Next-Generation Sequencing As A Novel Solution For Diagnosing Multidrug-Resistance Tuberculosis


  • Winda Medical Faculty Lampung University
  • Mirza Junando
  • Ervina Damayanti



Mycobacterium tuberculosis, Multidrug Resistance Tuberculosis, Next-Generation Sequencing


Tuberculosis (TB) is an infectious disease usually caused by the bacterium Mycobacterium tuberculosis (MTB). Based on WHO, in 2022, new TB cases and TB-related deaths are expected to be 6.4 million and 1.6 million cases respectively with Indonesia in second place with the largest burden of TB in the world. The number of cases has increased by around 4.5% compared to the previous year. With timely diagnosis and treatment with first-line antibiotics for six months, most people who develop TB can be cured and further transmission of infection can be prevented. Conventional diagnostic methods take a long time to obtain results, causing delays in diagnosis and delay in therapy. Next-generation sequencing (NGS) technology, especially whole genome sequencing (WGS) for TB, offers the most comprehensive and fast approach for molecular-based DST so that TB therapy can be given earlier and more effectively.


Bhowmik D, Chandira RM, Jayakar B, Sampath Kumar KP. Recent trends of drug used treatment of tuberculosis. J Chem Pharm. 2009; (1): 113–133.

World Health Organization. WHO Consolidated Guidelines on Drug-resistant Tuberculosis Treatment. Geneva; 2019.

WHO. Global tuberculosis report 2022; 2022.

Walker T, Radcliffe J, Way H. Headington. DNA sequencing predicts 1st-line tuberculosis drug susceptibility. The New England Journal of Medicine. 2018; 379(15): 1403-1415.

Dahanayake MH dan Jayasundera ACA. Nano-based drug delivery optimization for tuberculosis treatment: A review. J Microbiol Methods. 2021; 181:106-127.

Gilpin C, Korobitsyn A, Weyer K. Current tools available for the diagnosis of drug-resistant tuberculosis. Therapeutic Advances in Infectious Diseases. 2016; 3(6):145-151

WHO. Catalogue of Mutations in Mycobacterium tuberculosis Complex and Their Association with Drug Resistance; 2021.

WHO. Automated Real-time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance: Xpert MTB/RIF Assay for the Diagnosis of Pulmonary and Extrapulmonary TB in Adults and Children; 2013.

Schumacher SG, Sohn H, Qin ZZ, Gore G, Davis JL, Denkinger CM, et al. Impact of molecular diagnostics for tuberculosis on patient-important outcomes: a systematic review of study methodologies. PLoS One. 2016; 11(3): e0151073.

Hain Lifescience GmbH. GenoType MTBDRplus VER 2.0; 2021.

Hain Lifescience GmbH. GenoType MTBDRsl VER 1.0 and VER 2.0; 2021.

Mishra H, Reeve B, Palmer Z, Caldwell J, Dolby T, Naidoo C, et al. Diagnostic accuracy and predictive value of Xpert Ultra and Xpert MTB/RIF for tuberculosis diagnosis in an HIV-endemic setting with a high burden of previous tuberculosis. Lancet Respir Med. 2020; (8): 368–382.

Guglielmetti L, Sougakoff W, Maitre T, Brossier F, Jarlier V, Robert J, et al. Poor performance of rapid molecular tests to define eligibility for the shortcourse multidrug-resistant tuberculosis regimen. Clin. Infect. Dis. 2019; 68: 1410–1411.

Iketleng T, Lessels R, Dlamini MT, Mogashoa T, Mupfumi L, Moyo S, et al. Mycobacterium tuberculosis next-generation whole genome sequencing: opportunities and challenges. Tuberc Res Treat. 2018; 1-8.

Witney AA, Gould KA, Arnold A, Coleman, D, Delgado R, Dhillon J, et al. Clinical application of whole-genome sequencing to inform treatment for multidrug-resistant tuberculosis cases. J Clin Microbiol. 2015; 53: 1473–1483.

