Sequelae following an epidemic of meningococcal meningitis in Niger in 2022

Abdoul-Aziz Idrissa; Salifou Atti; Roger Kiamvu Wasaulua; Serge Kazadi; Ousmane Sani; Elhadji Ibrahim Tassiou; Ousmane Guindo; Georges Tonamou; Iza Ciglenecki; Matthew E. Coldiron

doi:10.1371/journal.pone.0323223

Peer Review History

Original SubmissionOctober 3, 2024
3 Oct 2024 Author Response https://doi.org/10.1371/journal.pone.0323223.r001
5 Nov 2024 Decision Letter - Kelli Barr, Editor PONE-D-24-43633Sequelae following an epidemic of meningococcal meningitis in Niger in 2022PLOS ONE Dear Dr. Coldiron, 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. Both reviewers identified parts of your manuscript that need clarification to better understand your data. Please submit your revised manuscript by Dec 20 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. 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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: Yes Reviewer #2: No ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This manuscript is a very well written account of sequelae following an epidemic of meningococcal disease in Niger in 2022 due to serogroup C. It is very timely as there is short fall in data on sequelae in developing countries. This will be of benefit in the WHO roadmap of defeating meningitis by 2030. Minor Comments 1. Was this all presenting as meningitis or meningitis/septicaemia? 2. Add the manufacturer of the ACW polysaccharide vaccine & add narrative as to why a polysaccharide vaccine for MenC was used in under 2 years of age when it is not efficacious? 3. Add a comment on the delay with administration of polysaccharide vaccination ie over 14 weeks and the benefits of conjugate vaccine eg MenFive that is now being utilised in Nigeria. 4. Where any strains cultured ie is the clonal complex of the the MenC strain known, if so please add. Reviewer #2: Review of Sequelae following an epidemic of meningococcal meningitis in Niger in 2022 The manuscript ‘Sequelae following an epidemic of meningococcal meningitis in Niger in 2022’ describes a follow-up survey of survivors of a meningococcal serogroup C epidemic in Niger to determine the burden of sequelae in this setting. The paper is very well written and clearly describes in detail the methodology used as well as the findings and implications. These results provide a valuable insight into the lasting impact of meningococcal epidemics in low income countries. It would be of interest to epidemiologists, public health practitioners and health policy experts. I have a few suggestions that need to be addressed before the paper is accepted. Major comments Results: The results state there were 61/521 living patients with sequelae (11.7%), however the total number of cases in Table 5 is 67 (29+15+9+6+4+4) so the sequelae rate would be 67/521=12.9%. Please correct or explain the difference in the figures. Results: The headline sequelae rate for all of the 521 living cases was 12-13% but we know this includes cases caused by other bacteria (and maybe viruses). It would be interesting to see what the sequelae burden/profile was for the 149 confirmed MenC cases only. Table 4 states that 18% of MenC confirmed cases has sequelae (which is higher than the overall 12-13% rate). Please could you add in an additional column to Table 5 to describe the sequelae profile of just the MenC cases. Although the case numbers are lower, it will give us a strain-specific view of the impact of the meningococcal epidemic, without the extra noise associated with the other non-MenC cases. Line 228-232: The authors state that 27 additional cases that weren’t on the initial linelisting were identified during the follow-up survey. But these don’t seem to be included in the analysis itself (the 570 number is used, not the 597). Please make it clear and explain if and why they weren’t included. Lines 244-249: Do you have any information on timing of vaccination? The results states how many cases were vaccinated but it doesn’t state whether the vaccines were given before or after disease onset. Figure 1 suggests there were cases after the vaccination campaign began, so could there have been vaccine failures/break through cases (i.e. cases in vaccinated individuals)? Lines 244-249: The authors included vaccination data only for the 165 confirmed cases, but are there data available for the non-confirmed followed-up cases (i.e. the 570)? If so, please add these in. Table 4: I suggest another row is added in under the PCR results with the data for the cases that weren’t tested/laboratory confirmed (maybe change “PCR results” to “Laboratory confirmation”). This will better illustrate how the confirmed cases compare to those that weren’t laboratory confirmed in terms of % with sequelae. Line 260: “Prophylaxis was reported by at least one person in 215 of the 570 households (38%)”. But the 570 figure is for individual cases, not households. So the percentage figure is incorrect. What was the total number of households included in the analysis? This needs to be stated and the percentage figure corrected. Minor comments Line 54-55. “in Africa” repeated, would rephrase Line 57: would add ‘typically’- “typically presenting with sudden onset fever with headache and stiff neck” Line 61- need reference(s) for the 5-10% figure. ****** 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: Ray Borrow 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. https://doi.org/10.1371/journal.pone.0323223.r002
