Dear Dr. Avoka,

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.

ACADEMIC EDITOR: 

• The authors should address all comments raised by both reviewers (Dr. Sandra Sipetic Grujicic and Dr. Kunchok Dorjee).

In addition to comments given by the reviewers, address the following points (Academic editor comments):

Methods

the following points should be clearly identified/corrected:

• Clearly identify the study population for determination of prevalence 
• clearly state the model of analysis that help to determine cOR, aOR, p-values
• As stated in the Manuscript - the main outcome variable was the prevalence of DR-TB in the four study sites (what is the other outcome variable (if any)? and What was the possible categories in prevalence determination?)
  - As stated in the Manuscript - all susceptible TB cases were also extracted but as cases of interest. (what was the denominator to calculate the prevalence?)

Result

• - Title of table1a and 1b not clear (reported TB cases (1038) vs TB cases (839) should be clearly define). The two table can be merged and should have complete title description
• Table 2,3 & 4 have the same objective - better to re analyze all independent variables with outcome variable and produce one table containing cOR, aOR and p-value rather than three tables

Discussion

• remove subtitles under discussion section

Reference

• the references were not exhaustive e.g. Sambas etal was missed

Please submit your revised manuscript by Aug 17 2024 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,

Moges Desta Ormago, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

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

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 suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. 

The American Journal Experts (AJE) (https://www.aje.com/) is one such service that has extensive experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. Please note that having the manuscript copyedited by AJE or any other editing services does not guarantee selection for peer review or acceptance for publication. 

Upon resubmission, please provide the following:

The name of the colleague or the details of the professional service that edited your manuscript

A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a *supporting information* file)

A clean copy of the edited manuscript (uploaded as the new *manuscript* file)

3. In the online submission form, you indicated that "The data underlying the results presented in this study are available from the corresponding author upon request."

All PLOS journals now require all data underlying the findings described in their manuscript to be freely available to other researchers, either 1. In a public repository, 2. Within the manuscript itself, or 3. Uploaded as supplementary information.

This policy applies to all data except where public deposition would breach compliance with the protocol approved by your research ethics board. If your data cannot be made publicly available for ethical or legal reasons (e.g., public availability would compromise patient privacy), please explain your reasons on resubmission and your exemption request will be escalated for approval.

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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?

Reviewer #1: Yes

Reviewer #2: Partly

**********

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

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: "Prevalence and Factors Influencing Drug-Resistant Tuberculosis in four Regions of Ghana"

The paper is well written, and the topic is current. It is a retrospective study. The data refer to the period 2018-2022. years. It is proposed to publish with minimal corrections:

The title of the paper is short and clear, in accordance with the objectives of the research.

Summary

1. The second sentence should be excluded. Not needed.

2. It is not explained what the abbreviation BMI, SHS means.

3. Is there a significant correlation between minor adverse drug reaction and major adverse drug reaction variable?

4. When writing the p value, please enter ˂0.0001 in all places in the introduction.

5. There is an association between BMI and adverse reactions, please indicate whether lower or higher BMI value. The clear connection described is not enough. It is seen only through the conclusion.

6. Enter commas between the minimum and maximum values of the confidence interval.

Introduction

Short and clear. It answers the described problem under consideration. At the end, the goal of the research was defined. It is necessary that the goal of the research be identical both in the summary and at the end of the introduction.

Methods

Well described. It is necessary to describe and explain BMI in the "data extraction" part, and not to be described in the "data analysis" part. Transfer data about BMI to "data extraction". Define which are dependent and which are independent variables within regression analysis. There are no clearly defined categories for all the variables included in the research, and for outcomes. Also, not all outcomes are explained, e.g. major and minor adverse reactions…….

Define the method of calculating the prevalence….

Results

It is necessary to express all percentages in the text and tables with numbers with one decimal place. Please correct. Attachment titles are not adequate.

Join table one and b. Correct the title of the table 1 and b. For example - Demographic characteristics, habits and other characteristics of persons with TB in 4 regions of Ghana.

Table 2 and 3 have the same title. You must enter a number and percentage for each variable in Tables 2, 3, and 4.

No data is entered on graph 1 regarding the x and y axes.

Under each table enter explanations for abbreviations, statistical tests

Discussion

According to the research results. It would be very important if you explained the data analysis in the "Methods" section, just as you divided the discussion of the results into three parts.

Please remove the first two sentences from the discussion.

Conclusion

Correct

Literature

Number of references greater than 30. Adequately cited.

Correct everywhere the way of citing multiple references in the work. For example (5-9) or (5,7,11).

Reviewer #2: The two main objectives of this study were to determine the prevalence of DR-TB and factors associated with development of DR-TB in Ghana. The objectives are important. Below are comments I have largely focussed on methods.

Methods:

1) Retrospective analysis of DR-TB data from four regions of Ghana were carried out. To determine prevalence, defining the population base in which the outcome is determined is important - sampling method. Authors need to clearly state how the DR-TB cases were sampled. As written, I had to assume that DR-TB cases were measured among all TB cases. If this is the case, it needs to be stated clearly. presenting at various treatment centers in the four regions.

