Global epidemiology of tuberculosis. In: Seminars in respiratory and critical care medicine. Thieme Medical Publishers; 2018. p. 271–85.
2. Gupta S, Kakkar V. Recent technological advancements in tuberculosis diagnostics–A review. Biosens Bioelectron. 2018;115:14–29.
3. Ong CWM, Migliori GB, Raviglione M, MacGregor-Skinner G, Sotgiu G, Alffenaar J-W, et al. Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). Eur Respir J. 2020;56(4).
4. Noviyani A, Nopsopon T, Pongpirul K. Variation of tuberculosis prevalence across diagnostic approaches and geographical areas of Indonesia. PLoS One. 2021;16(10):e0258809.
5. Lolong DB, Aryastami NK, Kusrini I, Tobing KL, Tarigan I, Isfandari S, et al. Nonadherence to anti-tuberculosis treatment, reasons and associated factors among pulmonary tuberculosis patients in the communities in Indonesia. PLoS One. 2023;18(8):e0287628.
6. Ryu YJ. Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms. Tuberc Respir Dis (Seoul). 2015;78(2):64.
7. Nachiappan AC, Rahbar K, Shi X, Guy ES, Mortani Barbosa Jr EJ, Shroff GS, et al. Pulmonary tuberculosis: role of radiology in diagnosis and management. Radiographics. 2017;37(1):52–72.
8. Marais BJ, Pai M. New approaches and emerging technologies in the diagnosis of childhood tuberculosis. Paediatr Respir Rev. 2007;8(2):124–33.
9. Singer-Leshinsky S. Pulmonary tuberculosis: Improving diagnosis and management. Jaapa. 2016;29(2):20–5.
10. Wei M, Zhao Y, Qian Z, Yang B, Xi J, Wei J, et al. Pneumonia caused by Mycobacterium tuberculosis. Microbes Infect. 2020;22(6–7):278–84.
11. Ryndak MB, Laal S. Mycobacterium tuberculosis primary infection and dissemination: a critical role for alveolar epithelial cells. Front Cell Infect Microbiol. 2019;9:299.
12. Moule MG, Cirillo JD. Mycobacterium tuberculosis dissemination plays a critical role in pathogenesis. Front Cell Infect Microbiol. 2020;10:65.
13. Ahmad S. New approaches in the diagnosis and treatment of latent tuberculosis infection. Respir Res. 2010;11:1–17.
14. Behr MA, Kaufmann E, Duffin J, Edelstein PH, Ramakrishnan L. Latent tuberculosis: two centuries of confusion. Am J Respir Crit Care Med. 2021;204(2):142–8.
15. Hunter RL, Actor JK, Hwang S-A, Karev V, Jagannath C. Pathogenesis of post primary tuberculosis: immunity and hypersensitivity in the development of cavities. Ann Clin Lab Sci. 2014;44(4):365–87.
16. Fogel N. Tuberculosis: a disease without boundaries. Tuberculosis. 2015;95(5):527–31.
17. Ganchua SKC, White AG, Klein EC, Flynn JL. Lymph nodes—The neglected battlefield in tuberculosis. PLoS Pathog. 2020;16(8):e1008632.
18. Zhuang L, Yang L, Li L, Ye Z, Gong W. Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention. MedComm. 2024;5(1):e419.
19. Cambier CJ, Falkow S, Ramakrishnan L. Host evasion and exploitation schemes of Mycobacterium tuberculosis. Cell. 2014;159(7):1497–509.
20. Cardona P-J. Understanding Tuberculosis: Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity. BoD–Books on Demand; 2012.
21. Xia L, Zhu S, Chen C, Rao Z-Y, Xia Y, Wang D-X, et al. Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006–2015. BMC Infect Dis. 2020;20:1–12.
22. Im C, Kim Y. Spatial pattern of tuberculosis (TB) and related socio-environmental factors in South Korea, 2008-2016. PLoS One. 2021;16(8):e0255727.
23. Mohidem NA, Osman M, Hashim Z, Muharam FM, Mohd Elias S, Shaharudin R. Association of sociodemographic and environmental factors with spatial distribution of tuberculosis cases in Gombak, Selangor, Malaysia. PLoS One. 2021;16(6):e0252146.
24. Raj A, Singh N, Gupta KB, Chaudhary D, Yadav A, Chaudhary A, et al. Comparative evaluation of several gene targets for designing a multiplex-PCR for an early diagnosis of extrapulmonary tuberculosis. Yonsei Med J. 2016;57(1):88–96.
25. Chin KL, Sarmiento ME, Norazmi MN, Acosta A. DNA markers for tuberculosis diagnosis. Tuberculosis. 2018;113:139–52.
26. Neshani A, Kamali Kakhki R, Sankian M, Zare H, Hooshyar Chichaklu A, Sayyadi M, et al. Modified genome comparison method: a new approach for identification of specific targets in molecular diagnostic tests using Mycobacterium tuberculosis complex as an example. BMC Infect Dis. 2018;18:1–9.
