Dear Dr. Seposo,

Thank you very much for submitting your manuscript "Socio-economic factors and its influence on the association between temperature and dengue incidence in 61 Provinces of the Philippines, 2010-2019" 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.

The reviewers raised concerns about the descriptions of the data, definitions of covariates, theoretical background for using the 18-week maximum lag, visualizations of the dlnm outputs, and the large uncertainty for the estimated effects in Figure 5.

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,

Qu Cheng, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Justin Remais

Section Editor

PLOS Neglected Tropical Diseases

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The reviewers raised concerns about the descriptions of the data, definitions of covariates, theoretical background for using the 18-week maximum lag, visualizations of the dlnm outputs, and the large uncertainty for the estimated effects in Figure 5.

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: I document major concerns in the attached. I am concerned about the omission of precipitation in the model, and in the parameterization of certain socioeconomic variables (e.g., is urban population used or percent urban population used?)

Reviewer #2: 1. The objectives of the study clearly articulated with a clear testable hypothesis stated - 1. to examine the association between dengue and temperature in multiple locations in the Philippines, and 2. to explore the modification role by socioeconomic factors.

2. The study design is appropriate to address the stated objectives - a modelling analysis has been carried out.

3. The population is clearly described and appropriate for the hypothesis being tested.

4. Correct statistical analysis were used to support conclusions - meta-regression is common to be used to summarize the effect size of the association.

5. There are concerns about ethical or regulatory requirements being met - No ethical statement has been mentioned.

Reviewer #3: Yes to all these questions.

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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 document major concerns in the attached. I am concerned that the authors do not specific over which lags the exposure-response dimensions are calculated, nor for what temperature comparison the lag response dimension is calculated. I am also concerned about why the temperature-response relationship is highly uncertain for one SES axes of comparison, but not the other

Reviewer #2: Yes

Reviewer #3: I have a question regarding Figure 3 and the description about it in the manuscript. I raised this question in my reviewer attachment.

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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: I document major concerns in the attached. The authors should take care not to confuse interpretation of effect modification with main effects. Such is the case, for instance, in poverty incidence.

Reviewer #2: Yes

Reviewer #3: Yes to all.

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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: I recommend minor revision.

--------------------

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, authors examine how various socio-economic factors (including poverty, urbanization, and health-care expenditures) modify the temperature-dengue incidence across provinces in Philippines. They do so using a two-stage distributed lag non-linear model with meta-analysis. This research question is of importance, and the DLNM model is a good approach for this question. However, I have some methodological questions as well as some concerns with the presentation and interpretation of the results.

Reviewer #2: This is a modelling study 1. to examine the association between dengue and temperature in multiple locations in the Philippines, and 2. to explore the modification role by socioeconomic factors. Some comments:

1. According to the journal policy, the data are required to be shared to ensure a reproducibility.

2. The study findings are highly consistent with some others in South Asian settings that have not been cited e.g. doi.org/10.1016/j.jiph.2017.12.006, doi.org/10.1016/j.envint.2022.107518. Please discuss.

3. Please describe what is "ERA5-land"? Is the data source reliable?

4. What is the resolution of the socioeconomic factors?

5. Maximum lag of 18 weeks is too long even lag plot may support the assumption. Justification should be given.

6. A symbol cannpt be showed in line 129.

7. The first paragraph of results should report the incidence rate rather than number of cases.

8. The major concern of the study is that the uncertainty of categories is very large in the socioeconomic factors (Figure 5), so the results of the effect modification is very inconclusive. Even household size i don't think it is a effect modifier given both groups show a similar pattern. The authors should think of other ways to examine the modification effect.

Reviewer #3: (No Response)

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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 #2: No

Reviewer #3: 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:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: PlosNTDs_dengue_temp_SES.docx

Attachment

Submitted filename: Review for PNTD-D-23-00460.docx

Dear Dr. Seposo,

Thank you very much for submitting your manuscript "Socio-economic factors and its influence on the association between temperature and dengue incidence in 61 Provinces of the Philippines, 2010-2019" 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).

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,

Qu Cheng, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Justin Remais

Section Editor

PLOS Neglected Tropical Diseases

***********************

The reviewers still have minor suggestions regarding the visualizations, descriptions of the methods, and the interpretations of the results.

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 are clear (to describe the association between temperature and dengue incidence in the Philippines and to examine effect modification by SES variables) and the study design and DLNM is appropriate. No ethical concerns.

Reviewer #2: Yes to all

Reviewer #3: Yes to all.

--------------------

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: Generally yes. Please see comments for a few points raised, including about the axis of Figure 4, the need to state a reference level for Figure 4, and concerns about the model fit for the model using poverty incidence in the interaction variable.

Reviewer #2: Yes to all

Reviewer #3: Yes to all.

--------------------

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: Generally, yes. Please see comments for a few points raised about interpretation of main effects vs. interaction and interpretation of the model fit using poverty incidence in the interaction term.

Reviewer #2: Yes to all

Reviewer #3: Yes to all.

--------------------

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: Accept

Reviewer #3: Minor revision

--------------------

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: The authors have addressed my comments well.

Reviewer #3: Thank you for addressing my comments. I still have one question regarding the revised effect modification analysis. The authors stated that they centered the effect modifier by the 5th and 95th percentile values and ran the model (eq 2). Does it mean that the authors ran sperate models, one with effect modifier centered by the 5th percentile and the other with effect modifier centered by the 95th percentile? Or there is just one model with the effect modifier transformed to categorical values (0:<5th percentile, 1: 5-95th, 2:>95th) ? I think this part needs some further illustration so it is better understood by the general audience.

--------------------

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 #2: No

Reviewer #3: 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:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

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: PlosNTDs_dengue_temp_SES_rev2.docx

Dear Dr. Seposo,

We are pleased to inform you that your manuscript 'Socio-economic factors and its influence on the association between temperature and dengue incidence in 61 Provinces of the Philippines, 2010-2019' 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,

Qu Cheng, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Justin Remais

Section Editor

PLOS Neglected Tropical Diseases

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