Revision 1
20 Dec 2024 Author Response Reviewer #1: This manuscript is a very well written account of sequelae following an epidemic of meningococcal disease in Niger in 2022 due to serogroup C. It is very timely as there is short fall in data on sequelae in developing countries. This will be of benefit in the WHO roadmap of defeating meningitis by 2030. Authors’ response: Thank you for this comment. Minor Comments 1. Was this all presenting as meningitis or meningitis/septicaemia? Authors’ response: During the epidemic, the only case definitions used in health facilities were those referred to in the article, the usual WHO case definition. It is therefore possible that cases with meningococcaemia alone were therefore not captured in the surveillance system. 2. Add the manufacturer of the ACW polysaccharide vaccine & add narrative as to why a polysaccharide vaccine for MenC was used in under 2 years of age when it is not efficacious? Authors’ response: We have added the manufacturer (Finlay) and corrected the error – the campaign indeed targeted persons 2-29 years of age. 3. Add a comment on the delay with administration of polysaccharide vaccination ie over 14 weeks and the benefits of conjugate vaccine eg MenFive that is now being utilised in Nigeria. Authors’ response: We thank the reviewer for this comment – and have added this point into the discussion. 4. Where any strains cultured ie is the clonal complex of the the MenC strain known, if so please add. Authors’ response: Unfortunately, these data were not available. Where culture was performed, results were not linked into the databases that were used for this study. Reviewer #2: Review of Sequelae following an epidemic of meningococcal meningitis in Niger in 2022 The manuscript ‘Sequelae following an epidemic of meningococcal meningitis in Niger in 2022’ describes a follow-up survey of survivors of a meningococcal serogroup C epidemic in Niger to determine the burden of sequelae in this setting. The paper is very well written and clearly describes in detail the methodology used as well as the findings and implications. These results provide a valuable insight into the lasting impact of meningococcal epidemics in low income countries. It would be of interest to epidemiologists, public health practitioners and health policy experts. I have a few suggestions that need to be addressed before the paper is accepted. Major comments Results: The results state there were 61/521 living patients with sequelae (11.7%), however the total number of cases in Table 5 is 67 (29+15+9+6+4+4) so the sequelae rate would be 67/521=12.9%. Please correct or explain the difference in the figures. Authors’ response: We thank the reviewer for catching this. Both the proportion reported in the text and the proportions in the table are correct: some patients reported more than one sequela. This was obliquely referenced in the text, and we have added clarification in the Table legend to ensure that this is more easily understood. Results: The headline sequelae rate for all of the 521 living cases was 12-13% but we know this includes cases caused by other bacteria (and maybe viruses). It would be interesting to see what the sequelae burden/profile was for the 149 confirmed MenC cases only. Table 4 states that 18% of MenC confirmed cases has sequelae (which is higher than the overall 12-13% rate). Please could you add in an additional column to Table 5 to describe the sequelae profile of just the MenC cases. Although the case numbers are lower, it will give us a strain-specific view of the impact of the meningococcal epidemic, without the extra noise associated with the other non-MenC cases. Authors’ response: We thank the reviewer for this comment. We have added two columns (n and %) to Table 5, and added a sentence in the discussion section, as indeed, the prevalence of deafness was 10% and paralysis 6.4% among those with confirmed NmC, which is a point worth highlighting. Line 228-232: The authors state that 27 additional cases that weren’t on the initial linelisting were identified during the follow-up survey. But these don’t seem to be included in the analysis itself (the 570 number is used, not the 597). Please make it clear and explain if and why they weren’t included. Authors’ response: These cases were not included in our clinical descriptions as there was no additional information available regarding their clinical course (because they were not in the linelist). We have added a sentence in the results section to clarify this and justify their exclusion from the descriptions. Lines 244-249: Do you have any information on timing of vaccination? The results states how many cases were vaccinated but it doesn’t state whether the vaccines were given before or after disease onset. Figure 1 suggests there were cases after the vaccination campaign began, so could there have been vaccine failures/break through cases (i.e. cases in vaccinated individuals)? Authors’ response: Thanks for this point – which has been a recurring question in this area which has received multiple vaccination campaigns. Specific dates of vaccination were difficult to obtain in the survey – few participants had vaccination cards. In the four cases that did have dates, all vaccinations happened post-illness in 2022. In the end, it’s a very interesting question but not one that we’re really able to comment on given the data at our disposal. Lines 244-249: The