Dear Mr Tilahun,

Thank you very much for submitting your manuscript "Effectiveness of intralesional sodium stibogluconate (IL SSG) for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Christine A Petersen

Deputy Editor

PLOS Neglected Tropical Diseases

Christine Petersen

Deputy Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: Please see attached document for comments to the authors.

Reviewer #2: The objectives are well defined, and in general the design used seems correct, using the definition of a pragmatic trial. However the sample size seems small, and should be calculated or explained. Statistical analysis seems correct.

In page 6, I think that there is a mistake about the IL SSB schedule, that was administered weekly and not every 2 weeks. Please correct.

I have no concerns about ethical in this study.

Reviewer #3: Objective of this study is very nicely explained. Study Design appropriate, however I have few minor comments.

1. Please provide the details of the procedure for administration of intralesional SSG (Line 107-117).

2. Please provide the limitation or success of other treatment approaches (Line 70-74). Authors has mentioned that thermotherapy/ cryotherapy or paramomycine treatment is recommended, however it is not clear if these study not done yet or these treatments are not effective; please make this statement clear.

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Please see attached document for comments to the authors.

Reviewer #2: Results are well described and analised. However, in page 8, authors should give more details about "traditional and modern treatments". In page 10, it should be informed dosage and schedule of systemic treatment for those who were not cured. Table 1 should provide information regarding what the authors call "traditional tretament".

Reviewer #3: Results were very clearly presented

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: Please see attached document for comments to the authors.

Reviewer #2: In discussion, page 14, lines 311-313 the sentence is confusing. Please explain better.

Conclusion is supported by the data and public health relevance is addressed.

Reviewer #3: Conclusion supported by the data presented. This study definitely addressed solution for the LCL caused by Leishmaniasis infection which is a real public health challenge at Ethiopia.

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Please see attached document for comments to the authors.

Reviewer #2: In general the modifications required are few, so I think that minor revision applies. Authors should also inform in the abstract and in page 4 (first paragraph) the cure rate of systemic treatment or what they mean with "relatively hard to treat" (abstract) or "difficult to treat" (page 4).

Reviewer #3: This study is very important addition for the Leishmania field. I would recommend for accepting this article after minor revision.

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: Please see attached document for comments to the authors.

Reviewer #2: It is an important contribuiton showing that IL SSB unfortunately has a low cure rate and important morbidity in CL at Ethiopia, and therefore patients deserve a better therapy. The pragmatic design is well justified in this setting. All modifications required are listed in other sections.

Reviewer #3: (No Response)

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Ranadhir Dey

Figure Files:

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Reproducibility:

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Attachments

Attachment

Submitted filename: PNTD-D-21-01609_Review.docx

Dear Mr Tilahun,

We are pleased to inform you that your manuscript 'Effectiveness of intralesional sodium stibogluconate for the treatment of localized cutaneous leishmaniasis at Boru Meda general hospital, Amhara, Ethiopia: Pragmatic trial' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Christine A. Petersen

Deputy Editor

PLOS Neglected Tropical Diseases

Christine Petersen

Deputy Editor

PLOS Neglected Tropical Diseases

***********************************************************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: All reviewer comments were addressed appropriately.

Reviewer #2: No comments.

**********

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: All reviewer comments were addressed appropriately.

Reviewer #2: No comments.

**********

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: All reviewer comments were addressed appropriately.

Reviewer #2: No comments.

**********

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: All reviewer comments were addressed appropriately.

Reviewer #2: No comments.

**********

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: All reviewer comments were addressed appropriately.

Reviewer #2: No comments.

**********

PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No