Dear Mr Hu:

Thank you very much for submitting your manuscript "Heatwaves and dengue outbreaks in Hanoi, Vietnam: new evidence on early warning" (PNTD-D-19-01089) for review by PLOS Neglected Tropical Diseases. Your manuscript was fully evaluated at the editorial level and by independent peer reviewers. The reviewers appreciated the attention to an important topic but identified some aspects of the manuscript that should be improved.

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Sincerely,

David W.C. Beasley

Associate Editor

PLOS Neglected Tropical Diseases

Scott Halstead

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 although in attached Word doc some clarification in the stats would be helpful. I am also interested to know what effect inclusion of district as random factor would have. Spatial scale seems very large but perhaps this was not the case.

Reviewer #2: The objective of the study is clearly stated although there is no testable hypothesis provided. The population has been described with mention of what is known of the disease prevalence. The sample size is sufficient though the geographical coverage is not wide enough to allow for wider applicability of the findings. There are no concerns on the ethical requirements.

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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: Results are good. As stated in attached Word doc, needs some work (Fig 5 I can't read) and perhaps an additional one or two results would be of general interest.

Reviewer #2: Results are clearly presented and match the analysis plan with good quality figures generated and provided.

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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, again perhaps addition of one or two limitations, especially with regard to serotype and herd immunity.

Reviewer #2: Specific comments

1. The authors state clearly how high temperatures that occur as heatwaves affect occurrence of dengue outbreaks in the following lines; “Line 350: we found that temperature was responsible for a large number of dengue cases”. Then goes on to state in line 367: Noticeably, heatwaves had a much longer delayed effect on large dengue outbreaks than small and medium outbreaks” and line 371 that These findings may suggest that not only have heatwaves delayed the timing of dengue outbreak but also increased the magnitude”

It is unclear to me (and possibly for other readers who will be interested in this work) how the delay is conceived. What would have been the expected timing of the outbreaks following a heat wave? If increased magnitude of outbreak is bad as would be expected, is increased delayed outbreak a good thing? How can this delay be explained in terms of disease incidence vis a vis rise in temperature and what are the implications to public health?

2. In an attempt to provide biotic explanation to the model, authors have made statements that need clarification. In line 375 “long-lasting high temperatures affect the mosquito population and in line 376 “High temperatures during heatwaves may exceed the threshold for mosquito survival and mosquito population would be greatly reduced”. How would this result in increased cases or outbreaks? It sounds like it would have the opposite effect.

In real life scenario, increased temperature can affect mosquito population negatively if the relative humidity is low. However, in high humidity, mosquito survival would not be much affected, but the high temperature would increase the virus development time (extrinsic incubation period, EIP) in the mosquito hence increasing the transmission rate. This can be considered in explaining the effect of temperature on transmission hence increased outbreaks.

3. The authors should explain how these findings have relevance to dengue outbreak prevention and 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: Please see attached doc.

Reviewer #2: Revisions should entail clarification of issues raised in the conclusion above.

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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: Please see attached doc

Reviewer #2: Overall general comments; The paper is well written and addresses a re-emerging disease of growing public health concern that is greatly influenced by climatic factors. There are a few grammatical errors that the authors can address by having a third party read through for language editing. Apart from addressing the specific comments mentioned above which will clarify and improve the manuscript, I find the paper is suitable for publication in PLOS NTD.

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Reviewer #1: Yes: Richard Paul

Reviewer #2: Yes: Rosemary Sang

Attachments

Attachment

Submitted filename: Cheng et al.docx

Dear Mr Hu,

We are pleased to inform you that your manuscript, "Heatwaves and dengue outbreaks in Hanoi, Vietnam: new evidence on early warning", has been editorially accepted for publication at PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted and sent to production you will need to complete our formatting changes, which you will receive in a follow up email. Please note: your manuscript will not be scheduled for publication until you have made the required changes. One of the reviewers has also made some recommendations regarding additional minor edits to improve the clarity of certain portions of the manuscript that we also ask you to address during final editing for publication.  

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Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

David W.C. Beasley

Associate Editor

PLOS Neglected Tropical Diseases

Scott Halstead

Deputy Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

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 thank the authors for their careful consideration of my previous comments/suggestions. It now reads very well and is very clear.

However, the paper could do with a thorough check of the English. With no disrespect intended to the English of the main authors, perhaps some of the middling native English speakers could read this through as well. Fresh eyes to spot the errors.

For example (and there are issues throughout, albeit minor)

In the abstract

Conclusions: The short-term association between temperature and dengue risk varied by

52 the level of outbreaks and temperature seem more likely affect large outbreaks. Moreover,

53 heatwaves may delay the timing and increase the magnitude of dengue outbreaks.

Highlighted sentence doesn’t make sense. The “seem more likely affect large outbreaks” hangs on its own.

Author summary

73 such as El Niño event and extreme hot summer can affect dengue incidence rate

“event… summer ….. rate” should be plural

……. Many other examples throughout

“Finally” Figure 5 legend shows “Dealyed….”

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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: Yes: Rick Paul