Dear Prof. Karunaweera,

Thank you very much for submitting your manuscript "Spatiotemporal transmission of cutaneous leishmaniasis in Sri Lanka and future case burden estimates" 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,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Epco Hasker

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: Yes

Reviewer #2: my comments are attached.

Reviewer #3: Partially.

Reviewer #4: Major Revision

Reviewer #5: Please mention from where did you obtain meteorological data.

How many clinically confirmed cases you included for this study?

What are the tests you applied to analyze risk factors

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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: Yes

Reviewer #2: my comments are attached.

Reviewer #3: Yes

Reviewer #4: Minor Revision

Reviewer #5: fig 1 (b) incidence rate - which year? ?

Add p values for each clinical factors in every districts

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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: Yes

Reviewer #2: my comments are attached.

Reviewer #3: Yes

Reviewer #4: Major Revision

Reviewer #5: conclusions supported by the data presented

limitations of analysis clearly described

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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: Minor Revision

Reviewer #2: my comments are attached.

Reviewer #3: (No Response)

Reviewer #4: (No Response)

Reviewer #5: (No Response)

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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: In this study the authors addressed spatiotemporal transmission of cutaneous leishmaniasis and predicted future case burden in Sri Lanka. The objective of this study is clear, the data are well-analyzed, and the results are well-presented. This analytic model will be a powerful tool for the prediction of future risk of leishmaniasis, and contribute to the control of this disease I enjoyed reading this manuscript. Following is a minor comment.

1. The data of figure 5 is not explained well in the text. I recommend mentioning about it more detail in the text, or move this figure into a supplemental figure.

Reviewer #2: my comments are attached.

Reviewer #3: The paper ‘Spatiotemporal transmission of cutaneous leishmaniasis in Sri Lanka and future case burden estimates’ covers a very relevant and urgent topic in the Sri Lank context.

Below you can find recommendations to further improve this investigation:

L99 – Please provide a detailed information about this upsurge in leishmaniasis cases. This is critical to justify the need for the present study.

L128-138 – The sections about the study area and data sources is very incomplete. The following information needs to be included:

a. Description of the territorial units of analysis, more precisely population size (mean and SD or median and IQR)

b. Description of the information systems that collect and provide data on leishmaniosis cases (flow of information from diagnosis until register in the database; coverage; existence of changes in data quality through time, etc.)

c. Description of the climatic data, more precisely the data source, temporal resolution and number of meteorological stations in the climate network from Sri Lanka.

If data sources are prone to any type of information and selection bias, that needs to be discussed in the limitations section of the manuscript.

L148 – Please clarify the concept of transmission synchrony. The readers may not know this term.

L190 – Please indicate the R packages used for the analysis.

L180 – The authors do not use climatic variable to make the space-time predictions. However, the authors found that climatic factors played a role in the infections. Could it be possible to make predictions based on meteorological scenarios (high, low, medium precipitation year; high, low, medium temperature year)? I believe it would be an interesting add-on to the present or future research.

Figure 1 – To make the figure more informative I recommend numbering the districts and add the names as a legend of the figure.

Reviewer #4: (No Response)

Reviewer #5: Don't start sentences as "we.................. Please write in a scientific way.

Please give your suggestions more about how a high correlation between neighboring districts and incidence rate of leishamaniasis in endemic regions.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Ana Isabel Ribeiro

Reviewer #4: No

Reviewer #5: Yes: Lahiru Sandaruwan Galgamuwa

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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Attachments

Attachment

Submitted filename: PNTD-D-20-02228_reviewer-1.pdf

Attachment

Submitted filename: Rewiever Comments.pdf

Dear Prof. Karunaweera,

We are pleased to inform you that your manuscript 'Spatiotemporal distribution of cutaneous leishmaniasis in Sri Lanka and future case burden estimates' 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,

Alberto Novaes Ramos Jr

Associate Editor

PLOS Neglected Tropical Diseases

Epco Hasker

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: Yes

Reviewer #3: The authors addressed my previous concerns in the revision

Reviewer #4: Yes

Reviewer #5: yes

**********

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: Yes

Reviewer #3: The authors addressed my previous concerns in the revision

Reviewer #4: Yes

Reviewer #5: yes

**********

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: Yes

Reviewer #3: (No Response)

Reviewer #4: Yes

Reviewer #5: yes

**********

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 #3: no

Reviewer #4: Accept

Reviewer #5: Accept

**********

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: The paper was revised properly.

Reviewer #3: The authors addressed my previous concerns in the revision

Reviewer #4: I have read with interest your manuscript as well as reviewers’ concerns and your response. The revisions that you made to the manuscript are very effective in addressing the remaining concerns. The revised manuscript is overall well-written, well-structured and clear. So, in my opinion, the manuscript is well-suited for publication in PLOS Neglected Tropical Diseases.

Reviewer #5: Accept

**********

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 #3: Yes: Ana Isabel Ribeiro

Reviewer #4: No

Reviewer #5: Yes: Lahiru Sandaruwan Galgamuwa