Dear Dr. Gomes,

Thank you very much for submitting your manuscript "The efficacy of topical, oral and surgical interventions for the treatment of tungiasis: a systematic review of the literature." 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. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

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

[1] A letter containing a detailed list of your responses to all 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).

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Thank you again for your submission to our journal. 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,

Joseph M. Vinetz

Deputy Editor

PLOS Neglected Tropical Diseases

Joseph Vinetz

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: (No Response)

Reviewer #2: The authors aimed to to assess the efficacy of currently available topical, oral, and surgical interventions for the treatment of tungiasis, which is clearly delineated by the hypothesis. The study design is appropriate, with enough articles included for a PRISMA-compliant systematic review. Furthermore, the authors followed all applicable regulatory guidelines during this study.

Reviewer #3: The purpose of this paper was to collect information and find the most efficacious treatment for Tungiasis, and this paper accomplishes that very well.

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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: (No Response)

Reviewer #2: The presented results appear to be more about methods than key findings and should be updated. Furthermore, the information in the tables is detailed and easy to understand. The figures are adequate and of sufficient quality in accordance with the journal's guidelines.

Reviewer #3: The results and analysis were clear and the treatment overview was extremely helpful.

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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: (No Response)

Reviewer #2: Significant findings of this study support conclusion. This study's limitations are appropriately described. More robust discussion about the study's potential prospects for advancing public health relevance is required.

Reviewer #3: The conclusions are directly supported by the data. Limitations were explained and presented accordingly. The support of Dimeticone as treatment is well founded but in this paper there is a lack of explanation. The occlusive action is mentioned but not explained. I would include a section explaining the method of action of this treatment. I would also suggest that the authors include a image of the the different types of treatments after application, and if possible a graphic depicting what a individual Tunga penetrans looks like and why the occlusive nature of this treatment works.

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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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: The paper does need some minor grammatical revisions for more concise wording and make the paper easier to read.

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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: Manuscript PNTD-D-21-00651 reviewed the progress of treatment of the neglected disease tungiasis mostly occurred in South America and Africa. The clinical trials included in this review article supported the application of topical drugs such as dimeticones as the encouraging yet cost-effective therapy for the treatment of this disease. The paper is well organized and written. The conclusions drawn from this review paper are of great values for the clinical trials as well as the regulatory purposes in the affected countries. I recommend to accept this manuscript without further changes.

Reviewer #2: This is a well-executed important study with apparent strength. The review is registered prospectively, and the authors investigate the efficacy of various interventions for the treatment of tungiasis. To avoid publication and language bias, the review employs the Cochrane Risk of Bias Tool and the Critical Appraisal Tool. This article's rationale and novelty statement should be elaborated at the appropriate place. Here are the key issues with this article: What about the studies that were excluded during the qualitative analysis of the articles (case series, case reports, and trials)? How did they fail to contribute to the study, and how did their exclusion affect the study's outcome? The materials and methods must explicitly state how the studies' risk of bias and assessment of quality studies was judged. Please ensure that the search and inclusion of studies is as up to date as possible.

Reviewer #3: Overall this paper adequately accomplishes its goal. I do want to reiterate the need for a explanation of the method of action of this treatment. Understanding how this treatment works on a physical level when compared to other treatments is of paramount importance.

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Reviewer #1: No

Reviewer #2: Yes: Amit Kumar Srivastava

Reviewer #3: Yes: Jonathan A. Niezgoda

Figure Files:

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Data Requirements:

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References

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.

Dear Dr. Gomes,

We are pleased to inform you that your manuscript 'The efficacy of topical, oral and surgical interventions for the treatment of tungiasis: A systematic review of the literature' 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,

Joseph M. Vinetz

Deputy Editor

PLOS Neglected Tropical Diseases

Joseph Vinetz

Deputy Editor

PLOS Neglected Tropical Diseases

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