Dear Dr. Jung,

Thank you very much for submitting your manuscript "Age, period, and cohort effects of Clonorchis sinensis infection prevalence in the Republic of Korea: insights and projections" 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.

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,

Ran Wang, M.D.

Academic Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

Section 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: See the attachment.

Reviewer #2: The manuscript did not mention the actual size of investigated population that included in the analysis, which should be provided in the revised version.

Reviewer #3: The 'Age-period-cohort modeling' should be emphasized, including which references were made, how specific calculations were made, and what each coefficient represents.

Reviewer #4: Methods applied to existing data seem appropriate.

As no new data was collected, the ethical considerations of collecting survey data were not necessary to mention.

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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: See the attachment.

Reviewer #2: Fig 3, there is one blue line, but two shadows (light blue and gray) in each panel.

It seems that gray shadows are not described, suggested to remove them.

Then, you could zoom in on the Y axis.

Reviewer #3: Lines 230-233 The data sources for 2015-2021 should be supported by literature, or relevant tables should be listed in the attachment. Why is there no relevant data for 2013 and 2014?

Reviewer #4: Results are described clearly and appropriately.

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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: See the attachment.

Reviewer #2: (No Response)

Reviewer #3: Is there a comparison and discussion between this model and similar models that have already been publicly published?

Reviewer #4: Conclusions support intervention strategies used in the past and in the present.

Some additional comparison with similar data from China for clonorchiasis would be useful to the reader and further support their conclusions.

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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: Major revisioin.

Reviewer #2: (No Response)

Reviewer #3: Major Revision

Reviewer #4: Well written with no editorial changes suggested.

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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: 1. Authors has poor knowledge of the distribution of Clonorchis sinensis. Did C. sinensis only endemic to Korea, China and northern Vietnam? In addition, authors made serious mistake. Taiwan is one province of China, so the “Taiwan” should be deleted in this sentence in line 67. Please check and correct.

2. Why use the data from 1981-2012? And what’s the basis? After all, it has been too many years since then.

3. It’s 2024 now. While the study projected the age-stratified prevalence up to 2023 which is not real-time enough, and did not provide the latest data.

4. What’s the basis for dividing age groups? This should be described.

5. All tables should be shown as three-line.

Reviewer #2: The manuscript use published data and generate new analysis in particular with the cohort factor. It is a brief research note. Here below are some key points needed to be addressed in the revised version.

1. Line 67, "countries", "China", "Taiwan". When mentioning "countries", it is inproper to put China and Taiwan on the same position, you may use"regions, including... Chinese mainland, Taiwan...". or "countries, including... China (with Taiwan province)...".

as well as at Line298 (e.g., China, Taiwan...)

2. Line 93, "decline in national prevalence to 1.9% by 2012", Is this 1.9% only for C. sinensis?

Maybe the following way is more clear, "...prevalence to 1.9% by 2012 for C. sinensis, comprising 73% of the total positivity rate for all intestinal parasitic infections, the country continues to face areas with high endemicity [5]".

3. In the case of older persons have higher infection proportion,

did authors exclude the possibility effect of accumulation of raw fish consumption?

4. Discussion should highlight the important effect of widespread allocation of praziquantel since 1983 and the government elimination program since 2005, which reform the trend of going down.

5. Author may discuss: the younger generation (those born in the cohort of 1952 or later) that consuming less raw fish may largely influence by food imported from overseas, and having a keen interest in exploring new eating cultures.

Reviewer #3: This research applied the age-period-cohort modeling approach to nationally representative C. sinensis infection prevalence data from 1981–2012 in Korea, and the model was used to predict the incidence in the next few years. Overall, this study has certain novelty and practical value. However, some questions need to be addressed or answered.

Specific comments

Line 67, Line 298: Please refer to the literature to correctly explain the relations between China and Taiwan（For example, doi: 10.1016/S0140-6736(15)60313-0. doi: 10.1016/j.biotechadv.2018.02.008.）

Fig 3 : What the light and dark shades of blue represent？

Lines 230-233: It was observed that the incidence of Fig3D and E was increased in the high age group, which is not consistent with the result description.

Reviewer #4: The article by Sung-mok Jung et al. explores the use of clonorchiasis survey data to model the impact of age cohorts and location on the prevalence of clonorchiasis in Korea during a successful intervention campaign. The study depends heavily on available datasets that are more than ten years old and they use more recent survey data from high prevalence regions to assess the results of their models. Similar studies have been conducted in China for C. sinensis but similarities in trends observed were not compared/contrasted herein. In particular, how more recent geospatial data in China compares to the correlations observed in prevalance vs. region herein. Some bias in sampling regions with recent comparative data was inevitable due to the reduced prevalance, but should be discussed, perhaps? The results of the article support the importance of considering age group/cohorts when designing intervention strategies. The authors have not provided any changes/modifications from existing intervention methods (education programmes, targeted treatment to reduce parasite load etc.); only that is appears to work well

Other comments:

Author summary is very similar to the abstract. It would be good to review to address accessibillity for a broader audience.

Line 72. Not just transmission to humans

Line 246 247. Is there evidence that age cohort has not been taken into consideration for interventions? It is my understanding that this is known and has been considered in current efforts.

Line 258 to 261. Should also comment on the first intermediate host as well.

Lines 269 to 273. Would modelling low and high risk regions (based on correlation mentioned) be more informative for providing recommendations for future intervention strategies? For example, would the model behave differently in high risk regions?

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Reviewer #1: No

Reviewer #2: Yes: De-Hua Lai

Reviewer #3: No

Reviewer #4: 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:

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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: comments and suggestions - PLOS NTD.docx

Dear Dr. Jung,

Thank you very much for submitting your manuscript "Age, period, and cohort effects of Clonorchis sinensis infection prevalence in the Republic of Korea: insights and projections" 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,

Ran Wang, M.D.

Academic Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

Section Editor

PLOS Neglected Tropical Diseases

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

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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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

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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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

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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: (No Response)

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

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: Accept

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

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: After carefully reviewing the revised manuscript of the author, it is found that the author has carefully revised the comments and suggestions of the reviewer, only one issue should be address.

L66-68, “Clonorchis sinensis (C. sinensis)...... including the Republic of Korea (hereafter “Korea”), mainland China, Taiwan, and northern Vietnam [1–3]” should be replaced with “Clonorchis sinensis (C. sinensis), a prevalent intestinal helminth primarily endemic to the East Asian countries, including the Republic of Korea (hereafter “Korea”), China, and Vietnam [1–3]”.

L298, Please delete Taiwan.

It is well known that Taiwan is a province of China, so it is not appropriate to put China and Taiwan together. It is suggested to delete the words "Taiwan" in these sentences.

Please check all text and revise it.

Reviewer #2: (No Response)

Reviewer #3: This study builded and applied the age-period-cohort modeling approach to nationally representative C. sinensis infection prevalence data from 1981–2012 in Korea, in order to provide valuable insights for future public health planning and resource allocation. This research has certain scientific value and reference significance, I agree to publish.

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.

Dear Dr. Jung,

We are pleased to inform you that your manuscript 'Age, period, and cohort effects of Clonorchis sinensis infection prevalence in the Republic of Korea: insights and projections' 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,

Ran Wang, M.D.

Academic Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

Section Editor

PLOS Neglected Tropical Diseases

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