PNTD-D-24-01393

Scrub typhus in pregnancy: A 10-year multicenter study in resource-limited settings in China

PLOS Neglected Tropical Diseases

Dear Dr. Wang,

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Kind regards,

Craig W. Roberts

Guest Editor

PLOS Neglected Tropical Diseases

Mathieu Picardeau

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

Additional Editor Comments :

Please address all reviewer comments in your revised manuscript.

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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: Objective clear , study design- appropriate ,statastics correctly used

Reviewer #2: 1. Please provide the day of illness on which treatment was begun.

2. A single titer of 1:80 of Proteus OXK agglutination is not specific. What is the incidence of titer of 1:80 in healthy persons in Yunnan? As recognized by the authors, Weil Felix serology is not specific. A fourfold rise or greater in titer would be supportive of the diagnosis for purposes of this study. According to the diagnostic criteria, exposure to a disease endemic area, rash, and a titer of 1:80 would be confirmatory of the diagnosis. This is not sufficient. Many diseases could meet these criteria.

3. Table 1 what does "duration of fever, dates" mean? Does this reflect the entire course of illness or the number of days prior to treatment?

4. Tables 1, 2, and 3: What is the difference between "Weil-Felix test" and "positive Weil-Felix test"?

5. Lines 411 and 412: Please cite a reference documenting congenital anomalies due to vertically transmitted Orientia tsutsugamushi. I do not believe that this occurs.

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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: All matched

Reviewer #2: The results should be separated into groups that are documented by seroconversion or by only a single Weil-Felix titer and the presence of an eschar

The study contains a robust number of cases, the great majority of which manifested eschar and an interesting analysis of the fetal outcomes by trimester.

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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: Please add ICU / hdu admissions also.ST with pneumonia frequently need icu admissions. Add this important finding also .could not understand the rationale of using chloramphenicol in pregnancy, please elaborate . Thanks

Reviewer #2: The conclusions are difficult to assess owing to the inadequate confirmation of the diagnosis of scrub typhus.

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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: Minor revision.

Reviewer #2: See below

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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: Please add ICU / hdu admissions also.ST with pneumonia frequently need icu admissions. Add this important finding also .could not understand the rationale of using chloramphenicol in pregnancy, please elaborate . Thanks

Reviewer #2: If the authors stratified their results according to confirmed cases vs cases based upon the clinical diagnosis only, this might be a useful contribution of new knowledge.

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Reviewer #1: Yes:  Minakshi Rohilla

Reviewer #2: No

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Dear Doctor Wang,

We are pleased to inform you that your manuscript 'Scrub typhus in pregnancy: A 10-year multicenter study in resource-limited settings in China' 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.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Craig W. Roberts

Guest Editor

PLOS Neglected Tropical Diseases

Mathieu Picardeau

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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