First detection of Crimean Congo Hemorrhagic Fever antibodies in cattle and wildlife of southern continental France: Investigation of explanatory factors

Célia Bernard; Andrea Apolloni; Vladimir Grosbois; Armelle Peyraud; Phonsiri Saengram; Ferran Jori; Eva Faure; Nicolas Keck; Raphaëlle Pin; Olivier Ferraris; Loic Comtet; Benoit Combes; Matthieu Bastien; Valentin Chauvin; Laure Guerrini; Philippe Holzmuller; Laurence Vial

doi:10.1371/journal.pone.0331875

Peer Review History

Original SubmissionMay 19, 2025
19 May 2025 Author Response Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. https://doi.org/10.1371/journal.pone.0331875.r001
4 Jun 2025 Decision Letter - Bekir Oguz, Editor Dear Dr. Bernard, 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 Jul 19 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 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. 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'. 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If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. Additional Editor Comments (if provided): [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? Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? -->?> Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available??> The PLOS Data policy Reviewer #1: Yes Reviewer #2: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English??> Reviewer #1: Yes Reviewer #2: No ****** Reviewer #1: Crimean-Congo Hemorrhagic Fever Virus (CCHFV) infections are widely distributed across Africa, Eastern Europe, the Middle East, and Asia, largely mirroring the natural habitats of its principal vector, Hyalomma spp. ticks. Rural populations, particularly those engaged in livestock farming, are at increased risk of infection through tick bites or direct contact with viremic animals. In recent years, CCHFV has also emerged as a growing public health concern in Europe. The detection of the virus in ticks, seropositivity in vertebrate hosts, and reported clinical cases in more than ten European countries underscore the virus’s expanding geographic footprint. Notably, new emergence and local transmission have been documented in countries such as Bulgaria, Greece, Spain, and Portugal, highlighting the urgent need for region-specific surveillance and control strategies.Recent studies conducted in Corsica and Spain further demonstrate the expanding range of CCHFV. In France, serological findings suggest that the virus may be present in various tick species, domestic animals, and potentially in humans. These findings imply that the virus, once believed to be confined to specific geographic regions, could continue spreading northward within Europe. In this context, the current study contributes valuable insights by emphasizing the importance of updated epidemiological data. Wildlife surveillance, when utilized as an early warning system, can help trace the virus’s circulation before clinical cases appear. In the near future, comprehensive studies integrating both serological and virological methods will be essential to accurately map the true distribution and transmission dynamics of CCHFV across the continent. Reviewer #2: The paper, First detection of Crimean Congo Hemorrhagic Fever antibodies in cattle and wildlife of southern continental France: investigation of explicative factors documents the detection of CCHF in the French mediterranean region in 2008 to 2022 using serological tests. It also reports animal-level and ecological factors that are associated with exposure in livestock and wildlife. The main comments I have are: 1. Statistical modelling – given that many variables were offered for statistical modelling using hierarchical multivariable regression model, a formal approach for identifying orthogonal variables for inclusion must be used to improve the efficiency of the analysis. This will include using causal web models, directed acyclic curves etc. I recommend that this approach is included in the analysis. 2. The language should be reviewed to improve its presentation in consistent English language Other comments: Line 43: CCHF has significant public health impacts in regions where the disease is endemic. So even if it does not expand its geographical range, the disease still has high public health significance. I suggest rewording this statement to reflect that fact Line 69 and other places, I suggest replacing my study with our study Line 89 and 104: say humans are infected not contaminated Line 91: Is WHO a reference? Line 143/148: delete detecting in the title since it is already implied in the sentence Line 176: Start the line with text (45). Same as line 209 Line 529: use spatial coverage Line 530. Put a full stop after level Line 587: Use a different work instead of demonizing Line 651: this should be multivariable model not multivariate model ****** 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 Attachments Attachment Submitted filename: Reviewed manuscript PONE-D-25-20397.pdf https://doi.org/10.1371/journal.pone.0331875.r002
Revision 1
30 Jul 2025 Author Response Response to Reviewers – Manuscript PONE-D-25-20397 We thank the Academic Editor and the reviewers for their constructive and insightful comments. We have carefully revised the manuscript to address all points raised. Below, we provide detailed responses to each comment. All changes have been made in the revised manuscript and highlighted using tracked changes. Reviewer #1 We thank the reviewer for their thoughtful overview and contextual framing of the current epidemiological situation of Crimean-Congo Hemorrhagic Fever Virus (CCHFV) in Europe. We fully agree that future integrated studies combining serological and virological approaches will be key to better mapping and understanding the dynamics of CCHFV transmission in Europe. All the changes suggested in the document have been taken into account. Comment : As stated in the discussion section, lines : 367 -368''other tick species may also be effective.'' Therefore, in the introduction section, brief information can be given about tick diversity in regions where the disease has been detected, especially in Spain, and about possible vectors other than hyalomma spp. in France. It will be more informative for the readers. Response: We would like to thank the reviewer for his comment. We decided to add a sentence to be more informative. “Other tick species such as Rhipicephalus bursa and Dermacentor marginatus have occasionally been found carrying CCHFV in southwestern Europe, but their role in transmission remains uncertain. In France, despite the presence of multiple tick genera, only H. marginatum has been found positive to date”. Reviewer #2 We thank the reviewer for their constructive feedback and suggestions to improve the manuscript. Below, we provide point-by-point responses to each comment. Comment: 1. Statistical modelling – given that many variables were offered for statistical modelling using hierarchical multivariable regression model, a formal approach for identifying orthogonal variables for inclusion must be used to improve the efficiency of the analysis. This will include using causal web models, directed acyclic curves etc. Response: Thank you for this suggestion. In response, we constructed