Dear Mrs Russell,

Thank you very much for submitting your manuscript "Optimal control prevents itself from eradicating stochastic disease epidemics" 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.

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).

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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,

Varun Dutt, Ph.D

Academic Editor

PLOS Computational Biology

Thomas Leitner

Section Editor

PLOS Computational Biology

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Reviewer's Responses to Questions

Comments to the Authors:

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

Reviewer #1: In this manuscript, the authors highlight the use of stochastic models over deterministic continuous optimal control models for epidemic control problems. The Authors consider cases of small populations of infected hosts where eradication is a feasible scenario, to show the application of stochastic models and comparisons to simpler priority-based controls.

I suggest the following edits for revision

1. I suggest rewriting the author summary to make it more clear. In Author summary:

- Optimisations –spelling check

- Allocating limited resources to reduce the impact of an epidemic is important across human, animal and plant health. – not clear

- For example, deciding which infected plants to remove first to reduce ecosystem or agricultural losses from an invasive plant disease [ is important/critical?] – incomplete sentence.

- A common approach to these optimisations is to model the epidemic as a totally

predictable (deterministic) process and modern algorithms allow these optimisations to

scale to large, real-world problems (e.g. allocating resources across a landscape).

Which optimizations are being referred here?

2. Introduction - Management aims vary dependent on the scenario and pathosystem in question (see [6] for a review of the equivalent problem in the context of established invasive species). Which management?

3. There are Hyphens (-) inside a few of the sentences throughout.

4. It is mentioned that the plausible assumptions is that human decision making happens at discrete intervals and that there may be some delay between the decision making and the action being carried out. In that case, is this delay incorporated in the ODE’s or anywhere else? If not, give reasons

5. FIGURES placements need to be fixed. Some of them overflowing from the page and not labeled

6. Consistency in references to citations

Reviewer #2: Review uploaded as attachment.

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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: Yes

Reviewer #2: Yes

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: PLOS_Comp_Bio_Review-2.pdf

Dear Mrs Russell,

We are pleased to inform you that your manuscript 'Optimal control prevents itself from eradicating stochastic disease epidemics' 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,

Varun Dutt, Ph.D

Academic Editor

PLOS Computational Biology

Thomas Leitner

Section Editor

PLOS Computational Biology

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Reviewer's Responses to Questions

Comments to the Authors:

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

Reviewer #1: All the comments have been addressed.

Reviewer #2: I like the changes you have made since the first review. Specifically, I think you now do a better job situating your work relative to the standard assumptions (deterministic ODEs) and other control literature.

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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: None

Reviewer #2: Yes

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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