PCLM-D-23-00099

Crowded and warmer: unequal dengue risk at high spatial resolution across a megacity of India

PLOS Climate

Dear Dr. Romeo-Aznar,

Thank you for submitting your manuscript to PLOS Climate. After careful consideration, we feel that it has merit but does not fully meet PLOS Climate’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Sep 21 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at climate@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pclm/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Xavier Rodo

Academic Editor

PLOS Climate

Journal Requirements:

1. Please note that PLOS CLIMATE has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, all author-generated code must be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/climate/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse.

2. Please include a complete copy of PLOS’ questionnaire on inclusivity in global research in your revised manuscript. Our policy for research in this area aims to improve transparency in the reporting of research performed outside of researchers’ own country or community. The policy applies to researchers who have travelled to a different country to conduct research, research with Indigenous populations or their lands, and research on cultural artefacts. The questionnaire can also be requested at the journal’s discretion for any other submissions, even if these conditions are not met.  Please find more information on the policy and a link to download a blank copy of the questionnaire here: https://journals.plos.org/climate/s/best-practices-in-research-reporting. Please upload a completed version of your questionnaire as Supporting Information when you resubmit your manuscript.

3. We ask that a manuscript source file is provided at Revision. Please upload your manuscript file as a .doc, .docx, .rtf or .tex.

Additional Editor Comments (if provided):

Dear Authors,

Despite your work has not received fully positive comments, the study has also potential interest to readers. I think there is room for addressing all issues raised, so please try to adapt the study accordingly.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does this manuscript meet PLOS Climate’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I don't know

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Climate does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The manuscript entitled "Crowded and warmer: unequal dengue risk at high spatial resolution across a megacity of India" seeks to provide a better understand of dengue transmission in Delhi using remote sensing temperature and vector carrying capacity in a high-resolution (250x250m) grid. Although studies investigating how local factors govern disease transmission are critical for disease managing, surveillance and vector control tools, this study has some important points that need further explanation by authors to access its relevance for a public health audience. Please, find below my comments.

1. Line 102. The study uses data from temperature and measure its spatial variation, i.e., temperature is a pivotal component of the manuscript. Therefore, there is no need to use the jargon of climate change to boost manuscript relevance.

2. Line 314. The concept of carrying capacity for mosquitoes is controversial and should be deeply explored, or at least acknowledged in the Discussion section. As carrying capacity (K) one could point as the maximum population size of that biological species that can be maintained in a given area/environment. What would be the carrying capacity for Aedes aegypti, considering its basic biology and life-history traits? The argument of K under areas with different socioeconomic statuses is too simplistic. Looking into Aedes aegypti biology, there are always people not bitten, breeding sites not harvested, there are always a section of our ankles that a few more mosquitoes could bite. Thus, what factors actually prevent Aedes aegypti density to increase beyond the estimate K? This is a critical point of this manuscript that was not deal by authors, and it has several consequences on the results.

3. Line 346. Why humans (N) influence mosquito carrying capacity rather than M (mosq population) itself?

Why instead of using local human population data to infer about mosquito population data, authors did not pursued in collaboration with local public health people estimates about vector population size, perhaps available at the same (or similar) spatial resolution?

4. Line 349. As several other metropolis endemic for dengue, Dehli certainly has a surveillance system based on mosquito collection. And, honestly speaking, the argument "it remains extremely challenging to sample and quantify mosquito numbers, we rely on the eesults obtained in (20) where mosquito numbers were inferred from human population density." must not be presented in these terms in a scientific manuscript.

5. Line 351. In reference 20, mosquito numbers are inferred from the human population density. Here, authors infer that production of breeding sites depends of socio-economic conditions of the local human population, which also affects temperature. Both variables share a common source of spatial variation and are influenced by human density, as they are higher in highly dense areas. The conclusion is that more dengue transmission is found in highly dense areas, but it wouldn't be obvious considering the two variables and how they were both measured? I am not into the mathematical part of the manuscript, but it seems a full circle of inferences, too speculative.

