Dear Dr. Lai:

Thank you very much for submitting your manuscript "Assessment of control strategies against Clonorchis sinensis infection based on a multi-group dynamic transmission model" (#PNTD-D-19-01903) 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 problem, but raised some substantial concerns about the manuscript as it currently stands. These issues must be addressed before we would be willing to consider a revised version of your study. We cannot, of course, promise publication at that time.

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We hope to receive your revised manuscript by Feb 18 2020 11:59PM. If you anticipate any delay in its return, we ask that you let us know the expected resubmission date by replying to this email.

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Sincerely,

jong-Yil Chai

Guest Editor

PLOS Neglected Tropical Diseases

Banchob Sripa

Deputy Editor

PLOS Neglected Tropical Diseases

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This manuscript describes about control strategies of clonorchiasis in China. It is interesting but needs some revisions before finally accepted. Please read carefully the reviewers' comments and properly address the points. Perhaps something like a flow diagram of the control measure(s) can be added for better understanding of the study. Please consider reducing unnecessary statements throughout the manuscript. The figure quality needs to be improved.

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, and the methods of statistical analysis seems to be good enough.

Reviewer #2: The manuscript described deterministic compartment control model for clonorchiasis by aiming for a long term outcome. Overall the objective is clear and by simulation of the model, the long term out comes can be assessed. The field data from an endemic area was used to validate the model prediction but there is no statistical support for that?.

Reviewer #3: (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: The result was described clearly.

Reviewer #2: I think for general reader who are not statistician, the results presented should be improved in a way that readers can easily follow the results. Perhaps something like a flow diagram of the control measure(s) can be added. Also for example the data in Figure 2 for human 1 ,2 and 3 in X-axis needed more clarification whether it means 3 human cases or not. I am not sure the quality of Figure 1 is adequate.

Reviewer #3: (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: The conclusions are definite and fine. However, it is a prediction, so the true figures will be know far later. Anyway, it is an interesting data and conclusion.

Reviewer #2: The current conclusion is wake and a more explicit conclusion is needed such that the actual outcomes from different intervention measures can be appreciated and think about utility and their effectiveness.

Reviewer #3: (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: No, it is fine.

Reviewer #2: (No Response)

Reviewer #3: (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: This is very well designed study and also well written, and a kind of innovative way of controlling clonorchiasis in China for a long term. It may be applied to other neighboring countries having clonorchiasis/ opisthorchiasis endemic area. I suppose this mathematical model is useful to implement the control measures, although in nature it may not be achieved easily. There is human food habit, which is not easily changeable by education or knowledge.

Few questions:

1) At the end of abstract: Several sustainable strategies were provided, which could lead to infection control within 10 years. -> By any strategies, clonorchiasis can be controlled down to infection control level within 10 years? Looks too simple or some additional explanations are needed.

2) Too long introduction with well know facts, and too many references are there. Hope to reduce the length and numbers of references.

3) Maybe a map to show Fusha Town’s location is recommended. There is not significant moving in/out people from the Town. The Town seems to be close to the big city, not sure though. Is it not an important variable for this kind of analysis to predict the future?

Thank you!

Reviewer #2: The manuscript provided insightful modelling for design and choosing the right control strategy but overall the flow of the manuscript is difficult to follow for general reader. To increase clarity regarding the control measures and their effectiveness will be helpful.

Reviewer #3: It is recommended to reduce the length by deleting unnecessary sentences.

Line 91, 96; It is not directly infected by C. sinenesis, but by metacercariae of C. sinenesis.

Lines 237-240; Even though a part of the results is based on the studies reported findings, the survey period in references should be described.

Finally, I thought it would be better to publish it in local journals.

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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.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Dear Dr. Lai,

We are pleased to inform you that your manuscript 'Assessment of control strategies against Clonorchis sinensis infection based on a multi-group dynamic transmission model' 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 within two working days 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,

jong-Yil Chai

Guest Editor

PLOS Neglected Tropical Diseases

Banchob Sripa

Deputy Editor

PLOS Neglected Tropical Diseases

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

The revised manuscipt has been much improved according to the reviewers' comments. It seems now to be acceptable by PLoS NTD.

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: Methods are all adquately described.

Reviewer #2: The authors have made considerable improvement in the revised version.

**********

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 all adquately described, much more clear than before.

Reviewer #2: There are additional calrification and figure.

**********

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: Conclusions are fine, not skewed.

Reviewer #2: OK.

**********

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: It is fine to accept as it is.

Reviewer #2: (No Response)

**********

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: The manuscipt is good although not very innovative. It is enough for publicaion at Plos NTD, I believe.

Now I would like to say only one thing. Before submiting the original paper, it would be better to check the paper thoroughly including the length of introducion, discussions or references. Revision should be minimized according to only reviewers' recommendations and comments. I suppose authors changed the whole paper more than indications given by the reviewers. I do not know the situation well, however, the authors seemed to refer the paper to someone who is more professional to prepare a revision. It is at least small violation, I suppose. Next time, hope to remind.

Thank you, and good luck!

Reviewer #2: The revised ms is still rather difficult to follow by general readers in Tropical Medicine and Parasitology.

**********

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: Tai-Soon Yong

Reviewer #2: No