Dear Dr. Dorneles:

Thank you very much for submitting your manuscript "Occupational exposure to human brucellosis infection: a systematic review and meta-analysis" (#PNTD-D-19-01642) for review by PLOS Neglected Tropical Diseases. Your manuscript was fully evaluated at the editorial level and by independent peer reviewers. The reviewers appreciated the attention to an important problem, but raised some substantial concerns about the manuscript as it currently stands. These issues must be addressed before we would be willing to consider a revised version of your study. We cannot, of course, promise publication at that time.

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Sincerely,

Tao Lin, DVM, MSc

Associate Editor

PLOS Neglected Tropical Diseases

Elsio Wunder Jr

Deputy 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: PRISMA recommendations have been proficiently followed

Reviewer #2: (No Response)

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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: See general and specific comments

Reviewer #2: (No Response)

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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: See general and specific comments

Reviewer #2: (No Response)

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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: Include S4 Appendix in the manuscript

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: General comments

In order to add new knowledge through the review, the following points should be taken in consideration in a revised manuscript:

- For 1538 cases, there was only 106 isolation of Brucella spp, i.e. less than 7%. Therefore, all the discussion related to the importance of Brucella species per worker category should be introduced by a word of caution

- Specify per worker category the number of Brucella isolation.

- A specific section devoted to human brucellosis due to RB51 should be included, although the vast majority of such cases are linked to the consumption of raw milk.

- Why is B. canis not discussed in this review although it appears in figure 2?

- Laboratory workers: specify the importance of this group in countries where brucellosis has been eradicated. In addition, it would be worth to mention that mis diagnosis (as Ochrobactrum antropi) occurs regularly

Consider including S4 Appendix in the manuscript.

Although the systematic review is proficiently executed, the information is to a large extent not new. Therefore, the authors should discuss in dept which new information has been generated through their work. In this perspective, the meta-analysis is perhaps the most interesting part of this research.

Specific comments

Title: not Ok, I suggest: Occupational exposure to Brucella spp.: a systematic review and meta-analysis

L27: live attenuated anti-brucellosis vaccines

L41: different wildlife species

L45: live attenuated anti-brucellosis vaccines

L69-72: introduce the DALY concept

L76: live attenuated anti-brucellosis vaccines

L167-169: specify to which animal species the aborted fetus belongs

L189: live attenuated anti-brucellosis vaccines

L222: reports on contamination by b. suis biovar 2 in France should be mentioned in this section

L258-264: the explanation is imported cases of brucellosis in non-endemic countries, not scientific interest

L271: B. abortus is the most important species isolated in ref 86. However, other references, particularly from China show that B. melitensis is the most important species, whereas in Kazakhstan, B. melitensis is exclusively isolated from human patients

L272-274: the symptoms are for all Brucella species. It is thus incorrect to ascribe them to B. abortus

L343: all systematic review should follow the PRISMA statement

274: Brucella melitensis in not more pathogenic than B. abortus in humans. It is just the most prevalent species!

L281: reference

L304: laboratory worker: see general comment

L325: hunters: for which countries is this group important?

L293: it should be highighted her and in the abstract that veterinarians are th groups for which exposure to vaccine strains is the most important

L326-328: this is a wrong statement. B. suis infection is mainly due to contact and dressing of carcasses, not consumption of meat

L340: wording: expressive?

L350: L354: The Ine Health concept comes out of the blue and should either be deleted or better explained

Figure 2: this figure may give a wrong impression because the status towards brucellosis has changed (several countries became "officially free" from brucellosis) during the study period. For example, for Germany, Canada, USA abattoir workers are mentioned although this is not true anymore. In addition, an explanation must be given on why only veterinarians in India and only abattoir workers in Nigeria are reported while many rural worker are reported in other African countries. Answers to this type of questions would possibly generate new information.

Reviewer #2: See attached document

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Reviewer #1: Yes: Jacques Godfroid

Reviewer #2: No

Attachments

Attachment

Submitted filename: Critique.docx

Dear Dr. Dorneles,

We are pleased to inform you that your manuscript 'Occupational exposure to Brucella spp.: a systematic review and meta-analysis' 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 within two working days 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,

Tao Lin, DVM, MSc

Associate Editor

PLOS Neglected Tropical Diseases

Elsio Wunder Jr

Deputy Editor

PLOS Neglected Tropical Diseases

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