Register      Login
Microbiology Australia Microbiology Australia Society
Microbiology Australia, bringing Microbiologists together
RESEARCH ARTICLE

Recent developments in the diagnosis of drug-resistant tuberculosis

Mark P Nicol A B and Helen Cox B
+ Author Affiliations
- Author Affiliations

A School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia Email: mark.nicol@uwa.edu.au

B Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa

Microbiology Australia 40(2) 82-86 https://doi.org/10.1071/MA19023
Published: 18 April 2019

Abstract

Urgent steps are required to control the drug-resistant tuberculosis (TB) epidemic worldwide. Individualised treatment, using detailed drug-susceptibility test results to guide choice of antibiotics, improves patient outcomes and minimises adverse effects. Recent years have seen substantial advances in our ability to provide rapid, detailed drug-resistance profiles using genotypic methods for detection of mutations conferring drug-resistance. Rapid testing using real-time PCR to target the most important drug-resistance mutations allows the diagnosis of drug resistance to be made with the first diagnostic test, even in low resource settings. The use of whole genome sequencing to infer resistance to a range of different drugs facilitates earlier tailoring of therapy and detection of resistant subpopulations in mixed infections. Low burden countries, such as Australia are well positioned to lead the development and refinement of these new methods, to accelerate the incorporation of these new tools into TB control programs in high burden countries.


References

[1]  WHO (2018) Global tuberculosis report 2018. World Health Organization, Geneva.

[2]  Kendall, E.A. et al. (2015) Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis. Lancet Respir. Med. 3, 963–972.
Burden of transmitted multidrug resistance in epidemics of tuberculosis: a transmission modelling analysis.Crossref | GoogleScholarGoogle Scholar | 26597127PubMed |

[3]  WHO (2017) Global tuberculosis report 2017. World Health Organization, Geneva.

[4]  Ferlazzo, G. et al. (2018) Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study. Lancet Infect. Dis. 18, 536–544.
Early safety and efficacy of the combination of bedaquiline and delamanid for the treatment of patients with drug-resistant tuberculosis in Armenia, India, and South Africa: a retrospective cohort study.Crossref | GoogleScholarGoogle Scholar | 29452942PubMed |

[5]  van Altena, R. et al. (2015) Highly successful treatment outcome of multidrug-resistant tuberculosis in the Netherlands, 2000–2009. Int. J. Tuberc. Lung Dis. 19, 406–412.
Highly successful treatment outcome of multidrug-resistant tuberculosis in the Netherlands, 2000–2009.Crossref | GoogleScholarGoogle Scholar | 25859995PubMed |

[6]  Brode, S.K. et al. (2015) Multidrug-resistant tuberculosis: treatment and outcomes of 93 patients. Can. Respir. J. 22, 97–102.
Multidrug-resistant tuberculosis: treatment and outcomes of 93 patients.Crossref | GoogleScholarGoogle Scholar | 25493698PubMed |

[7]  Rigouts, L. et al. (2013) Rifampin resistance missed in automated liquid culture system for Mycobacterium tuberculosis isolates with specific rpoB mutations. J. Clin. Microbiol. 51, 2641–2645.
Rifampin resistance missed in automated liquid culture system for Mycobacterium tuberculosis isolates with specific rpoB mutations.Crossref | GoogleScholarGoogle Scholar | 23761146PubMed |

[8]  Zetola, N.M. et al. (2014) Clinical outcomes among persons with pulmonary tuberculosis caused by Mycobacterium tuberculosis isolates with phenotypic heterogeneity in results of drug-susceptibility tests. J. Infect. Dis. 209, 1754–1763.
Clinical outcomes among persons with pulmonary tuberculosis caused by Mycobacterium tuberculosis isolates with phenotypic heterogeneity in results of drug-susceptibility tests.Crossref | GoogleScholarGoogle Scholar | 24443546PubMed |

[9]  Lawn, S.D. and Nicol, M.P. (2011) Xpert(R) MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol. 6, 1067–1082.
Xpert(R) MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance.Crossref | GoogleScholarGoogle Scholar | 21958145PubMed |

[10]  Steingart, K.R. et al. (2013) Xpert(R) MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst. Rev. 1, CD009593.

[11]  Sanchez-Padilla, E. et al. (2015) Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland. N. Engl. J. Med. 372, 1181–1182.
Detection of drug-resistant tuberculosis by Xpert MTB/RIF in Swaziland.Crossref | GoogleScholarGoogle Scholar | 25785984PubMed |

[12]  Kohli, M. et al. (2018) Xpert((R)) MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance. Cochrane Database Syst. Rev. 8, CD012768.
| 30148542PubMed |

[13]  Dorman, S.E. et al. (2018) Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study. Lancet Infect. Dis. 18, 76–84.
Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.Crossref | GoogleScholarGoogle Scholar | 29198911PubMed |

[14]  Ling, D.I. et al. (2008) GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur. Respir. J. 32, 1165–1174.
GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 18614561PubMed |

[15]  Barnard, M. et al. (2012) The diagnostic performance of the GenoType MTBDRplus version 2 line probe assay is equivalent to that of the Xpert MTB/RIF assay. J. Clin. Microbiol. 50, 3712–3716.
The diagnostic performance of the GenoType MTBDRplus version 2 line probe assay is equivalent to that of the Xpert MTB/RIF assay.Crossref | GoogleScholarGoogle Scholar | 22972826PubMed |

[16]  Theron, G. et al. (2014) The diagnostic accuracy of the GenoType((R)) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst. Rev. 10, CD010705.

