PONE-D-21-16070Estimated incidence and Mortality Rate of Traumatic Brain Injury among Children (0-18 years) in Sub-Saharan Africa. A Systematic and Meta-Analysis.PLOS ONE

Dear Dr. Ackah,

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. The reviewers raised several important issues that must be addressed before this paper can be considered for publication. In addition, please have the manuscript reviewed by an individual with expertise in written English before submitting the revision.

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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

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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: No

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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 presents a systematic review and meta-analysis to determine incidence and mortality rate in TBI for children in Sub-Saharan Africa (SSA). A total of 13 hospital-based articles were included, reporting on a total of 40687 children with TBI. Pooled mortality rate was 8% with substantial variation across regions. The pooled “incidence proportion of TBI” is reported at 18%.

Whilst I am very happy to see a manuscript on TBI originating from SSA (grossly under-represented in the TBI literature), there are a couple of issues which should be addressed:

1.: Please report your age definition for a pediatric population also in the abstract.

2.: It may be due to my ignorance (in which case I beg forgiveness), but what do you mean by a “pooled incidence proportion of TBI”? Proportion of what? Of all patients seen with TBI? Please clarify.

3.: The review reports on a total of 40687 pediatric patients reported in 13 manuscripts. However, I note that the majority of these come from a single study (92%: Lalloo et al 2004). How did you deal with the over-representation of this study? I further note that in terms of incidence, this study appears to be a substantial outlier (Fig 1)

4.: The heterogeneity between studies is large – Is it then appropriate/permissible to do a meta-analysis?

5.: The mortality rate you report is really a Case fatality rate, being only based on hospital series. Is there any way you could put this in perspective to population-based mortality rates?

Reviewer #2: Thank you fort he opportunity to review this important paper. Although I really can grasp the conclusions and recognise the importance of signaling and preventing traumatic Brain Injuries, I have some comments on the paper.

1. Abstract (and also in Methods) : explain abbreviation AJOL

Page 3: Introduction:

Non degenerative injuries tot he head region: this is a confusing term. Better name it Aquired Brain Injury following trauma. In general - to stress the importance of prevention of TBI- I miss an alinea on the burden of ABI in children who survive, in terms of the phenomenon of growing into deficit with increasing cognitive problems as they grow up and as an important cause of lack/ diminishment of future opportunities or down right dependency in adulthood / contributing cause of poverty.

Page 7: Study characteristics:

It would help to explain in which setting data were obttained in different studies. University/ general large or smaller hospitals?? Any idea how many of the children in the different studies were classified as mild, intermediate or severe TBI?? Do for example children with mild TBI in western SSC reach a hospital/ are counted?? This could really chance the estimated numbers of this study.

At what moment was the GCS measured? Admission tot he hospital/ the lowest measured/ at discharge?? GCS is mentioned but the relevance is not further discussed in the paper.

Page 8: Table 1

I miss in the column “duration” the correct year of the reference of Schrieff et al

In the result section there is mention of : Error! Reference source not found - several times: I presume this is an error itself??

In the discussion I miss discussion of factors as: availability of hospitals with neurosurgical and / or intensive care facilities / organisation of health care/ availability of facilities in general as a factor contributing tot the high mortality. There is a dramatic difference between mortality rates in South Africa and West African SSC. There maybe more contributing factors than a chaotic traffic situation causing this difference

Reviewer #3: The authors present results from a systematic review and meta-analysis of TBI among children in Sub-Saharan Africa. They identified 13 studies that reported on mortality from TBI and 4 studies that included information on incident TBI. They further summarize results across studies on the mechanism of injury. The manuscript will be strengthened if the authors consider the following points:

