Dear Dr. Mangano,

Thank you very much for submitting your manuscript "Comparative evaluation of plasma biomarkers of Schistosoma haematobium infection in endemic populations from Burkina Faso" 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.

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[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).

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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,

Uwem Friday Ekpo, PhD

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: -Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

Yes

-Is the study design appropriate to address the stated objectives?

Yes

-Is the population clearly described and appropriate for the hypothesis being tested?

Yes

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

Yes

-Were correct statistical analysis used to support conclusions?

Yes

-Are there concerns about ethical or regulatory requirements being met?

No

Reviewer #2: The objectives of the study are clearly stated. The study design is appropriate. The population is clearly described and appropriate. Correct statistical methods were used. There are no ethical or regulatory requirement concerns.

A few suggestions …

The authors should consider providing a power analysis or mention their sample size calculations.

Line 257: Please specify the type of confidence intervals used.

Line 258: Did you fit unadjusted and adjusted logistic regression models? Please specify the variables considered and/or used in the final model(s). Did you obtain/report odds ratios? Please clarify.

Lines 259-262: Why did you use Spearman (for ranked data) as opposed to Pearson (for normal data) to examine correlations with antibody levels and antigen concentration? You then used linear regression to examine antibody levels and antigen concentration, which requires normal data. If these variables were transformed to normalize them, please specify so here. What variables were considered for the linear regression models?

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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: -Does the analysis presented match the analysis plan?

Yes

-Are the results clearly and completely presented?

Yes

-Are the figures (Tables, Images) of sufficient quality for clarity?

Yes

Reviewer #2: The results match the analysis plan for the most part. The results are clearly presented. Most tables and figures are appropriate. A few suggestions …

Table 1: Consider including the total N in a table footnote so you can delete the N total column (feels unnecessary to have a whole column for a single number).

Lines 322-325: Are these unadjusted or adjusted logistic regressions models? Are there any variables you could consider in adjusted models? If so, a table of the results would be needed. Throughout the paper, P-values not really needed since you report 95% CI, which show the significance.

For all tables with 95% CIs, consider combining the statistic with the corresponding CI so you do not have multiple LCL and UCL column labels. For example, in Table 3, you could use Se (95% CI), Sp (95% CI), Agreement, Cohen’s K as the columns.

Did you actually use any linear regression models? No related results were reported in the text.

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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: -Are the conclusions supported by the data presented?

Yes

-Are the limitations of analysis clearly described?

Yes

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

Yes

-Is public health relevance addressed?

Yes

Reviewer #2: Conclusions are supported by the data presented. Limitations are clear. Authors do discuss public health relevance.

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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: See attached document

Reviewer #2: Please review once more for typos such as the following …

Line 87: ‘generation’ should be plural

Line 167: remove ‘)’ before the period

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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: Strength

One of the challenges in the develop of high sensitive and specific point of care diagnostic tools which can be used low resource endemic areas is the lack of appropriate diagnostic tools. The Composite Reference Standard

(CRS) and Latent Class Analysis (LCA) methods described in the manuscript by Mireille Ouedraogo and colleagues can be used as references for new diagnostic tools for NTDs.

Limitation

Considering that schistosomiasis is mostly endemic in poor resource areas the techniques described in this manuscript will not be applicable in these settings. The techniques described are expensive, they require sophisticated laboratories and trained personnel among other things especially the PCR methods so the is still need to develop tools for use in poor endemic settings.

Reviewer #2: Overall the paper is well written, and the public health relevance is clear. The statistical methods and overall conclusions are appropriate. Addressing some of the gaps mentioned in the methods and results will strengthen the manuscript even more.

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Reviewer #1: No

Reviewer #2: No

Figure Files:

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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.

Attachments

Attachment

Submitted filename: Plasma biomarkers manuscript review.docx

Dear Dr. Mangano,

We are pleased to inform you that your manuscript 'Comparative evaluation of plasma biomarkers of Schistosoma haematobium infection in endemic populations from Burkina Faso' 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

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Your revised manuscript is now acceptable by PLoS NTD.