-->PNTD-D-25-00379

Elucidating the causal mechanisms of Taenia solium transmission in humans, pigs and the environment: a global systematic review.

PLOS Neglected Tropical Diseases

Dear Dr. Carabin,

Thank you for submitting your manuscript to PLOS Neglected Tropical Diseases. After careful consideration, we feel that it has merit but does not fully meet PLOS Neglected Tropical Diseases'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 submit your revised manuscript within 60 days Nov 10 2025 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 plosntds@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pntd/ 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 editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to any formatting updates and technical items listed in the 'Journal Requirements' section below.

* 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, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Benn Sartorius, PhD

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

Journal Requirements:

1) Please upload all main figures as separate Figure files in .tif or .eps format. For more information about how to convert and format your figure files please see our guidelines:

https://journals.plos.org/plosntds/s/figures

2) We have noticed that you have uploaded Supporting Information files, but you have not included a list of legends. Please add a full list of legends for your Supporting Information files after the references list.

3) Some material included in your submission may be copyrighted. According to PLOSu2019s copyright policy, authors who use figures or other material (e.g., graphics, clipart, maps) from another author or copyright holder must demonstrate or obtain permission to publish this material under the Creative Commons Attribution 4.0 International (CC BY 4.0) License used by PLOS journals. Please closely review the details of PLOSu2019s copyright requirements here: PLOS Licenses and Copyright. If you need to request permissions from a copyright holder, you may use PLOS's Copyright Content Permission form.

Please respond directly to this email and provide any known details concerning your material's license terms and permissions required for reuse, even if you have not yet obtained copyright permissions or are unsure of your material's copyright compatibility. Once you have responded and addressed all other outstanding technical requirements, you may resubmit your manuscript within Editorial Manager.

Potential Copyright Issues:

i) Figure 1. Please confirm whether you drew the images / clip-art within the figure panels by hand. If you did not draw the images, please provide (a) a link to the source of the images or icons and their license / terms of use; or (b) written permission from the copyright holder to publish the images or icons under our CC BY 4.0 license. Alternatively, you may replace the images with open source alternatives. See these open source resources you may use to replace images / clip-art:

- https://commons.wikimedia.org

- https://openclipart.org/.

4) Please amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

1) State what role the funders took in the study. If the funders had no role in your study, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

2) If any authors received a salary from any of your funders, please state which authors and which funders.

5) Please ensure that the PRISMA flowchart describing the included/excluded literature is uploaded as Figure 1. Information about the PRISMA guidance, and blank flowcharts and checklists, can be found here: http://www.prisma-statement.org/.

6) As required by our policy on Data Availability, please ensure your manuscript or supplementary information includes the following:

- A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.

- For every excluded study, the table should list the reason(s) for exclusion.

- If any of the included studies are unpublished, include a link (URL) to the primary source or detailed information about how the content can be accessed.

- A table of all data extracted from the primary research sources for the systematic review and/or meta-analysis. The table must include the following information for each study:

- Name of data extractors and date of data extraction

- Confirmation that the study was eligible to be included in the review.

- All data extracted from each study for the reported systematic review and/or meta-analysis that would be needed to replicate your analyses.

- If data or supporting information were obtained from another source (e.g. correspondence with the author of the original research article), please provide the source of data and dates on which the data/information were obtained by your research group.

- If applicable for your analysis, a table showing the completed risk of bias and quality/certainty assessments for each study or outcome.  Please ensure this is provided for each domain or parameter assessed. For example, if you used the Cochrane risk-of-bias tool for randomized trials, provide answers to each of the signalling questions for each study. If you used GRADE to assess certainty of evidence, provide judgements about each of the quality of evidence factor. This should be provided for each outcome.

- An explanation of how missing data were handled.

This information can be included in the main text, supplementary information, or relevant data repository.

Note: If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise.

Comments to the Authors:

Please note that one review is uploaded as an attachment.

Reviewers' Comments:

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 comments on the attached reviewer comments document

Reviewer #2: -Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

The present study is a systematic review, and the objective was to identify the risk factors of T. solium infection in humans, pigs, and the environment. The authors set a goal and sought to determine whether the risk factors for acquiring human cysticercosis, porcine cysticercosis, or Taenia solium taeniasis have been adequately studied. They also sought to determine whether any of the risk factors studied for one form of the disease could be applied to another. Whether there was a connection between the objective and the hypothesis for this type of review.

Is the study design appropriate to address the stated objectives?

