PONE-D-23-07536Social-behavioral insights in understanding Tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocolPLOS ONE

Dear Dr. Mohd Shariff,

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.

Overall, the protocol is well written and I thought the authors could generate very relevant and comprehensive scientific evidence on the impact of COVID-19 on tuberculosis transmission. It is suggested

 1. Define well the inclusion/exclusion criteria of the participants.

2. Specify how the sample size calculation was developed.

3. Deepen the discussion of the manuscript, especially in the interpretation and implications of the information findings.

4. Review the writing of the article, from the use of punctuation to the coherence of the sentences

Please submit your revised manuscript by  April 15. 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,

Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS ONE

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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 

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https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

- https://doi.org/10.1186/1471-2334-9-197

- https://doi.org/10.1093/ije/dyg098

- http://dx.doi.org/10.1136/bmjopen-2020-044746

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

3. Please provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

4. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Partly

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: No

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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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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: No

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Dears

Thank you very much for the opportunity to review this interesting study protocol that is proposed to investigate Tuberculosis transmission pattern during the COVID-19 pandemic period.

Overall, the protocol is well written, and I believed authors could generate very relevant and comprehensive scientific evidence on the impact of COVID-19 in TB transmission. I understood the authors presented rigorous methodology with robust molecular investigation techniques and detailed sampling and analytical approaches, which is also great to link epidemiological, clinical and social network data to inform better understanding of TB transmission dynamics during the pandemic.

Hence, at this stage I have no major comments except asking the respected authors to provide further explanation for the following few points.

# 118-119: “A retrospective population-based …. study of patients diagnosed with TB will be carried out from 1st January 2022 to 31st December 2024 “while target population for this study is all PTB patients notified during the peak season of the pandemic in year 2020 and 2021. Can you please redefine your study design and period? Here I understood that though most of the clinical and demographic data will be retrieved from the national TB database (MyTB), you had also a plan to collect additional data until 2024- this indicated both prospective and retrospective approach. If you are still stick with histories of social networking during the pandemic and not include any prospective information, the study period would be 2021-2022.

#156 Is it relevant to mention “Unwilling to participate or lack of consent” as one of the exclusion criteria? If possible, can you also reconsider the importance of Transfer out cases for social network interview as they probably have independent contribution on TB transmission or MTBC strain clustering? - my opinion.

Sputum sample collection and culturing procedure is not clear for me. When how and who performed smear and culture? Are you going to re-processed stored sputum samples, or do you think the one that was done as part of the routine service can fit for your study? - I think it is better to elaborate your quality control methods. Related to this, can you also reflect the estimated number of cases and eligible samples that would be adequate enough to answer your research question?

# 245-46: Interviews will be conducted either through telephone call, face to face interviews in the clinic or online survey form. Do you think the later two works in your setting to collect information from TB patients who completed their treatment before a year?

# 251-52 Each participant will be given full autonomy to participate or withdraw from the study at any time without jeopardising their ongoing anti-TB treatment. Do you think or expecting patients who are still on treatment?

#302-04, I agreed a Multivariable Multinomial Logistic regression will be an appropriate method to control potential confounding effects if you are only included individual level data but TB transmission; social networking and molecular epidemiology, might have hierarchical (multi-level) structure: hence it would be also better to think about other statistical modeling techniques (mixed effect or multilevel regression analysis) to adjust and/or identify the effect of geographical or other cluster (group) covariates.

Oops! The discussion section explained some of the above points, but it would be better to include in the method section of the protocol while that will be further discussed as part of the final study limitation.

Regards

Reviewer #2: Respected editorial board,

It is a privilege to be considered as a reviewer for your prestigious journal. I have been recommended to review the protocol titled “Social-behavioural insights in understanding Tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocol” with no personal conflicts of interests as declared. The protocol addresses an important issue, the social-behavioural dynamics of the TB transmission. The study aims to facilitate TB screening and active mapping of social contacts for effective formulation of preventive and preparedness strategies to interrupt TB transmission. However, the study being a retrospective is likely to have various limitations. The authors have embraced their strengths yet have overlooked to mention major limitations in the methodology.

