PONE-D-20-40788

Spatial clustering and temporal trend analysis of international migrants diagnosed with tuberculosis in Brazil: Are we really managing to control the disease?

PLOS ONE

Dear Dr. Mascarello,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

This is an important and relevant paper. The paper makes an important contribution to discuss this neglect issue in Brazil, especially when considering migrants. However, based on the reviewers and my own reading I believe the paper should revised some points: 

1. please, revise the context. I think that the paper has data to analyze if there are more migrants with TB in the country and where are they, but is limited in the discussion on how the country is dealing with the issue;
2. I share a concern with one the reviewers on the method. Please, the methods part could be more developed and indicate more details on the methods. Here are few reasons and doubts:
   1. spatial clusters assume that we have a continum of cases (in any variable of interest) - but this is not the case in the analysis since you are working with a very specific sub-population group. It would be important to clarify this question in the paper and also discuss possible limitations of the method in the study
   2. similarly, in recent years there was an increase of immigrans to Brazil. So, the time trend analysis should take that into consideration. How the increase in inflow might impact the analysis and observed trends? What are the alternatives to that? Not only that, but also the profile of migrants might have changed and they would also impact in the discussion of time trends
   3. Please, based on the analysis and discussion - the paper could improve the discussion of public health policy implications. 
   4. Please, see also detailed comments by the reviewers. 

Please submit your revised manuscript by Apr 15 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Bernardo Lanza Queiroz, Ph.D

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient data used in your retrospective study, including: a) whether all data were fully anonymized before you accessed them; b) the date range (month and year) during which the records were accessed.

3. We note that Figures 1-3  in your submission contain map images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software (Google Maps, Street View, and Earth). For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright.

We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:

(1) You may seek permission from the original copyright holder of Figures 1-3 to publish the content specifically under the CC BY 4.0 license. 

We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:

“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”

Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission.

In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].”

(2) If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.

The following resources for replacing copyrighted map figures may be helpful:

USGS National Map Viewer (public domain): http://viewer.nationalmap.gov/viewer/

The Gateway to Astronaut Photography of Earth (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/

Maps at the CIA (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.html

NASA Earth Observatory (public domain): http://earthobservatory.nasa.gov/

Landsat: http://landsat.visibleearth.nasa.gov/

USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://eros.usgs.gov/#

Natural Earth (public domain): http://www.naturalearthdata.com/

4. Please ensure you have discussed any potential limitations of your study in the Discussion.

5. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "supporting information" files

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study showed excellent quality and the authors developed an important proposal for the epidemiological scenario of tuberculosis in Brazil.

The issue with immigrants needs to be discussed and studied more deeply, especially in Brazil. This priority group requires differentiated actions and strategies by health managers.

The authors clarified the Brazilian situation in recent years, but it could be interesting to discuss more deeply the limitations of access and the impact of social determinants on this group, a fact that can interfere in the control and spread of the disease.

I congratulate the group of authors for their clear and coherent writing as well as for the methodological process of spatial and temporal analysis that was conducted.

Reviewer #2: General comments

This descriptive study of TB among migrants is very relevant in a context of recent increased migration in Brazil. The paper is generally clear but I have some major concerns on the applicability of Getis-Ord Gi* analysis and time trends analysis to state that answer the study objective and describe that there is an increase number of TB cases among migrants in Brazil. By using spatial clusters, we are assuming that there is a continuum of cases within a given space, so the applicability of this method to analyse clusters within a subgroup (migrants) should be added as a limitation. Similarly, the limited applicability of time trends analysis in the context of a high influx of migrant populations to Brazil during the study period should be additionally discussed in the paper.

Other major points that may improve the quality of the paper include:

1. The title should be reconsidered – the results from this study can really bring light to if Brazil is managing to control the disease.

2. The overall language of the abstract is a little stigmatizing and differ from the overall language of paper, which was adequately written. The authors should try not to use sentences that bring old but already deconstructed myths about migrants (e.g., “Tuberculosis (TB) in migrants concerns health authorities worldwide, due to the potential for spread of the disease.”)

3. The methods are not properly referenced – all the analysis that are not very usual (e.g., Getis-Ord Gi analysis) should be adequately referenced.

