Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study

Tobias O. Apinjoh; Vincent N. Ntui; Hanesh F. Chi; Marcel N. Moyeh; Cabrel T. Toussi; Joel M. Mayaba; Livinus N. Tangi; Pilate N. Kwi; Judith K. Anchang-Kimbi; Jodie Dionne-Odom; Alan T. N. Tita; Eric A. Achidi; Alfred Amambua-Ngwa; Vincent P. K. Titanji

doi:10.1371/journal.pone.0275370

Peer Review History

Original SubmissionDecember 31, 2021
7 Jul 2022 Decision Letter - José Luiz Fernandes Vieira, Editor PONE-D-21-41105Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern CameroonPLOS ONE Dear Dr. Opinjoh 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:All changes recommended by reviewers are mandatory to improve the quality of your manuscript.Please insert comments here and delete this placeholder text when finished. 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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, José Luiz Fernandes Vieira 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. Title in the uploaded manuscript exceeded 250 character limit. Please shorten the title to comply with journal requirements. 3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. [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: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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: 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: Dear authors. First, I want to congratulate your study. However, after analysis, some questions must be answered or justified before publication. Their study deals with “Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon”. I. Abstract section: includes all necessary information. II. Introduction: It includes all the necessary information, so you could mention other studies that were effective in this context and even the limitation in your state of the art. This way we will have more robustness in the study. III: Methodology: where was the material used for detection, on filter paper, for example, or was the material in natura? – this information must be described; in addition, I did not identify the process of sample feasibility, before carrying out the PCR process; as well, the criteria for admission of the drug to the patient, dosage and/or conflicting factors of the process were not described. However, it would be ideal to demonstrate the adverse reactions that these patients had after using the drug. IV: Results: includes all necessary information. V: Discussion: would you be able to correlate this process with the possible pharmacogenomic influence on patients, perhaps, this will give you the necessary answers from both positive and negative results. Finally, I congratulate you on your study and wish you success. Reviewer #2: Comments: 1. Abstract: Line 39: A sentence should not start with number. No perspectives were drawn from this study in the conclusion section. Line 53: May be country to be added here. 2. Introduction: Line 85: Harrington et al. 2012. There is a lack of consistency in the reporting of reference, as some are in number. Same for reference in line 95, ect…. Line 96: the term effect is not adequate for this type of study. Association is preferable, as indicated in the title of the paper. 3. Method section: In the ethic section, the suggestion is to provide the reference number of the ethical approval. Line 121: reference 16 is cited. In fact this sentence is not from that reference when assessed in the reference list. Line 144: reference to be numbered. Line 157: when was haemoglobin assessed? At enrolment or at delivery? Data analysis: The analytic section is less developed than it should be. The authors should provide more details here. Also, Line 200: what were the criteria of having a variable in the multivariate model in tables that content adjustment? Also, it is not clear in this section that logistic regression has been used, although OR was seen in the tables. Line 202: Chi Square test was used. Can the authors provide the Chi Square test used? As this is cohort study, what is the rationale of using odds ratio instead of risk ratio? 4. Results: In table 2: Fever at enrolment; What is the difference between the Febrile and Axillar temperature >= 37.5? The prevalence of low birthweight seems to be very low. What is the authors’ impression on this, as in many study conducted in sub Saharan Africa this is about 10% ? Line 252: the numerator reported here (35) is different from the sample size (57) to estimate the geometric mean of parasitemia. Can the authors explain that? Line 255: The term chemoprophylaxis is used. However, the authors were assessing IPTp. These two terms are different. The term IPTp is preferred. Same for line 289. Line 303: the term birth weight is used in two words. However, in many parts of the document, it is written in a single word. Line 307: Similarly, to line 260, the term Effect is not appropriate, as this is an association study and not effect study. Table 4: The authors seem to have no difference in term of birth weight in different groups of IPTp. Can the authors provide any explanation of that? Table 4 and Figure 3: There seems to be a discrepancy between Table 4 and Figure 3 regarding the association between IPTp usage and dosage and malaria infection. Is there any explanation of that? 5. Discussion: There is a mixture of Harvard and Vancouver across all the discussion section. Please correct. 6. Conclusion: One would like to have at least a sentence for perspective in the context of this study. Can the authors provide one? ****** 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: Luann Wendel Pereira de Sena Reviewer #2: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. Attachments Attachment Submitted filename: Dear authors.pdf Attachment Submitted filename: Comments-KK.docx https://doi.org/10.1371/journal.pone.0275370.r001
Revision 1
13 Aug 2022 Author Response Reviewer Comment Response Reviewer 2 Abstract: Line 39: A sentence should not start with number. Corrected to start with ”About” 25% No perspectives were drawn from this study in the conclusion section. Future studies should be carried out in hyperendemic malaria foci where the parasitemia levels are substantially higher in order to confirm the efficacy of IPTp-SP Line 53: May be country to be added here. The country “Cameroon” where this study was undertaken has been added to the keywords as suggested Introduction: Line 85: Harrington et al. 2012. There is a lack of consistency in the reporting of reference, as some are in number. Same for reference in line 95, ect…. All inconsistencies in citation and references have been corrected in line with journal specifications Line 96: the term effect is not adequate for this type of study. Association is preferable, as indicated in the title of the paper. This has been corrected in the manuscript to “relationship” since pregnancy outcomes were not associated submicroscopic infection Method section: In the ethic section, the suggestion is to provide the reference number of the ethical approval. The reference number of the ethical approval (ref. No2019/09/1188/CE/CNERSH/SP) has now been provide as suggested Line 121: reference 16 is cited. In fact this sentence is not from that reference when assessed in the reference list. Thanks for the correction and apologies for the mix-up. The correct reference (16 and not 15) has now been cited in the text. Line 144: reference to be numbered. Corrected as suggested Line 157: when was haemoglobin assessed? At enrolment or at delivery? Haemoglobin levels were assessed at enrolment and has now been indicated as such in the manuscript Data analysis: The analytic section is less developed than it should be. The authors should provide more details here. This section has now been further developed and relevant details provided as recommended Line 200: what were the criteria of having a variable in the multivariate model in tables that content adjustment? Also, it is not clear in this section that logistic regression has been used, although OR was seen in the tables. The use of logistic regression and criteria for including variables in multivariate models has now been detailed in the analysis section Line 202: Chi Square test was used. Can the authors provide the Chi Square test used? As this is cohort study, what is the rationale of using odds ratio instead of risk ratio? The corresponding chisquare statistics has now been incorporated into the table as suggested. The analysis in question relates to the risk of the participants at one time point (enrolment) and not following the semi-longitudinal outcome Results: In table 2: Fever at enrolment; What is the difference between the Febrile and Axillar temperature >= 37.5? Fever at enrolment was classified in different ways. Current fever was defined as body temperature ≥37.5°C, with febrile individuals defined as participants with current fever or history of fever at enrolment. This has now been clarified under the “Data Collection and Definition of terms’ section in the manuscript The prevalence of low birthweight seems to be very low. What is the authors’ impression on this, as in many study conducted in sub Saharan Africa this is about 10%? This may be due to multiple factors including the status, nutrition and adherence of the mothers to control and intervention strategies. We note that most of the women were aged > 25 years, multigravidae, IPTp-SP users of atleast 3 doses at term, which factors have been shown to contribute to improved pregnancy outcome. Line 252: the numerator reported here (35) is different from the sample size (57) to estimate the geometric mean of parasitemia. Can the authors explain that? This can be explained by the fact that a few samples assessed for P. falciparum infection by peripheral blood smear microscopy were not assessed by PCR and vice versa. Such discrepancy would accrue to damaged slides during transportation/processing or indeterminate PCR results. Line 255: The term chemoprophylaxis is used. However, the authors were assessing IPTp. These two terms are different. The term IPTp is preferred. Same for line 289. This has been corrected in the manuscript as suggested Line 303: the term birth weight is