6. Line 353. Authors make reference for a paper (Telle et al. 2016 REF#21) that used data as dengue cases reported by Delhi surveillance system from 2008-2010. In this manuscript, authors presented data gathered from 2013-2015. Among several other cities in emerging economies, Delhi is probably going through rapid urban and socioeconomic transformation. How effective are the relations observed in 2008-2010 for a extrapolation around 5 years later?

7. Line 355. How human density was estimated in those big modern skyscrapers?

8. Line 363. The mosquito Aedes aegypti, the primary vector of dengue, is known to be a domestic species that often do the feeding, breeding and resting indoor. How would indoor temperature (the one that really matters for Aedes aegypti) correlate with surface thermal data remotely gathered?

9. Line 363. Besides, authors are using a variable that is affected by human activity to later conclude that poorest areas with high human density has a greater risk for dengue transmission. Isn't it a tautological explanation?

10. Line 372. Original data was gathered in the winter season, but please specify the exact period for it, i.e., naming the months or period of data collection.

11. Line 373. Couldn't get the meaning of that sentence.

12. Line 374. Case report must be deeply explained. For instance, all suspected cases were sent for diagnosis?

Among those, what is the % of positive? Authors used only those ELISA-positive cases? No additional tests, considering cross-reactions among serotypes? Which serotype?

13. Line 385. Despite the ethical approval was conceived to other published manuscript, it is recommended to add the number of such approval in this manuscript as well.

14. Line 110. As mentioned above, authors relied in a very specific temperature, one that is not that I would assume to directly influence mosquito biology. Based on the principle of transparency, I would recommend to describe it as "land surface temperature" within the manuscript.

15. Line 113. Authors mentioned that temperature (that impacts biological parameters of the mosquito and the pathogen within the mosquito). But it is not the "same temperature". The land surface temperature and the indoor temperature are correlated somehow, but in an unknown way, or at least in a way not approached in here. So, this difference must be addressed.

16. Line 119. Maybe adding a Ombrothermic curve as a supplementary file would be a good visualisation output.

17. Line 120. I would recommend adding a new Figure in 1A about human demography.

18. Line 122. Considering both variables used, T and V/n, can vary as a function of human density and therefore share avcommon source of spatial variation, shouldn't we expect a priori that their combination would boost the spatial role of human density in dengue epidemiology?

19. Line 124. Not clear how mosquito recruitment in urban landscapes intrinsically related to human activities. Population recruitment in ecology means the process by which new individuals are added to a population, whether by birth and maturation or by immigration. It was not measured and is a concept different than K.

20. Line 139. Considering the Figure 1, N means mosquitoes? Males and females? Males or females?

21. Line 167. Authors mention the percentage of units at high risk for dengue transmission, but it would be informative to add in the methods the number of units in the city. Furthermore, also specify whether a unit is a 250x250m in case I assumed it correctly.

22. Line 205. Please amend the statement. There are several variables able to drive dengue epidemiology. Despite my criticism on how the two variables were built, authors observed that two of them are able to well describe dengue transmission in Delhi. But they can be useless in other endemic settings, or have a subtle relevance in other context. They are among the most relevant dengue drivers, but not the only known two variables.

23. Line 214. Authors mentioned "The synergistic action of the two drivers especially affects the least developed areas of the city, with 70% of the winter cases reported from within socio-economic units classified as deprived, and only 22% and 8%, from medium and rich typologies respectively.". In order to atest whether it is proportionally or disporportionally affected, what is the coverage of low, medium and high socio-economic areas?

24. Line 231. Authors have conducted any correction regarding human demography per spatial unit to test whether more cases occur in the highly dense areas, proportionally to their population size?

Reviewer #2: Review of "Crowded and Warmer: unequal dengue risk at high spatial resolution in a megacity of India ”

Manuscript number: PCLM-D-23-00099

Authors: Romeo-Aznar et al., 2023

Recommendations: Major revisions

The paper by Romeo-Aznar et al. investigates the impact of temperature and vector carrying capacity during the winter season in Delhi, at high spatial resolution. The authors show a synergistic effect of temperature and population density on simulated Ro values for Delhi. This work also underlines the inequality in exposure to dengue risk amongst the poorest and wealthiest populations in the city. Overall, it’s a interesting study that should be published in PlosClimate. However, there are clarifications and potential additional analysis that would strengthen their findings and the usefulness of such research for local public health authorities. In the following, find a few comments that should improve the scientific quality of the manuscript.

