PONE-D-23-42570Operational indicators for pulmonary tuberculosis diagnosis in people living with HIV before and after Xpert MTB/RIF implementation in the state of São Paulo, BrazilPLOS ONE

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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: Partly

Reviewer #2: Yes

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

Reviewer #1: No

Reviewer #2: No

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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: No

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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: No

Reviewer #2: Yes

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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 is very important because it is needed to improve the diagnosis of pulmonary TB in people living with HIV. However, the ecological design is not the type of study to conclude that people in the study need fewer treatments for TB. In addition, the authors compare the rates of unconfirmed diagnoses before and after the introduction of Xpert, but, they don't express this with a p-value (Table 3).

Reviewer #2: The manuscript by Faria et al. is an ecological study with time series analysis, investigating the impact of GeneXpert molecular testing implementation on confirmatory rates of pulmonary tuberculosis (PTB) among people living with HIV (PLHIV) across 21 municipalities in the State of São Paulo, Brazil, from 2010 to 2020. The findings demonstrate a decreasing trend in non-confirmed PTB rates among PLHIV, especially in locations with greater testing coverage.

Specific comments to the authors:

Minor comments:

1. In the Introduction section (lines 93-98), the authors mention a review manuscript conducted by their own group, without providing specific details on the overall conclusions drawn by this review, and without contextualizing the novelty of their current study. Additionally, the reference citation (Ref # 17) should be given in English, as there is a PDF source available and entitled “Effectiveness of GeneXpert® in the diagnosis of tuberculosis in people living with HIV/AIDS”.

2. It is recommended to provide clearer explanations in the Methods section regarding the molecular testing conducted with the GeneXpert® system. Specifically, clarify whether both versions of the test (Xpert® MTB/RIF and Xpert® Ultra) were utilized, and indicate whether the tests were conducted in a single reference laboratory or across multiple laboratories in the 21 municipalities. If the testing occurred in different laboratories, it is advisable to include details about the equipment used, particularly if the different equipment were all of the same model.

3. Concerning patient data, particularly alcohol and tobacco consumption (Lines 125-126), is there quantitative data available (e.g., for smoking, data on pack years)? It would be beneficial to include statistical analyses to assess the impact of smoking and alcohol drinking on comorbidity. Additionally, please reassess whether these variables are suitable to be considered as comorbidities in the context of the study, or if it would be more appropriate to include them as factors influencing comorbidities (such as diabetes and immunodeficiencies).

4. The authors should review grammar throughout the manuscript text, mainly in the Methods and Results sections. For example, in the Methods section, please review the grammar and conciseness of the information provided in Lines 129-135, as the text is not easy to follow. The same for the text presented in Lines 158-173.

5. Figure 1 (x-axis) label is written in Portuguese, and it should be translated to English.

6. Figure 2 legend will benefit from a more detailed explanation of the data.

7. In Lines 202-203, the authors state that, “Despite being available, not all PTB cases had a molecular test ordered and performed and the coverage of the exam varied among municipalities.” Please provide an explanation.

8. The authors should verify the text for typographical errors.

Major comments:

1. Did the authors adhere to a study guideline, such as STARD2015: An Updated List of Essential Items for Reporting Diagnostic Accuracy Studies, or any other pertinent guidelines for ecological time series studies in human health research? Please provide justification. If applicable, I suggest evaluating the study against suitable guidelines and citing the sources accordingly. While the authors have referenced (Ref # 18): Kleinbaum DG, Kupper LL, Morgenstern, H. Epidemiologic Research: Principles and Quantitative Methods. New York: John Wiley & Sons, 1982, it is advisable to incorporate an established and up-to-date guideline to ensure methodological rigor and transparent reporting of results.

2. In the Results section, Table 1 requires formatting. Furthermore, while the authors mention that they analyzed the study variables using descriptive statistics, it would be advantageous to include p-values for the data presented in this table. I recommend incorporating statistical analysis to determine whether a significant difference exists, given that the study's objective is to examine and compare non-confirmed pulmonary tuberculosis diagnoses before and after the implementation of GeneXpert® testing. If there are no statistically significant differences observed in any of the characteristics (before and after testing implementation), this should be clearly stated. Similarly, for Table 2, consider including p-values associated with the data for statistical analysis. Additionally, in the footnote of this table, it states: "Source: Authors, 2023." Please review this statement as it seems unnecessary.

3. In the Results section, the authors mention differences in ethnicity among individuals included in the study, particularly regarding characteristics such as TB/HIV coinfection (Lines 258-265). While it's understandable that this is a description of the data, it's important for the authors to ensure the use of appropriate language when reporting ethnicity. I recommend consulting the following guideline for guidance: Flanagin A, Frey T, Christiansen SL; AMA Manual of Style Committee. Updated Guidance on the Reporting of Race and Ethnicity in Medical and Science Journals. JAMA. 2021 Aug 17;326(7):621-627. PMID: 34402850.

4. In the Conclusions section, the authors should consider to include that centralized care of TB patients in specialized outpatient clinics, along with the presence of a reference hospital, appears to facilitate the implementation of standardized diagnostic, treatment, and follow-up protocols, including the integration of molecular testing into routine clinical practice.

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Reviewer #1: Yes: Ivette Valcárcel Valcárcel

Reviewer #2: No

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Operational indicators for pulmonary tuberculosis diagnosis in people living with HIV before and after Xpert MTB/RIF implementation in the state of São Paulo, Brazil

PONE-D-23-42570R1

Dear Dr. Andrade,

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.

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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 #1: All comments have been addressed

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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

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

Reviewer #1: Yes

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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

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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

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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: I consider that the original study titled Operational indicators for pulmonary tuberculosis diagnosis in people living with HIV before and after Xpert MTB/RIF implementation in the state of São Paulo, Brazil, by Dr. Rubia Laine de Paula Andrade, was corrected appropriately, describing methods, results, and conclusion accord to the reporting guidelines. And the results are important for the implementation of tuberculosis control policies.

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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

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