Peer Review History
Original SubmissionFebruary 27, 2022 |
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PONE-D-22-05903Childhood meningitis in rural Gambia: 10 years of population-based surveillancePLOS ONE Dear Dr. Ikumapayi, 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. Two reviewers agreed that your manuscript would benefit from further changes and made many constructive comments. Please address all of them before resubmitting. Please submit your revised manuscript by May 16 2022 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:
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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. [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 Reviewer #3: Partly ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes Reviewer #3: 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 Reviewer #3: 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 Reviewer #3: 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: In this article, the authors describe the disease burden and microbiological features of acute bacterial meningitis, non-bacterial meningitis, and suspected meningitis in rural Gambia through analysis of population-based surveillance data during 2008-2018. This is an interesting and important paper, but some re-structuring, elaboration, and clarifications are needed to help the reader interpret the results. Major comments: 1. The presentation of etiology in the results section includes serotype and serogroup results for Neisseria meningitidis and Haemophilus influenzae; however, serogrouping and serotyping of these two pathogens, respectively, are not mentioned in the methods. Please discuss in the methods section. 2. The percentages in Table 1 for age categories are confusing to interpret, as they do not add up to 100%. Additionally, in the text, the primary outcomes of interest are stated as incidence of ABM and NBM vs. CSM, but in Table 1, the groupings don’t reflect this (NBM and CSM are combined into a single category). I would recommend re-grouping the categories in the table to align with the text. a. In particular, lines 173-174 reference Table 1 to compare gender distribution of ABM and NBM, but table 1 does not have NBM by itself, so the comparison between ABM and NBM can’t be made. I recommend either removing or rephrasing this sentence or re-structuring the table. 3. Figure 1 shows that patients who only had a CSF collected were much more likely to be positive (92/(92+258) = 26%) than those who had both blood and CSF (53/(53+711) = 7%). This suggests that there is something systematically different between patients who had both blood and CSF collected and those who had CSF alone. Can the authors shed light on this point? Were blood samples collected only if they couldn't get a CSF or if the CSF was negative? It would be interesting to see data on the concordance between blood and CSF culture results. a. In addition, it would be helpful to provide more information in the methods on specimen collection methods/criteria, particularly the volume of specimen collected for each patient and if there were different criteria for collecting blood vs. CSF specimens. Minor Comments: 1. The authors mention that children with clinical signs of meningitis who had a positive rapid ICT diagnostic test for malaria and normal leukocyte count were excluded from the analysis. It would be interesting to know how many children were excluded from the analysis each year for this reason. a. In addition, in lines 184-187, an association is made between high meningitis incidence and increased cerebral malaria in 2011. If there was a greater number of patients who tested positive for malaria in 2011 compared to other years, please state this to substantiate the claim of association. Lastly, discussion of this interpretation should be in the discussion section instead of results. 2. There is little information provided on patients presenting with clinical meningitis signs without a sample collected are accounted for in the analysis, although they account for over 10% of patients with clinical signs of meningitis (172/1,599). It would be helpful to discuss barriers that contributed to no samples being collected among these patients, and if possible, the case fatality rate or any follow-up clinical observations made of these patients. 3. Throughout the paper, the authors do not mention the role of seasonality in their analysis. Literature suggests that the Gambia experiences similar meningitis season patterns as seen in other meningitis belt countries. It would be interesting to see how the incidence of ABM, NBM, and CSM differ between the dry and rainy seasons during the 10 years. An epi curve could be helpful to depict this relationship. 4. Line 67: “meningitis-belt” should not be hyphenated. 5. Line 68: the authors say that the region “still” experiences high rates of meningitis. It could be helpful to provide some context – “still” in reference to when? Or the authors can just say a region that has historically experienced high rates… 6. Typo in line 72: “N. meningitides” should be “N. meningitidis” 7. Line 97: sentence starting with “The estimated…,” should be moved to results section. 8. Lines 121-124 “All bacterial antigen…” should be moved to results section. 9. In the second half of table 1 (Died, Survived, Total), the percentages would be more informative if they were presented as row percentages, showing case fatality rate for ABM, CSM, and NBM (instead of breaking down the percentage of deaths into disease categories). 10. In Table 2a, there is a sharp decline in number of cases and incidence reported in 2016 and 2017 for NBM and ABM, and to a lesser extent, CSM. Are there any hypothesized reasons for this? 11. Line 201-202 states CFR “varied significantly” and references Figure 2a, but this figure does not present any statistical testing results. I recommend changing the wording to something along the lines of “varied drastically.” 