27. Machado D, Couto I, Viveiros M. Advances in the molecular diagnosis of tuberculosis: from probes to genomes. Infect Genet Evol. 2019;72:93–112.
28. Oktariana D, Argentina F, Hafy Z, Salim EM, Kurniati N, Rahadiyanto KY, et al. Association of −819 t/c il-10 gene promoter polymorphisms with susceptibility to leprosy in south sumatera indonesia. Lepr Rev. 2021;92(2):162–9.
29. Oktariana D, Saleh I, Hafy Z, Liberty IA. Peran Polimorfisme Promotor Gen Interleukin-10 pada Penyakit Kusta: Tinjauan Sistematik. Journal Of The Indonesian Medical Association. 2023;73(1):15-24.
30. Ventimiglia G, Pesaturo M, Malcolm A, Petralia S. A miniaturized silicon lab-on-chip for integrated PCR and hybridization microarray for high multiplexing nucleic acids analysis. Biosensors. 2022;12(8):563.
31. Chen S, Liu H, Li T, Lai W, Liu L, Xu Y, et al. Using Microfluidic Chip and Allele-Specific PCR to Rapidly Identify Drug Resistance-Associated Mutations of Mycobacterium tuberculosis. Infect Drug Resist. 2023;4311–23.
32. 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;47:4065–75.
33. Ai J-W, Zhou X, Xu T, Yang M, Chen Y, He G-Q, et al. CRISPR-based rapid and ultra-sensitive diagnostic test for Mycobacterium tuberculosis. Emerg Microbes Infect. 2019;8(1):1361–9.
34. Huang Z, Zhang G, Lyon CJ, Hu TY, Lu S. Outlook for CRISPR-based tuberculosis assays now in their infancy. Front Immunol. 2023;14:1172035.
35. Sam IK, Chen Y-Y, Ma J, Li S-Y, Ying R-Y, Li L-X, et al. TB-QUICK: CRISPR-Cas12b-assisted rapid and sensitive detection of Mycobacterium tuberculosis. J Infect. 2021;83(1):54–60.
36. Kaminski MM, Abudayyeh OO, Gootenberg JS, Zhang F, Collins JJ. CRISPR-based diagnostics. Nat Biomed Eng. 2021;5(7):643–56.
37. Cao L, Cui X, Hu J, Li Z, Choi JR, Yang Q, et al. Advances in digital polymerase chain reaction (dPCR) and its emerging biomedical applications. Biosens Bioelectron. 2017;90:459–74.
38. Lawn SD, Dheda K, Kerkhoff AD, Peter JG, Dorman S, Boehme CC, et al. Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies. BMC Infect Dis. 2013;13:1–9.
39. Petralia S, Conoci S. PCR technologies for point of care testing: progress and perspectives. ACS sensors. 2017;2(7):876–91.
40. McNerney R, Zignol M, Clark TG. Use of whole genome sequencing in surveillance of drug resistant tuberculosis. Expert Rev Anti Infect Ther. 2018;16(5):433–42.
41. Lam C, Martinez E, Crighton T, Furlong C, Donnan E, Marais BJ, et al. Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection. Int J Infect Dis. 2021;113:S48–54.
42. MacGregor-Fairlie M, Wilkinson S, Besra GS, Goldberg Oppenheimer P. Tuberculosis diagnostics: overcoming ancient challenges with modern solutions. Emerg Top life Sci. 2020;4(4):435–48.
43. Besser J, Carleton HA, Gerner-Smidt P, Lindsey RL, Trees E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clin Microbiol Infect. 2018;24(4):335–41.
44. Zhong Y, Xu F, Wu J, Schubert J, Li MM. Application of next generation sequencing in laboratory medicine. Ann Lab Med. 2021;41(1):25–43.
45. Satta G, Lipman M, Smith GP, Arnold C, Kon OM, McHugh TD. Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? Clin Microbiol Infect. 2018;24(6):604–9.
46. Oktariana D, Argentina F, Lusiana E, Tamzil NS. Identifikasi Polimorfisme Titik -1082 Promoter Gen IL-10 pada Penderita Kusta. Sriwij J Med. 2020;3(1):33–8.
47. Walzl G, McNerney R, du Plessis N, Bates M, McHugh TD, Chegou NN, et al. Tuberculosis: advances and challenges in development of new diagnostics and biomarkers. Lancet Infect Dis. 2018;18(7):e199–210.
2. Gupta S, Kakkar V. Recent technological advancements in tuberculosis diagnostics–A review. Biosens Bioelectron. 2018;115:14–29.
