Imported severe malaria and risk factors for intensive care: A single-centre retrospective analysis

Alessandra D’Abramo; Luciana Lepore; Marco Iannetta; Saba Gebremeskel Tekle; Angela Corpolongo; Laura Scorzolini; Nazario Bevilacqua; Andrea Mariano; Maria Letizia Giancola; Antonella Vulcano; Micaela Maritti; Alessandro Agresta; Mario Antonini; Umberto D’Alessandro; Emanuele Nicastri; Spallanzani Group for Malaria Study

doi:10.1371/journal.pone.0225135

Peer Review History

Original SubmissionJune 13, 2019
4 Sep 2019 Decision Letter - Luzia Helena Carvalho, Editor PONE-D-19-16792 Imported severe malaria and risk factors for intensive care: a single-centre retrospective analysis. PLOS ONE Dear Dr Iannetta, Thank you for submitting your manuscript to PLoS ONE. After careful consideration, we felt that your manuscript requires substantial revision, following which it can possibly be reconsidered, thus governing the decision of a “major revision”. Regarding the study design, there are significant concerns raised by reviewers. According to Reviewer # 1, the criteria for IC admission is not clear and whether or not patients presented dual pathologies. Reviewer #2 recommend to use the STROBE checklist to improve the reporting quality of results. Of further relevance, both reviewers complain that conclusion must translate the results, and authors needs to adjust that. Finally, the low number of IC patients may compromise the MS’s conclusion, and authors should include study limitation. For your guidance, a copy of the reviewers' comments was included below. We therefore invite you to submit a revised version of the manuscript paying close attention to the specific points raised by both reviewers. We would appreciate receiving your revised manuscript by September 30 . When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Luzia Helena Carvalho, Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 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 http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.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: 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 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: No 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: This a retrospective single-centre review of imported severe malaria. I have the following comments: 1) What were the pre-existing admission criteria for admission to IC? 2) A total of 10 cases needing IC are reported although the reason for admission were cerebral malaria (7), shock (6) a nd ARDS (4) which totals 17, were there any patients that had dual pathologies? 3) ICU vs non-ICU patients had slower parasitemia but did the ICU patients have higher parasitemia to start off with which could explain the slower clearance? 4) 6 patients were reported as requiring vasoplressor drugs for shock but there is no mention of fluid resuscitation used. This may relevant particualry in light of the FEAST study. 5) There were no deaths or sequelae reported yet the conclusions state 'a multidisciplinary approach might be encouraged... in order to improve outcome', what outcome are they trying to improve? Furthermore what and whom should be part of a multi-disciplinary approach'? Reviewer #2: This is a simple, concise cross-sectional study of medical record data from patients with severe malaria to assess predictive risk factors associated to the need of intensive care (IC) at a referral hospital in Italy. Authors used five prognostic malaria scores to analyse the need of IC and applyed malaria-specific and general scores to identify severe malaria patients. The manuscript is well written, clear and intelligible. However, authors should make some changes to the manuscript in order to better interpret and conclude the results. 1) Authors are recommended to use the STROBE checklist to improve the reporting quality of results. 2) Some limitations of the study should be discussed, such as the low number of patients requiring intensive care, especially if the species was P. vivax. In addition, the cross-sectional design of the study precludes a more conclusive inference from the study results. 3) The conclusion of the study should be presented more clearly and objectively. In the Summary, for example, the conclusion presented does not translate the results found in the study. ****** 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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0225135.r001
Revision 1
27 Sep 2019 Author Response REVIEWER #1 This a retrospective single-centre review of imported severe malaria. I have the following comments: 1) What were the pre-existing admission criteria for admission to IC? A: The admission criteria adopted for IC admission were: - Glasgow Coma Scale <11; - Presence of multiple convulsions; - Respiratory distress with PaO2/FiO2 Ratio <100); - Conditions requiring mechanical ventilation and/or non-invasive ventilation; - Circulatory collapse or shock and/or MAP <70 mmHg, requiring vasopressor drugs; - Conditions requiring close monitoring and/or prolonged sedation. We included the IC admission criteria in the manuscript. 2) A total of 10 cases needing IC are reported although the reason for admission were cerebral malaria (7), shock (6) and ARDS (4) which totals 17, were there any patients that had dual pathologies? A: In our study, 7 patients presented more than one clinical picture at the moment of the admission in the IC, therefore the number of the events (17) is greater than the number of patient (10). A sentence was added in the text, accordingly. 3) ICU vs non-ICU patients had slower parasitemia but did the ICU patients have higher parasitemia to start off with which could explain the slower clearance? A: As showed in Table 1, there is no difference in basal parasitemia between ICU vs non-ICU (p= 0.811). Moreover, the data is confirmed at the univariate analysis. 4) 6 patients were reported as requiring vasopressor drugs for shock but there is no mention of fluid resuscitation used. This may relevant particuarly in light of the FEAST study. A: According to the protocol of our Institute, the use of vasopressor drugs is secondary to the fluid resuscitation failure. 5) There were no deaths or sequelae reported yet the conclusions state 'a multidisciplinary approach might be encouraged... in order to improve outcome', what outcome are they trying to improve? Furthermore what and whom should be part of a multi-disciplinary approach'? A: As suggested by the reviewer, we modified the conclusion of the manuscript. REVIEWER #2 This is a simple, concise cross-sectional study of medical record data from patients with severe malaria to assess predictive risk factors associated to the need of intensive care (IC) at a referral hospital in Italy. Authors used five prognostic malaria scores to analyse the need of IC and applyed malaria-specific and general scores to identify severe malaria patients. The manuscript is well written, clear and intelligible. However, authors should make some changes to the manuscript in order to better interpret and conclude the results. 1) Authors are recommended to use the STROBE checklist to improve the reporting quality of results. A: According to reviewer’s suggestion we modified the methods section using the STROBE checklist, which will be uploaded as a supplementary file. 2) Some limitations of the study should be discussed, such as the low number of patients requiring intensive care, especially if the species was P. vivax. In addition, the cross-sectional design of the study precludes a more conclusive inference from the study results. A: We thank the reviewer for the suggestions. The text has been modified accordingly, introducing sentences showing some limitations of the study. 3) The conclusion of the study should be presented more clearly and objectively. In the Summary, for example, the conclusion presented does not translate the results found in the study. A: The conclusion has been modified accordingly, introducing sentences that reflect the results showed in the text. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0225135.r002
