How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis

PLOS Neglected Tropical Diseases

Dear Dr. Ellis,

Thank you for submitting your manuscript to PLOS Neglected Tropical Diseases. After careful consideration, we feel that it has merit but does not fully meet PLOS Neglected Tropical Diseases'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.

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We look forward to receiving your revised manuscript.

Kind regards,

Song Liang

Academic Editor

PLOS Neglected Tropical Diseases

Francesca Tamarozzi

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

Journal Requirements:

1) Please ensure that the CRediT author contributions listed for every co-author are completed accurately and in full.

At this stage, the following Authors/Authors require contributions: John Ellis, Nyamai Mutono, Andreia Vasconcelos, Mwangi Thumbi, Deirdre Hollingsworth, and Roy Anderson. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

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Reviewers' Comments:

Comments to the Authors:

Please note that one of the reviews is uploaded as an attachment.

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)

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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: (No Response)

Reviewer #2: (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: (No Response)

Reviewer #2: (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 Response)

Reviewer #2: (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: Comments attached

Reviewer #2: This manuscript explores the impact of improved drug efficacy on schistosomiasis mass drug administration (MDA) using a mathematical model. While the study has some novelty and public health relevance, the model suffers from several key methodological flaws that require significant revisions.

Major Weaknesses:

1.The model assumes perfect mixing within the population, neglecting heterogeneity in contact rates, activity patterns, and environmental exposures. This oversimplification likely biases the results and inflates the predicted effectiveness of interventions.

2.The model uses idealized drug assumptions, particularly regarding the 24-week slow-release formulation, which lacks real-world evidence. Furthermore, it assumes similar drug mechanisms for juvenile and adult worms, disregarding potential differences in drug pharmacokinetics and mechanisms of action.

3.Although the authors use two models, the validation focuses only on the consistency of main conclusions, not on thorough verification of the model’s parameterization, assumptions, and results across different scenarios. This limited validation is insufficient to address the model’s inherent limitations.

4.The model does not adequately account for real-world complexities of MDA implementation, such as poor drug adherence, population mobility, and the synergistic effects of multiple interventions. This disconnect limits the practical applicability of the findings.

Recommendation:

Given the aforementioned methodological shortcomings, I recommend a Major Revision. The authors must:

1.Thoroughly discuss the limitations of the model and clarify how these limitations may affect the results.

2.Revise or reconsider the drug assumptions to be more realistic, and perform sensitivity analysis.

3.Employ a more comprehensive validation approach to ensure the robustness of the model results.

4.Incorporate more real-world complexities in the model to improve its practical implications.

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Reviewer #1: Yes:  Berhanu Erko

Reviewer #2: No

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Reproducibility:

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Attachments

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Submitted filename: renamed_d1681.pdf

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Submitted filename: PNTD-D-24-01468_Ref.pdf

Dear Dr. Ellis,

We are pleased to inform you that your manuscript 'How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis' 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,

Song Liang

Academic Editor

PLOS Neglected Tropical Diseases

Francesca Tamarozzi

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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