4. In the two last paragraph of the results section, the authors describe the results for the association between TB incidence and social vulnerability. These results are relation to TB incidence overall or among migrants? This is not clear and, if it is overall, this analysis should be included as part of the objectives of the study as they differ from the overall objective of the paper. On the other hand, if this analysis refers to TB incidence among migrants, which denominator was used to calculate incidence?

5. The discussion do not included problems or suggestions on how to reduce social vulnerabilities of migrants so Brazil can diagnose and treat migrants timely. Also, the authors discussed their findings based on a limited number of references and do not adequately referenced the literature from the field - the authors should consider discussing the results in the light of other studies analysing TB characteristics in Brazil and other LMIC. Please see the lancet series of migration and health and other SR of TB among migrants.

6. The conclusion should be more straightforward and aligned to the overall study objective.

**********

6. 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 #1: Yes: SHIRLEY VERONICA MELO ALMEIDA LIMA

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-20-40788R1

Spatial clustering and temporal trend analysis of international migrants diagnosed with tuberculosis in Brazil

PLOS ONE

Dear Dr. Arcencio,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Although the revised manuscript (R1) has been judged substantially improved in comparison with the original submission, there are important suggestions, comments and questions made by reviewer two still incompletely addressed. Please, make sure to completely address each question, comment and suggestion made by reviewer two to the R1 then resubmit it along with detailed explanations of how they were incorporated in the paper. Please, pay particular attention to the issue raised by that reviewer about tuberculosis among migrants in São Paulo.

Please submit your revised manuscript by Jun 11 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Albert Schriefer, M.D., Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

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.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: In general, the study improved substantially since the first version of the manuscript. The main concerns/suggestions are listed below:

Abstract

Please revise the sentence “The study revealed the impact of TB in migrants. Based on the findings, if TB surveillance is not intensified in these areas, there will likely be an increase in cases in adjacent regions, making the target defined by the End TB Strategy more difficult to achieve”. How can the paper really revealed the impact of TB in migrants if it is not possible to determine the incidence of TB among migrant populations? If TB cases are being diagnosed and treated, why would the authors expect an increase in cases in adjacent regions is expected?

Introduction

The sentence “Several studies have shown the impact of migration on the resurgence and spread of TB in Europe” is inaccurate. The references 2 and 6-11 do show that cases among migrants pose challenges to local programmes but not necessarily that transmission contributes to it – e.g., Hargreaves (2017) show that there is low proportion of cases due to transmission from migrants to the local community, and that this is restricted to some communities. I suggest to remove the word spread.

Discussion

Page 18, row 338 – It needs to be more clear that the authors are referring to cases in “temporal trends of TB in migrants as increasing”.

Page 21, rows 387-393 - The authors say that TB cases among migrants in São Paulo have been stationary since 2014 and “Another hypothesis is underreporting and/or underdiagnosis in this population from 2014 to 2017, since the city did not report any migrants diagnosed with TB during that period.”. Nevertheless, the study by Pescarini (2018) (ref 38) reports data on over 335 migrants from South-American countries in 2013/2014 in Central areas from the municipality of São Paulo. There was any change in the National or State TB registry that may have caused this change? Please clarify the differences found and how these changes could have impacted the analysis.

**********

7. 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 #1: Yes: SHIRLEY VERÔNICA MELO ALMEIDA LIMA

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Spatial clustering and temporal trend analysis of international migrants diagnosed with tuberculosis in Brazil

PONE-D-20-40788R2

Dear Dr. Arcencio,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Albert Schriefer, M.D., Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have addressed the main points raised in the previous version. However, there are two points I would like to raise that might reflect my personal opinion (but that might still be relevant):

1. The study justification states that there is a lack of studies on the potential resurgence of TB in Brazil due to migration (and that is a big gap in the literature), which I disagree with as Brazil is still a high burden TB country with approximately 30 thousand TB cases a year. I think the study is very important to guide actions as this population is very vulnerable, but it is unlikely that those cases make TB incidence to increase substantially.

2. Regarding the interpretation of the results, there is still some room for potential discriminatory language (e.g., abstract: “ensuring that these cases concluded their treatment and avoiding that they could spread the disease to the other regions or scenarios.”). In the scenario of xenophobia all over the world, including in Brazil, I believe we should be careful saying that migrants could spread a disease that is not even controlled in the country.

**********

7. 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: Julia Pescarini