PONE-D-20-34803

The Epidemiology of first and second-line drug-resistance Mycobacterium tuberculosis complex common species: Evidence from selected TB treatment initiating centers in Ethiopia.

PLOS ONE

Dear Dr. Dagne,

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Seyed Ehtesham Hasnain

Academic Editor

PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publications, which needs to be addressed:

https://synapse.koreamed.org/articles/1091312

https://www.scirp.org/pdf/AiM20120300014_34905242.pdf

http://etd.aau.edu.et/bitstream/handle/123456789/7091/17.GENENE%20BEKELE.pdf?sequence=1

https://www.mdpi.com/2079-6382/3/3/317/htm

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Additional Editor Comments:

Major Revision

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

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Reviewer #1: Comments:

While reviewing this article, actual findings are quite common and well known facts for TB prevalent countries worldwide. However, the DR-TB facts may differ for Ethiopia. Data may provide the treatment utility and recommendations in present scenario for TB programme successfully progresses. Following are some suggestions which can make the manuscript stronger and beneficial for the readers:

Abstract:

• Word limits excided as per Journal guidelines. Should be modified.

• Conclusive statement should be modified to give actual interpretation of present study. Its known fact that the higher prevalence of DR TB always associated with previously treated TB patients.

Introduction:

• Add reference in line no. 67.

• Abbreviation must require for Mycobacterium tuberculosis (M. tuberculosis/ MTB) upon first appearance in the text (Line no 63).

• Author should advice to write few points about different molecular diagnostics modalities used presently in the referral laboratories.

• Abbreviation required for XDR-TB.

Method:

• While recruitment of subject, authors were enrollment only TB confirmed patients using Xpert MTB/RIF and Smear microscopy, then how they get NTM among 204 TB confirmed specimens (same statement written in abstract section)?

• Reference numbering required corrections and rearrangement.

• Abbreviation must require for GLI, LJ, ZN, MGIT, NTM, MTBC, NTRL, BHI, MTB, PCR….. upon first appearance in the text.

• While writing Genotype CM, AS and MTBC assays, author should advice to write it separately. Because CM/AS kit used for NTM speciation and MTBDR V.2 assay used for indentify DR-TB.

• In patient history, alcoholism and smoker status of patient as well as house hold contact should be noted if possible. Because these habits are strongly associated with TB disease and attributed to DRTB and recurrence.

Results:

• Authors were excluded all the contaminated culture from the present study. During NTM isolation M. fortuitum (two isolates) also fall under RGM and its growth looks like contamination, how author identify the same from contaminated culture?

• Author should mention the critical concentration of all drugs used in phenotypic DST. And for Moxifloxacin, WHO recommended two critical concentrations (0.25 and 1.0 ul/ml), author should also write about this.

• Abbreviate of drugs were written in very casual manner, please correct (RMP, OFL…).

• If possible, authors should also provide the data of TB-HIV co-infected patients. Because, they may have negative in sputum smear microscopy and required initial TB treatment.

• Resent molecular DST was used to identify the first line (Rifampicin and Isoniazid) drugs resistant pattern in resent study. It is advised to talk about these results in Result section also.

Reviewer #2: Clinical studies involving identification of drug resistance can be very useful in providing AMR data to the Tuberculosis Control programme of ethiopia. The results of this study has provided very less scope on scientific research outcome. However, if the author can plan for performing DNA sequencing or genotyping from the drug resistant samples. The output can be of more scientific importance and will show how drug resistant strains prevalent in that region are spreading the transmission of this disease. future work can be planned accordingly.

Reviewer #3: Ayinalem Alemu et al in their study has demonstrated a epidemiological survey among TB patients with moderate to significant resistant to 1st / 2nd line of TB Drugs.

The study is complete within its scope and I have following minor remarks to the author which need attention by the authors

1. What is underlying reason of the resistant in TB patients ? If this is clear off then this study would have global impact in term of designing suitable therapeutics for changing drug response in resistant cases.

2. Can author include some immune / blood parameters like PMN, monocyte populations, TLC / lymphocyte populations and some Th1 parameters so that we can corelate them with the resistant phenotype.

3. Ideally author should quantify the number of foamy macrophages populations which are believed to support opportunistic survival of drug resistant strain of TB and believed to have influence on the disease pattern

4. What does author mean with Poly / mono resistance among patient, how author determine this

5. whether patients resistant for 1st generation drug be resistant to 2nd generation drugs as well and vice versa ?

6. Why retreated cases are showing more resistant pattern over acute cases ?

7.from their work it is not clear why authors did not included Rapamycin / bedaquiline group in their cohort.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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The Epidemiology of first and second-line drug-resistance Mycobacterium tuberculosis complex common species: Evidence from selected TB treatment initiating centers in Ethiopia.

PONE-D-20-34803R1

Dear Dr. Dagne,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Seyed Ehtesham Hasnain

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

In this manuscript the Authors studied "The Epidemiology of first and second-line drug-resistance Mycobacterium tuberculosis complex common species: Evidence from selected TB treatment initiating centers in Ethiopia. I have gone through this revised manuscript and the Authors response to reviewers comments. There were several issues raised by the Reviewers and Authors have comprehensively addressed all the issues. Modifications have been done in the conclusive statement to give actual interpretation of the present study. Authors have included the critical concentration of all drugs in the revised manuscript line 209-212. Appropriate corrections have been made in the references. Underlying reasons for the resistance in TB patients have been clearly clarified by the Authors in the revised manuscript. All other explanations provided by the Authors to the queries of the Reviewers are quite satisfactory.

Reviewers' comments: