PONE-D-21-22192

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

PLOS ONE

Dear Dr. Oliveira,

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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?

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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: Abstract

- Background must clearly describe the purpose of the study.

- Methods must describe: the type of study design and the method used (ACCESSMOD), the data collection and analysis, and the measures used in the description of Results, summarizing what was presented in the Methods section of the manuscript.

- In Results, the states that present the longest time to health units should be highlighted.

Background

- The paragraphs in lines 106-113 and 127-138 would be more suitable in the Methods section and not in the Background.

- The last paragraph of the Background should describe the purpose of the study.

Methods

- The type of study design must be described in the first paragraph.

- After the subtitle and paragraph referring to “Distance calculation”, it is necessary to describe in detail the tabulation and data analysis process, as well as the measures which were used, statistical tests and the level of significance considered.

- The authors used 3 distinct geographic analysis units: macro-regions, federative units (states and Federal District) and municipalities. This should also be described in Methods.

Results

- In lines 277-285, I suggest that the calculation of the incidence rate be revised, since the indicator in the DF, São Paulo and Salvador has been presented as 0.05. It would be more appropriate to work with the indicator per 100,000 inhabitants.

Discussion

It is important to discuss not only the innovation proposed by this study, but also its limitations, at the end of the section.

Reviewer #2: Snakebite accidents are, in some regions, relevant public health issues. The WHO's recognition, including this problem in the list of neglected tropical diseases, was an important step towards the production of more knowledge on the subject and, mainly, the mobilization of governments and other institutions to reduce the damage caused by this type of event. The manuscript has the merit of addressing this topic, which is of regional relevance in Brazil.

I understand that the central focus of the work and its strength are in the application of the method that analyzes the distance between health units and population distribution. As the author himself mentions, it could be used for other health situations. The problem is using this single analysis to base the entire discussion of the manuscript.The subject of snake accidents ends up being secondary and treated in a superficial way or weakly based on the results obtained from the performed analyses. Fundamental factors were left out or were superficially addressed, if we consider the endo f the title “Timely access possibilities.” For example, the availability of serum.

The manuscript ignores the limited availability of the serum and, therefore, assumes the existence of an unlimited amount of the product. It assumes that adequate allocation in health units would only lack evidence-based rationalization (the model presented, for example). Unfortunately, that's not the reality. The distribution of sera is fundamentally conditioned by its availability.

The WHO classification itself highlights this discussion. It is not just the affected population that defines an illness as neglected. The industry's insufficient investment as well. In the case of the production of serums, this is even more sensitive, since the production, usually, has to be regionalized according to the specificity of the snake species, with specific distribution.

Not every population more than two hours away from the health units that provide serum is under the same risk of snakebiting. The categorization of the most isolated populations in terms of risk would be essential to better qualify the analysis and enable a prioritization criterion to support decision-making and suggest “timely access possibilities” as the title says. Municipalities with higher incidences are briefly mentioned, but the discussion is not go further.

Furthermore, the quality of the information is not discussed. For example, when commenting on the large number of cases in the city of São Paulo, the author mentions only the large population of the city as an explanation and does not assess the possible effect on the notifications of the existence of very important references (regional and national) in the treatment of snakebite accidents, located in its territory.

For these reasons, it seems a little ambitious to discuss "timely access possibilities", based almost exclusively on the distance between the population and the health unit, without analyzing risk, serum availability, health system configuration, information quality.

There are some problems with the references. For example, information on the WHO classification of snakebites as a neglected tropical disease is referenced to the article "Longbottom J, Shearer FM, Devine M, Alcoba G, Chappuis F, Weiss DJ, Williams, DJ. Vulnerability to snakebite envenoming: A global mapping of hotspots. The Lancet. 2018; 392(10148): 673-84". However, the information is not from this article, which cites original information from WHO document "Report of the tenth meeting of the WHO Strategic and Technical Advisory Group for neglected tropical diseases. World Health Organization, Geneva2017".

In my opinion, the work presented allows discussing only the geographic distribution of the population in relation to the units that provide serum, without assuming that this analysis is sufficient to think about strategies for expanding access to services.

Reviewer #3: This manuscript assessed the accessibility to antiophidic sera in the Brazilian context. Snakebite accidents are a neglected public health problem in the country; the knowledge aimed at by the present study is certainly relevant to health policy and planning in many remote and rural areas. The text is well written and can be read smoothly. However, it is poorly organized.

The Introduction is unnecessarily too large. It should have ended in line 97, after stating the study objective. Using different geographical areas (lines 97-8) in the approach is related to Methods, not the Introduction. That this analysis allows discussing accessibility to other health services (lines 99-105) is a matter for Discussion. The remaining four paragraphs (lines 106-138) pertain to Methods, an essential part of Methods.

Figure 1 (lines 142, 163-5) should be replaced in Results. Just describing which were the variables collated in this study is enough for this segment of Methods. Depicting graphically the Results is a strength of the study. The maps provide a synthetical perception of the problem by region, state, and town. However, I missed a tabular display of cities and towns with higher or lower accessibility, maybe as a supplement. Such information would be critical to document the problem and guide solution attempts at the municipal level.

The figures have poor visual accuracy; they need a higher resolution. They also need a more explicative heading. Figure 1’s heading is meaningless. Figures 2-4’s headings are relatively interchangeable; I missed an unequivocal indication of which figure is showing accessibility by which criteria.

I observe that the North region had a higher number of snake accidents (Figure 5) and the most significant travel challenge (Figures 2-4). This remark is the study’s conclusion; it could not have been preliminarily stated in the Introduction (lines 92-4) without referring this information to the literature or to empirical data (which, of course, were subsequently reported).

I missed the acknowledgment of study limitations. The Discussion’s last paragraph pointed out the strength of having gathered an extensive, nationwide database. However, traveling to the health unit that offers sera is not the only interval to the treatment. In particular, the period from the casualty and the access to transport may result in a significant preliminary delay. This study cannot infer this matter, though this delay can enlarge the time to treatment. I suggest that the authors discuss this issue as a study limitation.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Jose Leopoldo Ferreira Antunes

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PONE-D-21-22192R1Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilitiesPLOS ONE

Dear Dr. Oliveira,

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 consider all comments

Please submit your revised manuscript by 16 Oct. 2021. 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,

Ahmed Mancy Mosa, Ph.D.

Academic Editor

PLOS ONE

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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.

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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: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

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: Yes

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: N/A

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: Abstract

- Methods must describe: the type of study design.

Methods

- Data analysis: it is necessary to describe, as well as the association measures which were used, the statistical tests and the level of significance considered.

Reviewer #2: I'd like to thank all the authors for their answers. The theme is relevant to public health, especially because it affects more seriously socially vulnerable communities. I have no further comments.

Reviewer #3: (No Response)

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Jose Leopoldo Ferreira Antunes

[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.]

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Attachments

Attachment

Submitted filename: Review October1st.pdf

Geographical accessibility to the supply of antiophidic sera in Brazil: Timely access possibilities

PONE-D-21-22192R2

Dear Dr. Oliveira,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Ahmed Mancy Mosa, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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

**********

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

**********

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

Reviewer #1: 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

**********

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. 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: (No Response)

**********

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