Dear Dr macherera,

Thank you very much for submitting your manuscript "An assessment of risk factors for contracting rabies in Ward 30, Murewa District, Zimbabwe" for consideration at PLOS Neglected Tropical Diseases. 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.

The authors present an examination of risk factors for rabies in Ward 30, Murewa District, Zimbabwe. They identify risks associated with low awareness of rabies risks and levels of unvaccinated dogs as primary concerns. The paper provides a nice visual spatial analysis of dog bites, jackal presence, and rabies positive cases. There are issues with clarity in the methods that impede the interpretation of the results that needs to be addressed.

The methods section could use more clarity. The methods state that “one family member from each household that had a rabies case was selected for a proxy interview using a questionnaire”. Were these households that had human rabies cases? Elsewhere, the authors state that there were 4 rabies positive cases. So does this mean that only 4 households were surveyed? Where then does the 191 sample size come from. Please clarify. Some terms that were used were also confusing and inconsistently used (e.g., respondent, participant). In the results, the authors talk about 263 respondents. Where does this number come from? Only 191 were able to respond to the questionnaire, so the 263 individuals should not be called respondents but perhaps ‘enrollees’. How were they enrolled? What questions were asked on the questionnaire? A table of results from these questions would help.

Understanding how the people surveyed were selected is critical for readers to understand the implications of these results. The authors state that “dog owners were more likely to contract rabies as compared to non-dog owners”. This makes is sound like surveys were conducted on a cross section of people that include dog owners and non-dog owners and households that had rabies cases and those that did not. The sampling that was described does not make it clear who was surveyed and therefore it is not possible to have confidence in this statement. In the Limitation section of the discussion the authors mention that the 263 mentioned are dog bite cases. That would mean that the implications for these results can only be applied to people who have been bitten by a dog, this needs to be stated clearly. Also, in the author summary it is mentioned there are 938 dog bites, how does that relate to the 263 mentioned here?

Detailed comments:

Author summary:

• Include Zimbabwe in the description of the study area in the author summary.

• It is surprising you are able to get a significant result in a difference in proportions when you only have 4 positive cases. Please describe this more clearly.

Introduction:

• Rabies has no cure, but it is preventable with prophylaxis and this should be mentioned.

Methods:

• Change “It is fairly reliable” to “The rainfall is fairly reliable”

• Describe what the Likert Scale does and why it is used.

• Provide more detail on the sampling approaches, not just naming the methods. What is the population from which each sample is taken (who could be selected)? How many samples are taken? Be clear about the different target populations (all humans, humans who reported dog bites and went to the hospital, etc.)

Results:

• Provide the sample sizes along with the proportions for result.

• A table of the questionnaire results would be useful, similar to Table 1.

• Provide the numerators and denominators for the tests on the likelihood of contracting rabies.

Limitations:

• Not all dog bite cases could be reached and there was GPS uncertainty are in the same sentence suggesting these are related points, why?

• Why do you believe the conclusions can be applied to all of Murewa District? This is not clear.

Conclusions:

• Can you quantify the risks based on the spatial maps produced?

Figures:

• Figure 1: the boarder colors for Ward 30 and Murehwa Wards are indistinguishable, please correct this.

• Figure 1: in the text it suggests that areas are not yet developed and the map is referenced, but that information is not discernable from this map.

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,

Amy J Davis, Ph.D.

Associate Editor

PLOS Neglected Tropical Diseases

Sergio Recuenco

Deputy Editor

PLOS Neglected Tropical Diseases

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

The authors present an examination of risk factors for rabies in Ward 30, Murewa District, Zimbabwe. They identify risks associated with low awareness of rabies risks and levels of unvaccinated dogs as primary concerns. The paper provides a nice visual spatial analysis of dog bites, jackal presence, and rabies positive cases. There are issues with clarity in the methods that impede the interpretation of the results that needs to be addressed.