Being a clinical concern and a relevant research question with an expected large sample size, after a few satisfactory revisions on the presentation and some concerns , it would be worth considering for publication in your scientific journal.

Respected researcher,

the protocol titled “Social-behavioural insights in understanding Tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocol” addresses an important issue, the social-behavioural dynamics of the TB transmission. The study aims to facilitate TB screening and active mapping of social contacts for effective formulation of preventive and preparedness strategies to interrupt TB transmission.

Multiple previous studies have demonstrated a plausible theoretical parameter for risk of transmission of TB, however with the large number of patients planned to undergo genomic mapping for deciphering the same, makes this study unique and worthy of appraisal.

There were a few concerns raised by the reviewer which may need to be addressed by the authors for better understanding and scientific soundness of the article.

The study being a retrospective one with electronic data collection fails to have a prospective evaluation of the TB cases and contact tracing or testing of the exposed. As researchers have honestly highlighted several potentials bias like selection bias, recall bias, missing data , non-response bias and the unmeasured underlying disease status are a major limitation of the retrospective electronic data collection.

Authors are suggested to elaborate upon the criteria of inclusion of suspected TB cases as its likely to make the interpretation of TB epidemiology questionable. The methodology needs to mention the SNA questionnaire that the researchers intend to use .

For statistical validity it is suggested that the authors additionally mention the calculation of the sample size based on previously conducted prevalence or incidence studies in the region for tuberculosis. The represented population of TB cases maybe an underestimation as the TB centres included may be limited. Furthermore, the study is planned to include sputum positive and negative cases both whereas the genotypic study is being conducted only among confirmed cases , leading to a smaller sample size.

Researchers have proposed a novel methodology to establish contact tracing and transmission of tuberculosis , however, pathogenesis of tuberculosis is different from that the STDs. As the latent period of tuberculosis maybe longer than even a few years in certain cases, it shall be difficult to ascertain when the patient was infected and to determine the causality with COVID-19 restrictions.

There are few fundamental flaws in the article writing including punctuations, flow of thought, comprehension, and grammatical errors. Lack of clarity of discussion are further concerns which the authors are requested to improve upon. Overestimated conclusions with a poorly powered observation study could send a wrong message and needs to be paraphrased for generalisability.

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Reviewer #1: Yes: Hawult Taye Adane

Reviewer #2: No

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PONE-D-23-07536R1Social-behavioral insights in understanding Tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocolPLOS ONE

Dear Dr. Mohd Shariff,

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. It is suggested:

1. Better explain the aspects related to the study design

2. Specify ethical aspects, how informed consent was achieved and ethical aspects such as patient autonomy

3. Delve into sputum culture and collection procedures.

4. Review the discussion both in form and substance, it should be written more clearly and objectively.

  Please submit your revised manuscript by Jun 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,

Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

[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.

Social-behavioral insights in understanding Tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocol

PONE-D-23-07536R2

Dear Dr. Mohd Shariff,Noorsuzana Mohd Shariff,

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,

Oriana Rivera-Lozada de Bonilla

Academic Editor

PLOS ONE

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

**********

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

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: I would like to thank authors who made the required revision and response to my previous comment.

Though, I am still not clear about the design (study period and sampling procedure, this is a very detailed protocol and well written

I thought this is Cross-sectional study with retrospective data collection from PTB patients diagnosed during 2020 and 2021 . Hence, Authors should reconsidered my previous comment and re-phrase the statements under line 117-118).....epidemiological cohort study of patients diagnosed with TB will be carried out from 1st January 2022 to 31st December 2024. I understood the later is used to refer the time when authors plan to undertake the study but this my confuse readers and there might be misunderstanding on the actual period for source of data.

Except the above issue , I have no major concerns and this protocol can be accepted for publication

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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

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