Dear Mrs strang,

Thank you very much for submitting your manuscript "Gestational toxoplasmosis treatment changes the child's prognosis: a cohort study in southern Brazil" 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.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[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).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

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,

Hamed Kalani

Academic Editor

PLOS Neglected Tropical Diseases

Ricardo Fujiwara

Section Editor

PLOS Neglected Tropical Diseases

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Reviewers' comments:

Reviewer 1:

1. In the field of sample size and compliance with ethical requirements, there is a little ambiguity, which should be given more comprehensive explanations and evidence by the authors.

2. Toxoplasma gondii should be written in italics throughout the manuscript.

Reviewer 2:

1. The authors need to include the information on how the serological tests to detect IgG and IgM antibodies to T. gondii were performed? Did they use commercial kits for this purpose? If this is the case, they need to provide name of the kits and name of the companies that provide the kits.

2. The first paragraph of the Results section (Page 11): The authors state “All children started drug treatment in the maternity ward and 52/61 were suspended after three reducing serological tests (anti-T. gondii IgG)”. This statement makes readers to consider that 9 (61-52 =9) children showed serological evidence for having congenital infection. The authors also state “Among the eleven infected children, three were detected after discontinuing the medications”. These statements together make readers to consider 12 (9 + 3= 12) children were congenitally infected. However, the actual number of infected children was 11. The authors need to provide additional information to explain these numbers.

3. In relation to neutropenia in congenitally infected children, the authors referred an article an occurrence of neutropenia in a murine model of acute T. gondii infection. The authors need to include the information that this murine model is a lethal infection of animals with the virulent RH strain of the parasite. The authors also need to be more careful about applying the information from this murine model of the lethal infection to congenitally infected children.

4. Among 11 congenitally infected children, 5 were asymptomatic. It is important to provide the information on whether treatment of their mothers makes any association to determine their infected children become symptomatic or asymptomatic.

5. It is also important to perform the analysis on whether neutropenia is associated with symptomatic infection or not.

6. The authors need to provide more detailed descriptions in the description in the last paragraph of the “Results” section. This description needs to include what each of Figs. 2a, 2b, and 2c indicates and how these figures need to be read. It is also helpful to explain what each of Supplemental Figures 1, 2, and 3 indicates.

7.The end of the first paragraph on page 16: The meaning the following sentence is unclear; “Bearing this in mind and given the data that point to the presence of more virulent strains in Brazil (greater chance of tissue damage in infected children), the protocol is to discharge all children born to a mother with acute toxoplasmosis with triple treatment (SPF).”

8. In Supplemental Tables, all abbreviations (e.g. MTyes) need to be spelled out at the bottom of each Table.

9. It is unclear what Supplemental Figure 4 indicates.

10.. It will be helpful to include the information on what genotypes of T. gondii are abundant in the southern Brazil, where this clinical study was performed.

Figure Files:

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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your 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 Mrs strang,

Thank you very much for submitting your manuscript "Gestational toxoplasmosis treatment changes the child's prognosis: a cohort study in southern Brazil" 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.

The authors responded to the comments, and the manuscript needs to be carefully checked in terms of writing (for example: line 219 has a dot added after the parentheses and should be deleted) and the sentences need to be strengthened in terms of academic writing.

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.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[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).

Important additional instructions are given below your reviewer comments.

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,

Hamed Kalani

Academic Editor

PLOS Neglected Tropical Diseases

Ricardo Fujiwara

Section Editor

PLOS Neglected Tropical Diseases

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

The authors responded to the comments, and the manuscript needs to be carefully checked in terms of writing (for example: line 219 has a dot added after the parentheses and should be deleted) and the sentences need to be strengthened in terms of academic writing.

Figure Files:

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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your 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

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.

Dear Mrs strang,

We are pleased to inform you that your manuscript 'Gestational toxoplasmosis treatment changes the child's prognosis: a cohort study in southern Brazil' 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,

Hamed Kalani

Academic Editor

PLOS Neglected Tropical Diseases

Ricardo Fujiwara

Section Editor

PLOS Neglected Tropical Diseases

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