Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific region

Ki Hyun Lee; Awachana Jiamsakul; Sasisopin Kiertiburanakul; Rohidas Borse; Vohith Khol; Evy Yunihastuti; Iskandar Azwa; I. Ketut Agus Somia; Romanee Chaiwarith; Thach Ngoc Pham; Suwimon Khusuwan; Cuong Duy Do; Nagalingeswaran Kumarasamy; Yasmin Gani; Rossana Ditangco; Oon Tek Ng; Sanjay Pujari; Man Po Lee; Anchalee Avihingsanon; Hsin-Pai Chen; Fujie Zhang; Junko Tanuma; Jeremy Ross; Jun Yong Choi

doi:10.1371/journal.pone.0306245

Peer Review History

Original SubmissionSeptember 26, 2023
17 Nov 2023 Decision Letter - Masoud Foroutan, Editor PONE-D-23-29849Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific regionPLOS ONE Dear Dr. Choi, 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. ============================== ACADEMIC EDITOR: Please submit your revised manuscript by Jan 01 2024 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. 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, Masoud Foroutan, Ph.D; Assistant Professor Academic Editor PLOS ONE Journal requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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 2. Note from Emily Chenette, Editor in Chief of PLOS ONE, and Iain Hrynaszkiewicz, Director of Open Research Solutions at PLOS: Did you know that depositing data in a repository is associated with up to a 25% citation advantage (https://doi.org/10.1371/journal.pone.0230416)? If you’ve not already done so, consider depositing your raw data in a repository to ensure your work is read, appreciated and cited by the largest possible audience. You’ll also earn an Accessible Data icon on your published paper if you deposit your data in any participating repository (https://plos.org/open-science/open-data/#accessible-data). 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: “The TREAT Asia HIV Observational Database is an initiative of TREAT Asia, a program of amfAR, The Foundation for AIDS Research, with support from the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Cancer Institute, the National Institute of Mental Health, National Institute on Drug Abuse, the National Heart, Lung, and Blood Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute of Diabetes and Digestive and Kidney Diseases, and Fogarty International Center, as part of the International Epidemiology Databases to Evaluate AIDS (IeDEA; U01AI069907). The Kirby Institute is funded by the Australian Government Department of Health and Aging and is affiliated with the Faculty of Medicine, UNSW, Sydney. The content of this publication is the sole responsibility of the authors and does not necessarily represent the official views of any of the governments or institutions mentioned above.” We note that you have provided funding information that is currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: “The authors received no specific funding for this work.” Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 4. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. "Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. [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: No Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: No ****** 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: No ****** 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 ****** 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: 1. Because patient geographical distribution and infection period difference are also critical for toxoplasmosis infection, the manuscript needs to analyze these data. 2. Because many patients have not taken ART and lack CD4 & viral load data, these data deficiencies could interfere with the risk factors assessment. 3. The IVDU etiology and HBV infection should be considered as counfounding factors and these factors are highly associated to socioeconomic status which could be the risk factor of toxoplasmosis infection. 4. The disease type of toxoplasmosis should be described in this manuscript. Reviewer #2: In this paper, Hyun Lee et all present a retrospective/prospective case control study to assess risk factors for toxoplasmosis in PLWH in the ASIA Pacific region. With the current use of ART worldwide, opportunistic infections associated to AIDS are infrequent and deserve less attention. Thus, the effort of the authors in conducting this study should be recognized. However, the study has some important limitations. -Despite in the Methods section they comment that “controls without VL or CD4 unavailable within the matched timeframe were not selected because they were considered key covariates”, 62.5% and 83.8% of controls were not tested for CD4 or VL respectively (compared with 23.4% and 70.3% in cases). Could the authors clarify this relevant aspect of their study? -In the abstract they say that 71% of toxo pts had CD4 < 200 , that means that 29% had >200, what is surprising as almost all PLWH with toxo have CD4 < 200 and mostly <100. But in fact, as 23.4% of these cases were not tested for CD4, only 14/206 (7.6%) with tested CD4 had CD4 >200, thus about 92% of tested pts, had CD4 <200. Thus, the sentence in the abstract should be modified, and it should be also mentioned in the Results and Discussion sections.. -It is well known that cotrimoxazole protects against toxo in immunosuppressed PLWH. The fact that in this study it seems that no differences in cotrimoxazole use was found between cases and controls, suggests that adherence to prophylaxis might be an issue in this population. Authors should comment this aspect in the Discussion section. -In the multivariate analysis, variables have been adjusted for CD4 count? It may be that PLWH being IDU or HBV+ had lower CD4 count (as probably occurred with pts not receiving ART) and if adjusting results may vary. -I would say immune reconstitution instead of immune reconstruction ****** 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: Yes: Tun-Chieh Chen 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. https://doi.org/10.1371/journal.pone.0306245.r001
Revision 1
18 Dec 2023 Author Response Response to Reviewers’ comments Reviewer #1 1. Because patient geographical distribution and infection period difference are also critical for toxoplasmosis infection, the manuscript needs to analyze these data. Author’s response #1 We agree with the reviewer that geographical distribution and infection period differences are important in toxoplasmosis infection. Like the reviewer, we are aware of the importance of these two factors, and therefore have designed our study to analyse the site and time effect by matching by site and time period of toxoplasmosis infection so that cases and controls were compared within the same site and in a similar time frame. Matching by site and time period removed the known confounding effects of the two risk factors and allowed for comparison of cases and controls without the influence of these factors. Although matching does not output the effect sizes in the regression table for site and time period of infection (unlike the regular unmatched analyses), the regression model had “analysed” or taken into account these two factors by way of matching through the use of conditional logistic regression “conditioned on matched pairs”. Therefore, site and time were analysed by conditional logistic regression through matching. Unfortunately, we are not able to provide the number of cases by individual site to maintain confidentiality for the network, however we have listed the countries that were included, and have also further clarified the matching in our methods. “To account for differences in site and time period, prospective cases were matched to prospective controls, while retrospective cases were matched to retrospective controls from the same site and time period.” “Factors associated with toxoplasmosis were analyzed using conditional logistic regression to account for matching.” “A total of 269/9576 (2.8%) PLWH were diagnosed with toxoplasmosis from a subset of 19 TAHOD sites from Cambodia, China, Hong Kong SAR, India, Indonesia, Japan, South Korea, Malaysia, the Philippines, Singapore Taiwan, Thailand, and Vietnam, and were matched to 538 controls.” 2. Because many patients have not taken ART and lack CD4 & viral load data, these data deficiencies could interfere with the risk factors assessment. Author’s response #2 Thank you for your comment. As you said, it is disappointing that many of the subjects did not have CD4 or VL values. But while revising the paper this time, we excluded people without CD4 values, and found the vast majority (93.2%, instead of the previous 71%) were advanced HIV with a CD4 count of less than 200. Like your good opinion, most of the people who actually participated in the study lacked of data, but I think these results will be valuable. 3. The IVDU etiology and HBV infection should be considered as counfounding factors and these factors are highly associated to socioeconomic status which could be the risk factor of toxoplasmosis infection. Author’s response #3 We would like to thank the reviewer for this suggestion. Injecting drug users (IDU) are normally known to be associated with hepatitis C co-infection, rather than hepatitis B. From our analysis, hepatitis C was not significant in the multivariate analysis. We have also tested for collinearity between mode of HIV exposure and HBV and found that there was no collinearity between the two variables (mean VIF=1.00). 4. The disease type of toxoplasmosis should be described in this manuscript. Author’s response #4 We have updated the Materials and Methods section as follows; (page 5, line 133) Definition of toxoplasmosis We defined meaningful toxoplasma infection as definitive and presumptive toxoplasmosis, and definitive toxoplasmosis means patients who confirmed toxoplasmosis by microscopy (histology or cytology). Presumptive toxoplasmosis means patients whom suspicious toxoplasmosis of brain satisfying all three of the following. (i) Recent onset of a focal neurological abnormality consistent with intracranial disease or a reduced level of consciousness; (ii) Evidence by brain imaging (computed tomography or nuclear magnetic resonance) of a lesion having a mass effect or the radiographical appearance of which is enhanced by injection of contrast medium or consistent symptomatic presentation; (iii) Serum antibody to toxoplasmosis or successful response to therapy for toxoplasmosis. Reviewer #2 1. Despite in the Methods section they comment that “controls without VL or CD4 unavailable within the matched timeframe were not selected because they were considered key covariates”, 62.5% and 83.8% of controls were not tested for CD4 or VL respectively (compared with 23.4% and 70.3% in cases). Could the authors clarify this relevant aspect of their study? Author’s response #1 We apologize if this was unclear. We excluded controls without both CD4 AND VL, but allowed controls to be included if they had either a CD4 or a VL available, in order to maximize our sample size. We have clarified this in our methods: “The controls were randomly selected and were required to have at least a CD4 or VL available within the matched timeframe as they were considered key covariates in the study. Controls without both viral load and CD4 available were not selected.” 2. In the abstract they say that 71% of toxo pts had CD4 < 200 , that means that 29% had >200, what is surprising as almost all PLWH with toxo have CD4 < 200 and mostly <100. But in fact, as 23.4% of these cases were not tested for CD4, only 14/206 (7.6%) with tested CD4 had CD4 >200, thus about 92% of tested pts, had CD4 <200. Thus, the sentence in the abstract should be modified, and it should be also mentioned in the Results and Discussion sections. Author’s response #2 We would like to thank the reviewer for this suggestion. As you mentioned, I agreed to calculate the proportion of people whose CD4 values were measured, so we revised the abstract and result sections of the main text as follows, and additionally mentioned this in the discussion, as follows; (page 12, line 223) “Excluding 63 out of 269 people without CD4 values, 192 (93.2%) had CD4 ≤200 cells/µL and 162 (78.6%) had CD4 ≤100 cells/µL.” “Furthermore, CD4 value was lower in the toxoplasmosis group compared to the control. Excluding cases without CD4 test results, the majority had advanced HIV, with 93.2% having CD4 ≤200 cells/µL. Assuming the same seroprevalence as site matching was performed, low CD4 count is a prominent risk factor for overt toxoplasma infection. Therefore, immune reconstitution through early diagnosis and use of ART remains an important task.” 3. It is well known that cotrimoxazole protects against toxo in immunosuppressed PLWH. The fact that in this study it seems that no differences in cotrimoxazole use was found between cases and controls, suggests that adherence to prophylaxis might be an issue in this population. Authors should comment this aspect in the Discussion section. Author’s response #3 Thank you for your comments. In fact, although the CD4 count was lower in the case group compared to the control, it was not significantly higher in those who took cotrimoxazole for prophylactic purposes. In fact, the overall cotrimoxazole administration before and after diagnosis was high in the case group. But there was no difference when analyzed with preventive purposes and it means that there may have been a problem with adherence, and this is an important result, so details about this have been added in the discussion section as follows; (page 12, line 243) “Also, prophylactic cotrimoxazole administration did not contribute to lowering the risk of toxoplasmosis. When we first analyzed cotrimoxazole administration before and after the diagnosis of toxoplasmosis, cotrimoxazole administration was significantly high in the case group. But when limited to prophylactic use, there was no difference from the control group. This suggests that there might be a problem with medication compliance, but our study cannot prove it.” 4. In the multivariate analysis, variables have been adjusted for CD4 count? It may be that PLWH being IDU or HBV+ had lower CD4 count (as probably occurred with pts not receiving ART) and if adjusting results may vary. Author’s response #4 The multivariate results were adjusted for CD4. 5. I would say immune reconstitution instead of immune reconstruction Author’s response #5 As suggested, we have modified the pointed words in Conclusion section. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0306245.r002
2 May 2024 Decision Letter - Masoud Foroutan, Editor PONE-D-23-29849R1Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific regionPLOS ONE Dear Dr. Choi, 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 16 2024 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. 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, Masoud Foroutan, Ph.D.; Assistant Professor Academic Editor PLOS ONE Journal Requirements: 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. [Note: HTML markup is below. Please do not edit.] 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 #3: (No Response) ******** 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 #3: (No Response) ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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 #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 #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: 1. Thanks for your responses to the questions, and then it makes the information from the manuscript more clear. However, the case distribution and diagnosis time period are also interesting for the readers. Although these factors were matched for the analysis. I recommend that you can provide information about the case's geographical and time period distribution in a small table or in the supplement material. It is much better for the reference of our readers. Reviewer #3: Dear Author, please: Use keywords based on MESH. Mention the prevalence and risk factors in the title. Many sources are old. Please use new sources from the last 5 years ****** 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: Yes: Tun-Chieh Chen Reviewer #3: 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. https://doi.org/10.1371/journal.pone.0306245.r003
Revision 2
10 Jun 2024 Author Response Reviewer #1 1. Thanks for your responses to the questions, and then it makes the information from the manuscript more clear. However, the case distribution and diagnosis time period are also interesting for the readers. Although these factors were matched for the analysis. I recommend that you can provide information about the case's geographical and time period distribution in a small table or in the supplement material. It is much better for the reference of our readers. Author’s response #1 We added the information about [Year of toxoplasmosis diagnosis] as supplementary 1 to the first paragraph of the “Demographics and clinical characteristics of the study population” of Result section. Reviewer #3 1. Dear Author, please: Use keywords based on MESH. Mention the prevalence and risk factors in the title. Many sources are old. Please use new sources from the last 5 years Author’s response #1 We modified the keywords to be MESH-based, and since prevalence cannot be inferred from our study, only risk factors are mentioned in the title. Lastly, we made some revisions referenced in this study. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0306245.r004
14 Jun 2024 Decision Letter - Masoud Foroutan, Editor Risk factors for toxoplasmosis in people living with HIV in the Asia-Pacific region PONE-D-23-29849R2 Dear Dr. Choi, 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. If you have any questions relating to publication charges, 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, Masoud Foroutan, Ph.D; Assistant Professor 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 #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 #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? 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 #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 #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 #3: (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 #3: No ******** https://doi.org/10.1371/journal.pone.0306245.r005
Formally Accepted
21 Jun 2024 Acceptance Letter - Masoud Foroutan, Editor PONE-D-23-29849R2 PLOS ONE Dear Dr. Choi, 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 If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks 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. 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 Dr. Masoud Foroutan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0306245.r006

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .