Dear Dr Freitas,

Thank you very much for submitting your manuscript "Spatio-temporal modelling of the first Chikungunya epidemic in an intra-urban setting: the role of socioeconomic status, environment and temperature" 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.

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[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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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,

Pedro F. C. Vasconcelos

Deputy Editor

PLOS Neglected Tropical Diseases

Pedro Vasconcelos

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: The data source is introduced, but little discussion is given to the data generating mechanism. That is, how does the epidemic in the population relate to the observations. Is there evidence for asymptomatic and undetected transmission? Are there disparities in recording cases? This should be addressed.

Line 221: It may not make a difference, but a quantitative convergence diagnostic like the Gelman and Rubin diagnostic is preferable to visual assessment.

Statistical Analysis Generally: I'd be interested to see a posterior predictive p-value to assess the final model fit. I think the model is meaningful and useful even if the fit is questionable, but it would be good to higlight this kind of limitation.

The proposed model is not dynamic in the same way that compartmental techniques are, so this is one area where limitations of the proposed method may arise.

I applaud the authors for making their code available.

Reviewer #2: (No Response)

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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: I found the results to be well articulated.

Reviewer #2: (No Response)

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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: Overall the conclusions are well stated and the limitations well articulated. One area where this should be expanded is the same as mentioned previously - the difference between the techniques proposed and mechanistic models which account for transmission dynamics. To be clear, I think the authors' approach is reasonable, but it should be placed in the context of the wider stochastic epidemic modelling literature.

Reviewer #2: (No Response)

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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: Overall, the manuscript is well written and clear, both in terms of methodology and problem description. There are a few minor language issues to double check, mainly consisting of issues of word choice and numerical agreement. Here are a few examples - overall the writing is quite good.

Abstract

"Green" areas should be clarified. Environments with vegetation are likely heterogeneous with respect to the factors identified.

Summary

- Line 42: "transmitted viruses"

- Line 45: "status plays"

- Line 47: "improving ... is"

Introduction

- Line 61: facilitating the establishment of a

- Line 63: citation needed - antibody tests can certainly be cross-reactive between these viruses

- Line 66: "conditioned by" -> "favorable to"

- Line 73: "data regarding the"

- Line 93: "favor contact" (remove "the"), "the human" -> "humans"

- Line 96: "disease epidemics"

- Line 98: "including intrinsic conditional"

Reviewer #2: (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: Overall this is a strong manuscript in need of a few additional areas of discussion, and ideally some investigation of model fit (beyond the relative measures of information criteria).

Reviewer #2: The authors present a study of the first chikungunya outbreak in Rio de Janeiro in 2016, and analyze this dataset of notified cases by neighborhood and week using Bayesian (intrinsic conditional autoregressive [ICAR]) spatio-temporal models to understand the drivers of this outbreak. They investigate effects of temperature, and include this as both a direct and a decaying effect, socioeconomic status, and green space. Covariate effects are allowed to vary over time, so that they can tease apart whether the importance of different factors changes as the epidemic progresses. I think this is a strong and helpful piece of work. The insights on how socioeconomic status of neighborhoods is tied to transmission early on in the pandemic, and as it fades, but is essentially absent during the peak, is particularly interesting. I offer the following comments in the hope they can improve the paper further:

Socioeconomic status was based on an index, which was an average of eight normalized indicators. I am always somewhat uncomfortable with indicator variables, because the interpretation of an arithmetic average of normalized values becomes difficult to interpret – why not use a subset of the indicators directly as variables? Would it not be much more helpful to know whether it is water supply that leads to vulnerability, or sewage or garbage collection, and how important these different factors are relative to each other?

Green areas: can you explain in more detail why you combined these various “natural” areas into green space for your analysis? Areas like agricultural land are not associated typically with Ae. aegypti, while something like canopy cover could certainly lead to more favorable microclimates for this species. (in other words, the composite variable might end up not having an effect because it combines both positive and negative land use elements).

Although the minimum temperature can certainly be important, so can the maximum (e.g., temperatures that are overly hot can impair mosquitoes as well). Why only pick the minimum here?

I appreciate the mention of limitations in the discussion. For the third of those (people potentially getting infected in neighborhoods other than where they live), I’d like to see some more discussion, as with the other limitations: what do we know about this, how likely is it, how would you change your modelling approach to account for it if you think it likely is important?

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Reviewer #1: No

Reviewer #2: No

Figure Files:

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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 Freitas,

We are pleased to inform you that your manuscript 'Spatio-temporal modelling of the first Chikungunya epidemic in an intra-urban setting: the role of socioeconomic status, environment and temperature' 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,

Pedro F. C. Vasconcelos

Deputy Editor

PLOS Neglected Tropical Diseases

Pedro Vasconcelos

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: The authors did a good job of responding to both my comments and those of the other reviewer.

**********

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 figures generally appear pixelated, and should be regenerated as high resolution raster or as vector image files.

**********

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: My comments have been addressed, via the expanded discussion of the authors' techniques relative to alternatives.

**********

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: I recommend to accept this manuscript.

**********

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)

**********

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