PNTD-D-24-01494Evaluating the effectiveness and sustainability of a primary healthcare strategy to reduce the prevalence of strongyloidiasis in endemically infected Indigenous communities in northern Australia.PLOS Neglected Tropical Diseases Dear Dr. Page, 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. Please submit your revised manuscript within 30 days Apr 15 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosntds@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pntd/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: * A rebuttal letter that responds to each point raised by the editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to any formatting updates and technical items listed in the 'Journal Requirements' section below. * A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. * An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. We look forward to receiving your revised manuscript. Kind regards, Eduardo José Lopes-Torres, Ph.D.Academic EditorPLOS Neglected Tropical Diseases Krystyna CwiklinskiSection EditorPLOS 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

Reviewers' comments: 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: All questions and criteria are met in the manuscript.

Reviewer #2: It would be good to provide more information about the ELISA testing. How were results standardized over time? What was the turnaround time before results were returned to the clinic?

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: All questions and criteria are met in the manuscript.

Reviewer #2: Are the data sufficient to look at incidence?

What do the communities think about the project?

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: All questions and criteria are met in the manuscript.

Reviewer #2: What has been done to scale up the intervention to other communities?

Why doesn’t Australia procure WHO prequalified generic ivermectin?

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: None.

Reviewer #2: The manuscript is well written.

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 manuscript "Evaluating the effectiveness and sustainability of a primary healthcare strategy to reduce the prevalence of strongyloidiasis in endemically infected Indigenous communities in northern Australia" describes the use of serology for Strongyloides combined with treatment as a strategy for controlling strongyloidiasis in an endemic area with an Indigenous population. The United Nations 2030 Agenda for Sustainable Development aims to end epidemics of AIDS, tuberculosis, malaria, and tropical diseases, such as soil-transmitted helminthiasis. However, within the context of soil-transmitted helminthiasis, efforts are primarily focused on ascariasis, trichuriasis, and hookworm, with little attention given to the control of strongyloidiasis. In the manuscript from northern Australia, the authors present an experience report that shows a reduction in disease rates, which seems to be a promising strategy, though it requires further follow-up to be validated.

The manuscript is written in a simple and straightforward manner, and although the data presented in this paper are linked to a previous publication, it is still understandable.

Below are some considerations regarding the manuscript:

1. The data in Table 1 and S1 Table need to be reviewed. This also impacts the specific values described in the sections "Final evaluation 2012–2020" and "Analysis of data from the implementation phase 2012–2016."

2. Were the 13 individuals who had a negative diagnosis in the previous serology but tested positive in a new test, treated? Was there therapeutic success?

3. Were the 17 individuals who remained serologically positive after treatment retreated? What was the protocol for cases where individuals remained positive throughout the periodic testing?

4. In endemic areas, the main hypothesis for persistent infection is reinfection, but we cannot exclude the possibility of parasitic resistance, especially considering the limited therapeutic options available for the treatment of these infections. Therefore, it is important to discuss this issue in the manuscript, and to acknowledge the inability to differentiate between reinfection and resistance as a limitation of the study.

5. The authors state: "Persons who stayed positive were significantly younger (median age 31 years; IQR = (21, 42)) compared with persons who became negative (median age 39 years; IQR = (28, 51); p<0.001; Mann-Whitney test). Reinfected persons were on average older (median age 42 years; IQR = (31, 50)) compared to persons with no reinfection (median age 35 years; IQR = (24, 47); p=0.032; Mann-Whitney test)." Is there any hypothesis to explain this finding? This data was not well discussed.

6. Were health education strategies employed during the study? Typically, education activities are crucial for reducing prevalence in endemic areas where selective treatment is carried out.

Reviewer #2: In this manuscript, Page and colleagues report on the sustainability of a Strongyloides control program implemented through the routine health care system in indigenous communities in Australia. The results show that this strategy results in a dramatic reduction in disease prevalence over time.

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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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: Maria Fantinatti

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] Figure resubmission: 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. If there are other versions of figure files still present in your submission file inventory at resubmission, please replace them with the PACE-processed versions. Reproducibility: To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit 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

Dear Dr Page,

We are pleased to inform you that your manuscript 'Evaluating the effectiveness and sustainability of a primary healthcare strategy to reduce the prevalence of strongyloidiasis in endemically infected Indigenous communities in northern Australia.' 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,

Eduardo José Lopes-Torres, Ph.D.

Academic Editor

PLOS Neglected Tropical Diseases

Krystyna Cwiklinski

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

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

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)

**********

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)

**********

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)

**********

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)

**********

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: (No Response)

Reviewer #2: (No Response)

**********

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: Maria Fantinatti

Reviewer #2: No