Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

Dear Mr. Carmichael,

Thank you very much for submitting your manuscript "Variable bites and dynamic poplations; new insights in Leishmania transmission." 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.

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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,

José M. C. Ribeiro

Associate Editor

PLOS Neglected Tropical Diseases

Jesus Valenzuela

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 objectives of the study are clear. The authors develop a mathematical model using experimental data based on two recently published papers. Please see attached review report.

Reviewer #2: Yes, the model is clearly formulated

Reviewer #3: Yes

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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: Please see attached review report.

Reviewer #2: Yes, my response refers to the algebraic steps regarding the modeling approach.

Reviewer #3: Yes

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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: Please see attached review report

Reviewer #2: Yes, the conclusions follow the modeling formulation.

Reviewer #3: Yes

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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 review report.

Reviewer #2: (No Response)

Reviewer #3: None

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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 review report.

Reviewer #2: See attached.

Reviewer #3: Re. Carmichael et al.

The authors present a mathematical model of Leishmania transmission integrating two recent major findings in this field, built upon data acquired from another study into Leishmania infection in sand flies. They find that the distribution of amastigotes across the skin available for pick up, will have more of an influence on parasite transmission in short lived flies, whereas the presence of retroleptmonads and reamplification of the pool of metacyclic promastigotes in response to a second bloodmeal has a greater effect in longer lived flies.

I am not a mathematical expert, so I cannot comment on that side of this work, but I can offer insight into the Leishmania-sand fly interaction.

On the whole I found this a really well designed and written piece of work, which brings fresh insight to the studies on which it is based. Below are the main comments I have:

1. Clarity is needed on how you derived the retroleptomonad differentiation and replication rates and metacyclic differentiation rates? You quote personal communication with a co-author but this is needs to be explained in greater detail. It is also a discussion point as it raises gaps in our current knowledge.

2. The authors should consider incorporating the findings of Giruad et al. 2019, Communications Biology, into their discussion. They found that heterogeneity in the quality of the transmission (% metacyclics and non-metacyclics deposited) impacts on the course of the infection and transmission back to sand flies. This introduces the possibility of some sand flies acting as super-spreaders. Interestingly, the quality of the transmitted dose can also vary as the (primary) infections mature in the sand fly. This study did not look at the transmission dynamics from second bloodmeal fed flies.

3. Finally, as the interpretation of the author’s model has a lot to do with the lifespan of the infected vector, the authors should incorporate the role of parasite-induced mortality into it. In the discussion, the authors highlight that there is uncertainty in this area because there is a lack of evidence from wild populations. By extension, this argument could apply to all the data within this model. Surely, if sand fly longevity is an important to understand the implications of this model then it should form part of it, particularly, as there is sufficient data in the literature to do this. If this is not possible, the author’s should speculate on how this will influence their model in the discussion.

In conclusion, the study is excellent – it is impactful and offers fresh insight into the complex interaction between parasite, vector and host and is able to make important points relevant to the control of leishmaniasis. I believe this work is worthy of publication in PLoSNTD, if parasite-induced mortality forms a part of their model.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Figure Files:

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Attachments

Attachment

Submitted filename: Review report.docx

Attachment

Submitted filename: PNTD-D-20-01530Review.pdf

Dear Mr. Carmichael,

We are pleased to inform you that your manuscript 'Variable bites and dynamic poplations; new insights in Leishmania transmission.' 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,

José M. C. Ribeiro

Associate Editor

PLOS Neglected Tropical Diseases

Jesus Valenzuela

Deputy Editor

PLOS Neglected Tropical Diseases

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