Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria—A pilot study

Esther O. Oluwole; Titilope A. Adeyemo; Gbemisola E. Osanyin; Oluwakemi O. Odukoya; Phyllis J. Kanki; Bosede B. Afolabi

doi:10.1371/journal.pone.0242861

Peer Review History

Original SubmissionAugust 21, 2020
23 Sep 2020 Decision Letter - Ambroise Wonkam, Editor PONE-D-20-26306 Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria------A pilot study PLOS ONE Dear Dr. OLUWOLE Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ============================== Please submit your revised manuscript by 22 Decemeber 2020. 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Ambroise Wonkam, MD, PhD 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 note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 3. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. 4. In the Methods, please discuss whether and how the questionnaire was validated and/or pre-tested. If this did not occur, please provide the rationale for not doing so. Additional Editor Comments: Dear Authors, Your paper addresses and important question of public health importance in Africa, and globally: the screening of Sickle cell disease. Although the authors have a genuine attempt to address your request question, in its present form, the methodology and quality of the reporting need some major improvement as indicated by both reviewers. Moreover, more background information on the setting (Nigeria) are needed to put the paper into context. Population size? SCD incidence and prevalence? General level of formal education? Poverty indices? National health system? Available public health policies and current practices regarding SCD screening; Availability and access to comprehensive services for SCD prevention and care. Please carefully address point-to-point the editor and reviewers’ comments, as this is expected to improve the quality of your text. [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: 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: No 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 is an interesting and useful article describing the authors’ experience studying the feasibility and acceptability of early infant screening for sickle cell disease among mothers and their newborns attending a community health center in Lagos for routine immunization. It also reports on the ease of use and accuracy of HemoTypeSC compared to HPLC in determining Hb genotypes among young infants. They studied 291 mother/infant pairs and ~86% of the mothers accepted screening. The breakdown of Hb genotypes was in agreement with previous reports from Nigeria. Moreover, HemoTypeSC was easy to use and showed 100% specificity and sensitivity in identifying those with abnormal Hb genotypes. Thus, this article builds on previous positive reports for HemoTypeSC in other parts of Nigeria. While the study was well designed and executed, the style of writing needs considerable improvement. In general terms, I would advise the authors to refer to the diagnoses as Hb genotypes instead of phenotypes so as not to be confused with clinical phenotypes. There’s need to include in the introduction, the justification for using POCT in newborn screening in preference to other available screening methods especially in resource-poor areas. A brief mention of previous work with HemoTypeSC in Nigeria and other places is also apropos. There are many grammatical and syntax issues and the authors are advised to review the whole manuscript carefully in this regard. Some suggested corrections are outlined below: Abstract: Line 31, should read “……comprehensive management is not…..” Line 39, should read “The haemoglobin genotype of mother-infant pairs…..” Line 41, should read “Data were analysed with SPSS version 22”. Introduction: The whole of the introduction needs to be restructured. Currently it just one long paragraph and it does not flow well. Apart from briefly introducing sickle cell disease epidemiology, it should focus on the problems associated with newborn screening and the current methods as mentioned above Line 59 - 62, “In high income countries where the infrastructure for universal newborn screening, early intervention and comprehensive care exist, mortality has reduced from 16% to <1% with less than 1% global disease burden and over 90% of babies born with SCD surviving into adulthood”. It is not clear if the 16 to 1% figure is referring to overall mortality or only in childhood. Materials and Methods Lines 88 – 90. The sentence “The State has the highest population in Nigeria with twenty local government areas (LGA), and this study took place in one of them which was selected by simple random sampling through ballot” needs to be restructured. Lines 127 – 133. Most of the description of HemoTypeSC given here rightly belongs in the introduction. Line144, should read: “…heelprick of each of the infants by trained ….” Line 147, The infants’ blood samples were….” Line 153, should read “…. while the results of the confirmatory test were communicated….” Line157 – 162. This section, starting with “Feasibility..” should be in a new paragraph. Moreover, it is not clear how the authors arrived at the cut-off figures quoted. Are they from previous studies? If so, the source should be referenced; otherwise their basis should be explained. Results: Line 174, should read, “Socio-demographic characteristics of mother-infant pairs”. Line 206, should read, “Ninety-four (74.6%) of 126 mothers who refused….” Line 218, delete “the cost