Targeted genome sequencing for tuberculosis drug susceptibility testing in South Africa: A proposed diagnostic pipeline
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In July 2023, the World Health Organization (WHO) began recommending targeted next-generation sequencing (tNGS), due to its ability to detect resistance to many drugs with a single test. In March 2023, South Africa further adopted the GeneXpert® XDR cartridge, which detects mutations associated with resistance to second-line injectable drugs. Here, we consider the feasibility for implementing tNGS in South Africa, what such a facility might look like and the specific context of this upper-middle-income country. Whilst the WHO now recommends tNGS for TB diagnostics and DST, there are many economic and infrastructural challenges opposing its deployment. In lieu of this, we instead recommend a stratified diagnostic pipeline that utilises South Africa's existing GeneXpert technologies, in an attempt to reduce the costs associated with implementation of tNGS.
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Reviewer comments have been sufficiently addressed and I welcome your manuscript for publication in Access Microbiology.
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This is a study that would be of interest to the field and community. The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
Please add more studies where targeted genome sequencing has been successfully been used for diagnosing drug resistance in tuberculosis. Give more evidence of economically feasible methods of employing this method of TB diagnosis in third-world or developing countries.
Please rate the quality of the presentation and structure of the manuscript
Good
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
1. Very interesting and informative paper which is well organised with sections clearly demarcated. The sections systemically work through the current practice, new WHO recommendations and how these may be practically implemented in the South African health care system. 2. Further review and analysis of up to date literature required. There have been a number of recent papers published on this topic, particularly focussing on tNGS pilot studies and diagnostic implementation in Sub Saharan Africa, in countries with similar TB rates (Namibia 446/100,000 & DRC). For example; Araujo et al (2023), Implementation of targeted next-generation sequencing for the diagnosis of drug-resistant tuberculosis in low-resource settings: a programmatic model, challenges, and initial outcomes, Frontiers in Public Health & …
Comments to Author
1. Very interesting and informative paper which is well organised with sections clearly demarcated. The sections systemically work through the current practice, new WHO recommendations and how these may be practically implemented in the South African health care system. 2. Further review and analysis of up to date literature required. There have been a number of recent papers published on this topic, particularly focussing on tNGS pilot studies and diagnostic implementation in Sub Saharan Africa, in countries with similar TB rates (Namibia 446/100,000 & DRC). For example; Araujo et al (2023), Implementation of targeted next-generation sequencing for the diagnosis of drug-resistant tuberculosis in low-resource settings: a programmatic model, challenges, and initial outcomes, Frontiers in Public Health & Kayomo, M.K et al (2020) Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB: results of a national survey in Democratic Republic of the Congo. Sci Rep 10 to name a few articles. I think it would be prudent to review & discuss these and other appropriate recently published studies as some of the mentioned limitations and challenges of implementation of tNGS have also been addressed. Also in section 6.2 comparison is made with an Indian trial as stated 'similar TB burden'. However this is much lower in WHO statistics (168/100,000) compared to DRC & Namibia mentioned above, so comparison with these papers may be more appropriate in this context. 3. The WHO documents need to be referenced correctly rather than just their title, especially as these documents are updated at various intervals and therefore important to know which version of the article/guidelines have been accessed. This includes: Reference 8: Use of targeted next-generation sequencing to detect drug-resistant tuberculosis. Reference 27: . The use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Mycobacterium tuberculosis complex: technical guide. It is mentioned a couple of times that Deeplex Myc-TB tests for 9 addition drugs than GeneXpert XD - it may be worth clarifying which additional drugs are tested - ie 2nd or 3rd line therapies or combination. There are also a few grammatical errors which should be amended: line 86/87: next-generation sequencing NGS - should have () around NGS Line 88: First time acronym DST is mentioned - please write out in full with DST in brackets
Please rate the quality of the presentation and structure of the manuscript
Good
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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