authors included vaccination data only for the 165 confirmed cases, but are there data available for the non-confirmed followed-up cases (i.e. the 570)? If so, please add these in. Authors’ response: We have added this information at the reviewer’s suggestion. There were no differences in vaccination coverage between confirmed and non-confirmed cases. Table 4: I suggest another row is added in under the PCR results with the data for the cases that weren’t tested/laboratory confirmed (maybe change “PCR results” to “Laboratory confirmation”). This will better illustrate how the confirmed cases compare to those that weren’t laboratory confirmed in terms of % with sequelae. Authors’ response: These data are already presented as the last line of Table 4 in the row “PCR not performed”. We have changed the title of that section of the table to “Laboratory confirmation” at the reviewer’s suggestion and hope this will help clarify. Line 260: “Prophylaxis was reported by at least one person in 215 of the 570 households (38%)”. But the 570 figure is for individual cases, not households. So the percentage figure is incorrect. What was the total number of households included in the analysis? This needs to be stated and the percentage figure corrected. Authors’ response: Thanks to the reviewer for pointing out this error, which has now been corrected. 534 individual households were represented. Minor comments Line 54-55. “in Africa” repeated, would rephrase Authors’ response: The second “in Africa” has been deleted. Line 57: would add ‘typically’- “typically presenting with sudden onset fever with headache and stiff neck” Authors’ response: We have updated. Line 61- need reference(s) for the 5-10% figure. Authors’ response: The reference has been added. Attachments Attachment Submitted filename: Response to reviewers 20241220.docx https://doi.org/10.1371/journal.pone.0323223.r003
14 Mar 2025 Decision Letter - Ray Borrow, Editor PONE-D-24-43633R1Sequelae following an epidemic of meningococcal meningitis in Niger in 2022PLOS ONE Dear Dr. Coldiron, 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 minor points raised during the review process. Please submit your revised manuscript by Apr 28 2025 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. 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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. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed Reviewer #3: (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 Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes Reviewer #3: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes Reviewer #3: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: (No Response) Reviewer #3: Please find attached Reviewer Comments. A couple of comments and suggestions have been highlighted to be effected by the authors. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy . Reviewer #2: No Reviewer #3: Yes: George Gyamfi-Brobbey ******** [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: Reviewer 3 Comments.docx https://doi.org/10.1371/journal.pone.0323223.r004
Revision 2
28 Mar 2025 Author Response Line 24 – 26: Please break the first sentence into 2 parts – seems too long and contain 2 main info. Authors’ response: We thank the reviewer for these positive comments. Line 71 – 75: are you able to state the current treatment guidelines in Niger for treating sequelae following meningococcal meningitis. If Corticosteroids are prescribed by some doctors, do they do so by their own discretion? Authors’ response: We have added additional information that neither empiric steroid use nor standard sequelae screening are part of current Nigerien guidelines. Line 80 – 82: is/was there a follow up to ascertain the effectiveness of the vaccination campaign in this cohort, especially in those under 5 years? Authors’ response: We have specified that no formal VE evaluations took place following the polysaccharide campaigns of 2021 and 2022. Lines 93 and 97: “Suspected case” rather? Authors’ response: We have corrected this terminology. Line 114: Consider “Verbally” informed consent…… Authors’ response: We have corrected this terminology. Line 125 – 126: please change to 16th and 30th November 2022; and similar references throughout the script. Authors’ response: These changes have been made throughout. Line 172 – 174: Can you please add the complete in-text reference, year of publication of these ethical guidelines and owners/authors. Authors’ response: This reference has been added. Line 193: 1001, comma not needed in the figure. Authors’ response: This has been deleted. Line 297: Please delete “during the epidemic.” Authors’ response: This has been deleted. https://doi.org/10.1371/journal.pone.0323223.r005
6 Apr 2025 Decision Letter - Ray Borrow, Editor Sequelae following an epidemic of meningococcal meningitis in Niger in 2022 PONE-D-24-43633R2 Dear Dr. Coldiron, 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, Ray Borrow, Ph.D., FRCPath Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0323223.r006
Formally Accepted
Acceptance Letter - Ray Borrow, Editor PONE-D-24-43633R2 PLOS ONE Dear Dr. Coldiron, 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 You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days 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 Prof. Ray Borrow Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0323223.r007

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