Asymptomatic carriage of Plasmodium falciparum in children no longer targeted for seasonal malaria chemoprevention and with a history of exposure to this strategy: A cross sectional study in southern Senegal

Isaac Akhénaton Manga; Abdoulkarim Mhadji; Aminata Lam; Marie Pierre Diouf; Pab Carole Minlekib; Fassiatou Tairou; Amadou Seck; Babacar Faye; Magatte Ndiaye; Jean Louis Abdourahim Ndiaye

doi:10.1371/journal.pone.0318037

Peer Review History

Original SubmissionAugust 29, 2024
29 Aug 2024 Author Response https://doi.org/10.1371/journal.pone.0318037.r001
17 Oct 2024 Decision Letter - José Luiz Fernandes Vieira, Editor PONE-D-24-37026Malaria prevalence in children with history of exposure to seasonal malaria chemoprevention: a cross sectional study in southern SenegalPLOS ONE Dear Dr. Isaac Manga, 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: Dear AuthorThe manuscript titled "Malaria Prevalence in Children with a History of Exposure to Seasonal Malaria Chemoprevention: A Cross-Sectional Study in Southern Senegal" holds significant scientific merit, particularly given the importance of the study's region. However, the reviewers have pointed out several issues that need to be addressed in order to enhance the quality of the manuscript. Thus, several revisions are necessary based on the reviewers' suggestions. ============================== Please submit your revised manuscript by Dec 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. 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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. 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. 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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: Partly ******** 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: 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: No ****** 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 study titled "Malaria prevalence in children with a history of exposure to seasonal malaria chemoprevention: a cross-sectional study in southern Senegal" addresses a critical issue in malaria control and elimination—the burden of asymptomatic cases or parasite reservoirs that need to be addressed to eliminate the disease. However, significant revisions are required. Title: The manuscript title should be revised because the definition of a malaria case (fever or history of fever during the last 48 hours with a positive test, such as RDT, blood smear, or PCR) is not clearly stated. Therefore, "malaria prevalence" may not be appropriate for the title. Methodology: Study site: The authors provide a brief description of these areas. However, a more detailed account of the malaria epidemiology (incidence or prevalence, transmission season, etc.) is needed. Sample size calculation: The authors mention, “To detect about 40% of malaria cases, the number of children needed for this study was estimated at 250 using Epi Info.” To determine the sample size, the prevalence or expected prevalence of asymptomatic malaria based on previous studies should be used. Line 86: How was the history of exposure to SMC evaluated? Did the children have SMC ID cards? Line 90: The estimated sample size was 250 children. How were these participants distributed across the four regions or health districts (Kédougou, Kolda, Sédhiou, and Tambacounda)? More information is needed on how the participants were selected. Sociodemographic characteristics of the study population: The distribution of participants by region or health district should be provided. Line 143: “Prevalence of malaria” should be changed to “Prevalence of asymptomatic malaria.” Line 148: The authors state that “Among these children (11 years old), 27.6% (95% CI = 17.5-37.7) reported taking SMC in 2013; 19.2% (95% CI = 13.7-24.7) in 2014; and 18.4% (95% CI = 10.3-26.5) in 2015.” Is it realistic to expect 11-year-olds to answer this type of question accurately? Line 149: “No malaria cases were noted...” should be revised, as this study does not deal with malaria cases. Additionally, in this section, the distribution of asymptomatic malaria by region or health district should be provided. Discussion: Line 164-165: The authors should avoid comparing the prevalence of asymptomatic cases from this study with the national malaria prevalence. The study in Gabon (line 168, ref. 17) targeted malaria cases in adolescents using microscopy diagnosis. Line 173: The authors state, “Our study also showed that regular use of SMC prevents parasite transmission.” How does it show this? Conclusion: Line 196: The authors state, “Extending the SMC target to Senegal could help the country achieve its goal of eliminating malaria by 2030.” However, the results of this study do not fully support such a conclusion. Moreover, language levels need to be improved Reviewer #2: Overall comment:There is a need to review the entire manuscript for clarity of the language and for language correction . A review by an English native speaker would help. Additionally, and specially for the discussion and conclusion sections, a carefully review of the statements and related reference checks is needed. Specific comments: L31.. The study... not "this"... L122-123: There were other quantitative variables apart of age? If no please clarify. L127: Plese specify the age of the children requiring assent... Results L13- to 142: A sugestion for improving this descriptin for clarity: "The sex ratio (M/F) of the 226 children included in this study was 1.05. However, gender information was missing for 2.2% of the children. The children were between 11 and 14 years old, with a mean age of 11.9 years (±0.8). The majority were 11 or 12 years old, accounting for 35.4% (95% CI = 29.2-41.6) and 46% (95% CI = 39.5-52.5) of the population, respectively. Age information was missing for 0.4% (95% CI = 0-1.3) of the children. Most of the children (87.6%; 95% CI = 85.4-89.8) had received SMC in 2014, followed by 38.5% (95% CI = 35.3-41.7) in 2015 