Experimental animal models and their use in understanding cysticercosis: A systematic review

Muloongo C. Sitali; Veronika Schmidt; Racheal Mwenda; Chummy S. Sikasunge; Kabemba E. Mwape; Martin C. Simuunza; Clarissa P. da Costa; Andrea S. Winkler; Isaac K. Phiri

doi:10.1371/journal.pone.0271232

Peer Review History

Original SubmissionJanuary 20, 2022
28 Apr 2022 Decision Letter - Adler R. Dillman, Editor PONE-D-22-01651Experimental animal models and their use in understanding cysticercosis: A systematic reviewPLOS ONE Dear Dr. Sitali, 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 submit your revised manuscript by Jun 12 2022 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 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. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf [Note: HTML markup is below. Please do not edit.] 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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: N/A ****** 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 ****** 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: No Reviewer #2: 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: The article entitled “Experimental animal models and their use in understanding cysticercosis: A systematic review” reported the results of a systemic review without meta-analysis on the question: What are the experimental animal models and their use in understanding cysticercosis. It was a good start that the authors mentioned NCC, which would be interesting for the relevant field if the question is to identify animal models for NCC. Unfortunately, the authors didn’t form an exclusive question, thus failing to write a scientifically sound review. The purpose of a systematic review is to draw conclusions based on the evidence to answer the well-defined and narrow question. On another note, it appears to me that the authors are often confused about different species of Taenia and the diseases that may cause in humans. Also the paper was not carefully written including the references provided. Thus, I suggest the authors reconstruct their questions to improve the review. Here are a few examples: Line65: “T. asiatica, T. solium and T. saginata share the same intermediate host.” This is scientifically wrong. But later in Line69, authors stated “……share the same definitive host” Line169, “infecting material used (eggs, …. cysticerci)” cysticerci should not be used for infection of the purpose. Line244- 248, is under the subtitle Taenia solium, but, as a matter of fact, reference#57 and 58 are about T. saginata. Thus, the authors finding is not valid. References: #8, the year is 2020, should remove 2007; #57, missing journal name Reviewer #2: It is an interesting article where a systematic bibliographical review is carried out, of the different animal models that have been developed to study the interaction between Taenia spp. and its intermediate host. It should be accepted with some major changes My biggest criticism is in the section on the strengths and weaknesses of the animal models, should be highlighted as a tool to understand the pathogenesis of neurocysticercosis. As the reproducibility of the animal model, the clinical picture and pathology that develops. As for example, the use of pigs to study NCC has the advantage of being the natural host, however it is difficult to have a good reproducibility of the experimental infection of the central nervous system, while the use of rats presents a high reproducibility, but has the disadvantage of not being the natural host. The use of immunosuppressed animals has many limitations to understand the host-parasite interaction. To have animal model with characteristic of clinical symptoms and pathology similar to human , it is help to study the disease. My minor criticism is in Table 1, the study by Alan Mejia Maza (2018) should be included, where they use the NCC rat model, in which they compare two routes of infection (intracranial and oral). On the other hand, in Table 1, in the published article by Verastegui et al. (2015), the number of cysts obtained in rats with NCC is reported. ****** 6. 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.] 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Review PONE-D-22-01651.pdf https://doi.org/10.1371/journal.pone.0271232.r001
Revision 1
15 Jun 2022 Author Response 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: The article entitled “Experimental animal models and their use in understanding cysticercosis: A systematic review” reported the results of a systemic review without meta-analysis on the question: What are the experimental animal models and their use in understanding cysticercosis. It was a good start that the authors mentioned NCC, which would be interesting for the relevant field if the question is to identify animal models for NCC. Unfortunately, the authors didn’t form an exclusive question, thus failing to write a scientifically sound review. The purpose of a systematic review is to draw conclusions based on the evidence to answer the well-defined and narrow question. On another note, it appears to me that the authors are often confused about different species of Taenia and the diseases that may cause in humans. Also the paper was not carefully written including the references provided. Thus, I suggest the authors reconstruct their questions to improve the review. Authors’ response: We note here the reviewer’s comments. As outlined by the reviewer, the main question we asked in this systematic review was: What are the experimental animal models and their use in understanding cysticercosis? Thus, we aimed at identifying animal models that have been used to understand cysticercosis (including neurocysticercosis), the infection caused by larvae of the tapeworm of the genus Taenia. Therefore, the systematic review investigated experimental animal models and their use in understanding both cysticercosis and NCC. We understand that NCC is what has made Taenia solium be of public health concern and that it would have been more specific had we only restricted the review to NCC. However, this systematic review was guided by the following research questions: 1) What animal experimental models (species of animals used and method of inducing disease) have been used to understand cysticercosis? 2) What are the strengths and weaknesses of these experimental models? 3) What sample sizes have been used? 4) Have the models contributed significantly to the understanding of cysticercosis? A meta-analysis was not done because characteristics of study populations (age, sex, breed or strain of animals) and interventions used in the selected animal models were too dissimilar to combine and therefore opted for a narrative synthesis of the findings. The following where the data items Name of species of animals used, number of species of animals used, Taenia species used, age of the animals used, number of the animals used, breed or strain of the animals used, sex, method of infection (oral, surgical or any other method employed in the study), infecting material used (eggs/proglottids/oncospheres) and the cysticerci recovery rate. Here are a few examples: Line65: “T. asiatica, T. solium and T. saginata share the same intermediate host.” This is scientifically wrong.But later in Line69, authors stated “……share the same definitive host” Authors’ response: The error of T. asiatica, T. solium and T. saginata sharing the same intermediate host has been corrected as observed by the reviewer (see Lines 68-70 of the revised manuscript). Revised sentence reads as:‘‘ The genus Taenia contains many species that infect humans and domestic animals. Of these, T. solium and T. asiatica eggs can infect pigs if they ingest eggs excreted from human tapeworm carriers whereas cattle serve as intermediate hosts for T. saginata ’’ Line169, “infecting material used (eggs, …. cysticerci)” cysticerci should not be used for infection of the purpose. Authors’ response: We agree with the reviewer that the studies which used initial stage cysticerci to induce NCC be removed. The two studies were thus removed from the review as suggested and cysticerci deleted from all sections were it appeared (see table 3 in revised manuscript). Descriptive statistics was redone to reanalyse the proportions because of this deletion and the concerned references were deleted from the reference list. Therefore, the reference list was re-numbered. Line244- 248, is under the subtitle Taenia solium, but, as a matter of fact, reference#57 and 58 are about T. saginata. Thus, the authors finding is not valid. Authors’ response: The reference 57 and 58 were misplaced during the formatting process. The two references have been deleted from lines 244-248 and now been placed under the correct subtitle of T. saginata. (See Lines 275- 278 of the revised manuscript). References: #8, the year is 2020, should remove 2007; #57, missing journal name Authors’ response: Reference #8 year has been corrected to 2020 (see lines 571-573 of the revised manuscript); Reference #57 missing journal name has been included (Canadian Journal of veterinary research), see line 762-764 of the revised manuscript. Reviewer #2: It is an interesting article where a systematic bibliographical review is carried out, of the different animal models that have been developed to study the interaction between Taenia spp. and its intermediate host. It should be accepted with some major changes My biggest criticism is in the section on the strengths and weaknesses of the animal models, should be highlighted as a tool to understand the pathogenesis of neurocysticercosis. As the reproducibility of the animal model, the clinical picture and pathology that develops. As for example, the use of pigs to study NCC has the advantage of being the natural host, however it is difficult to have a good reproducibility of the experimental infection of the central nervous system, while the use of rats presents a high reproducibility, but has the disadvantage of not being the natural host. The use of immunosuppressed animals has many limitations to understand the host-parasite interaction. To have animal model with characteristic of clinical symptoms and pathology similar to human, it is help to study the disease. Authors’ response: The section of weaknesses and strengths has been edited to incorporate the reviewers’ suggestions, (see lines 412-442 of the revised manuscript). My minor criticism is in Table 1, the study by Alan Mejia Maza (2018) should be included, where they use the NCC rat model, in which they compare two routes of infection (intracranial and oral). Authors’ response: The study by Alan M. Maza 2019 has been included in Table 1 and Table 5 and cited in the section for models inducing NCC (see line 323-326 in the revised version).The publication has also been added to the Reference list (see line number 607-609 in the revised version). Descriptive statistics was redone to reanalyse the proportions because of this addition and the reference list numbering edited (see edited reference list of the revised manuscript). On the other hand, in Table 1, in the published article by Verastegui et al. (2015), the number of cysts obtained in rats with NCC is reported. Authors’ response: The number of cysts obtained in the rats by Verastegui et al (2015), has been included in Table 1 (1-4 cysts per rat). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0271232.r002
27 Jun 2022 Decision Letter - Adler R. Dillman, Editor Experimental animal models and their use in understanding cysticercosis: A systematic review PONE-D-22-01651R1 Dear Dr. Sitali, 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, Adler R. Dillman, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Thank you for your point-by-point response to reviewer concerns. Reviewers' comments: https://doi.org/10.1371/journal.pone.0271232.r003
Formally Accepted
8 Jul 2022 Acceptance Letter - Adler R. Dillman, Editor PONE-D-22-01651R1 Experimental animal models and their use in understanding cysticercosis: A systematic review Dear Dr. Sitali: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Adler R. Dillman Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0271232.r004

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