Dear Dr Weerasuriya,

Thank you very much for submitting your manuscript "Updating contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination" for consideration at PLOS Computational Biology.

As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

Reviewer 2 raises important points regarding the reasoning and motivations that led to the choices in translating empirical data on contact matrices (main suggestion 1). We believe the issues raised require detailed attention from the authors since they represent major weaknesses in this manuscript.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Claudio José Struchiner, M.D., Sc.D.

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor-in-Chief

PLOS Computational Biology

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Reviewer 2 raises important points regarding the reasoning and motivations that led to the choices in translating empirical data on contact matrices (main suggestion 1). We believe the issues raised require detailed attention from the authors since they represent major weaknesses in this manuscript.

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: This manuscript presents a well written if rather technical modelling analysis of the impact of assumptions of contact structures on results of a mathematical transmission model of TB in India. In essence, the authors' work shows that they don't, so it is a "negative" result.

I am not an expert in TB modelling, so I cannot assess the relevance and appropriateness of the modelling assumptions, although they appear to make sense.

One major issue is that their assessment relies quite heavily on a contact structure from the POLYMOD paper, which is based on data collected from Europe. It would be important to conduct some form of sensitivity analysis, e.g. using possibly data from a different setting, which might be a better reflection of social interactions in India. Finally it was also not clear to me whether the level of future vaccination coverage could play a role for results.

It would also be important to make the model code available to other researchers in a public depostory.

Minor comments

p. 3 l.45 Vaccines can hardly be considered to be new tools. Please rephrase.

p. 23 Fig. 1 Describe what C, A & E means in legend.

p. 27 Update Citation 8. This has in the mean time been published in PNAS

Appendix:

p. 6 penultimate line Update Figure crossref.

p. 9 Figure 2 C: Please detail which lines are overlaid.

p. 21 line 2. sentence needs to be completed.

p. 28 missing in fastprogression

p. 29 missing space in adulttargeted

Reviewer #2: PCOMPBIOL-D-21-01594

The authors use and adapt a version of a previously developed and published model to explore whether temporal changes in age-specific contact patterns will have implications for the population-level impact of adult TB vaccines. The authors model four different ways in which age-specific contacts change over time, which is adapted from a previous study exploring how empirical data on age-specific contact can be applied in general. Specifically, the authors explore models that incrementally

(i) forces "reciprocity" in the number of between-age-group contacts at the size of age-groups change;

(ii) preserves "assortativity" in between-age-group contacts or the propensity to contact someone in certain age-group over others; and

(iii) preserves the total number of contacts in the population as the population sizes change.

The methods are very well detailed in the supplementary materials, and the findings are described fairly well.

The authors find that in the context of the epidemiological impact of adult TB vaccines that is deployed in a high burden setting like India, these do not significantly change the results.

Overall, I find this study methodologically sound, and the questions addressed to be of significance (but perhaps not as well motivated).

My main suggestions for the authors are as follows:

1. The main question, why and how these specific features about translating empirical data on contact matrices matter, is not motivated adequately.

This could partially be addressed by (i) describing in what form these empirical data are, and why precisely these modeling choices have to be made -- currently, it relies on the authors reading previous papers to understand these precisely;

(ii) laying out the potential reasonings behind a specific model (beyond just to get the numbers to add up); and

(iii) potential implications of the specific modeling choices, especially in the context of vaccines.

As it stands, it feels more like an extended sensitivity analysis, attempting to cover all bases -- but if framed better,

it could get at important questions at the heart of the matter about what empirical data are telling us, and why they matter.

2. Why POLYMOD? Authors justify that India-specific data were not available in a fully representative form (though arguably a state within India is more representative that European nations), but why not data from a similarly densely populated China or has household structures that are more in line with Kenya?

The specific choice of contact matrix data may not matter for the main question, but I think it worth authors addressing this choice.

3. To what degree are diary-based contact patterns applicable to TB, where the transmission is airborne?

This is a general comment on the use of these data -- I would appreciate if the authors could provide their take on this: to what degree this is a data limitation (and these are the best data we have), or

whether they believe that these data are fairly good representation of the age-specific contact patterns.

4. Are the results generalizable? I think it would be great if the authors could speak to:

(i) whether their finding (no significant difference) is tied to the choice of contact matrix (also relates to point 2), and/or

(ii) the projected demographic changes in India.

One suggestion here, if logistically possible, would be to conduct sensitivity analyses with one of the alternative contact matrix data and or demographic changes.

Minor points.

5. Title: Suggest specifying age-specific contact structure, since contact structure can be based on other non-age related factors

6. Fig 1: Suggest spelling out C, A, and E.

7. Introduction, lines 62-65: Please include references: it will also make help make authors point more clear.

Reviewer #3: Please see the attached review letter.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No: 

Reviewer #2: None

Reviewer #3: Yes

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Figure 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. 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 us at figures@plos.org.

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Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

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To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: PCOMPBIOL-D-21-01594.pdf

Dear Dr Weerasuriya,

Thank you very much for submitting your manuscript "Updating contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination" for consideration at PLOS Computational Biology. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Reviewer 2 has a few very minor suggestions for your consideration prior to acceptance.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Claudio José Struchiner, M.D., Sc.D.

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor-in-Chief

PLOS Computational Biology

***********************

A link appears below if there are any accompanying review attachments. If you believe any reviews to be missing, please contact ploscompbiol@plos.org immediately:

[LINK]

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: All comments have been adressed.

Reviewer #2: Authors have revised the manuscript to meaningfully address or provide thoughtful additions to all reviewer comments.

Minor points.

1. Suggest including "age-specific" in the title.

2. line 94, "interact with" is written twice

3. Suggest including a caveat that although these specific results were not affected, including county-specific contact patterns could be important for general transmission modeling with age-specific contact patterns, just as incorporating evolving demographic changes.

Reviewer #3: Thank you for addressing the comments raised in my initial review.

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: None

Reviewer #3: Yes

**********

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

Reviewer #3: No

Figure 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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References:

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.

Dear Dr Weerasuriya,

We are pleased to inform you that your manuscript 'Updating age-specific contact structures to match evolving demography in a dynamic mathematical model of tuberculosis vaccination' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Claudio José Struchiner, M.D., Sc.D.

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor-in-Chief

PLOS Computational Biology

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