and 33.6% (95% CI = 30.5-36.8) in 2013. Children who had received SMC in both 2013 and 2014 accounted for 23% (95% CI = 17.5-28.5), while those who had been exposed in 2013, 2014, and 2015 (3 years) represented 8.4% (95% CI = 4.8-12). Only 0.4% (95% CI = 0-1.3) had received SMC for four consecutive years (2013-2016). (S2 Table). If the authors agree, the same suggestion may be used for the following sections on results. L144: Please check the use of singular or plural verbs... It should be "were"... L145-146: Suggestion to improve for clarity: The number of malaria-positive cases was higher in females, 54.5% (95% CI = 39.8-69.2), compared to males, 43.2% (95% CI = 28.6-57.8). L150-151: Suggestion for correction in language: " Among the 44 children who tested positive for malaria by PCR..." L159-163: Apart of improving the text for clarity, it is obvious that if you compare different diagnostic methods the results may be different. I would suggest, if any, relate to studies using the same diagnostic approach or , if not available, explore aditional explanations for the diferences found. L167-170: From my understanding your study recruited participants with a malaria RDT negative and no symptoms of malaria (which includes fever). Now you are referring to studies with patients positive by microscopy to malaria and with fever. Again, you are comparing diferent methodologies and populations. Please use apropriate references for the discussion. L175: All referenced studies here (references 3,4,11) are related to effectiveness of the SMC, not "in vivo efficacy"... Please check and re-write accordingly. L196-199: These a recommendations, not conclusions. Please check and clarify. ****** 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: Pedro Aide ******** [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". 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Revision 1
1 Dec 2024 Author Response Reviewer #1: The study titled "Malaria prevalence in children with a history of exposure to seasonal malaria chemoprevention: a cross-sectional study in southern Senegal" addresses a critical issue in malaria control and elimination—the burden of asymptomatic cases or parasite reservoirs that need to be addressed to eliminate the disease. However, significant revisions are required. Title: The manuscript title should be revised because the definition of a malaria case (fever or history of fever during the last 48 hours with a positive test, such as RDT, blood smear, or PCR) is not clearly stated. Therefore, "malaria prevalence" may not be appropriate for the title. Response: we have changed the title which is now : “Asymptomatic carriage of Plasmodium falciparum in children no longer targeted for chemoprevention of seasonal malaria and with a history of exposure to this strategy: a cross sectional study in southern Senegal.” Methodology: Study site: The authors provide a brief description of these areas. However, a more detailed account of the malaria epidemiology (incidence or prevalence, transmission season, etc.) is needed. Sample size calculation: The authors mention, “To detect about 40% of malaria cases, the number of children needed for this study was estimated at 250 using Epi Info.” To determine the sample size, the prevalence or expected prevalence of asymptomatic malaria based on previous studies should be used. Response: We rewrote the methodology, explaining the epidemiological aspects that led to the choice of the study area. We also reviewed the sample size calculation, showing that this study was part of a project to evaluate the impact of SMC on the immunity of children who had benefited from this strategy. Therefore, we repeated the calculation of the sample size needed for this study and stated our inclusion criteria. Line 86: How was the history of exposure to SMC evaluated? Did the children have SMC ID cards? Response: To assess the history of exposure to SMC, we relied on the parents' memories. Card storage is difficult in rural areas. Line 90: The estimated sample size was 250 children. How were these participants distributed across the four regions or health districts (Kédougou, Kolda, Sédhiou, and Tambacounda)? More information is needed on how the participants were selected. Sociodemographic characteristics of the study population: The distribution of participants by region or health district should be provided. Response: Children were recruited from different regions on the basis of the case-control study. Line 143: “Prevalence of malaria” should be changed to “Prevalence of asymptomatic malaria.” Response: We changed it by Asymptomatic carriage of Plasmodium falciparum Line 148: The authors state that “Among these children (11 years old), 27.6% (95% CI = 17.5-37.7) reported taking SMC in 2013; 19.2% (95% CI = 13.7-24.7) in 2014; and 18.4% (95% CI = 10.3-26.5) in 2015.” Is it realistic to expect 11-year-olds to answer this type of question accurately? Response: We modified the sentence to show that the parents who answered the questions Line 149: “No malaria cases were noted...” should be revised, as this study does not deal with malaria cases. Additionally, in this section, the distribution of asymptomatic malaria by region or health district should be provided. Response: No parasite carriage was noted among those exposed in 2013, 2014, 2015 and 2016 is the sentence we proposed and we also gave the distribution of Plasmodium carriage by regions as you asked. Discussion: Line 164-165: The authors should avoid comparing the prevalence of asymptomatic cases from this study with the national malaria prevalence. The study in Gabon (line 168, ref. 17) targeted malaria cases in adolescents using microscopy diagnosis. Line 173: The authors state, “Our study also showed that regular use of SMC prevents parasite transmission.” How does it show this? Response: We have rewritten the discussion to reflect your recommendations, which we believe are relevant. You can see this in the newly submitted