a directed acyclic graph (DAG) to represent the hypothesized causal relationships between the exposure, explanatory variables, and CCHFV seropositivity in both livestock and wildlife. This DAG, based on literature and expert knowledge, was used to identify potential confounding structures and guide the variable selection process in the hierarchical multivariable models. The DAG is now provided as Supplementary Figure S1. In parallel, we performed correlation tests on the variables retained in our final models (after the dredge step and selection of the best-fitting model). These tests showed that the variables were not significantly correlated. In addition, mean comparison tests indicated that the group means were significantly different. Comment: 2. The language should be reviewed to improve its presentation in consistent English. Response: The entire manuscript has been thoroughly reviewed by a native English speaker and edited to ensure consistency, clarity, and correct grammar throughout. Comment: Line 43: CCHF has significant public health impacts in regions where the disease is endemic. So even if it does not expand its geographical range, the disease still has high public health significance. I suggest rewording this statement to reflect that fact. Response: We agree and have reworded this sentence to reflect that CCHF remains a significant public health concern regardless of its geographic expansion. Comment: Line 69 and other places: replace "my study" with "our study" Response: All instances of “my study” have been replaced with “our study” for consistency and appropriate authorship tone. Comment: Line 89 and 104: say "humans are infected" not "contaminated" Response: We have replaced “contaminated” with “infected” in both instances (lines 89 and 104), which is the accurate term for human exposure to CCHFV. Comment: Line 91: Is WHO a reference? Response: We have changed the reference in the manuscript. Comment: Line 143/148: delete "detecting" in the title since it is already implied in the sentence Response: The term “detecting” has been removed from the respective sentences for conciseness and clarity (lines 143 and 148). Comment: Line 176 and 209: Start the line with text instead of a number (e.g., "(45)") Response: We have revised the formatting to ensure that each sentence starts with text before the reference, as suggested. Comment: Line 529: use "spatial coverage" Response: We have replaced the original term with “spatial coverage” in line 529. Comment: Line 530: put a full stop after "level" Response: A full stop has been added after “level” (line 530). Comment: Line 587: use a different word instead of "demonizing" Response: We have replaced “demonizing” with a more appropriate term (“stigmatizing”) to improve tone and clarity (line 587). Comment: Line 651: use "multivariable model" instead of "multivariate" Response: We have corrected the term to “multivariable model” in line 651 to accurately reflect the modelling approach. Journal Requirements 1. Formatting Response: The manuscript has been updated to match the PLOS ONE style and formatting requirements. File names have also been adjusted accordingly. 2. LaTeX template Response: We acknowledge the request to format our manuscript using the PLOS LaTeX template. However, due to technical constraints, we were unfortunately not able to implement this formatting for the current version of the revised submission. We hope the current formatting remains acceptable for evaluation purposes, and we remain available to reformat the manuscript using the template if required at a later stage. 3. Financial disclosure update Response: We have added the required sentence: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.” This has been added to both the cover letter and the manuscript. 4. Figures 1–3 – Copyright compliance Response: The maps used in Figures 1–3 were generated from publicly available data sources (e.g., Natural Earth, BD Forêt, CORINE Land Cover). We confirm that no copyrighted images (e.g., Google Maps) were used. All sources have been cited in the figure legends, and figures comply with the CC BY 4.0 license. Alternatively (if needed), reworked figures are provided to ensure compliance. 5. Reference check Response: We have reviewed all references and confirm that none are retracted. The reference list has been updated to ensure completeness and accuracy. Attachments Attachment Submitted filename: Response to Reviewers.pdf https://doi.org/10.1371/journal.pone.0331875.r003
4 Aug 2025 Decision Letter - Bekir Oguz, Editor Dear Dr. Bernard, 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. 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 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, Bekir Oguz Academic Editor PLOS ONE Journal Requirements: 1. 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. 2. 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. Additional Editor Comments: Dear author, your article requires revision. Please make the required corrections and re-upload. Best regards. [Note: HTML markup is below. Please do not edit.] [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. https://doi.org/10.1371/journal.pone.0331875.r004
Revision 2
19 Aug 2025 Author Response We have carefully revised the manuscript according to the journal’s requirements. Specifically: We reviewed the reference list to ensure completeness and accuracy. No retracted references were identified. We revised the manuscript according to the PLOS ONE Word template. We uploaded the revised figures to the PACE tool to ensure they meet formatting standards. Attachments Attachment Submitted filename: Response_to_Reviewers_auresp_2.pdf https://doi.org/10.1371/journal.pone.0331875.r005
22 Aug 2025 Decision Letter - Bekir Oguz, Editor First detection of Crimean Congo Hemorrhagic Fever antibodies in cattle and wildlife of southern continental France: investigation of explanatory factors PONE-D-25-20397R2 Dear Dr. Bernard, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. For questions related to billing, please contact billing support . 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, Bekir Oguz Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Author, The article has been edited in accordance with the feedback provided by the reviewers. I would say that it is acceptable as it is. Best regards Reviewers' comments: https://doi.org/10.1371/journal.pone.0331875.r006
Formally Accepted
Acceptance Letter - Bekir Oguz, Editor PONE-D-25-20397R2 PLOS ONE Dear Dr. Bernard, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps. Lastly, 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. You will receive an invoice from PLOS for your publication fee after your manuscript has reached the completed accept phase. If you receive an email requesting payment before acceptance or for any other service, this may be a phishing scheme. Learn how to identify phishing emails and protect your accounts at https://explore.plos.org/phishing. If we can help with anything else, please email us at customercare@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 Professor Bekir Oguz Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0331875.r007

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