3. Ong CWM, Migliori GB, Raviglione M, MacGregor-Skinner G, Sotgiu G, Alffenaar J-W, et al. Epidemic and pandemic viral infections: impact on tuberculosis and the lung: A consensus by the World Association for Infectious Diseases and Immunological Disorders (WAidid), Global Tuberculosis Network (GTN), and members of the European Society of Clinical Microbiology and Infectious Diseases Study Group for Mycobacterial Infections (ESGMYC). Eur Respir J. 2020;56(4).
4. Noviyani A, Nopsopon T, Pongpirul K. Variation of tuberculosis prevalence across diagnostic approaches and geographical areas of Indonesia. PLoS One. 2021;16(10):e0258809.
5. Lolong DB, Aryastami NK, Kusrini I, Tobing KL, Tarigan I, Isfandari S, et al. Nonadherence to anti-tuberculosis treatment, reasons and associated factors among pulmonary tuberculosis patients in the communities in Indonesia. PLoS One. 2023;18(8):e0287628.
6. Ryu YJ. Diagnosis of pulmonary tuberculosis: recent advances and diagnostic algorithms. Tuberc Respir Dis (Seoul). 2015;78(2):64.
7. Nachiappan AC, Rahbar K, Shi X, Guy ES, Mortani Barbosa Jr EJ, Shroff GS, et al. Pulmonary tuberculosis: role of radiology in diagnosis and management. Radiographics. 2017;37(1):52–72.
8. Marais BJ, Pai M. New approaches and emerging technologies in the diagnosis of childhood tuberculosis. Paediatr Respir Rev. 2007;8(2):124–33.
9. Singer-Leshinsky S. Pulmonary tuberculosis: Improving diagnosis and management. Jaapa. 2016;29(2):20–5.
10. Wei M, Zhao Y, Qian Z, Yang B, Xi J, Wei J, et al. Pneumonia caused by Mycobacterium tuberculosis. Microbes Infect. 2020;22(6–7):278–84.
11. Ryndak MB, Laal S. Mycobacterium tuberculosis primary infection and dissemination: a critical role for alveolar epithelial cells. Front Cell Infect Microbiol. 2019;9:299.
12. Moule MG, Cirillo JD. Mycobacterium tuberculosis dissemination plays a critical role in pathogenesis. Front Cell Infect Microbiol. 2020;10:65.
13. Ahmad S. New approaches in the diagnosis and treatment of latent tuberculosis infection. Respir Res. 2010;11:1–17.
14. Behr MA, Kaufmann E, Duffin J, Edelstein PH, Ramakrishnan L. Latent tuberculosis: two centuries of confusion. Am J Respir Crit Care Med. 2021;204(2):142–8.
15. Hunter RL, Actor JK, Hwang S-A, Karev V, Jagannath C. Pathogenesis of post primary tuberculosis: immunity and hypersensitivity in the development of cavities. Ann Clin Lab Sci. 2014;44(4):365–87.
16. Fogel N. Tuberculosis: a disease without boundaries. Tuberculosis. 2015;95(5):527–31.
17. Ganchua SKC, White AG, Klein EC, Flynn JL. Lymph nodes—The neglected battlefield in tuberculosis. PLoS Pathog. 2020;16(8):e1008632.
18. Zhuang L, Yang L, Li L, Ye Z, Gong W. Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention. MedComm. 2024;5(1):e419.
19. Cambier CJ, Falkow S, Ramakrishnan L. Host evasion and exploitation schemes of Mycobacterium tuberculosis. Cell. 2014;159(7):1497–509.
20. Cardona P-J. Understanding Tuberculosis: Analyzing the Origin of Mycobacterium Tuberculosis Pathogenicity. BoD–Books on Demand; 2012.
21. Xia L, Zhu S, Chen C, Rao Z-Y, Xia Y, Wang D-X, et al. Spatio-temporal analysis of socio-economic characteristics for pulmonary tuberculosis in Sichuan province of China, 2006–2015. BMC Infect Dis. 2020;20:1–12.
22. Im C, Kim Y. Spatial pattern of tuberculosis (TB) and related socio-environmental factors in South Korea, 2008-2016. PLoS One. 2021;16(8):e0255727.
23. Mohidem NA, Osman M, Hashim Z, Muharam FM, Mohd Elias S, Shaharudin R. Association of sociodemographic and environmental factors with spatial distribution of tuberculosis cases in Gombak, Selangor, Malaysia. PLoS One. 2021;16(6):e0252146.
24. Raj A, Singh N, Gupta KB, Chaudhary D, Yadav A, Chaudhary A, et al. Comparative evaluation of several gene targets for designing a multiplex-PCR for an early diagnosis of extrapulmonary tuberculosis. Yonsei Med J. 2016;57(1):88–96.