The methods section could use more clarity. The methods state that “one family member from each household that had a rabies case was selected for a proxy interview using a questionnaire”. Were these households that had human rabies cases? Elsewhere, the authors state that there were 4 rabies positive cases. So does this mean that only 4 households were surveyed? Where then does the 191 sample size come from. Please clarify. Some terms that were used were also confusing and inconsistently used (e.g., respondent, participant). In the results, the authors talk about 263 respondents. Where does this number come from? Only 191 were able to respond to the questionnaire, so the 263 individuals should not be called respondents but perhaps ‘enrollees’. How were they enrolled? What questions were asked on the questionnaire? A table of results from these questions would help.

Understanding how the people surveyed were selected is critical for readers to understand the implications of these results. The authors state that “dog owners were more likely to contract rabies as compared to non-dog owners”. This makes is sound like surveys were conducted on a cross section of people that include dog owners and non-dog owners and households that had rabies cases and those that did not. The sampling that was described does not make it clear who was surveyed and therefore it is not possible to have confidence in this statement. In the Limitation section of the discussion the authors mention that the 263 mentioned are dog bite cases. That would mean that the implications for these results can only be applied to people who have been bitten by a dog, this needs to be stated clearly. Also, in the author summary it is mentioned there are 938 dog bites, how does that relate to the 263 mentioned here?

Detailed comments:

Author summary:

• Include Zimbabwe in the description of the study area in the author summary.

• It is surprising you are able to get a significant result in a difference in proportions when you only have 4 positive cases. Please describe this more clearly.

Introduction:

• Rabies has no cure, but it is preventable with prophylaxis and this should be mentioned.

Methods:

• Change “It is fairly reliable” to “The rainfall is fairly reliable”

• Describe what the Likert Scale does and why it is used.

• Provide more detail on the sampling approaches, not just naming the methods. What is the population from which each sample is taken (who could be selected)? How many samples are taken? Be clear about the different target populations (all humans, humans who reported dog bites and went to the hospital, etc.)

Results:

• Provide the sample sizes along with the proportions for result.

• A table of the questionnaire results would be useful, similar to Table 1.

• Provide the numerators and denominators for the tests on the likelihood of contracting rabies.

Limitations:

• Not all dog bite cases could be reached and there was GPS uncertainty are in the same sentence suggesting these are related points, why?

• Why do you believe the conclusions can be applied to all of Murewa District? This is not clear.

Conclusions:

• Can you quantify the risks based on the spatial maps produced?

Figures:

• Figure 1: the boarder colors for Ward 30 and Murehwa Wards are indistinguishable, please correct this.

• Figure 1: in the text it suggests that areas are not yet developed and the map is referenced, but that information is not discernable from this map.

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: See attachment

Reviewer #2: Objectives of the study is clear, but population description could be improved to make clearer if only people in households with rabies cases, houses with bitten people or houses in general were interviewed.

Study design is appropriate but there is no mention of sample size or sampling methodology in the strata of Ward 30.

Statistical analysis in general are ok, however for dogs and jackals’ spatial analysis, the procedures should be described with more detail.

I understand this study was in an outbreak context, however, IRB permits should be mentioned, especially in children are included in the study population.

--------------------

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Yes

Reviewer #2: Analysis matches the plan, however, not all variables described at the beginning of results are mentioned or tested in the analysis section. Furthermore, definitions of the categories of some variables are not provided. Results also may need more order to improve readability. Dogs and jackal’s spatial analysis could be better explained and connected.

I would recommend presenting statistical analysis in a separate table. Descriptive table 1 and all figures requires minor editions. Figure are of enough quality, but they need bigger font sizes in the figure themselves and in the legends.

--------------------

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: Conclusions supported by data. More details required on limitations.

Reviewer #2: Conclusions are supported but I considered that there are more limitations that the one mentioned.

--------------------

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Minor revision

Reviewer #2: I recommend to be careful with spaces after dots and some words throughout the document and also format of numbers in English. An extra table to present analysis and bigger font sizes in figures and their legends would help the readers.

--------------------

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: See attachment

Reviewer #2: This study provides great information collected from an outbreak and contributes to rabies endemic countries fight against rabies. Relevance of the study even increases considering that in the study area there are multiple hosts that allows rabies virus circulation for health authorities to be vigilant.

