Dear Dr. Talhari,

Thank you very much for submitting your manuscript "Zoonotic Sporotrichosis Outbreak: Emerging Public Health Threat in the Brazilian Amazon." 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.

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[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,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

Joshua Nosanchuk

Section 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: The methods were clearly defined. The study design is adequated and address the objectives of the study. The statiscal analysis udes was adequated.

Reviewer #2: See Editorial and data presentation modifications

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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: The results were clearly presented including some nice figures. Please, insert a graphic curve representation of the exponetial number of the cases during the period of the study.

Reviewer #2: See Editorial and data presentation modifications

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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: The authors discussed the data very clearly, annd the public health was addressed very well.

Reviewer #2: See Editorial and data presentation modifications

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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, insert a graphic curve representation of the exponetial number of the cases during the period of the study.

Reviewer #2: Please consider the following suggestions as a contribution to improve the article for the journal readers.

1. Although the title suggests that authors will show data from the Braziliian Amazon region, in Methods it seems that data came only from Amazon state. Is that true?

2. Authors should change animal owners and ownership for guardians since nobody is the owner of other living being.

3. Figure 1 in Introduction is out of purpose and unnecessary. It should be withdrawn.

4. I did not see a statement about Ethics Committee. Could you please provide it?

5. Methods: “An ecologic study was performed by assessing the official registers of human and animal sporotrichosis diagnosed in the state of Amazon from 2020 to 2023.” Could you please provide which official registers and if it is available for everyone? Were they state or federal? SINAM? GAL? For more reliable data please specify better in the text.

6. Methods: “In the state of Amazon, both human and animal diseases are of mandatory

reporting.” The authors mean all human and animal disease or this is just for sporotrichosis? Since when has this been done? Do you think it is underreported? Are all demographic and clinical data reported in the official registers? Please, add a comment.

7. How were the diagnosis made? Was it an epidemiological inference?

There were 950 human cases diagnosed, but only 633 had culture made. Of these only 78 (12.3%) were positive for Sporothrix spp, and 65 out of 78 were identified as S. brasiliensis. Could you explain these data better? Which one was the species of these 13 Sporothrix not brasiliensis identified?

8. Statistical analysis were from the 950 patients?

9. Please standardize the binomial writing S. braSiliensis and not braZiliensis throughout the text.

10. Do official records report treatment outcome? Authors reported all cases were cured.

11. There was no hospitalization in these 950 patients? Anyone immunosupressed?

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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: No more comments.

Reviewer #2: To the Authors

This is an important and well-written article with a special epidemiological interest about the spread of zoonotic sporotrichosis to Amazon in Brazil. However some issues should be regarded.

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Reviewer #1: Yes: Paulo Ricardo Criado

Reviewer #2: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

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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. Talhari,

We are pleased to inform you that your manuscript 'Zoonotic Sporotrichosis Outbreak: Emerging Public Health Threat in the Amazon State, Brazil.' 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,

Joshua Nosanchuk, MD

Section Editor

PLOS Neglected Tropical Diseases

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Editorial note:  The authors are to be commended for their thoughtful and professional responses to the comments on the prior review.