Indeed, the study design was appropriate for meeting the objectives of this systematic review. The authors conducted multiple literature searches and followed the PRISMA guidelines for data analysis and the presentation of results.

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

Yes, the population was clearly described. The authors mention that they conducted a bibliographic review of articles on the epidemiology of Taenia solium up to May 2020. They consulted the PubMed, Web of Science, and CABAbstracts data bases without filters and in different languages. In the results section, they report that they found 2,113 studies that met the search terms, that 470 met the criteria for full reviews, and that only 158 met all the inclusion criteria.

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

The sample size is sufficient. Systematic reviews have been conducted with fewer than 50 articles reviewed, and they analyzed 158 articles

Were correct statistical analysis used to support conclusions?

This is a systematic review that does not require rigorous statistical analysis, so this section is appropriate. The information found in the 158 publications was not reported homogeneously, so the authors extracted the necessary information and found 833 associations, some stronger and others weaker, results that they qualitatively describe.

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

There are no concerns about compliance with ethical or regulatory requirements. The procedures followed are clearly explained. This is a systematic review

**********

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: see attached document

Reviewer #2: Does the analysis presented match the analysis plan?

The analysis presented is consistent with the objective of the study

-Are the results clearly and completely presented?

Yes, the results are clearly presented

Are the figures (Tables, Images) of sufficient quality for clarity? Figures are not of enough quality for clarity

Figure 1: The life cycle of Taenia solium.

The life cycle of Taenia solium must be modified. Several freely licensed images can be used without any problem. But if authors are going to make their own drawing of the parasite's life cycle, they can use different platforms like BioRender, Canva, or other systems to make images more similar to the real thing and make it clear what they're pointing out. The cysticerci, eggs, Taenia, and the pig don't look alike at all.

Figure 2: A PRISMA flowchart detailing their literature review.

Figure 2 needs more definition; the writing in the white and blue boxes is barely legible. Although it's a program-generated image, it could be improved, as it's not readable at normal size, let alone when enlarged.

**********

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: (No Response)

Reviewer #2: -Are the conclusions supported by the data presented?

Yes, conclusions are supported by the data presented in the revision

-Are the limitations of analysis clearly described?

The authors describe a limitation in their study in lines 351-355. The explanation is brief, and apparently, they were able to solve it adequately, on line 354

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

Yes, the authors discuss the results of the literature review. They identified new risk factors and confirmed those previously defined for several decades. Throughout the text, they discuss the various risk factors associated with contracting taeniasis, human cysticercosis, and porcine cysticercosis.

-Is public health relevance addressed?

Yes, reference was made to taeniasis, human cysticercosis, and porcine cysticercosis. The problems each disease causes in the host and its impact on the global population. The authors also investigated and defined risk factors for developing the disease in both hosts.

**********

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: Better take way messages should be crafted.

Reviewer #2: Authors should note the publication by Ngwili N, et al. (2021, A qualitative assessment of the context and enabling environment for the control of Taenia solium infections in endemic settings. PLoS Negl Trop Dis 15(6): e0009470. https://doi.org/10.1371/journal.pntd.0009470) in presenting their review as “the first to consider all hosts and diseases caused by Taenia solium. See abstract and general comments.

**********

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: (No Response)

Reviewer #2: The authors conducted a systematic review of the Taenia solium parasite, using the terms “Taenia solium” AND “epidemiology”) They looked for associations between risk factors for taeniasis, human cysticercosis, and porcine cysticercosis. They found a high number of associations, although most of them were weak. Despite this, they found important findings, as reported in lines 331-334.

However, the authors mention that there are no systematic reviews of TSCT that consider causes of human cysticercosis, human taeniasis, and porcine cysticercosis. Recent reviews summarize the prevalence and geographic distribution of disease in one species, or only consider causation in one species and one region (lines 72-75).

However, this justification is not entirely correct, as there are some systematic reviews that address this parasitic disease, taking into account human and porcine taeniasis and cysticercosis. An example of this is the publication by Ngwili N et al. (2021) A qualitative assessment of the context and enabling environment for the control of Taenia solium infections in endemic settings. PLoS Negl Trop Dis 15(6): e0009470. https://doi.org/10.1371/journal.pntd.0009470

In this systematic review, the authors considered the two hosts and three diseases (taeniasis, human cysticercosis, and porcine cysticercosis), and the literature search was global, from 1950 to 2019. Although they do not publicize their work with a One Health approach, Ngwili et al. took into account the same considerations as the present review.

