Thank you for the valuable comments and suggestions from the editor and reviewers. We have carefully revised the manuscript accordingly. A detailed point-by-point response has also been uploaded as “Response to Reviewers.docx”. The responses are provided below for reference.

Author_Response_Letter (Manuscript ID: PONE-D-26-00936)

Dear Editors and Reviewers:

We would like to thank the editors and reviewers’ work devoted to our manuscript entitled "Spatiotemporal patterns of prevalence and mortality from respiratory infections and tuberculosis across Japan and its prefectures" (Manuscript ID: PONE-D-26-00936). Those comments are all valuable and very helpful for revising and improving our paper. We have studied the comments carefully and made corrections that we hope to meet with approval.

Each concern is discussed in detail below. These revisions were performed to address the reviewers’ concerns. Thank you again for allowing us to resubmit our manuscript for your consideration.

Responses to Editorial Requirements

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Response: Thank you for this comment. We have carefully revised the manuscript according to the PLOS ONE formatting and file-naming requirements, including the title page, manuscript structure, tables, and figure formatting.

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Response: Thank you for this comment. We have added the required Data Availability Statement in the revised manuscript and submission form: “All data are in the manuscript and/or supporting information files.”

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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

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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/

Response: Thank you for this comment. We have regenerated Figure 3 and Figure S1 using an R-based workflow with publicly available administrative boundary data for Japan obtained through the geodata package (GADM level-1 boundaries). The maps were generated using R packages including sf, ggplot2, and geodata. No Google Maps, Google Earth, satellite imagery, or proprietary basemap was used; therefore, the revised figures do not involve copyrighted map or satellite image content.

The following text has been added to the Methods section (Statistical analysis subsection):

“All data management, analyses, visualizations, and map generation were performed in R (version 4.2.2; R Foundation for Statistical Computing, Vienna, Austria). Prefecture-level maps were generated using publicly available administrative boundary data for Japan obtained through the geodata package (GADM level-1 boundaries), without the use of proprietary basemaps or satellite imagery.”

The following statement has also been added to the captions of Figure 3:

“Maps were generated by the authors in R using publicly available administrative boundary data for Japan.”

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Response: We have added captions for all Supporting Information files at the end of the revised manuscript.

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Response: Thank you. No reviewers requested citation of additional specific references.

Responses to Reviewers

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: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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

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Reviewer #1: Yes

Reviewer #2: Yes

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

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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)

Response: We sincerely thank the reviewers for their valuable comments and suggestions. The manuscript has been carefully revised accordingly, and all revisions are detailed below.

Responses to Reviewer #1

Reviewer #1: The research article meets the criteria.

1. The source of the data used has been clearly explained

2. Legible and standard English has been used

3. Ethical considerations and protocol were followed

4. The study provides new insights for the scientific community

All in all, I believe that the article is fit for publication.

Response: We sincerely thank the reviewer for the positive evaluation and strong support of our work. We greatly appreciate the reviewer’s recognition of the methodological rigor, ethical compliance, and public health relevance of our study.

Responses to Reviewer #1

Reviewer #2: General Assessment

This manuscript presents a comprehensive spatiotemporal analysis of respiratory infections and tuberculosis (RIT) burden in Japan from 2010–2023 using Global Burden of Disease (GBD) estimates. The study integrates national and prefectural trends in prevalence, mortality, demographic stratification, and etiology-specific mortality patterns.

Overall, the study is methodologically sound, clearly written, and aligned with PLOS ONE’s scope of publishing robust, well-executed population health research. The analysis addresses an important public health question in the context of population ageing and provides policy-relevant insights. However, several issues need to be addressed before publication, primarily concerning clarity of definitions, consistency of reporting, interpretation of GBD uncertainty, and presentation quality.

see the attached filed for detailed report

Response: We sincerely thank the reviewer for the thoughtful and constructive comments. We have carefully revised the manuscript according to the comments in the attached detailed report. Detailed point-by-point responses are provided below.