7 Oct 2019 Decision Letter - Luzia Helena Carvalho, Editor PONE-D-19-16792R1 Imported severe malaria and risk factors for intensive care: a single-centre retrospective analysis. PLOS ONE Dear Dr Iannetta, Thank you for submitting your manuscript for review to PLoS ONE. After careful consideration, we feel that your manuscript will likely be suitable for publication if it is revised to address major points raised now by the reviewers. Specifically, the authors should clarify a couple of topics related to study design, including why they requested written informed consent from patients’ next of kin, since all patients are adults. A significant number of grammatical errors remained in the revised version of MS. Thus, the language needs to be properly adjusted otherwise it might compromise the publication. Finally, the reviewers complain about Data Availability that is not entirely accessible as stated by the authors. We would appreciate receiving your revised manuscript by October 30. When you are 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. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols 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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Luzia Helena Carvalho, Ph.D. Academic Editor PLOS ONE [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 #2: All comments have been addressed 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 #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: 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 #2: No 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 #2: (No Response) 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 #2: Although the authors stated that the study data is entirely available within the manuscript and in supplementary files, I have not had access to it completely. Reviewer #3: This is a cross sectional and retrospective study where clinical records for patients who were admitted with severe malaria from 2007 to 2015 were reviewed and analyzed by the authors. In this revised version of the manuscript, the authors have satisfactorily addressed comments that were raised by two reviewers. The manuscript is technically sound with the data used supporting the conclusion of the paper. All statistical analyses have been done appropriately and rigorously. Nevertheless I have the following concerns with the revised manuscript which the authors need to also look into: 1. The presentation of the manuscript is intelligible and uses Standard English though it will benefit from some language usage proofreading. 2. The authors need to clearly distinguish between actual recruitment of the patients and use of records for this research study. An example is where they write that they obtained written informed consent from the patients or their next of kin before enrollment into the study without detailing how they did it considering that by the time of this research the patients were not in hospital. 3. Further the authors write that they obtained written informed consent from patients’ next of kin, since all patients are adults aged above 18 years why was consent obtained from next of kin? 4. Authors should spell out all abbreviations the first time they are used in the write up – examples are INMI, h, P. vivax etc. ****** 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 #2: No Reviewer #3: Yes: Peter Makaula [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 to be viewed.] 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 us at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Reviewer notes.docx https://doi.org/10.1371/journal.pone.0225135.r003
Revision 2
25 Oct 2019 Author Response REVIEWER #2 1. Although the authors stated that the study data is entirely available within the manuscript and in supplementary files, I have not had access to it completely. A: In the previous revision, we have already uploaded the complete database as Supplementary file (page 23, download link). We will upload again the entire database as a supplementary file. If this is not enough, please let us know what we can do further. REVIEWER #3: This is a cross sectional and retrospective study where clinical records for patients who were admitted with severe malaria from 2007 to 2015 were reviewed and analyzed by the authors. In this revised version of the manuscript, the authors have satisfactorily addressed comments that were raised by two reviewers. The manuscript is technically sound with the data used supporting the conclusion of the paper. All statistical analyses have been done appropriately and rigorously. Nevertheless I have the following concerns with the revised manuscript which the authors need to also look into: 1. The presentation of the manuscript is intelligible and uses Standard English though it will benefit from some language usage proofreading. A: As suggested by the reviewer, the manuscript was widely revised for language editing. 2. The authors need to clearly distinguish between actual recruitment of the patients and use of records for this research study. An example is where they write that they obtained written informed consent from the patients or their next of kin before enrollment into the study without detailing how they did it considering that by the time of this research the patients were not in hospital. A: As suggested by the reviewer, we modified the text. According to the protocol in use in our Institute, each patient signs an informed written consent at the time of admission for research purposes and epidemiological investigations on infectious and tropical diseases. 3. Further the authors write that they obtained written informed consent from patients’ next of kin, since all patients are adults aged above 18 years why was consent obtained from next of kin? A: As suggested by the reviewer we modified the text. In case of person unable (e.g. coma state) to give consent, a relative/next of kin was asked to provide it. 4. Authors should spell out all abbreviations the first time they are used in the write up – examples are INMI, h, P. vivax etc. A: As suggested by the reviewer, we modified the text. Attachments Attachment Submitted filename: Response to Reviewers.doc.docx https://doi.org/10.1371/journal.pone.0225135.r004
30 Oct 2019 Decision Letter - Luzia Helena Carvalho, Editor Imported severe malaria and risk factors for intensive care: a single-centre retrospective analysis. PONE-D-19-16792R2 Dear Dr. Iannetta, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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 enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Luzia Helena Carvalho, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0225135.r005
Formally Accepted
5 Nov 2019 Acceptance Letter - Luzia Helena Carvalho, Editor PONE-D-19-16792R2 Imported severe malaria and risk factors for intensive care: a single-centre retrospective analysis. Dear Dr. Iannetta: I am 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 notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Luzia Helena Carvalho Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0225135.r006

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