Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana

Charles Nkansah; Simon Bannison Bani; Kofi Mensah; Samuel Kwasi Appiah; Felix Osei-Boakye; Gabriel Abbam; Samira Daud; Eugene Mensah Agyare; Peace Esenam Agbadza; Charles Angnataa Derigubah; Dorcas Serwaa; Francis Atoroba Apodola; Yeduah Quansah; Rahama Issah; Samuel Yennuloom Dindiok; Felix Ejike Chukwurah

doi:10.1371/journal.pone.0283427

Peer Review History

Original SubmissionOctober 18, 2022
3 Jan 2023 Decision Letter - Felix Chikaike Clement Wekere, Editor PONE-D-22-28777 Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana PLOS ONE Dear Dr. Nkansah, 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. The comments of two expert reviewers that assessed your manuscript are appended below. Both reviewers raise important concerns about some aspects of the methodology and presentation, which you should address carefully in your revised manuscript. Note the detailed presentation of your sample size calculation is accepted as it will enhance reproducibility. Kindly proofread the manuscript and make suggested edits to improve flow. Please submit your revised manuscript by Feb 17 2023 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, Dr. Felix C. C. Wekere 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. We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar. If you do not know anyone who can help you do this, you may wish to consider employing a professional scientific editing service. Whilst you may use any professional scientific editing service of your choice, PLOS has partnered with both American Journal Experts (AJE) and Editage to provide discounted services to PLOS authors. Both organizations have experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. To take advantage of our partnership with AJE, visit the AJE website (http://learn.aje.com/plos/) for a 15% discount off AJE services. To take advantage of our partnership with Editage, visit the Editage website (www.editage.com) and enter referral code PLOSEDIT for a 15% discount off Editage services. If the PLOS editorial team finds any language issues in text that either AJE or Editage has edited, the service provider will re-edit the text for free. Upon resubmission, please provide the following: The name of the colleague or the details of the professional service that edited your manuscript A copy of your manuscript showing your changes by either highlighting them or using track changes (uploaded as a supporting information file) A clean copy of the edited manuscript (uploaded as the new manuscript file) 3. 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: Kindly add the city and country of the manufacturer of the statistical software you used for analysis. Also, give the full meaning of the abbreviations at first use. [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: 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 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: 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: 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: the current study ascertained the prevalence of anti-EPO antibodies production and evaluated the antibodies’ relationship with Plasmodium falciparum malaria and malaria-related anaemia in pregnancy. this is a well written manuscript, the following suggestions/ questions will enhanced readers understandng 1. authors should state categorically how Plasmodium falciparum density and age relates to anti-EPO do anti-EPO enhanced or inhibit anti-EPO 2. Line 59 sentence .......... in both foetal and or maternal lives should be revised/rephrased to enhanced clarity 3.Line 100 define EPO first time usage 4. Line 74-76 ........but suggested via multiple mechanisms including suppression .....revise to enhance clarity of understanding 5. Sample size calculation as demonstrated in the manuscript is too detailed, authors should just state the name of the formulae, the prevalence used, referenced the articled from which it was sourced from and finally the sample size itself. 6. how did authors ensured that exclusion criteria were met ie P. falciparum-infected pregnant women with comorbidities (such as infections and other haematological disorders) were excluded. 7. line 100 subheading assessment of CBC should be changed to Measurement of CBC 8. Authors failed to demonstrate how they speciated P. falciparum from other Spp. of anopheles 9. Authors should move the limitation of the study from conclusion section to the discussion section Reviewer #2: The animal studies in the narration may not directly substitute for pregnant humans. The findings with animal studies that were not pregnant is far too wide for comparative analysis. The study is on human pregnant conditions, P. Falciparum and presence of antiEOP antibodies. It may not be absolutely necessary in the discussion page of this 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: Yes: Matthew Anyanwu ******** [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.0283427.r001
Revision 1
10 Jan 2023 Author Response Dear Editor, Thank you for your email. I am pleased to resubmit manuscript titled “Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana “for your consideration. Authors do appreciate your endless efforts to ensure improvement in the manuscript. The concerns raised by the editorial team have been addressed and highlighted below and marked in the respective sections in the manuscript. I look forward to your favourable response. Thank you. The manuscript was edited for language usage, spelling and grammar by Grammarly Inc. USA. General Comments 1. Initial incorrect spelling of the middle name of the last author Response: Authors middle name is correctly spelt: Ejike. This makes the full name Felix Ejike Chukwurah 2. Kindly add the city and country of the manufacturer of the statistical software you used for analysis. Response: This has been considered and inputs made 3. Also, give the full meaning of the abbreviations at first use. Response: This has been considered throughout the document Reviewer #1: 1. authors should state categorically how Plasmodium falciparum density and age relates to anti-EPO do anti-EPO enhanced or inhibit anti-EPO Response: P. falciparum density and younger age may stimulate the production of anti-EPO in pregnant women with malaria 2. Line 59 sentence .......... in both foetal and or maternal lives should be revised/rephrased to enhanced clarity Response: This has been revised accordingly 3. Line 100 define EPO first time usage Response: EPO is first defined in line 37 of the manuscript. 4. Line 74-76 ........but suggested via multiple mechanisms including suppression .....revise to enhance clarity of understanding. Response: This has been revised to ensure clarity 5. Sample size calculation as demonstrated in the manuscript is too detailed, authors should just state the name of the formulae, the prevalence used, referenced the articled from which it was sourced from and finally the sample size itself. Response: The detailed presentation of the sample size determination will allow for reproducibility. 6. how did authors ensured that exclusion criteria were met ie P. falciparum-infected pregnant women with comorbidities (such as infections and other haematological disorders) were excluded. Response: Clinical characteristics of the pregnant women (participants) were obtained from the ante-natal care (ANC) register, which contained results on HIV, HBsAg, HCV, Syphilis, Sickling test, Hb phenotype, G6PD test, routine examinations of stool and urine, etc. Pregnant women with comorbidities were excluded from the study, as shown in lines 149-150. 7. line 100 subheading assessment of CBC should be changed to Measurement of CBC Response: The subheading has been revised to read ‘Measurement of complete blood count’, and seen in line 165 8. Authors failed to demonstrate how they speciated P. falciparum from other Spp. of anopheles Response: This has been addressed and inserted in lines 198 to 205 9. Authors should move the limitation of the study from conclusion section to the discussion section Response: The limitation of the study has been moved from the conclusion to the discussion section as recommended. Reviewer #2: The animal studies in the narration may not directly substitute for pregnant humans. The findings with animal studies that were not pregnant is far too wide for comparative analysis. The study is on human pregnant conditions, P. Falciparum and presence of anti-EOP antibodies. It may not be absolutely necessary in the discussion page of this study. Response: This has been considered and revision made Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS.docx https://doi.org/10.1371/journal.pone.0283427.r002
6 Mar 2023 Decision Letter - Felix Chikaike Clement Wekere, Editor PONE-D-22-28777R1Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern GhanaPLOS ONE Dear Dr. Nkansah, 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. ============================== Your manuscript has been assessed by an expert reviewer, whose comments are appended below. The reviewer raised important concerns about some aspects of the Methodology and presentation, which you should address carefully in your revised manuscript. Kindly address each point carefully in your response to the reviewers’ document and revise the manuscript accordingly. ============================== Please submit your revised manuscript by Apr 20 2023 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, Felix Chikaike Clement Wekere 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. Additional Editor Comments: Kindly revise line 94 in the introduction. Suggestion: Delete the sentence completely as you did in the discussion section (i.e comparison with animal-mice), since your work is on humans it won't be appropriate referring to an animal study. In Table 1, remove the word 'years' after the different ages groups since you have written it in bracket in the preceding row. In Table 5 format as suggested above for Table 1. [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: (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 #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: 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: 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 ****** 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: Lines 419, 420, 421: The animal studies in the narration may not directly substitute for pregnant humans. The findings with animal studies that were not pregnant is far too wide for comparative analysis. The study is on human pregnant conditions, P. Falciparum and presence of antiEOP antibodies. It may not be absolutely necessary in the discussion page of this study. Similarly the study on children 0-10 years was conducted in Ghana which may be appropriate to mention but of no value to the current study. I observed also that few words of study limitations were written at the conclusion paragraph. May i suggest that it should come after the discussion paragraphs. ****** 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: Yes: Matthew Anyanwu ******** [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.0283427.r003
Revision 2
7 Mar 2023 Author Response Dear Editor, Thank you for your email. I am pleased to resubmit manuscript titled “Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana “for your consideration. Authors do appreciate your endless efforts to ensure improvement in the manuscript. The concerns raised by the editorial team have been addressed and highlighted below and marked in the respective sections in the manuscript. I look forward to your favourable response. Thank you. The manuscript was edited for language usage, spelling and grammar by Grammarly Inc. USA. General Comments 1. Kindly revise line 94 in the introduction. Suggestion: Delete the sentence completely as you did in the discussion section (i.e comparison with animal-mice), since your work is on humans it won't be appropriate referring to an animal study. Response: The entire sentence has been deleted as suggested 2. In Table 1, remove the word 'years' after the different ages groups since you have written it in bracket in the preceding row. In Table 5 format as suggested above for Table 1.Initial incorrect spelling of the middle name of the last author Response: The word ‘years’ has been deleted from both Tables 1 and 5 accordingly. Reviewer #2: The animal studies in the narration may not directly substitute for pregnant humans. The findings with animal studies that were not pregnant is far too wide for comparative analysis. The study is on human pregnant conditions, P. Falciparum and presence of anti-EOP antibodies. It may not be absolutely necessary in the discussion page of this study. Response: This has been considered and revision made Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS.docx https://doi.org/10.1371/journal.pone.0283427.r004
8 Mar 2023 Decision Letter - Felix Chikaike Clement Wekere, Editor Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana PONE-D-22-28777R2 Dear Dr. Nkansah, 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, Felix Chikaike Clement Wekere Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0283427.r005
Formally Accepted
21 Mar 2023 Acceptance Letter - Felix Chikaike Clement Wekere, Editor PONE-D-22-28777R2 Serum anti-erythropoietin antibodies among pregnant women with Plasmodium falciparum malaria and anaemia: A case-control study in northern Ghana Dear Dr. Nkansah: 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. Felix Chikaike Clement Wekere Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0283427.r006

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