1. Authors are encouraged to have the manuscript read by a native English speaker as there are numerous places where words are missing, phrasing is awkward, or grammar is incorrect. Examples include "children Traumatic Brain Injury" (in Abstract and elsewhere in manuscript), "10-15 age group 37%" (page 3), "concluded that majority of pediatric" (page 3), "children population" (page 4), "information were" (page 5), sentence starting with "Keywords such as" (page 5 -note there are also some missing quotation marks around the words and missing commas between the words), "broad perspectives parameter" (page 6), "studies into three" (page 6), "articles were remained after duplicate removed" (page 7), "The current reviewed showed that" (page 7), and "However, lower than reported in US trauma registry 22.8%" (page 11). Authors also use capitalization unnecessarily ("in Children" (page 3), "whereas Road traffic accidents" (page 3), "severe Pediatric TBI" (page 11), "that Children's TBI" (page 11)) or do not use it when it should be used ("west Africa" (page 2 and 9), "United states" (page 11), "and Mortality Rate" and "among Children" (page 13))

2. Table 1 should include the number of deaths for each study.

3. On page 6, authors state that the average NOS score from two reviewers was used as the final score. Were there any major differences between the reviewers?

4. On page 7 (and in the Abstract and Discussion), when authors present the percentages of RTA and Falls across studies, authors should clarify they are presenting the range of observed percentages, so readers don't think this is a confidence interval or some other estimated quantity.

5. Authors do not refer to any of the figures within the text of the manuscript.

6. Figure 1: authors should provide reasons for exclusion for the box of 200 that gets reduced to 70.

7. On page 9, authors talk about subgroup analyses related to levels of risk of bias, but authors have not yet summarized the studies according to risk of bias (that comes on page 10). Authors might consider reporting on the summary of the risk of bias earlier in the results, so the subgroup analysis has some context.

8. Figure 3 - there is a typo "Moderate Rrisk". Authors should also define in the figure caption what the p-value represents.

9. When authors report the sensitivity analysis of the estimated mortality by leaving one study out, they cite specific studies (page 10). They should be clear in the text that these cited references are the ones left out of the estimate. Also, authors refer to 4 studies for the 9% estimate. There are 4 different studies that when left out, the estimate is 9%, but the confidence interval is not the same across those 4 results. Authors might consider not citing the studies in the sentence, since readers can refer to the table to see which studies were removed for the different results.

10. In the discussion (page 12), authors refer to results about sex differences, but these were not presented in the manuscript.

Minor points:

1. Authors redefine acronyms multiple times (TBI is defined three times within the Abstract, LMIC is defined twice on page 3). Acronyms or abbreviations only need to be defined once in the Abstract (if used) and then once in the main body of the manuscript. Authors do not define AJOL, which appears both in the Abstract and in the body of the manuscript.

2. Throughout the manuscript (Abstract and main text), authors refer to a total of 40687 children across the 13 studies, but with the numbers provided in Table 1, the total number appears to only be 40685. Authors should carefully check the numbers and correct where needed.

3. on page 5, authors state the search was limited to 2000-December 2020. To be clear, authors should state January 2000 - December 2020.

4. on page 5, authors refer to S2 Table 2, but I believe it is S2 Table 1.

5. on page 7: "Glasgow Come Scale" should be "Glasgow Coma Scale"

6. There are several places in the manuscript with "Error! Reference source not found". Authors should check their references.

7. page 10: authors state there are 10 studies of moderate risk of bias, but this should be 9 (based on the cited references and Figure 3).

8. page 10: authors refer to S2 Table 2, but the file is called S3 Table 2. Also, in the table, the Egbonhou study does not have the risk level filled in.

9. Authors define RTA to be road traffic accidents, but then appear to switch to using RTI (maybe road traffic incidents) in the Discussion. Authors should be consistent in their terminology.

10. Figure captions all say "Figure 1"

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Reviewer #1: Yes: Andrew I.R. Maas

Reviewer #2: No

Reviewer #3: No

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PONE-D-21-16070R1Estimated incidence and Case Fatality Rate of Traumatic Brain Injury among Children (0-18 years) in Sub-Saharan Africa. A Systematic Review and Meta-Analysis.PLOS ONE

Dear Dr. Ackah,

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.