--------------------

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Reviewer #1: Yes: Dr France Ncube

Reviewer #2: 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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Reproducibility:

To enhance the reproducibility of your results, PLOS recommends that you deposit 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. For instructions see https://journals.plos.org/plosntds/s/submission-guidelines#loc-methods

Attachments

Attachment

Submitted filename: Reviewer comments on manuscript PNTD - 20- 00750.docx

Attachment

Submitted filename: Review_16ago2020.docx

Dear Dr macherera,

Thank you very much for submitting your manuscript "An assessment of risk factors for contracting rabies in Ward 30, Murewa District, Zimbabwe" for consideration at PLOS Neglected Tropical Diseases. 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.

Be consistent and clear throughout when referring to ‘cases’, be specific as to if you mean dog bite cases, suspected rabies positive cases, or something else.

In the abstract, define “the High Density Cluster”.

In the study area section, what are “Growth Points” and why is this term capitalized?

In Table 2, be clearer in the table caption or headers as to what the number column represents (e.g., number of people who identified dogs as being a rabies reservoir).

In Table 2, how are there 150 people who owned dogs, then in the next question only 49 people responded if their dog was vaccinated or not. 146 people having no pets does not make sense with 150 saying they own dogs. Please clarify.

In Table 3, give an example of how the questions were worded. The columns of ‘rabies’ and ‘no rabies’ are unclear. Were all people in the study asked these questions?

The inclusion of Table 3 is helpful. The contingency tables within it are useful. However, with only 4 suspected positive rabies cases the sample sizes are not sufficient to conduct a chi-square tests, see McHugh 2013. Therefore, the chi-square analyses should be removed from the manuscript. However, I think the value of the information being shown is still there even without these tests. It is still reasonable to look at odds ratios or risk ratios, as these are descriptive statistics and not statistical tests that have sample size requirements.

McHugh, M. L. 2013. The chi-square test of independence. Biochemia medica 23:143-149.

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,

Amy J Davis, Ph.D.

Associate Editor

PLOS Neglected Tropical Diseases

Sergio Recuenco

Deputy Editor

PLOS Neglected Tropical Diseases

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

Be consistent and clear throughout when referring to ‘cases’, be specific as to if you mean dog bite cases, suspected rabies positive cases, or something else.

In the abstract, define “the High Density Cluster”.

In the study area section, what are “Growth Points” and why is this term capitalized?

In Table 2, be clearer in the table caption or headers as to what the number column represents (e.g., number of people who identified dogs as being a rabies reservoir).

In Table 2, how are there 150 people who owned dogs, then in the next question only 49 people responded if their dog was vaccinated or not. 146 people having no pets does not make sense with 150 saying they own dogs. Please clarify.

In Table 3, give an example of how the questions were worded. The columns of ‘rabies’ and ‘no rabies’ are unclear. Were all people in the study asked these questions?

The inclusion of Table 3 is helpful. The contingency tables within it are useful. However, with only 4 suspected positive rabies cases the sample sizes are not sufficient to conduct a chi-square tests, see McHugh 2013. Therefore, the chi-square analyses should be removed from the manuscript. However, I think the value of the information being shown is still there even without these tests. It is still reasonable to look at odds ratios or risk ratios, as these are descriptive statistics and not statistical tests that have sample size requirements.

McHugh, M. L. 2013. The chi-square test of independence. Biochemia medica 23:143-149.

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 see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, PLOS recommends that you deposit 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. For instructions see http://journals.plos.org/plosntds/s/submission-guidelines#loc-materials-and-methods

Dear Dr macherera,

We are pleased to inform you that your manuscript 'An assessment of risk factors for contracting rabies in Ward 30, Murewa District, Zimbabwe' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

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 Neglected Tropical Diseases.

Best regards,

Amy J Davis, Ph.D.

Associate Editor

PLOS Neglected Tropical Diseases

Sergio Recuenco

Deputy Editor

PLOS Neglected Tropical Diseases

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

In Table 2, provide more detail about what ‘percentage’ means similar to the changes made to the number of participants. Perhaps change to ‘percentage of positive responses’.