Invasive Bacterial Meningitis in Mali: Molecular Detection and Serotype Distribution of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Dear colleagues!

Bacterial infections of the central nervous system, especially in children, often have extremely negative consequences. Therefore, if there is an opportunity to get vaccinated, you should use this opportunity. Our time is a time of contrasts, while some voluntarily refuse vaccination (the so-called anti-vaccinationists), others do not have the opportunity to get the desired dose. The overall impression of the article is quite positive, the material is written concisely, simply, and easily understandable.

But some questions and comments arose:

1. The data from 3 years ago is already a bit outdated, why didn't you conduct a study for example 2023-2025?

2. What is the overall vaccination rate in your country? I understand that it is low. I apologize, but in my opinion, it seems a bit strange that in a country with a low vaccination rate and a population of at least 20 million, there are 109 cases of bacterial meningitis in 2 years.

3. Taxonomic names of bacteria are written in italics, and after the first mention - abbreviated

4. Table 2. Distribution of bacterial meningitis according to vaccination status. - vaccination status is unknown - how is it? A person is vaccinated or not - there can be no other

5. Some links in the reference are not opened

6. In-text citations should be in square brackets

Some comments in the attached file.

Best wishes,

Reviewer

Comments for author File: Comments.pdf

Author Response

A point-by-point response

Manuscript Submission ID: microbiolres-4324758

Dear Editor and Reviewers 1,

Thank you for giving us the opportunity to submit a revised version of our manuscript entitled “Invasive Bacterial Meningitis in Mali: Molecular Detection and Serotype Distribution of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria.” We sincerely appreciate the time and effort the editor and reviewers devoted to evaluating our work, and we are grateful for the insightful comments and constructive suggestions provided. We have carefully addressed all comments, and the corresponding revisions have been incorporated into the manuscript. Below, we provide a detailed point-by-point response to each comment. For ease of reference, page and line numbers in yellow refer to the revised manuscript.

We hope that the revisions adequately address the concerns raised and that the manuscript is now suitable for publication. We remain at your disposal should you require any additional information or clarification.

 

Reviewer #1

Dear colleagues!

Bacterial infections of the central nervous system, especially in children, often have extremely negative consequences. Therefore, if there is an opportunity to get vaccinated, you should use this opportunity. Our time is a time of contrasts, while some voluntarily refuse vaccination (the so-called anti-vaccinationists), others do not have the opportunity to get the desired dose. The overall impression of the article is quite positive, the material is written concisely, simply, and easily understandable.

But some questions and comments arose:

Author’s response:

We sincerely thank the reviewer for the positive evaluation of our manuscript and for highlighting the importance of vaccination in preventing severe bacterial infections of the central nervous system in children. We appreciate the recognition of the clarity and accessibility of our work. We are grateful for the reviewer’s thoughtful comments and questions and have addressed each point in detail below.

Comments #1:

 

1. The data from 3 years ago is already a bit outdated, why didn't you conduct a study for example 2023-2025?

Author’s response:

We thank the reviewer for this important comment. The study was conducted using surveillance data collected between January 2021 and December 2022, which represented the most complete and validated dataset available at the time of analysis. Molecular typing and quality control procedures required additional processing and verification before analysis. Moreover, the objective of this study was to characterize circulating invasive bacterial strains during this surveillance period and assess vaccine-related serotype distribution. We acknowledge that more recent data would further strengthen epidemiological interpretation and have added this limitation in the discussion section. Continuous surveillance including more recent years is ongoing and will be the subject of future analyses. We have clarified this point in the manuscript in the limitation section Page 10 lines 389-389.

Comments #2:

2. What is the overall vaccination rate in your country? I understand that it is low. I apologize, but in my opinion, it seems a bit strange that in a country with a low vaccination rate and a population of at least 20 million, there are 109 cases of bacterial meningitis in 2 years.

Author’s response:

We thank the reviewer for this pertinent comment. Vaccination programs implemented in Mali have contributed to improving the epidemiological situation of bacterial meningitis. According to recent national reports, vaccination coverage against meningitis-related pathogens among children under 5 years reached approximately 94% in 2023. However, vaccine coverage remains heterogeneous across regions, and access to healthcare services is still limited in some settings.

