Dear Dr. da Silva,

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. Some of them can be discussed in the discussion section and/or as limitations; others will require further analysis. The acceptance of the paper in a second round of review will depend on how you address the feedback from Reviewers 1 and 2. Reviewer 1 recommended major revisions, and although Reviewer 2 recommended acceptance, their comments also reflect a major revision. 

We sincerely appreciate your patience throughout this process.

Warm regards,

Patricia Matsumoto

==============================

Please submit your revised manuscript by Nov 29 2025 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: https://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,

Patricia Matsumoto, 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. We note that Figures 2, 3, 4 and 6 in your submission contain [map/satellite] 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:

  a. You may seek permission from the original copyright holder of Figures 2, 3, 4 and 6 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].”

   b. 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. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

Comments:

Minors:

- Is the variable source described by the location of probable infection? Is there a chance that this data is recorded by the municipality of residence?

- Although the Discussion briefly mentions the implications of prisons, could you elaborate on how this relates to your results? From the map, there appear to be hotspots in areas with a high concentration of prisons. Please consider adding the locations of prisons in Brazil and examining whether these areas show stronger associations in your analyses. Alternatively, if such an analysis is beyond scope, could you at least cite published studies that document similar patterns?

- Rename the figure names as they appear in the manuscript;

- For the figure 'SVTT_2010a2023', consider including the capitals of each state or at least a point that represent them. In the legend, remove the border of polygons and add some space between them, as in the map, they don't have a border.  

- Change '—' for '–'

[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?

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

The PLOS Data policy

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

Reviewer #1: I would like to begin by congratulating the authors for the development of this study, which addresses in a timely and rigorous manner the spatiotemporal distribution of pulmonary tuberculosis in Brazil, with a focus on identifying priority areas for surveillance and intervention. This is a highly relevant topic for public health, especially in a country with significant territorial heterogeneity such as Brazil. The study aims to analyze the spatiotemporal distribution of pulmonary tuberculosis incidence rates in Brazil between 2001 and 2020 and to identify priority areas for disease surveillance and control. The following comments and suggestions are intended to contribute to the improvement of the manuscript.

1. Abstract

I recommend avoiding the use of abbreviations in the abstract. The journal advises minimizing abbreviations whenever possible.

I suggest making the conclusion more concise and highlighting the practical implications of the findings, such as the prioritization of specific areas for intervention.

2. Introduction

I recommend strengthening the theoretical background regarding the social and structural inequalities that influence the distribution of TB in Brazil, particularly in the territories identified as priorities.

3. Materials and Methods

I suggest reorganizing this section into clearer subsections to facilitate readability (e.g., “Unit of analysis,” “Data sources,” “Statistical analysis,” “Spatial analysis”).

I suggest justifying and referencing the exclusion of clusters with ≤2 municipalities, as the rationale presented (random fluctuation) lacks an explicit methodological foundation.

I recommend detailing the procedure used for the proportional redistribution of missing data (sex, age, municipality), including the statistical basis and potential limitations of this method.

I suggest including the limitations of the space-time scan statistic (STSS), particularly regarding its sensitivity to the spatial window boundaries and the lack of contextual variables.

4. Results

I recommend including a quantitative synthesis of the national-level results, such as the overall mean and annual trend of TB incidence in Brazil.

5. Discussion

I suggest condensing the discussion section to avoid repetition of the results and to make the text more analytical and less descriptive.

I recommend explicitly addressing the methodological limitations of the study, including ecological bias and the modifiable areal unit problem (MAUP).

I suggest expanding the discussion on the international and structural implications of the findings, including comparisons with other high TB burden countries in Latin America.

I recommend discussing the limitations of the temporal analysis in the context of the COVID-19 pandemic, considering the possible influence of changes in surveillance and reporting systems during that period.

6. Conclusion

I suggest rewriting the conclusion to avoid repeating content from the abstract and discussion, and to clearly state the original scientific contribution of the study.

I recommend highlighting the main novel findings with direct implications for TB surveillance and territorial planning in Brazil.

7. References

I suggest reviewing the formatting of the references to ensure full compliance with the style required by PLOS ONE, including the presence of DOIs and other mandatory elements.

Reviewer #2: The article “Space-time clustering and temporal trend analysis of pulmonary tuberculosis in Brazil, 2010-2023” aims to analyze space-time trends of PTB in Brazilian municipalities, mapping areas of greater risk and growth, and collaborating with the public health system through the evidence identified.

The paper's introduction presents a clear exposition of the problem, citing information at a global level and the scale of analysis (Brazil). It identifies the need for a temporal and spatio-temporal study of PTB and monitoring and control interventions and actions—especially with a focus on regionalized actions, due to Brazil's regional diversity.

The methodology is precise and robust, featuring sophisticated statistical analysis that is recommended for temporal and spatio-temporal analysis studies. The use of secondary data from DATASUS and IBGE allows for a comprehensive analysis of the scale of the study presented. Furthermore, the use of these open-access databases is a strong point of the study, although the authors mention it as a limitation because they do not analyze disaggregated data. In fact, disaggregated data can provide other clues and suggestions for the problem of PTB in Brazil, however, the greater the scale of detail, the lower the level of generalization for creating transmission models and identifying priority areas.

The use of Joinpoint Regression, Moran's I, Getis-Ord Gi* and SaTScan tools provides a comprehensive and methodologically powerful analysis. The integration between statistical information and spatial statistics takes into account a key element not mentioned in the work: the geography of PTB. Health-disease processes occur in geographical space and are therefore also conditioned/determined by the form of social production of this space. Literature on the subject of the Health Geography—much enriched in Brazil—may provide clues to this point that I would like to draw attention to.