I believe that this previous work should be taken into account since the present manuscript (Elias Jackson et al.) is not the first systematic review to focus on the three diseases and two hosts involved in the life cycle of Taenia solium.

**********

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

[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.]

Figure resubmission:

-->While revising your submission, we strongly recommend that you use PLOS’s NAAS tool (https://ngplosjournals.pagemajik.ai/artanalysis) to test your figure files. NAAS can convert your figure files to the TIFF file type and meet basic requirements (such as print size, resolution), or provide you with a report on issues that do not meet our requirements and that NAAS cannot fix.-->-->

After uploading your figures to PLOS’s NAAS tool - https://ngplosjournals.pagemajik.ai/artanalysis, NAAS will process the files provided and display the results in the "Uploaded Files" section of the page as the processing is complete. If the uploaded figures meet our requirements (or NAAS is able to fix the files to meet our requirements), the figure will be marked as "fixed" above. If NAAS is unable to fix the files, a red "failed" label will appear above. When NAAS has confirmed that the figure files meet our requirements, please download the file via the download option, and include these NAAS processed figure files when submitting your revised manuscript.-->

Reproducibility:

To enhance the reproducibility of your results, we recommend that authors of applicable studies 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. 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: Reviewer comments_ PNTD-D-25-00379.docx

Dear Dr. Jackson,

We are pleased to inform you that your manuscript 'Elucidating the causal mechanisms of Taenia solium transmission in humans, pigs and the environment: a global systematic review.' 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,

Joseph Raymond Zunt, PhD

Academic Editor

PLOS Neglected Tropical Diseases

Max Thomas Eyre, PhD

Section Editor

PLOS Neglected Tropical Diseases

Benn Sartorius

%CORR_ED_EDITOR_ROLE%

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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

p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; line-height: 16.0px; font: 14.0px Arial; color: #323333; -webkit-text-stroke: #323333}span.s1 {font-kerning: none

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 #2: Since the first version of the manuscript, authors set a goal and sought to determine whether the risk factors for acquiring human cysticercosis, porcine cysticercosis, or Taenia solium taeniasis have been adequately studied. They also sought to determine whether any of the risk factors studied for one form of the disease could be applied to another. Whether there was a connection between the objective and the hypothesis for this type of review.

Indeed, the study design was appropriate for meeting the objectives of this systematic review.

Yes, the population was clearly described. The authors mention that they conducted a bibliographic review of articles on the epidemiology of Taenia solium up to May 2020. They consulted the PubMed, Web of Science, and CABAbstracts data bases without filters and in different languages. In the results section, they report that they found 2,113 studies that met the search terms, that 470 met the criteria for full reviews, and that only 158 met all the inclusion criteria.

The sample size is sufficient. Systematic reviews have been conducted with fewer than 50 articles reviewed, and they analyzed 159 articles

This is a systematic review that does not require rigorous statistical analysis, so this section is appropriate. The information found in the 159 publications was not reported homogeneously, so the authors extracted the necessary information and found 833 associations, some stronger and others weaker, results that they qualitatively describe.

There are no concerns about compliance with ethical or regulatory requirements. The procedures followed are clearly explained. This is a systematic review

**********

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 #2: Does the analysis presented match the analysis plan?

The analysis presented is consistent with the objective of the study

-Are the results clearly and completely presented?

Yes, the results are clearly presented

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

In this second version, the authors made notable changes to the figures, especially Figures 1 and 2. The life cycle of Taenia solium is now clearer and more understandable. Figure 2 is more legible.

**********

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 #2: Are the conclusions supported by the data presented?

Yes, conclusions are supported by the data presented in the revision

-Are the limitations of analysis clearly described?

In this second version, the authors described in more detail the limitations they encountered in their bibliographic research.

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

Yes, the authors discuss the results of the literature review. They identified new risk factors and confirmed those previously defined for several decades. Throughout the text, they discuss the various risk factors associated with contracting taeniasis, human cysticercosis, and porcine cysticercosis.

-Is public health relevance addressed?

Yes, reference was made to taeniasis, human cysticercosis, and porcine cysticercosis. The problems each disease causes in the host and its impact on the global population. The authors also investigated and defined risk factors for developing the disease in both hosts.

**********

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 #2: The authors took into account observations on other publications related to the topic, that were mentioned in the previous review

**********

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 #2: This second version of the manuscript reads much better, and the authors took into account the observations of the different reviewers to enrich the manuscript, discuss it more thoroughly, and emphasize the most outstanding results.

**********

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 #2: No