used in two words. However, in many parts of the document, it is written in a single word. This has been corrected in the manuscript as suggested Line 307: Similarly, to line 260, the term Effect is not appropriate, as this is an association study and not effect study. This has been corrected in the manuscript as suggested Table 4: The authors seem to have no difference in term of birth weight in different groups of IPTp. Can the authors provide any explanation of that? Indeed. Although there was a trend in creasing birthweight with IPTp-SP use, there was no difference in different IPTp-SP groups. This suggest that although the chemotherapy is associated with protection from sub-microscopic parasitaemia, this does not translate into pregnancy outcome in terms of birthweight. It is possible that the low numbers of non IPTp-SP users at term may not be statistically powered to detect difference, if they do exist. Table 4 and Figure 3: There seems to be a discrepancy between Table 4 and Figure 3 regarding the association between IPTp usage and dosage and malaria infection. Is there any explanation of that? Table 4 and Figure 3 present completely different information vis-à-vis IPTp usage and dosage. While Table 4 compares pregnancy outcome (birthweight and APGAR score) across different IPTp usage and dosage groups, Figure 3 shows the association between IPTp-SP usage and dosage and the malaria parasite infection status Discussion: There is a mixture of Harvard and Vancouver across all the discussion section. Please correct. All inconsistencies in citation and references have been corrected in line with journal specifications Conclusion: One would like to have at least a sentence for perspective in the context of this study. Can the authors provide one? To conduct similar studies in a hyperendemic setting with higher parasitaemia levels and interrogate if IPTp induces protective responses to malaria Reviewer Comment Response Reviewer 1 I. Abstract section includes all necessary information All necessary information has been included II. Introduction It includes all the necessary information, so you could mention other studies that were effective in this context and even the limitation in your state of the art. This way we will have more robustness in the study. All necessary information has been included III: Methodology: where was the material used for detection, on filter paper, for example, or was the material in natura? – this information must be described; in addition, I did not identify the process of sample feasibility, before carrying out the PCR process; as well. This has been corrected in the manuscript to include details on filter paper type and sample storage conditions prior to PCR testing. The study describes status in natura as testing was done on samples directly collected from the women enrolled. the criteria for admission of the drug to the patient, dosage and/or conflicting factors of the process were not described. However, it would be ideal to demonstrate the adverse reactions that these patients had after using the drug. A subsection detailing IPTp-SP usage and dosage information has now been included in the methodology section. Note that the previous drug use was self-reported or documented from medical records and subsequent use captured by directly observed administration by health care personnel. IV: Results: includes all necessary information. All necessary information has been included V: Discussion would you be able to correlate this process with the possible pharmacogenomic influence on patients, perhaps, this will give you the necessary answers from both positive and negative results. Finally, I congratulate you on your study and wish you success. It would be interesting to correlate out observation with pharmacogenomics influence on participants, a perspective in view of future studies. Thank you for the brilliant suggestion. Attachments Attachment Submitted filename: Response to Reviewer Comments_MIP Manuscript 09082022.docx https://doi.org/10.1371/journal.pone.0275370.r002
16 Sep 2022 Decision Letter - José Luiz Fernandes Vieira, Editor Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon PONE-D-21-41105R1 Dear Dr.Tobias Apinjoh 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, José Luiz Fernandes Vieira 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 #1: 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 #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: Dear, Congratulations again for the study. All suggestions are fulfilled. Through the suggestions the text became more solid and understood. ****** 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: No ******** https://doi.org/10.1371/journal.pone.0275370.r003
Formally Accepted
22 Sep 2022 Acceptance Letter - José Luiz Fernandes Vieira, Editor PONE-D-21-41105R1 Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon Dear Dr. Apinjoh: 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. José Luiz Fernandes Vieira Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0275370.r004

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