Dear Dr. Ling,

Thank you very much for submitting your manuscript "Spatiotemporal distribution and sociodemographic, socioeconomic associated factors of primary and secondary syphilis in Guangdong, China, 2005-2017" 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.

Thank you for submitting this manuscript to PLoS Neglected Tropical Diseases which has now completed the review process. The reviews are favourable but specific changes to the manuscript have been suggested. In addition to responding to these, if you intend to resubmit a revised manuscript please add to the details in the methods on the source of the primary and secondary syphilis data - are they publicly available? is there a web link? and if not how would other researchers obtain these data?

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).

Important additional instructions are given below your reviewer comments.

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,

Graham P Taylor, MB, DSc

Associate Editor

PLOS Neglected Tropical Diseases

Mathieu Picardeau

Deputy Editor

PLOS Neglected Tropical Diseases

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Thank you for submitting this manuscript to PLoS Neglected Tropical Diseases which has now completed the review process. The reviews are favourable but specific changes to the manuscript have been suggested. In addition to responding to these, if you intend to resubmit a revised manuscript please add to the details in the methods on the source of the primary and secondary syphilis data - are they publicly available? is there a web link? and if not how would other researchers obtain these data?

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 objectives the study are clearly written, study design appropriate, sample size is ok for the study.

The statistical analysis done supports the conclusion.

Reviewer #2: The objectives of this study were clearly presented and easily tested. The study design appears appropriate to the hypotheses tested. This is a relatively simple and straightforward study that provides needed insight regarding the sociodemographic and socioeconomic factors surrounding P&S Syphilis transmission.

Line 121: Can you provide a map of the region both broad and fine scale (inset) to help the reader with the area?

Line 124: Start the sentence with, “In 2017, there was great…” and do not switch between tenses

Line 128: Check journal standards, but values less than 10 are spelled out, i.e., ‘nine’

Line 134: Does this surveillance system have an official name?

General: How often are cases reported? And what is the spatial resolution of those reports (to which level of governance are they aggregated?)

Line 137: “will be” or “was”? Check your use of tense throughout

Line 141: Do you mean ‘number of health institutions’?

Line 142: “person counts”? ‘number of people per square kilometer’ ?

Line 145: Add a comma after ‘structure’

Line 152: Replace ‘sunshine” with ‘daylight’

Lines 151-152: Provide the units in which these metrics were recorded. Were these data aggregated to the administrative units? If so, how?

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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 analysis presented match the analysis plan.

results clearly and completely presented

figures (Tables, Images) are of sufficient quality

Reviewer #2: Lines 203-205: “A peak period”? Is there a peak monthly period each year? Or were these data aggregated?

Line 207: Regarding the time series maps. It appears that the incidence rate hot spot moves from north to south regions, until the rate nearly dissolves. What is this pattern I’m seeing?

Line 208: The term ‘hot spot’ is used here, but it has a specific meaning in spatial analyses that were not conducted in this study. It would be best to find a different term.

Line 225: There is an unnecessary period after 1.17

Line 237: Change ‘autoregressive’ to ‘autoregression’

Line 254: Add ‘factors’ after sociodemographic

Spatial clusters identification: Does the algorithm determine grouping of years, or was this done by the authors?

Results: Avoid redundancy by either 1) putting your statistics in a table OR 2) adding them to the body of the text. Generally, you should not do both. Example Line 230

Results: I recommend that you create a map (or series of maps) that shows distribution of your variables (e.g., population density, net migration, health institutions, etc.). It would be very helpful to visualize these data spatially. It could just be an appendix or supplemental figure.

Results: Can you graphically present the U-shaped relationships you found in this study?

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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 data presented supports the conclusion

Reviewer #2: The conclusion are supported by the results and data.

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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: Accept

Reviewer #2: There is quite a bit of tense-switching throughout the manuscript (past, present, and future tenses were all noted). Please check thoroughly.

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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 Response)

Reviewer #2: Overall, this was simple and to the point. My recommendations are minor but strongly suggested.

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Reviewer #1: No

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.

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.

Attachments

Attachment

Submitted filename: Review_Apr20.docx

Dear Dr. Ling,

We are pleased to inform you that your manuscript 'Spatiotemporal distribution and sociodemographic and socioeconomic factors associated with primary and secondary syphilis in Guangdong, China, 2005-2017' 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,

Graham P Taylor, MB, DSc

Associate Editor

PLOS Neglected Tropical Diseases

Mathieu Picardeau

Deputy Editor

PLOS Neglected Tropical Diseases

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