12. Please clarify whether “Non-Hib” in Table 3 is meant to say, “Hi non-b” and change accordingly. 13. Lines 243-246: It is confusing why certain antibiotics are highlighted in the text and not others. I suggest providing a broader summary statement of the full breadth of testing that was done (e.g. most bacterial isolates were susceptible to clinically relevant antibiotics) and clearly explaining why certain results are referenced in the text (e.g. of antibiotics commonly used for ABM treatment...) 14. Lines 285-287 “Our study also showed…” presents new data analysis findings and is in the discussion section. Please move this to results. 15. The author references cumulative incidence from a study that was done in 2013 (line 309), but this value needs to be put in the context of specific time frame. Was it annual incidence? A specific period? Please specify. 16. Line 326 “against the emergence of antibiotics” – do you mean “antibiotic resistance?” Reviewer #2: This is a well-written article about the epidemiology of meningitis in Ghana between 2008 and 2017. While authors detected low number of culture positive cases and also high number of suspected meningitis cases due to malaria with neurological involvement, 10 years findings show accurate data for real world vaccine effectiveness. I have some minor points: 1- Authors need to add vaccine schedule for conjugated pneumococcal vaccine (3 plus one or 3 plus zero or other). 2- Case Fatality rate of pneumococcal meningitis and sepsis (positive blood culture) was very high, 34.1% (higher than Neisseria meningitidis). Authors have data about the case fatality rate for each serotypes (I know that the number cases for each serotypes was low but need to add some information about this high CFR for pneumococci, like underlying disease, age or other risk factors if available)? CFR of non-bacterial meningitis cases (culture and gram stain negative) were also higher than expected, 8.6% of children with pleocystosis dies. It is difficult to say something about exact etiological cause of this cases, (especially children below 2 years old) however it seems bacterial causes like S. pneumoniae or N. meningitidis (my personal opinion). 3- Maybe authors could add some information about newly authorized conjugated pneumococcal vaccine coverage (PCV15 and PCV20) for this settings, especially post PCV13 era. Reviewer #3: General comments The manuscript presents important epidemiological data on the incidence and case fatality rates for different clinical categories of meningitis (CSM, ABM, NBM [see below]) among rural Gambian children for an extended period of time (2008-2017). Critically, the data presented indicates case fatality rates for meningitis have not declined over time (Figure 2a). Similarly, the overall incidence for meningitis does not appear to have declined over time - Table 2a (despite vaccine strategies). Culture proven bacterial meningitis again appear to represent a low number of suspected cases. The manuscript highlights a gap in diagnosis, with continued high incidence of clinically suspected meningitis (and sub-groups), with child cases continuing to demonstrate poor outcome (particularly among ABM cases). The manuscript would benefit from some clarification of the methods and definitions employed. It would also benefit from more detailed documentation and employment of statistics to further support observations seen in the Tables/Graphs. Clinical Categories analysed:- CSM – clinically suspected meningitis ABM – acute bacterial meningitis NBM – non-bacterial meningitis In addition, the authors describe the current diagnostic pathway for The Gambia/Upper River Region of The Gambia. They highlight the need for “newer molecular diagnostics”, indicating some level of molecular testing is available (despite not being presented in this study). Specific comments Authors state (line 117) - “The definition of acute bacterial meningitis (ABM) was a CSF leucocyte count >5/mm3, and a positive culture of CSF or blood in a patient with clinical signs of meningitis”. However, they also state (line 170) “Blood and CSF were obtained from 764 children, blood only from 306, and CSF only from 171”. I understand from Figure 1 and ‘surveillance procedures’ that of the 1,427 samples cultures included in this study, 24/169 positive cultures, 34/41 contaminant and 248/1,217 Negative cultures, were derived from blood only samples (n=306). Is this correct? It would be useful to add the three clinical categories (CSM, ABM and NBM) to Figure 1 to clarify what sampling was performed for each category. Further methodological description is needed to confirm that whilst microbiological investigations were carried out on blood only sampling (n=306), ASM and NBM categories were confirmed via sampling of both blood and CSF, with a positive or negative culture in CSF and/or blood needed to fit either category, respectively. It would be useful to present the range for CSF white cell count among all ABM cases (where LP performed), particularly comparing CSF leukocyte count among ABM cases identified by positive CSF or blood culture. Among those cases where blood only was collected, how did authors distinguish between blood stream bacterial infection (positive blood culture) with impaired consciousness and acute bacterial meningitis (ABM)? ABM definition used in this manuscript doesn’t typically apply to infants under 1 month (CSF >5 cells/mm3 is defined as a normal among children <1 month of age). For infants under 1 month of age, higher levels (e.g. 10-22 cells/mm3) are accepted as a cut off for abnormal. What portion of ABM cases were aged under 1 month. Application of the CSF leukocyte cut-off <5cells/mm3 to children <1 month may potentially contribute to the manuscript’s high estimated incidence of NBM among children under 2months of age. Incorporating this cut off within the current ABM definition and reanalysing the category assignment for this age group is needed. How did the authors define children with symptoms of meningitis, positive CSF bacterial culture