Major Comments

1. Clarity and Conceptual Framing of RIT as a Composite Outcome

Issue:The manuscript defines RIT as a broad composite category including tuberculosis, upper and lower respiratory infections, otitis media, and COVID-19. While this follows GBD definitions, the biological and epidemiological heterogeneity of these conditions is substantial.

Concerns:

• Combining acute viral infections, bacterial pneumonias, tuberculosis, otitis media, and COVID-19 may obscure pathogen-specific trends and drivers.

• Interpretation of prevalence-mortality "decoupling" may differ substantially across components.

Recommendations:

• Explicitly justify the use of a composite RIT construct in the Introduction and Methods (beyond citing GBD conventions).

• In the Discussion, add a paragraph acknowledging how aggregation may mask divergent trends (e.g., TB vs. COVID-19 vs. pneumococcal disease).

• Consider adding a supplementary sensitivity analysis excluding COVID-19 deaths, given their strong influence post-2020.

Response: Thank you for this important comment. In response, we further clarified the rationale for using the composite RIT construct in the Introduction section. The following text was added:

“Within the GBD framework, RIT represents a standardized composite category integrating multiple major respiratory infectious conditions across populations and demographic groups. Although these conditions differ biologically and epidemiologically, evaluating them collectively may better reflect the overall healthcare and mortality burden imposed by respiratory infectious diseases in rapidly ageing societies such as Japan.”

In addition, we expanded the Discussion section to acknowledge the limitations of aggregating heterogeneous respiratory infectious diseases and the potential impact of COVID-19 on temporal trends. The following text was added:

“In addition, because RIT was analyzed as a composite category, aggregation of biologically heterogeneous conditions may mask pathogen-specific temporal patterns and epidemiological drivers. Furthermore, inclusion of COVID-19 within the standardized GBD framework likely contributed substantially to the mortality rebound observed after 2020 and may have influenced the observed prevalence–mortality divergence.”

2. Interpretation of Estimated Annual Percentage Change (EAPC)

Issue:EAPC results are central to the manuscript, yet interpretation is occasionally inconsistent with confidence intervals.

Examples:

• Several EAPCs are reported as positive or negative despite 95% Cls crossing zero, implying

no statistically supported monotonic trend

• Language such as "increased," "declined," or "upward trend" is sometimes used without caution.

Recommendations:

• Revise wording to distinguish point estimates from statistically supported trends.

• For EAPCs with Cls including zero, use neutral phrasing such as:

"No clear long-term monotonic trend was observed."

• Consider adding a short explanatory sentence in the Methods clarifying how EAPC uncertainty should be interpreted.

Response: Thank you for this important comment. In response, we added an explanatory statement in the “Temporal trend analysis” subsection of the Methods section to clarify interpretation of EAPC uncertainty. The following text was added:

“EAPC estimates with 95% confidence intervals crossing zero were interpreted as indicating no clear long-term monotonic trend.”

In addition, we revised several statements in the Results section to distinguish point estimates from statistically supported temporal trends. For EAPCs with confidence intervals including zero, more neutral wording such as “no clear long-term monotonic trend was observed” was adopted accordingly.

3. Use and Communication of GBD Uncertainty

Issue:While uncertainty intervals (Uls) are reported, their implications are not fully integrated into interpretation.

Concerns:

• Prefectural estimates, especially etiology-specific mortality, may have substantial uncertainty due to modeling.

• Readers may overinterpret small differences between regions or years.

Recommendations:

• Expand the Limitations section to more explicitly address:

• Uncertainty propagation in subnational GBD estimates

• Potential instability of prefectural-level etiology attribution

• Add a brief statement cautioning against overinterpretation of small regional differences.

Response: Thank you for this important comment. In response, we expanded the Limitations section in the Discussion to further address uncertainty in GBD-derived estimates, particularly at the prefectural and etiology-specific levels. The following text was added:

Attachments

Attachment

Submitted filename: Response to Reviewers.docx