Major points:

1 – One satellite image taken at 5am on the 15th of Nov 2013

The authors honestly discuss the limitations of their temperature data in discussion. However, their temperature estimates should be compared to at least one seasonal winter temperature average map to ensure that regional differences are conserved. Magnitude of temperature values should change though and impact the estimated value of Ro, in particular during mid-day late afternoon when temperatures usually climb up.

2 – Validation to develop

Model validation mostly rely on Fig 3 which is fine. However, a naïve reader would like to compare Ro maps with a map depicting the number of dengue cases (per district or per location using circles for example) in Delhi to compare hotspots and low case / risk values. This map could be added on Fig 2 for example. Consequently, in discussion, the authors could suggest the districts in Delhi for which vector control interventions should be conducted during the quieter winter season. Such information would be valuable for local vector control authorities and should be compared to current practices in Delhi.

2 – More details about the vector

Ae. aegypti is highly anthropophilic. Evidences from the scientific literature (Ponlawat et al., 2005 there are many other references on this issue) demonstrate that the urban strains of Ae aegypti primarily feeds on humans (95% of blood samples in gravid females is human blood). Hence, why you usually find them in warm and densely populated areas. They also feed at dawn and dusk and this important point should be mentioned. More details about the biology and feeding preferences of the mosquito should be added in Introduction.

Minor comments:

L34-35: “for emergent arboviruses which are responsible for… most commonly transmitted by Ae. aegypti in large tropical cities.” Other Aedes can transmit arboviruses but Ae aegypti is indeed the main vector in Tropical cities.

L40: “…of the reproductive number of dengue…” – Precise disease under scope (first mention in the abstract)

L43: “three consecutive boreal winters…” Worth mentioning once (boreal vs austral) to avoid confusion even if this is obvious.

L60: “for disease transmission”

L62: “of vector-borne diseases such as dengue fever and Zika which are primarily transmitted by the bites of Ae. aegypti in tropical urban settings.”

L65: “has underlined the importance”

L85: “… of UHI tends to positively correlate with…”

L88: “would be extremely valuable to optimize…”

L100: “are used to validate… Results highlight”

L102: “wider context of”

L106: Use subscripting for R0

L106:”R0 that measures the average number of…”

L109: “depends on model assumptions, ”

L122: “…from zero to… across the city.”

L124-125: Good point – but you need to state somewhere that Ae. aegypti in urban areas is highly anthropophilic, it feeds specifically on humans (hence why you also expect pop density to play a role). Ae albopictus would be different as it can feed on other hosts (mice, birds, dogs etc)

L132: “values of ?”

Fig 1 comments: Caption precise unit for population density (per km2?). The relationship between N and the vector carrying capacity is more or less linear for deprived and poor population (Fig 1B). However, for the wealthiest population, the function has a triangular shape with a decreasing linear relationship for N > 1000. The authors need to discuss this and suggest why.

L205: “taken together namely temperature and… ratio, produce … at high resolution within Delhi.”

L218: “a larger proportion of available man-made water containers.”

L219: “is also evident on simulated Ro risk maps..”

L220: “…as the Ro* threshold increases…”

References

Alongkot Ponlawat , Laura C. Harrington, Blood Feeding Patterns of Aedes aegypti and Aedes albopictus in Thailand , Journal of Medical Entomology, Volume 42, Issue 5, 1 September 2005, Pages 844–849, https://doi.org/10.1093/jmedent/42.5.844

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Reviewer #1: No

Reviewer #2: No

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PCLM-D-23-00099R1

Crowded and warmer: unequal dengue risk at high spatial resolution across a megacity of India

PLOS Climate

Dear Dr. Romeo-Aznar,

Thank you for submitting your manuscript to PLOS Climate. After careful consideration, we feel that it has merit and needs minor adjustments to fulfil PLOS Climate’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jan 04 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at climate@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pclm/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Xavier Rodo

Academic Editor

PLOS Climate

Journal Requirements:

1. Please note that PLOS CLIMATE has specific guidelines on code sharing for submissions in which author-generated code underpins the findings in the manuscript. In these cases, all author-generated code must be made available without restrictions upon publication of the work. Please review our guidelines at https://journals.plos.org/climate/s/materials-and-software-sharing#loc-sharing-code and ensure that your code is shared in a way that follows best practice and facilitates reproducibility and reuse.