of” Table 2: The title of the second column is not clear. It is certainly not frequency, but number (n) of individuals affected. The total of 291 can be moved to the title of the table. The section on “Reasons for not wanting self/child to be screened” should be in a separate table since the denominator is not 291, but the 126 that did not agree to be screened. It this is true, the percentages given in the table cannot be correct. Discussion: Apart from the accuracy of HemoTypeSC and its low cost, the other disadvantages of HPLC in a resource-poor environment should be stressed. These include the need for highly skilled personnel, reagents and electrical power, which, is quite often, not available. Line 292 - 293, should read “….with the creation of a comprehensive treatment center in each of the 6 geopolitical zones….” Line 305, what is DHS? Line 316, should read “The mothers of the two infants who were diagnosed…..” Line 330, a new paragraph should begin with the sentence, “The majority of the mothers…..” Reviewer #2: Review of Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria This paper appears to have two objectives, an evaluation of the HemoType SC diagnostic test and an assessment of haemoglobinopathy detection in primary health care centres. The sample population was drawn from 2 of 10 health centres in the Somolu Community of Lagos. Reference is made to a paper reporting that only 36% deliveries take place in health facilities in Nigeria yet 95% of the studied population delivered in hospitals/health centres. It would also be helpful to know what proportion of births attend ‘routine immunization clinics’. Although 291 mother/infant ‘units’ were admitted to the study, 41 (14%) refused screening and the principle reason appears to be that they believed that they and their spouses had an AA genotype. Using the Bio-Rad D-10 as a reference method, the performance of the diagnostic kit appears acceptable but the numbers are far too small for reliable assessment with the detection of only one SS, one SC and I CC baby. Overall 53 mothers were believed to have the sickle cell trait but the fathers of 2 infants with sickle cell disease were believed by the mother to have an AA phenotype. This new information should be presented in the results and not in the discussion, along with the possible explanation – were these beta thalassaemia traits, not the fathers, or assumed to be normal because they were well. The difference between ‘willingness’ and ‘affordability’ in Table 2 was not clear to this reviewer. Overall the paper is far too long and poorly organized, the numbers too small for reliable conclusions and with 95% deliveries occurring in hospital/health care centres, it seems that greater effort should be put into sample collection at birth. ****** 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:** Graham R Serjeant [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.0242861.r001
Revision 1
25 Oct 2020 Author Response Editor Comments: Your paper addresses and important question of public health importance in Africa, and globally: the screening of Sickle cell disease. Although the authors have a genuine attempt to address your request question, in its present form, the methodology and quality of the reporting need some major improvement as indicated by both reviewers. Moreover, more background information on the setting (Nigeria) are needed to put the paper into context. Population size? SCD incidence and prevalence? General level of formal education? Poverty indices? National health system? Available public health policies and current practices regarding SCD screening; Availability and access to comprehensive services for SCD prevention and care. Please carefully address point-to-point the editor and reviewers’ comments, as this is expected to improve the quality of your text. Author’s Comments: Thank you, sir, for your comments. The methodology and quality of the reporting has been reviewed with major improvement as indicated by the reviewers. Also, more background information on the setting (Nigeria) have been added to put the paper into context in the method section. (Page 6-7; Lines 134-148) We have carefully addressed the point-to-point the editor and reviewers’ comments, to improve the quality of the manuscript. Reviewer #1 Original comments of the reviewer Reply by the author(s)/ Changes Made Changes done on page number and line number General In general terms, I would advise the authors to refer to the diagnoses as Hb genotypes instead of phenotypes so as not to be confused with clinical phenotypes. Thank you, Sir, for all the comments. This has been corrected throughout the manuscript All pages Introduction There’s need to include in the introduction, the justification for using POCT in newborn screening in preference to other available screening methods especially in resource-poor areas. A brief mention of previous work with HemoTypeSC in Nigeria and other places is also apropos. These has been included in the introduction. Pages 4-5 Lines 90-99 There are many grammatical and syntax issues and the authors are advised to review the whole manuscript carefully in this regard. Some suggested corrections are outlined below: Grammatical and syntax issues have been addressed carefully. All pages Abstract: Line 31, should read “……comprehensive management is not…..” Corrected Pg. 2; Line 33 Line 39, should read “The haemoglobin genotype of mother-infant pairs…..” Corrected Pg. 2; Line 41 Line 41, should read “Data were