It is clear that the authors have an understanding of the subjects covered in the paper, and some methodological choices have been prioritized in this extensive and rigorous work. Some of the shortcomings are listed in the limitations section of the paper, such as: i) under-reporting; ii) inconsistency in the data; iii) use of aggregated data; iv) those relating to technique (spatio-temporal analysis techniques, MAUP, etc.).

Thus, I highlight some limitations/suggestions for the work. In particular, the areas with the highest demographic density, such as the aforementioned favelas in Rio de Janeiro, are proxies for analyzing the incidence of PTB in Brazil - in contrast to the quality of the data produced in remote/rural areas. From this question, which is deeply energized in urbanization debates in urban geography, a question arises: isn't it important to analyze the consistency and completeness of the data? Another question that I think is relevant to think about is whether there are relationships between the urban hierarchies of Brazilian municipalities and the regions of influence of the cities with the incidence of PTB over the time series. Graphs relating these hierarchies to incidence over time could add to a rich debate about how we are constructing Brazilian cities and regions and the impact this has on Brazilian public health—directly affecting the Unified Health System (SUS). Maps relating to this issue of centrality and the search for health services could add to the debate which, despite the exhaustive analysis presented, could be complemented with some social, economic and structural characteristics.

Other types of maps could correlate areas of socio-economic vulnerability with those with a higher incidence of PTB. The relationship in the Amazon region and the Central-West with precarious and slave labor in illegal mining, deforestation, and wildfires could provide clues to social aspects related to a comprehensive analysis of PTB in Brazil. On this subject, we should also pay attention to recent climatic events resulting from the global climate crisis.

With regard to these more political and social issues (although it is well known that health is a social product), in Figure 2 I identified the municipality of Campinápolis (MT) as an area with a high incidence of tuberculosis in all the periods analyzed. In Figure 3, this region of Campinápolis, in the Serra do Roncador, is home to a lot of illegal deforestation, wildfires and indigenous violence against the Xavantes ethnic group. Are these aspects related? Clearly, the aim of this paper was not to problematize this exact issue, but I recommend that you take a closer look at it in a future article and suggest the concept of necropolitics if you wish to delve deeper into these structural aspects.

Another aspect that I think is important to articulate is the analysis of data based on health regions. The authors clearly know and understand that the SUS is a hierarchical, regionalized, and municipalized health system. As such, resources for surveillance, education, and monitoring of PTB (and other diseases) go through these specific regional departments. If the data were also articulated regionally, it could contribute to the final recommendations made in the paper.

One point that we cannot avoid debating is the COVID-19 pandemic. The abrupt drop in the time series in 2020 and 2021 was mentioned by the authors in the paper and provides an interesting and factual view, since Brazil was one of the countries that recorded the most deaths from the disease, and, in places like the Amazon, there were total collapses of the health system. Another unexplored issue is the institutional dismantling of the SUS, which under Bolsonaro's government has seen major institutional attacks and changes of ministers and officials.

As a final addendum, I think it's relevant that the research brought up the debate on the 2030 Agenda and the complicated situation that Brazil currently finds itself in. In the future, the authors could include a more in-depth analysis with typologies of the municipalities that have historically shown a drop in the PTB trend and which are, or are not, in line with the global agenda. A municipality that has shown a consecutive increase in recent years may be within the limit stipulated by the 2030 Agenda, sparking new debates on the policy.

Finally, I congratulate the authors on the work they have presented, with many figures, tables, and a wealth of supplementary material that fully supports the reading and understanding of the work. Studying Brazil in its plurality and regional diversity spread over 5570 municipalities is a major challenge. Combating tuberculosis and other diseases in Brazil requires coordinated action, and, with this in mind, this work offers relevant insights for the study of tuberculosis in Brazil.

Without further ado, I am available for future dialogues to discuss the relationship between health and geography for future work—I believe that this relationship is fundamental for strengthening the SUS.

**********

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: No

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.

<p>Space-time clustering and temporal trend analysis of pulmonary tuberculosis in Brazil, 2010–2023

PONE-D-25-27079R1

Dear Dr. da Silva,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support .

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,

Patricia Matsumoto, Ph.D.

Academic Editor

PLOS One

Additional Editor Comments:

Apologies for the delay in finalizing the evaluation of your paper. I want to acknowledge the excellent job the authors have done in revising the manuscript. The paper is now much stronger, and it is clear that you incorporated the reviews with care and attention. I truly appreciate the effort in addressing each comment from the reviewers and myself, as well as the improvements made to the manuscript, figures, and supporting information.

I only have a few minor points for you to consider. These do not affect the merit of the work, but I believe they will help add the final touch to your manuscript. You don't need to answer them, but consider them for next editorial process.

Minor Points:

- Some institutional names are in Portuguese, while others are in English. Would the authors consider standardizing them?

- Line 22: consider specifying “regionally and nationally”, as the study is conducted at a national scale and can help the federal government in decision-making

- Could you provide a list of the 212 high-priority municipalities in the Supplementary Materials? This can serve for decision-making.

- Figure 6: Since you chose to include the municipal boundaries and they are currently in white, please consider changing them to light gray. This will improve visibility both in the Amazon region and in the white areas where boundaries disappear.

- Table S4: instead of repeating the captions, please add something such as “[continued...]”. As currently formatted, it appears to be a separate table.

Thank you for submitting your paper to PLOS ONE. We hope you will consider future submissions.

All the best,

Patricia