2. Please include the following request in the decision letter, and ping me with follow up. Please include a complete copy of PLOS’ questionnaire on inclusivity in global research in your revised manuscript. Our policy for research in this area aims to improve transparency in the reporting of research performed outside of researchers’ own country or community. The policy applies to researchers who have travelled to a different country to conduct research, research with Indigenous populations or their lands, and research on cultural artefacts. The questionnaire can also be requested at the journal’s discretion for any other submissions, even if these conditions are not met.  Please find more information on the policy and a link to download a blank copy of the questionnaire here: https://journals.plos.org/climate/s/best-practices-in-research-reporting. Please upload a completed version of your questionnaire as Supporting Information when you resubmit your manuscript.

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.

Additional Editor Comments (if provided):

Dear Authors,

I can accept your study without further delay provided you can address the minor point/s raised by reviewer two. Please explain to me in a response letter how you are addressing those (e.g. by adding a new figure or a table in the suppl. material..) and include an explicit reference to the high-risk districts in Delhi at least in the discussion section.

I look forward to your detailed reply.

Best regards

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

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2. Does this manuscript meet PLOS Climate’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available (please refer to the Data Availability Statement at the start of the manuscript PDF file)?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS Climate does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I would like to appreciate and congratulate the authors for the careful responses raised during peer review.

Reviewer #2: The reviewers addresses most of my concerns excepting one, e.g. the comment I made on validation.

The test they used reject a random distribution of cases relative to simulations (Ro or pop density only)

and provide only p values for different selected thresholds (Fig. 3).

I assume that the authors added black squares on Fig. 2 (with zoom in Fig S3 - S4 - S5 respectively corresponding to maps shown on Fig 2A - Fig 2B - Fig 2C) to depict where dengue cases were reported in Delhi.

First, details about these cases need to be added in the related figure captions (something along these lines "units where dengue cases were recorded are depicted by small black squares").

Second, there must be a number of cases reported per location - hence a simple scatter plot showing how Ro = f(cases) for concomitant locations could be added

Third, by eyeballing Fig 2C (or zoomed Fig S5) I counted about a third of points (black squares) falling into the high risk areas (in red) - most of them are included in the medium risk category.

You can correct me if I'm wrong but I assumed dengue observations to be depicted by black squares

Hence, given the strong statements (in abstract) about the ability of the Ro model in capturing high risk units, the authors should I think provide more metrics for validation in Supp Mat:

They could add:

a - Simple scatter plot showing how Ro (and N) evolves as a function of the number of reported cases for units for same locations

b - They could use colored circles, proportional to the number of cases and add it in a separate map

c- They also need to state that the N only model provide lower p-values than Ro, hence denoting a better accuracy at capturing high risk areas

Finally, the authors did not address one of my practical and (I hope) important comment.

They should provide advises about districts at high risk of dengue in Delhi in conclusion.

No-need to name them all but the Ro model tends to simulate large risk over the eastern part of the city.

They could also discuss how such hotspots are consistent with current vector control practices in place in Delhi.

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7. 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.

Do you want your identity to be public for this peer review? If you choose “no”, your identity will remain anonymous but your review may still be made public.

For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Crowded and warmer: unequal dengue risk at high spatial resolution across a megacity of India

PCLM-D-23-00099R2

Dear Dr. Romeo-Aznar,

We are pleased to inform you that your manuscript 'Crowded and warmer: unequal dengue risk at high spatial resolution across a megacity of India' has been provisionally accepted for publication in PLOS Climate.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow-up email from a member of our team. 

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.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they'll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact climate@plos.org.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Climate.

Best regards,

Xavier Rodo

Academic Editor

PLOS Climate

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Dear Victoria and co-authors,

I appreciate the efforts and clarifications provided in this review and I am pleased to accept your study for publication in PLoS Climate.

Reviewer Comments (if any, and for reference):