2) How are the four regions selected. How many regions are there? How many treatment centers were included? Answering these questions are important from generalizability perspective. If a convenience sampling approach was taken, it needs to be stated.

3) The inclusion criteria states that all DR-TB cases in four regions of Ghana. It also states that all susceptible TB cases were also extracted as cases of interest. The phrasing should be revised appropriately. One way to revise may be, 'all DR-TB cases out of all TB cases registered......". If including the susceptible new cases are optional, then how is the prevalence of DR-TB determined? What is the denominator? The exclusion criteria states, 'records of DR-TB cases from 2017 and below and 2023 were excluded'. Improve the english by using the words before 2017 or after 2023 instead of 'below'.

4) If determining risk factors for development of DR-TB is an objective, then including only DR-TB patients cannot allow the determination, as there is no comparator. How the statistical analysis is carried out to determine risk factors is not described. If the authors are meaning to say that sociodemographic and clinical risk factors associated with the development of DR-TB among all TB cases was assessed, then it should be stated clearly that the risk factors were compared between people that did and not have DR-TB.

5) No mention was made of Primary drug resistant TB. Do the DR-TB cases including both Primary and acquired DR-TB cases? If Primary DR-TB is included, then how are the association of adverse drug reactions with development of DR-TB relevant, since these primary DR-TB patients have not received any drug at the time of diagnosis.

6) It appears that diagnosis was happening through Xpert only. Are there any validation by culture or LPA? If diagnosis is only Xpert, RR-TB would be appropriate term.

Results:

1) Overall, the results would need to be better presented.

2) Prevalence of DR-TB was described for 3 regions, Ashanti, Eastern and Central. What is the fourth region?

3) Prevalence of DR-TB should be stratified by Primary Drug resistance or at least DR-TB among new cases and then DR-TB among retreatment cases.

4) What is SHS level of education? Why are more educated people more likely to have DR-TB

Discussion:

I am surprised that the discussion has no mention of the impact of Covid-19 on the case detection of DR-TB.

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: Yes:  Kunchok Dorjee

**********

[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.

Dear Dr. Avoka,

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.

Please submit your revised manuscript by Aug 16 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.

• 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,

Felix Bongomin, MB ChB, MSc, MMed, FECMM

Academic Editor

PLOS ONE

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: (No Response)

**********

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

Reviewer #3: Partly

**********

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

Reviewer #3: Yes

**********

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

The PLOS Data policy

Reviewer #3: Yes

**********

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

Reviewer #3: No

**********

Reviewer #3: The study is significant as it highlights the global variation in drug-resistant tuberculosis (DR-TB). It has been conducted on a large scale and represents an important contribution to the field. However, I have some concerns regarding the methodology and the interpretation of the results:

• The manuscript indicates that GeneXpert was the primary method used to validate DR-TB. However, the text does not specify what proportion of the study population underwent this testing. What percentage of the total population was tested for susceptibility to anti-TB drugs?

• Based on the text and the conclusions drawn, I strongly assume that only a small fraction of TB patients underwent these tests. Therefore, the prevalence of DR-TB should be calculated using only those cases that were tested.

• It is inappropriate to discuss alcohol consumption as a risk factor without further clarification, as alcohol consumption can vary widely in terms of quantity. It should be categorized by the amount consumed.

• Marital status or school attendance, considered indicators of close contact status, do not in themselves constitute risk factors for the onset or development of DR-TB. Close contact with an infected individual is a significant risk factor for exposure to the TB bacteria.

• The term "chronic condition" is not well-defined in the manuscript. Chronic diseases can differ greatly and have varying effects on the immune system, either directly or through the medications prescribed for them. They should not be grouped to that further specificity.

• It is unclear what is meant by "male class" and "female class." Is being classified as "male" or "female" itself a risk factor for DR-TB in the absence of other associated risk factors?

**********

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 #3: 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.

Dear Dr. Avoka,

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.

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

Your revision was evaluated by one the initial reviewers who was not satisfied. I ask you to carefully respond to the major comment of this reviewer and to clarify this issue.

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

Please submit your revised manuscript by Oct 03 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.

• 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,

Igor Mokrousov, Ph.D., D.Sc.

Academic Editor

PLOS ONE

Journal Requirements:

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. 

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: (No Response)

**********

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

Reviewer #3: Partly

**********

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

Reviewer #3: Yes

**********

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

The PLOS Data policy

Reviewer #3: No

**********

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

Reviewer #3: Yes

**********

Reviewer #3: My questions havenot been addressed fundamentally.Most important of them is that the primary objective of the study is to assess the prevalence of drug-resistant tuberculosis (DR-TB) in Ghana, with a conclusion stating that the prevalence is low.

However, the authors did not conduct their own investigation of the prevalence of DR-TB. In their response, they claim that this was not the aim of the study, but this contradicts the text of the manuscript and its conclusion. The authors only refer to prevalence data reported by other sources, which raises concerns about how the data was collected. In a scientific study, it is essential to provide such details clearly.

**********

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 #3: 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.

Prevalence and Factors Influencing Drug-Resistant Tuberculosis in four Regions of Ghana

PONE-D-24-05094R3

Dear Dr. Avoka,

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.

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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,

Igor Mokrousov, Ph.D., D.Sc.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: