Whole genome sequencing for the management of drug-resistant TB in low income high TB burden settings: Challenges and implications

Mahomed, Saajida; Naidoo, Kogieleum; Dookie, Navisha; Padayatchi, Nesri

doi:10.1016/j.tube.2017.09.005

Cited by 16 publications

(18 citation statements)

References 52 publications

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“…From a laboratory perspective, the resolution of a discordant result is challenging. Sequencing-based techniques may assist with the identification of exact single nucleotide polymorphisms that will be required to resolve a discrepancy [44] , [45] , [46] , [47] . In addition, a precision-based medicine approach, whereby selection of a treatment regimen is guided by characterization of different mutations shows promise.…”

Section: Discussionmentioning

confidence: 99%

Discordant line probe genotypic testing vs culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making

Mahomed

Mlisana

Cele

et al. 2020

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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The recommendations for Mycobacterium tuberculosis drug susceptibility testing include both phenotypic and genotypic methods. This concurrent use of differing testing platforms has created an emerging challenge of discordant results, creating a diagnostic dilemma for the laboratorians as well as attending clinicians. We undertook a retrospective study to determine the prevalence of discordant results between the MTBDR plus line probe assay and solid culture-based drug susceptibility testing for rifampicin and isoniazid. The analysis was conducted for the period January 2013 and December 2015 at the Inkosi Albert Luthuli Central Hospital. Rifampicin and isoniazid resistance testing data were “paired” on 8273 isolates for culture-based drug susceptibility testing and line probe assay. The latter method showed high sensitivity and specificity of 93% and 95% respectively for isoniazid testing. For rifampicin testing, sensitivity and specificity were 95% and 75%. Overall, discordance was 14.6% for rifampicin and 7.2% for isoniazid. This report is not intended to determine superiority of one method over another. It is merely to show that discordance does exist between different methods of testing. Given the burden of HIV and Tuberculosis in Sub-Saharan Africa, these findings have clinical significance and huge public health implications. Clinicians should understand the limitations of phenotypic testing methods.

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Section: Discussionmentioning

confidence: 99%

Discordant line probe genotypic testing vs culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making

Mahomed

Mlisana

Cele

et al. 2020

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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“…It also contributed to the notion that the majority of MDR-TB cases in endemic regions are likely to be due to transmission of already resistant strains rather than acquired drug resistance due to inadequate treatment or non-compliance [2,8,51e53]. The particular role and potential impact of WGS on lowering of TB rates overall in high-incidence settings has not been fully assessed [37,54].…”

Section: Considerations Regarding Specific High-risk Groups and Variomentioning

confidence: 99%

Role and value of whole genome sequencing in studying tuberculosis transmission

Nikolayevskyy

Niemann

Anthony

et al. 2019

Clinical Microbiology and Infection

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Background: Tuberculosis (TB) remains a serious public health threat worldwide. Theoretically ultimate resolution of whole genome sequencing (WGS) for Mycobacterium tuberculosis complex (MTBC) strain classification makes this technology very attractive for epidemiological investigations. Objectives: To summarize the evidence available in peer-reviewed publications on the role and place of WGS in detection of TB transmission. Sources: A total of 69 peer-reviewed publications identified in Pubmed database. Content: Evidence from >30 publications suggests that a cutoff value of fewer than six single nucleotide polymorphisms between strains efficiently excludes cases that are not the result of recent transmission and could be used for the identification of drug-sensitive isolates involved in direct human-to-human TB transmission. Sensitivity of WGS to identify epidemiologically linked isolates is high, reaching 100% in eight studies with specificity (17%e95%) highly dependent on the settings. Drug resistance and specific phylogenetic lineages may be associated with accelerated mutation rates affecting genetic distances. WGS can be potentially used to distinguish between true relapses and re-infections but in high-incidence low-diversity settings this would require consideration of epidemiological links and minority alleles. Data from four studies looking into within-host diversity highlight a need for developing criteria for acceptance or rejection of WGS relatedness results depending on the proportion of minority alleles. Implications: WGS will potentially allow for more targeted public health actions preventing unnecessary investigations of false clusters. Consensus on standardization of raw data quality control processing criteria, analytical pipelines and reporting language is yet to be reached.

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“…Although WGS is typically done from a cultured sample of M tuberculosis , which adds two to four weeks to the result time, efforts are under way to perform analyses directly on sputum. Sputum, however, is complicated by human and other bacterial DNA 69. The interpretation of genotypic results is also not always straightforward and large standardized databases with user friendly software are needed 6870.…”

Section: Genotypic and Phenotypic Drug Resistance Testingmentioning

confidence: 99%

Current and future treatments for tuberculosis

Lee

Xie

Barry

et al. 2020

BMJ

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Guidelines on the treatment of tuberculosis (TB) have essentially remained the same for the past 35 years, but are now starting to change. Ongoing clinical trials will hopefully transform the landscape for treatment of drug sensitive TB, drug resistant TB, and latent TB infection. Multiple trials are evaluating novel agents, repurposed agents, adjunctive host directed therapies, and novel treatment strategies that will increase the probability of success of future clinical trials. Guidelines for HIV-TB co-infection treatment continue to be updated and drug resistance testing has been revolutionized in recent years with the shift from phenotypic to genotypic testing and the concomitant increased speed of results. These coming changes are long overdue and are sorely needed to address the vast disparities in global TB incidence rates. TB is currently the leading cause of death globally from a single infectious agent, but the work of many researchers and the contributions of many patients in clinical trials will reduce the substantial global morbidity and mortality of the disease.

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Whole genome sequencing for the management of drug-resistant TB in low income high TB burden settings: Challenges and implications

Cited by 16 publications

References 52 publications

Discordant line probe genotypic testing vs culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making

Discordant line probe genotypic testing vs culture-based drug susceptibility phenotypic testing in TB endemic KwaZulu-Natal: Impact on bedside clinical decision making

Role and value of whole genome sequencing in studying tuberculosis transmission

Current and future treatments for tuberculosis

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