Dear Ms Nqweniso,

Thank you very much for submitting your manuscript "Influence of Soil-transmitted helminth infections on physical activity, physical fitness, and cardiovascular disease risk in primary schoolchildren from Gqeberha, South Africa" 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.

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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,

Sabine Specht

Academic Editor

PLOS Neglected Tropical Diseases

Eva Clark

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: The objectives of the study are clear. Power calculations are for the original study and this analysis is just from the baseline data. No concerns with ethics or regulatory. Measurement of variables of interest seem appropriate. In the intro, the causal pathway of physical activity, CVD risk and STH infection is not clear, which would change which variables are exposures versus outcomes. For the purpose of this study, a hypothesis could be stated to help the reader understand why the analysis is being chosen as it is. Based on the analysis, the STH infection is being treated as an exposure. If infection is only being evaluated as a dichotomous variable, why not use a chi-square test rather than an ANOVA?

Reviewer #2: There are some questions regarding the method:

1. In comparison to their non-infected peers, children infected with STH had lower mean grip strength scores, but higher mean VO2max estimation and higher levels of MVPA.

2. Why did the authors choose this measurement? Would it be the lifestyle that cause this difference? Can the infected children have more outdoor activities than the non-infected as mentioned?

3. Is the lower grip strength score associated with energy intake or excessive energy uses?

4. Any information collected on their habits or lifestyle beside the MVPA?

5. The authors have discussed this later in the discussion part, however if they had the data on characteristics of the physical activities of the school and the non-infected children, that might be useful information. If those children have similar physical activities levels, then it might be interesting to understand why they showed different results than other study.

6. More than 80% of the infected children has coinfection. Any plan on testing the stools with a more sensitive measurement such as PCR?

7, The VOmax and the MVPA results seem to show different between schools. Is there any characteristics information collected on the schools? The authors indeed did an analyses in one school with relatively high helminth prevalence. But I wonder whether the school itself and the children went to this school also had different characteristic than other schools.

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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: With almost half the cohort being dropped for missing data, some description of that group would be helpful to understand how missing data may be biasing the results. Table 1 by school is confusing as there is almost no STH in the schools except one. Is there a more informative way to structure this table? Many of the outcomes vary by age. How do the outcomes vary by gender. Is it shown how age and BMI are associated with STH infection? Table 1 by STH infection (yes/no) excluding your outcome variables would help indicate why and which variables you are treating as confounders.

For table 2, adjusted and unadjusted outcomes in one table would be helpful for comparison. And what is adjusted for, would relate to what is seen in table 1 as being associated with STH infection. Because STH infection numbers are so small, differences by intensity are even smaller. Did you consider combining light and moderate?

Reviewer #2: Yes.

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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: Drawing conclusions from intensity of infection and outcomes is challenged by small numbers. Focusing on conclusions based on infected or not may be more informative. In the paragraph starting on line 398, the causal pathway of physical activity, CVD and STH infection is hard to follow. The first sentence of the limitations states that the direction of the causality can not be inferred due to the cross sectional study design. I agree but the analysis is based on an assumption so interpreting the results aligned with the hypothesis of the study may help with clarity.

Reviewer #2: The authors have addressed the conclusion, the limitation and the strengths of the study, however they might want to explore studies related to the topic they raised such as studies done in Indonesia.

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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: The study is interesting and the authors presented the information nicely. Some refinement as noted above would help with clarity.

Reviewer #2: Dear Authors,

Thank you for the opportunity to review this interesting manuscript. The manuscript can potentially be published and might contribute to limited information in this field.

1. In the abstract the authors mentioned: STH infections have been associated with negative consequences for child physical and cognitive development and wellbeing. Thus, the aim of this study was to determine the association of STH infections in schoolchildren from Gqeberha, focusing on physical activity, physical fitness, and clustered cardiovascular disease (CVD) risk score.

-> Why it is important to check CVD risk score in the study?

The explanation of the connection has been mentioned in the background text. One short connecting sentence might need to be added in the abstract to make it a bit more clear.

2. Regarding the background and the discussion, I am surprised that the authors did not come through studies by Pasha et al, Wiria et al and Tahapary et al, as they specifically concern on metabolic syndrome, cardiovascular risk (and atherosclerosis), and insulin sensitivity (resistance) in association with helminth infection and population at risk of epidemiological transition. They also did cohort study on this topic. They also have data on children and adult if that regarding some cardiovascular risk factors.

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Reviewer #1: Yes: Helen Storey

Reviewer #2: Yes: Aprilianto Eddy Wiria, MD PhD

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Dear Ms Nqweniso,

We are pleased to inform you that your manuscript 'Associations between soil-transmitted helminth infections and physical activity, physical fitness, and cardiovascular disease risk in primary schoolchildren from Gqeberha, South Africa.' 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,

Sabine Specht

Academic Editor

PLOS Neglected Tropical Diseases

Eva Clark

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 #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 #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 #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 #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 #2: Thank you very much for the revision of the manuscript. It has been improved than the previous version.

I hope this can be addition to the published knowledge in the field of helminth infections and cardiovascular diseases.

**********

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 #2: Yes: Aprilianto Eddy Wiria, MD PhD