Response to ReviewersRevised Manuscript with Track ChangesManuscript

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

Additional Editor Comments :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: Rojelio Mejia, Irina Chis Ster, Martha E Chico, Irene Guadalupe, Andrea Arevalo-Cortes, Andrea Lopez, Aida Oviedo, and Philip J. Cooper. Please ensure that the full contributions of each author are acknowledged in the "Add/Edit/Remove Authors" section of our submission form.

The list of CRediT author contributions may be found here: https://journals.plos.org/plosntds/s/authorship#loc-author-contributions

2) We noticed that you used the phrase 'data not shown' in the manuscript. We do not allow these references, as the PLOS data access policy requires that all data be either published with the manuscript or made available in a publicly accessible database. Please amend the supplementary material to include the referenced data or remove the references.

Reviewers' comments:

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: Yes to all the above

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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: Yes to all the above

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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: YES to all the above

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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: Minor corrections

Abstract:

Methods - rephrase "studies for 8 years"

Results - Greater parasite numbers suggests intensity to me perhaps rephrase for clarity

Methods:

Maternal questionnaires were repeated when the child was... p. 8

Rephrase : Fit back" p. 11

Discussion:

Other systemic helminths were absent - please clarify p. 27

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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: The manuscript presents a comprehensive longitudinal study on the epidemiology of intestinal parasite infections (IPIs) and multiparasitism in a birth cohort from tropical Ecuador, utilizing molecular detection methods. The study addresses an important gap in understanding the impact of IPIs on childhood growth and hemoglobin levels. The findings are relevant to public health, particularly in endemic regions, and align with WHO priorities for reducing morbidity associated with parasitic infections. The study design is robust, and the use of molecular methods enhances the sensitivity of parasite detection. However, some areas require clarification or improvement to strengthen the manuscript.

1. Please use updated data and valid references for statistics on IPI-related prevalence and DALYs presented in the introduction.

2. Please clarify whether qPCR testing was performed on all samples at each time point or only on those that were microscopy-positive.

3. Please clarify how other unmeasured potential confounders (e.g., dietary intake, micronutrient supplementation) that could influence growth and hemoglobin outcomes might affect the results of this study.

4. The lack of a significant effect on anemia (despite lower hemoglobin levels) warrants further discussion. Could this be due to the low prevalence of hookworm (a major driver of anemia) in the cohort?

Reviewer #2: The authors should be commended on this powerful study with meticulous detail throughout. In particular, the major strength of the study is its longitudinal design covering child age from early childhood to school age. Consequently the impact of parasitism is clearly shown in contrast to short-term follow-up studies that mainly informed recent meta-analyses. Furthermore, the use of sensitive molecular detection methods allowed the identification of low intensity infections. As pointed out by the authors, the impact of specific parasite species was not possible but this study highlights the methodology in which future studies can be designed to delineate such species-specific impacts.

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Reviewer #1: No

Reviewer #2: No

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Dear Dr. Cooper,

We are pleased to inform you that your manuscript 'Epidemiology of intestinal parasite infections and multiparasitism and their impact on growth and hemoglobin levels during childhood in tropical Ecuador: a longitudinal study using molecular detection methods.' 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,

jong-Yil Chai

Section Editor

PLOS Neglected Tropical Diseases

Jong-Yil Chai

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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The revised manuscript is now acceptable for publication in PLoS NTD.