Cox H, Hughes J, Black J, Nicol MP. Precision medicine for drugresistant tuberculosis in high-burden countries: is individualised treatment desirable and feasible. Lancet Infect Dis. 2018; 18: 282 - 287.

Gygli SM, Borrell S, Trauner A, Gagneux S. Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives. FEMS Microbiol. 2017; 41: 354 - 373.

Nguyen QH, Contamin L, Nguyen TVA, Banuls AL. Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis. Evol Appl. 2018; 11: 1498 - 1511.

Swain SS, Sharma D, Hussain T, Pati S. Molecular mechanisms of underlying genetic factors and associated mutations for drug resistance in Mycobacterium tuberculosis. Emerg Microbes Infect. 2020; 9: 1651 - 1663.

Dookie N, Rambaran S, Padayatchi N, Mahomed S, dan Naidoo K. Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care. J Antimicrob Chemother. 2018; 73: 1138 - 1151.

Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V, Shea TP, et al. 2015. Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal. PLoS Med. 2015; 12: e1001880.

Manson AL, Cohen KA, Abeel T, Desjardins CA, Armstrong DT, Barry CE, et al. 2017. Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance. Nat Genet. 2017; 49: 395 - 402.

Dlamini MT, Lessells R, Iketleng T, de Oliveira T. Whole genome sequencing for drug-resistant tuberculosis management in South Africa: What gaps would this address and what are the challenges to implementation. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases. 2019; 16: 100115.

Hunter RL. The pathogenesis of tuberculosis: The early infiltrate of post-primary (adult pulmonary) tuberculosis: A distinct disease entity. Frontiers in Immunology. 2018; 9: 2108.

Palomino JC, Martin A. Drug resistance mechanisms in Mycobacterium tuberculosis. Antibiotics (Basel). 2014; 3(3): 317- 340.

Falzon D, Gandhi N, Migliori GB, Sotgiu G, Cox HS, Holtz TH, et al. Resistance to fluoroquinolones and second-line injectable drugs: Impact on multidrug-resistant TB outcomes. European Respiratory Journal. 2013; 42(1): 156-168.

Jeanes C, O’Grady J. Diagnosing tuberculosis in the 21st century – Dawn of a genomics revolution? International Journal of Mycobacteriology. 2016; 5(4): 384 - 391.

WHO. 2018. The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. WHO.

Cohen KA, Manson AL, Desjardins CA, Abeel T, Earl AE. Deciphering drug resistance in Mycobacterium tuberculosis using wholegenome sequencing: progress, promise, and challenges. Genome Medicine. 2019; 11: 45.

Tagliani E, Cirillo DM, Ködmön C, van der Werf MJ. EUSeqMyTB to set standards and build capacity for whole genome sequencing for tuberculosis in the EU. Lancet Infect Dis. 2018; 18:377.

Allix-Béguec, C, Arandjelovic I, Bi L, Beckert P, Bonnet M, Bradley P, et al. Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing. J Med. 2018; 379: 1403–1415.

McNerney R, Zignol M, Clark TG. Use of whole genome sequencing in surveillance of drug resistant tuberculosis. Expert Rev. Anti Infect. 2018; 16: 433 - 442.

Lee RS, Proulx JF, McIntosh F, Behr MA, Hanage WP. Previously undetected super-spreading of mycobacterium tuberculosis revealed by deep sequencing. 2018; 9: e53245.

Heyckendorf J, Andres S, Köser CU, Olaru ID, Schön T, Sturegård E, et al. What is resistance? impact of phenotypic versus molecular drug resistance testing on therapy for multi- and extensively drug-resistant Tuberculosis. Antimicrob. Agents Chemother. 2018; 62: 1 - 12.



How to Cite

Winda, Junando, M., & Damayanti, E. (2023). Next-Generation Sequencing As A Novel Solution For Diagnosing Multidrug-Resistance Tuberculosis. Medical Profession Journal of Lampung, 13(4), 563-568.