The relatively low number of reported cases in our study may be explained by several factors, including underdiagnosis, underreporting, limited access to healthcare, administration of antibiotics before hospitalization or lumbar puncture, and incomplete laboratory confirmation, particularly in remote areas. In addition, our analysis included only laboratory-confirmed cases identified through the national surveillance system.

Therefore, the 103 confirmed cases reported in this study do not represent the total burden or incidence of bacterial meningitis in Mali but rather correspond only to laboratory-confirmed cases with available CSF samples analyzed at the National Public Health Institute during the study period. We have clarified this point in the manuscript and emphasized that the true burden of invasive bacterial meningitis is likely underestimated due to surveillance and diagnostic limitations. Page 10 lines 390-396

Comments #3:

3. Taxonomic names of bacteria are written in italics, and after the first mention – abbreviated

Author’s response:

We thank the reviewer for this relevant comment. The taxonomic names of bacteria have been updated throughout the manuscript and are now italicized and abbreviated after their first mention, in accordance with scientific writing conventions. Please see the revised version of the manuscript  

 

Comments #4:

4. Table 2. Distribution of bacterial meningitis according to vaccination status. - vaccination status is unknown - how is it? A person is vaccinated or not - there can be no other

Author’s response:

We thank the reviewer. In our surveillance context, vaccination status was extracted from notification forms accompanying samples. For some patients, vaccination records or cards were unavailable, and information was missing; these cases were categorized as “unknown vaccination status.” We clarified this in the Methods and Discussion sections.

We clarified this point in the Table 2 legend to improve interpretation.

Comments #5:

5. Some links in the reference are not opened

Author’s response:

We would like to thank the reviewer for their valuable comments. The bibliography has been thoroughly reviewed, and broken links have been checked and corrected where possible. In the revised manuscript, the modification can be found in the references section from The page 11.

 

Comments #6:

6. In-text citations should be in square brackets

Author’s response:

Agree! In-text quotations have been formatted in square brackets, in accordance with the journal's guidelines.

 

All comments and suggestions in the attached file have been carefully reviewed and incorporated into the revised manuscript

Reviewer 2 Report

Comments and Suggestions for Authors

This is an interesting retrospective study examining laboratory findings over a 2 year period.
The study highlights the need for continuous monitoring and the application / development of appropriate vaccination strategy

 

Limitation, the data is representative of one site and findings may not represent other areas. The authors need to address this in the discussion.

L131: cross-sectional  study

L247: ? 1000 or 1001.

The numbers and percentages reported are inconsistent throughout the study. The authors need to check and verify all entries. (prevalnece, postivity rates , etc..)

L264: The reason for non-typing

L272: This is an interesting finding, although non significant, but would be helpful for the authors to speculate on the mechanism

Tables 2 and 3: what is meant by 5ans, 14ans? Unconventional pls adjust

Author Response

A point-by-point response

Manuscript Submission ID: microbiolres-4324758

Dear Editor and Reviewers 2,  

Thank you for giving us the opportunity to submit a revised version of our manuscript entitled “Invasive Bacterial Meningitis in Mali: Molecular Detection and Serotype Distribution of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria.” We sincerely appreciate the time and effort the editor and reviewers devoted to evaluating our work, and we are grateful for the insightful comments and constructive suggestions provided. We have carefully addressed all comments, and the corresponding revisions have been incorporated into the manuscript. Below, we provide a detailed point-by-point response to each comment. For ease of reference, page and line numbers refer to the revised manuscript.

We hope that the revisions adequately address the concerns raised and that the manuscript is now suitable for publication. We remain at your disposal should you require any additional information or clarification.

 

Reviewer #2

This is an interesting retrospective study examining laboratory findings over a 2 year period.
The study highlights the need for continuous monitoring and the application / development of appropriate vaccination strategy

Author’s response:

We thank the reviewer for this positive and encouraging feedback.

Comments #1:

Limitation, the data is representative of one site and findings may not represent other areas. The authors need to address this in the discussion.