analysed with SPSS version 22”. Corrected Pg. 2; Line 43 The whole of the introduction needs to be restructured. Currently it just one long paragraph and it does not flow well. Apart from briefly introducing sickle cell disease epidemiology, it should focus on the problems associated with newborn screening and the current methods as mentioned above Line 59 - 62, “In high income countries where the infrastructure for universal newborn screening, early intervention and comprehensive care exist mortality has reduced from 16% to <1% with less than 1% global disease burden and over 90% of babies born with SCD surviving into adulthood”. It is not clear if the 16 to 1% figure is referring to overall mortality or only in childhood. DONE accordingly This statement has been rephrased Pages 3-6; Lines 53-128 Pg.4; Lines 77-80 Materials and Methods Lines 88 – 90. The sentence “The State has the highest population in Nigeria with twenty local government areas (LGA), and this study took place in one of them which was selected by simple random sampling through ballot” needs to be restructured. The statement has been restructured Pg. 7 Line 150-151 Lines 127 – 133. Most of the description of HemoTypeSC given here rightly belongs in the introduction. The description of HemoTypeSC has been moved to the introduction. Pg. 5 Line 101-108 Line144, should read: “…heelprick of each of the infants by trained ….” Corrected Pg. 8; Line 188 Line 147, The infants’ blood samples were….” Corrected Pg. 9; Line 191 Line 153, should read “…. while the results of the confirmatory test were communicated….” Corrected Pg. 9; Line 201 Line157 – 162. This section, starting with “Feasibility.” should be in a new paragraph. Moreover, it is not clear how the authors arrived at the cut-off figures quoted. Are they from previous studies? If so, the source should be referenced; otherwise their basis should be explained. This section has been moved to a new paragraph The cut-off figures were the standard set for the feasibility before the study was conducted. These data shows that the intervention is practical and feasible. They were not quoted from previous study Pg. 9; Lines 207-212 Results: Line 174, should read, “Socio-demographic characteristics of mother-infant pairs”. Corrected Pg. 10; Line 231 Line 206, should read, “Ninety-four (74.6%) of 126 mothers who refused….” Corrected Pg. 12; Line 270 Line 218, delete “the cost of” Deleted Table 2: The title of the second column is not clear. It is certainly not frequency, but number (n) of individuals affected. The total of 291 can be moved to the title of the table. Frequency has been changed to number of participants (n) The total number of participants in each column/row has been indicated Pg. 13; Line 291 The section on “Reasons for not wanting self/child to be screened” should be in a separate table since the denominator is not 291, but the 126 that did not agree to be screened. It this is true, the percentages given in the table cannot be correct. Yes, 126 participants did not want their child to be screened. But the question referred to reasons why both mothers and child refused screening. Not only the infants. Moreover, the question had multiple responses and participants had opportunity to pick more than one answer. This was indicated by the sign () with the explanation given below the table. Table 2; page 13 Discussion: Apart from the accuracy of HemoTypeSC and its low cost, the other disadvantages of HPLC in a resource-poor environment should be stressed. These include the need for highly skilled personnel, reagents and electrical power, which, is quite often, not available. This point has been stated in the introduction. To avoid repetition in the discussion. Pg. 4; Lines 90-99 Line 292 - 293, should read “…with the creation of a comprehensive treatment center in each of the 6 geopolitical zones….” Corrected Pg. 16; Line 355 Line 305, what is DHS? demographic and health survey. Now included Pg. 17; Line 368 Line 316, should read “The mothers of the two infants who were diagnosed…..” Corrected Pg. 17; Line 379 Line 330, a new paragraph should begin with the sentence, “The majority of the mothers…..” Done. Pg. 18; Line 391 Reviewer #2: Reference is made to a paper reporting that only 36% deliveries take place in health facilities in Nigeria yet 95% of the studied population delivered in hospitals/health centres. Thank you, sir, for this point. The 95% in this study only attended antenatal clinic in hospital/health facilities but not delivered in same. Table 1; pg.11 Attachments Attachment Submitted filename: Response to Reviewers.docx* https://doi.org/10.1371/journal.pone.0242861.r002
11 Nov 2020 Decision Letter - Ambroise Wonkam, Editor Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria------A pilot study PONE-D-20-26306R1 Dear Dr. OLUWOLE 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, Ambroise Wonkam Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0242861.r003
Formally Accepted
23 Nov 2020 Acceptance Letter - Ambroise Wonkam, Editor PONE-D-20-26306R1 Feasibility and acceptability of early infant screening for sickle cell disease in Lagos, Nigeria------A pilot study Dear Dr. OLUWOLE: 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 Professor Ambroise Wonkam Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0242861.r004

Open letter on the publication of peer review reports

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

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

Learn more at ASAPbio .