You have addressed most of the concerns previously raised by the reviewers but there are a few minor issues that still need to be addressed.

Please submit your revised manuscript by Jan 02 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:

• 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. 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,

Richard Bruce Mink

Academic Editor

PLOS ONE

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Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. 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.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #3: (No Response)

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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

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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

Reviewer #3: Yes

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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: This manuscript is a revision of a previous submission. The authors have mostly addressed all reviewer comments appropriately. Overall, the manuscript is much improved. Personally, I would not really consider all changes an improvement, but this is not the fault of the authors as changes resulted from specific requests/suggestions of reviewers. There are a few relatively minor issues that remain or have arisen anew following the changes implemented:

1.: Abstract, Results: “The current reviewed” should be “The current review”.

2.: Introduction, line 1: I would suggest to change “acquired brain injuries” to “acquired brain injury”

3.: Results, page 8 at the bottom: The sentence “This also ranged from 5.1% in South Africa 29, and 41.2% in south Africa 26” reads a bit strange. It is strange that the extremes of the range are within one country (South Africa). On looking up the citation, they appear to even be from the same hospital, but over a different time period. I would suggest to either delete the entire sentence, to delete the specific mention of South Africa, or – if maintained – add an explanation.

Reviewer #3: The authors have addressed the majority of my earlier concerns. There remain a few minor points and some grammatical/English edits that should be addressed:

1. Abstract (Introduction section): "need for accurate" should be "need for an accurate"

2. Abstract (Results section):"The current reviewed showed" should be "The current review showed"

3. page 5 (1st line): "as the most cause" should be "as the most common cause" and "in all age group" should be "in all age groups"

4. page 5 (1st full paragraph): "need for accurate and" should be "need for an accurate and"

5. page 8 (Study Selection): "inclusion criteria and included" should be "inclusion criteria and were included"

6. Figure 1: in the authors' response to my comment about this Figure, they said the explanation for the reduction from 200 to 70 was due to duplicate records. Maybe there is just confusion in how to read their figure. Typically, these figures show how many articles are at each stage with an intermediate box that shows how many were excluded (and reasons for exclusion) at each stage. For example, their box for "Records after abstracts and title screened" has n=70 articles and the box to the right says that 40 were excluded which then yields the 30 articles in the next box. My original question had to do with the lack of boxes to the right for the 1st 2 boxes (articles identified through database and record after duplicate removed). So, did authors arrive at 200 articles from the original 820 after removing duplicates? If not, what were the reasons that reduced the number from 820 to 200? Similarly, what were the reasons for reducing the 200 articles to 70 articles?

7. page 9 (2nd to last line): change "from 5.1% in South Africa, and 41.2% in south Africa" to "from 5.1% to 41.2%".

8. page 12: change "This approximately corroborate with" to "This approximately corroborates with", "not surprising as study" to "not surprising as the study", "TBI cases hence" to "TBI cases and hence", and "well-coordinated effort are" to "well-coordinated effort is"

9. page 13: change "The current results is similar" to "The current results are similar"

10. page 13: I previously made a comment about the sex-differences in TBI - these are first mentioned in the Discussion. If authors feel this point is important enough to make in the Discussion, it should also be mentioned in the results.

11. page 14: change "fall predominant the cause" to "fall as the predominant cause" and remove "whooping" from the Conclusion section

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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.

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Reviewer #1: No

Reviewer #3: 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.]

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Estimated incidence and Case Fatality Rate of Traumatic Brain Injury among Children (0-18 years) in Sub-Saharan Africa. A Systematic Review and Meta-Analysis.

PONE-D-21-16070R2

Dear Dr. Ackah,

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.

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Kind regards,

Richard Bruce Mink

Academic Editor

PLOS ONE

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