25. Chin KL, Sarmiento ME, Norazmi MN, Acosta A. DNA markers for tuberculosis diagnosis. Tuberculosis. 2018;113:139–52.
26. Neshani A, Kamali Kakhki R, Sankian M, Zare H, Hooshyar Chichaklu A, Sayyadi M, et al. Modified genome comparison method: a new approach for identification of specific targets in molecular diagnostic tests using Mycobacterium tuberculosis complex as an example. BMC Infect Dis. 2018;18:1–9.
27. Machado D, Couto I, Viveiros M. Advances in the molecular diagnosis of tuberculosis: from probes to genomes. Infect Genet Evol. 2019;72:93–112.
28. Oktariana D, Argentina F, Hafy Z, Salim EM, Kurniati N, Rahadiyanto KY, et al. Association of −819 t/c il-10 gene promoter polymorphisms with susceptibility to leprosy in south sumatera indonesia. Lepr Rev. 2021;92(2):162–9.
29. Oktariana D, Saleh I, Hafy Z, Liberty IA. Peran Polimorfisme Promotor Gen Interleukin-10 pada Penyakit Kusta: Tinjauan Sistematik. Journal Of The Indonesian Medical Association. 2023;73(1):15-24.
30. Ventimiglia G, Pesaturo M, Malcolm A, Petralia S. A miniaturized silicon lab-on-chip for integrated PCR and hybridization microarray for high multiplexing nucleic acids analysis. Biosensors. 2022;12(8):563.
31. Chen S, Liu H, Li T, Lai W, Liu L, Xu Y, et al. Using Microfluidic Chip and Allele-Specific PCR to Rapidly Identify Drug Resistance-Associated Mutations of Mycobacterium tuberculosis. Infect Drug Resist. 2023;4311–23.
32. 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;47:4065–75.
33. Ai J-W, Zhou X, Xu T, Yang M, Chen Y, He G-Q, et al. CRISPR-based rapid and ultra-sensitive diagnostic test for Mycobacterium tuberculosis. Emerg Microbes Infect. 2019;8(1):1361–9.
34. Huang Z, Zhang G, Lyon CJ, Hu TY, Lu S. Outlook for CRISPR-based tuberculosis assays now in their infancy. Front Immunol. 2023;14:1172035.
35. Sam IK, Chen Y-Y, Ma J, Li S-Y, Ying R-Y, Li L-X, et al. TB-QUICK: CRISPR-Cas12b-assisted rapid and sensitive detection of Mycobacterium tuberculosis. J Infect. 2021;83(1):54–60.
36. Kaminski MM, Abudayyeh OO, Gootenberg JS, Zhang F, Collins JJ. CRISPR-based diagnostics. Nat Biomed Eng. 2021;5(7):643–56.
37. Cao L, Cui X, Hu J, Li Z, Choi JR, Yang Q, et al. Advances in digital polymerase chain reaction (dPCR) and its emerging biomedical applications. Biosens Bioelectron. 2017;90:459–74.
38. Lawn SD, Dheda K, Kerkhoff AD, Peter JG, Dorman S, Boehme CC, et al. Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies. BMC Infect Dis. 2013;13:1–9.
39. Petralia S, Conoci S. PCR technologies for point of care testing: progress and perspectives. ACS sensors. 2017;2(7):876–91.
40. McNerney R, Zignol M, Clark TG. Use of whole genome sequencing in surveillance of drug resistant tuberculosis. Expert Rev Anti Infect Ther. 2018;16(5):433–42.
41. Lam C, Martinez E, Crighton T, Furlong C, Donnan E, Marais BJ, et al. Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection. Int J Infect Dis. 2021;113:S48–54.
42. MacGregor-Fairlie M, Wilkinson S, Besra GS, Goldberg Oppenheimer P. Tuberculosis diagnostics: overcoming ancient challenges with modern solutions. Emerg Top life Sci. 2020;4(4):435–48.
43. Besser J, Carleton HA, Gerner-Smidt P, Lindsey RL, Trees E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clin Microbiol Infect. 2018;24(4):335–41.
44. Zhong Y, Xu F, Wu J, Schubert J, Li MM. Application of next generation sequencing in laboratory medicine. Ann Lab Med. 2021;41(1):25–43.
45. Satta G, Lipman M, Smith GP, Arnold C, Kon OM, McHugh TD. Mycobacterium tuberculosis and whole-genome sequencing: how close are we to unleashing its full potential? Clin Microbiol Infect. 2018;24(6):604–9.
46. Oktariana D, Argentina F, Lusiana E, Tamzil NS. Identifikasi Polimorfisme Titik -1082 Promoter Gen IL-10 pada Penderita Kusta. Sriwij J Med. 2020;3(1):33–8.
47. Walzl G, McNerney R, du Plessis N, Bates M, McHugh TD, Chegou NN, et al. Tuberculosis: advances and challenges in development of new diagnostics and biomarkers. Lancet Infect Dis. 2018;18(7):e199–210.