[17]  Rocchetti, T.T. et al. (2016) Validation of a multiplex real-time PCR assay for detection of Mycobacterium spp., Mycobacterium tuberculosis complex, and Mycobacterium avium complex directly from clinical samples by use of the BD Max open system. J. Clin. Microbiol. 54, 1644–1647.
Validation of a multiplex real-time PCR assay for detection of Mycobacterium spp., Mycobacterium tuberculosis complex, and Mycobacterium avium complex directly from clinical samples by use of the BD Max open system.Crossref | GoogleScholarGoogle Scholar | 27008873PubMed |

[18]  Xie, Y.L. et al. (2017) Evaluation of a rapid molecular drug-susceptibility test for tuberculosis. N. Engl. J. Med. 377, 1043–1054.
Evaluation of a rapid molecular drug-susceptibility test for tuberculosis.Crossref | GoogleScholarGoogle Scholar | 28902596PubMed |

[19]  WHO (2019) WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis: 2018 update. World Health Organization, Geneva.

[20]  WHO and FIND (2018) The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. World Health Organization and FIND, Geneva.

[21]  Starks, A.M. et al. (2015) Collaborative effort for a centralized worldwide tuberculosis relational sequencing data platform. Clin. Infect. Dis. 61, S141–S146.
Collaborative effort for a centralized worldwide tuberculosis relational sequencing data platform.Crossref | GoogleScholarGoogle Scholar |

[22]  The CRyPTIC Consortium and the 100,000 Genomes Project (2018) Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing. N. Engl. J. Med. 379, 1403–1415.
Prediction of susceptibility to first-line tuberculosis drugs by DNA sequencing.Crossref | GoogleScholarGoogle Scholar | 30280646PubMed |

[23]  Quan, T.P. et al. (2018) Evaluation of whole-genome sequencing for mycobacterial species identification and drug susceptibility testing in a clinical setting: a large-scale prospective assessment of performance against line probe assays and phenotyping. J. Clin. Microbiol. 56, e01480-17.
Evaluation of whole-genome sequencing for mycobacterial species identification and drug susceptibility testing in a clinical setting: a large-scale prospective assessment of performance against line probe assays and phenotyping.Crossref | GoogleScholarGoogle Scholar | 29167290PubMed |

[24]  Walker, T.M. et al. (2015) Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study. Lancet Infect. Dis. 15, 1193–1202.
Whole-genome sequencing for prediction of Mycobacterium tuberculosis drug susceptibility and resistance: a retrospective cohort study.Crossref | GoogleScholarGoogle Scholar | 26116186PubMed |

[25]  Outhred, A.C. et al. (2015) Added value of whole-genome sequencing for management of highly drug-resistant TB. J. Antimicrob. Chemother. 70, 1198–1202.
| 25492392PubMed |

[26]  Ezewudo, M. et al. (2018) Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase. Sci. Rep. 8, 15382.
Integrating standardized whole genome sequence analysis with a global Mycobacterium tuberculosis antibiotic resistance knowledgebase.Crossref | GoogleScholarGoogle Scholar | 30337678PubMed |

[27]  Ngo, T.M. and Teo, Y.Y. (2019) Genomic prediction of tuberculosis drug-resistance: benchmarking existing databases and prediction algorithms. BMC Bioinformatics 20, 68.
Genomic prediction of tuberculosis drug-resistance: benchmarking existing databases and prediction algorithms.Crossref | GoogleScholarGoogle Scholar | 30736750PubMed |

[28]  Metcalfe, J.Z. et al. (2017) Mycobacterium tuberculosis subculture results in loss of potentially clinically relevant heteroresistance. Antimicrob. Agents Chemother. 61, e00888-17.
Mycobacterium tuberculosis subculture results in loss of potentially clinically relevant heteroresistance.Crossref | GoogleScholarGoogle Scholar | 28893776PubMed |

[29]  Colman, R.E. et al. (2016) Rapid drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates directly from clinical samples by use of amplicon Sequencing: a proof-of-concept study. J. Clin. Microbiol. 54, 2058–2067.
Rapid drug susceptibility testing of drug-resistant Mycobacterium tuberculosis isolates directly from clinical samples by use of amplicon Sequencing: a proof-of-concept study.Crossref | GoogleScholarGoogle Scholar | 27225403PubMed |

[30]  Jain, M. et al. (2016) The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community. Genome Biol. 17, 239.
The Oxford Nanopore MinION: delivery of nanopore sequencing to the genomics community.Crossref | GoogleScholarGoogle Scholar | 27887629PubMed |

[31]  Cox, H. et al. (2018) Precision medicine for drug-resistant tuberculosis in high-burden countries: is individualised treatment desirable and feasible? Lancet Infect. Dis. 18, e282–e287.
Precision medicine for drug-resistant tuberculosis in high-burden countries: is individualised treatment desirable and feasible?Crossref | GoogleScholarGoogle Scholar | 29548923PubMed |