version. Conclusion: Line 196: The authors state, “Extending the SMC target to Senegal could help the country achieve its goal of eliminating malaria by 2030.” However, the results of this study do not fully support such a conclusion. Response: Here is the new conclusion of the study: This study found significant asymptomatic Plasmodium falciparum carriage in adolescents with a history of exposure to SMC. It was more pronounced in children who had moved from the target group of this strategy in Senegal. Older children are therefore a major reservoir of parasites, maintaining malaria transmission in the country. Moreover, language levels need to be improved: Response : As you will see in the new version, we asked a native english speaker to help us improve the language. Reviewer #2: Overall comment:There is a need to review the entire manuscript for clarity of the language and for language correction . A review by an English native speaker would help. Additionally, and specially for the discussion and conclusion sections, a carefully review of the statements and related reference checks is needed. Response: We asked a native English speaker to help us improve the language. Specific comments: L31. The study... not "this"... Response: We have rewritten the sentence to reflect your recommendation. L122-123: There were other quantitative variables apart of age? If no please clarify. Response: We reworded the sentence in the data analysis section to make it clearer, as the children's age was the only quantitative variable. L127: Please specify the age of the children requiring assent... Response: The assent of all the children (11-14 years old) included had also been obtained before the start of the study. Results L13- to 142: A sugestion for improving this descriptin for clarity: "The sex ratio (M/F) of the 226 children included in this study was 1.05. However, gender information was missing for 2.2% of the children. The children were between 11 and 14 years old, with a mean age of 11.9 years (±0.8). The majority were 11 or 12 years old, accounting for 35.4% (95% CI = 29.2-41.6) and 46% (95% CI = 39.5-52.5) of the population, respectively. Age information was missing for 0.4% (95% CI = 0-1.3) of the children. Most of the children (87.6%; 95% CI = 85.4-89.8) had received SMC in 2014, followed by 38.5% (95% CI = 35.3-41.7) in 2015 and 33.6% (95% CI = 30.5-36.8) in 2013. Children who had received SMC in both 2013 and 2014 accounted for 23% (95% CI = 17.5-28.5), while those who had been exposed in 2013, 2014, and 2015 (3 years) represented 8.4% (95% CI = 4.8-12). Only 0.4% (95% CI = 0-1.3) had received SMC for four consecutive years (2013-2016). (S2 Table). If the authors agree, the same suggestion may be used for the following sections on results. L144: Please check the use of singular or plural verbs... It should be "were"... L145-146: Suggestion to improve for clarity: The number of malaria-positive cases was higher in females, 54.5% (95% CI = 39.8-69.2), compared to males, 43.2% (95% CI = 28.6-57.8). L150-151: Suggestion for correction in language: " Among the 44 children who tested positive for malaria by PCR..." Response: To take account of your suggestions on how to present the results, the entire results section has been rewritten. Discussion section L159-163: Apart of improving the text for clarity, it is obvious that if you compare different diagnostic methods the results may be different. I would suggest, if any, relate to studies using the same diagnostic approach or , if not available, explore aditional explanations for the diferences found. L167-170: From my understanding your study recruited participants with a malaria RDT negative and no symptoms of malaria (which includes fever). Now you are referring to studies with patients positive by microscopy to malaria and with fever. Again, you are comparing diferent methodologies and populations. Please use apropriate references for the discussion. L175: All referenced studies here (references 3,4,11) are related to effectiveness of the SMC, not "in vivo efficacy"... Please check and re-write accordingly. Response: We have modified our discussion to take account of your recommendations, i.e. comparison with the same population and the same techniques used to test for Plasmodium. Our references have therefore been modified L196-199: These recommendations, not conclusions. Please check and clarify. Response: Here is the new conclusion of the study: This study found significant asymptomatic Plasmodium falciparum carriage in adolescents with a history of exposure to SMC. It was more pronounced in children who had moved from the target group of this strategy in Senegal. Older children are therefore a major reservoir of parasites, maintaining malaria transmission in the country. Attachments Attachment Submitted filename: Responses to reviewers.docx https://doi.org/10.1371/journal.pone.0318037.r003
9 Jan 2025 Decision Letter - José Luiz Fernandes Vieira, Editor Asymptomatic carriage of Plasmodium falciparum in children no longer targeted for chemoprevention of seasonal malaria and with a history of exposure to this strategy: a cross sectional study in southern Senegal. PONE-D-24-37026R1 Dear Dr. Isaac Manga 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, José Luiz Fernandes Vieira Academic Editor PLOS ONE Additional Editor Comments After carefully reviewing the changes made to the manuscript, I recommend its publication in PLOS ONE congratulations José Luiz Vieira Reviewers' comments: 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: (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 #1: No ******** https://doi.org/10.1371/journal.pone.0318037.r004
Formally Accepted
Acceptance Letter - José Luiz Fernandes Vieira, Editor PONE-D-24-37026R1 PLOS ONE Dear Dr. Manga, 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. José Luiz Fernandes Vieira Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0318037.r005

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