PONE-D-24-17908Hepatitis B infection in Lake Zone Tanzania: Demographics, antiretroviral therapy eligibility and antiviral therapy uptake among chronic hepatitis B patients at a tertiary hospital in North-Western TanzaniaPLOS ONE

Dear Dr. Mlewa,

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 07 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,

Jason T. Blackard, PhD

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. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (1) whether consent was informed and (2) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

If you are reporting a retrospective study of medical records or archived samples, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information.

Additional Editor Comments:

This is a cross-sectional study of HBV prevalence and treatment eligibility in Tanzania.  Given the burden of HBV in many resource-limited settings, foundational studies such as this one are needed.  However, the written requires significant improvement to make the manuscript methods and results clear and concise.  Editing by a native English speaker and/or professional editing service is needed.

Many complicated sentence structures should be re-written for clarity.  For example,

·      Among the efforts to prevent HBV infection and therefore reduce the risk of developing chronic HBV infection, in 1992, the WHO summoned every country to integrate HBV vaccination into their universal childhood vaccination programs by 1997 [7] so as to reduce the risks of acquiring HBV infection and therefore acute hepatitis B which can lead to chronic hepatitis B infection. 

·      Our results have shown that, although nearly all chronic hepatitis B-infected patients were older than 20 years, which was probably due to the effect of the national infantile-pediatric HBV vaccination program that started about 20 years ago, anti-HBV antiviral therapy uptake among the eligible patients according to the 2015 WHO-HBV prevention, management, and care guidelines for HBV infection was remarkably lower than the expectation of the WHO towards the elimination of HBV by 2030. 

This statement implies that HBV treatment rollout was not country-wide. Is that indeed the case?

·      Tanzania introduced HBV treatment in 2009 at the Bugando Medical Centre and in 2016 at Muhimbili National Hospital [8]. 

Batch testing for HBV DNA is mentioned in the Methods.  However, whether positive pools were then de-complexed and tested individually is not stated.  This is essential for accurate determination of HBV DNA prevalence and levels.

Delete this sentence:

·      Furthermore, the patients were categorized into male and female groups based on sex. 

Sex should be replaced with gender throughout the manuscript and tables.

HBVL should be replaced with HBV DNA.

The HBV DNA cutoff of 20000 should be replaced with 20,000 throughout the manuscript and tables.

Study limitations – there are several – should be clearly stated in the Discussion.  The study population is modest in size.

The Discussion is quite long and should be shortened / streamlined.

[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: No

Reviewer #2: Yes

**********

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

Reviewer #1: No

Reviewer #2: Yes

**********

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: Title: very long. can be shortened and made more explicit

Methods: The methods section combines a chart review with newly recruited patients. This creates a problem as the methods section technically must be reproducible. There is no way of knowing if the same laboratory methods, under similar conditions was used to generate data collected from the chart review. The study can be salvaged by describing either of the groups independently as two studies and not combining their data.

Data Analysis, Discussion and Conclusion: Due to the anomaly in the methods section, the data analysis , discussion and conclusion are not valid.

Reviewer #2: The study provides important results for a critical area in the African region. Below are some comments and questions for a better understanding of the study.

Introduction

1. The general situation of HBV treatment in Tanzania needs to be clarified. Are Bugando Medical Center and Muhimbili National Hospital the only sites that treat HBV in Tanzania?

2. Is there any information on the number of individuals on treatment among those diagnosed with HBV in Tanzania?

Methodology

3. I suggest that you briefly explain the principle of the formula used to calculate the sample size, including the numbers.

4. Is there information in the database about testing for other pathogens such as HIV, HCV, and HDV? Is testing routine in Tanzania?

5. Is there data on the algorithm used for HBsAg testing in the patients included in the study? Which test is used?

Results

6. Tables 1 and 2 could be merged into a single table. This would give a better view of the results.

7. Tables 1 and 2 can have two columns. One with the characteristic and the other with the absolute number and percentage, just indicate it in the column legend.

8. Other factors such as co-infection with HBV, HDV, and HCV were not taken into account in the eligibility for treatment. If there is no data, it is important to discuss it.

Discussion

9. The WHO recommendations for treatment were updated in 2024. The study was carried out under the 2015 recommendations, but it is also important that the results are discussed in the context of the new recommendations.

**********

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: 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.

Hepatitis B infection: Evaluation of demographics and treatment of chronic hepatitis B infection in Northern-western Tanzania

PONE-D-24-17908R1

Dear Dr. Mlewa,

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. If you have any questions relating to publication charges, 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,

Jason T. Blackard, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

None

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: Partly

**********

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: the reviewers comments have been addressed. The authors show no competing interests. Ethical approvals have been obtained and are in line with the Helsinki declaration.

Reviewer #2: Most of the questions have been answered. However:

Introduction

Figure 1/Table 1 is public, so it is unnecessary to include it in the manuscript.

Methodology/results

The sample explanation was clear, however, the combined analysis of data from retrospectively and prospectively recruited patients makes the analysis and interpretation of the results weak.

**********

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: No

Reviewer #2: No

**********