and CSF leukocytes below 5 cells/mm3? Were these cases defined as “contaminants” (documented in Figure 1)? It would be good to know what pathogens were detected in the ‘contaminant’ group. As the authors are aware, you can have meningitis (with CSF positive bacterial culture) without a raised CSF leukocyte count, particularly among immuno-supressed children. NBM is potentially a misleading term. I suggest renaming the “NBM – non-bacterial meningitis” clinical category to “SNBM – Suspected non-bacterial meningitis” or “NCM – non-categorised meningitis”, since no diagnostics were employed to identify viral or fungal pathogen, or exclude bacterial meningitis, whilst negative by culture, that may have been detected by molecular methods. Laboratory methods Authors do not provide information on which bacterial species were investigated using bacterial antigen tests. They do not provide information on which tests/kit were employed. Gold standard diagnosis is typically via culture (not antigen tests). It would be useful to present which ABM cases were identified using antigen tests only (i.e. culture negative) and the correspondence between culture positive and positive antigen tests for CSF or blood samples. Whilst CSF bacterial antigen test is not the gold standard, authors note CSF antigen were paired with CSF culture, and tested according to WHO procedures. They also indicate 100% accuracy of antigen tests compared with culture in CSF (lines 121-124). It would be useful for authors to additionally describe the common practise for laboratory diagnosis in the region within the ‘surveillance procedures’ (e.g. whether kits are employed for presumptive diagnosis whilst waiting for culture or confirmatory following culture or gram stain). Statistics Authors should define how p values, odds ratios and confidence intervals were derived and what software package was employed. Authors should also define and present further detail on how disease incidence was calculated. Results Table 1 Baseline Characteristics Unclear how the percentages (%) are derived in age sub-groups across the three clinical categories. I suggest the denominator should be all ages (within each clinical category). For example, in the sub-group <2 months within ABM <2mo n=27; all ages n=169 – therefore % aged 2mo is 27/169=16% (not 50% as presented) Odds ratios need to be presented with associated P values Similarly, for Outcome – denominator should be all cases (doesn’t make clinical sense to pick NBM as the reference group) Odds ratio should be associated with P values again So for ABM died n=49; Survived=120; % died 49/169= 28.99%; P value <0.001; odds ratio 2.97 NBM died n=18; Survived=191; % died 18/209 = 8.6%; P val. = 0.019; OR 0.53 CSM died n=134; survived n=915; % died = 134/1049 = 12.77; P val.=0.022; OR 0.68 Overall (all groups) died n=201; survived n=1226; % died 201/1427; = 14.1% i.e. ABM significant higher proportion of deaths in ABM group compared to proportion in all groups combined. and NBM and CSM significantly lower proportion of deaths compared to all groups combined (lowest among NBM) Table 3: It would be useful to present associated P values for each pathogen that shows a statistically higher number of cases associated with death compared to all pathogens across all ABM cases (or confirm no statistical difference for any individual pathogen). Table 4: It would be useful to present associated P values for Chi square test of vaccine associated vs non-vaccine associated serotypes pre and post PCV13 vaccine campaign. Table 5: Given the authors have extensive antibiotic resistance on bacteria from 2008-2017, the manuscript would be strengthened by examining this data for changes in antibiotic resistance patterns over time (at least for the more commonly identified pathogens [e.g. S.Pneu; H.Infl; N.Men]). Publications from other regions and other sub-Saharan countries (e.g. Malawi) are reporting increased antibiotic resistance rates over time. Discussion Line 263. “Over the study period, there was steady decrease in the incidence of ABM except in 2012...” This statement does not appear to reflect the results presented in Table 2a on ABM cases and estimated incidence between 2008-2017. Authors should ideally present statistical analyses in results to support their statement. One could potentially argue decline is only seen in 2016-2017. Authors briefly comment on the potential for missed diagnosis in the NBM category with prior-antibiotic use before LP (Line 278). Would be good to expand on the guideline’s vs practise for LP, and usage of empirical antibiotics in the region. Line 326 is incomplete/unclear: “emergence of antibiotics”, do you mean emergence of additional antibiotics or emergence of antibiotic resistance? Overall, the language used in the manuscript is clear, although there are minor typographical errors the authors should correct during revision. ********** 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? 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Revision 1 |
Childhood meningitis in rural Gambia: 10 years of population-based surveillance PONE-D-22-05903R1 Dear Dr. Ikumapayi, 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, Joël Mossong, PhD 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 #2: All comments have been addressed Reviewer #3: 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 #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: Authors made all revisions and the recent version of the manuscript is suitable for publication, if other Reviewer's and Editorial Board also agree Reviewer #3: The authors have made good approach at answering my main queries. ********** 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: No ********** |
Formally Accepted |
PONE-D-22-05903R1 Childhood meningitis in rural Gambia: 10 years of population-based surveillance Dear Dr. Ikumapayi: 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. Joël Mossong Academic Editor PLOS ONE |
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