Author’s response:

We thank the reviewer for this important comment. We agree that the findings may not fully represent the epidemiological situation across all regions of the country. Although data were collected through the national surveillance system coordinated by the National Institute of Public Health, differences in healthcare access, surveillance performance, case reporting, and laboratory diagnostic capacity may influence case detection. We have addressed this limitation by adding a specific section of study limitations describing potential limitations regarding representativeness and possible underestimation of the true burden of invasive bacterial meningitis. Page 10 lines 383-396

Comments #2:

L131: cross-sectional  study

Author’s response:  

We thank the reviewer for this comment. We agree that the term “cross-sectional study” did not accurately reflect the study design. The description has been revised to indicate that this study was a prospective observational study based on national surveillance data collected between January 2021 and December 2022, which better represents the continuous collection and analysis of cerebrospinal fluid samples during the study period. Please refer to methods section page 3 line 129.

Comments #3:

L247: ? 1000 or 1001.

Author’s response:

We thank the reviewer for identifying this inconsistency. The reported number was carefully verified, and the inconsistency was corrected throughout the manuscript. The total number of samples included in the analysis was 1000.

Comments #4:

The numbers and percentages reported are inconsistent throughout the study. The authors need to check and verify all entries. (prevalnece, postivity rates , etc..)

Author’s response:

We thank the reviewer for this careful observation. All reported numbers, percentages, prevalence estimates, and positivity rates were thoroughly reviewed and verified throughout the manuscript. Identified inconsistencies were corrected to ensure accuracy and consistency across the text, tables, and figures.

Comments #5:

L264: The reason for non-typing

Author’s response:

We thank the reviewer for their insightful comments.                                          

We clarified that 17 pneumococcal-positive samples could not be typed because the PCR assay targeted only 21 serotypes and some circulating strains were outside the panel.

Page 7, line 266-268.

Comments #6:

L272: This is an interesting finding, although non significant, but would be helpful for the authors to speculate on the mechanism

Author’s response:

L272: We thank the reviewer for this relevant observation. Although this result is not statistically significant, we have expanded the Discussion section to propose hypotheses and biological or epidemiological mechanisms that could explain this observation.

Comments #7:

Tables 2 and 3: what is meant by 5ans, 14ans? Unconventional pls adjust

Author’s response:

We agree ! This was a mistake. We corrected to years thank you.          

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Dear colleagues!

The authors systematically revised the article, which significantly improved its quality.

However, some points from my previous review were not taken into account, namely:

lines 250-252 - “Among the 1,000 patients included, 56.6% were vaccinated, 17.1% were unvaccinated, and 26.3% had unknown vaccination status.”- it is better to provide information in quantitative numbers — “Among the 1,000 patients included, 566 were vaccinated, 171 were unvaccinated, and 263 had unknown vaccination status.”

line 252-253 - “The proportion of positive cases was higher among unvaccinated subjects (19.3%) compared with vaccinated subjects (8.3%)...” - replace subjects → persons

In my opinion, the “Limitations” section is unnecessary. All that is needed is to add a paragraph in the “Materials and Methods” section that would begin with the words “Limitations of our study are related to ....”

Regards,

Reviewer

Author Response

A point-by-point response

Manuscript Submission ID: microbiolres-4324758

Dear Editor and Reviewers, 

Thank you for giving us the opportunity to submit a revised version of our manuscript entitled “Invasive Bacterial Meningitis in Mali: Molecular Detection and Serotype Distribution of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria.” We sincerely appreciate  continued time and effort the editor and reviewers devoted to evaluating this. We are grateful for the positive assessment of the revised manuscript, as well as for the additional constructive comments provided.

We have carefully considered all remaining comments and incorporated the corresponding revisions into the manuscript where appropriate. Below, we provide a detailed point-by-point response to each comment. For ease of reference, page and line numbers highlighted in yellow refer to the revised manuscript.

We hope that the revisions adequately address the remaining comments. We remain available should any additional clarification or modification be required.

Thank you again for your valuable feedback and constructive suggestions.

Reviewer #2

Dear colleagues!

The authors systematically revised the article, which significantly improved its quality.

However, some points from my previous review were not taken into account, namely:

Author’s response:

Thank you. We hope that the revisions made have now adequately addressed the remaining concerns.

Comments #1:

lines 250-252 - “Among the 1,000 patients included, 56.6% were vaccinated, 17.1% were unvaccinated, and 26.3% had unknown vaccination status.”- it is better to provide information in quantitative numbers — “Among the 1,000 patients included, 566 were vaccinated, 171 were unvaccinated, and 263 had unknown vaccination status.”

Author’s response:

Agreed! We have revised the sentence by replacing percentages with absolute numbers. The text now reads:

“Among the 1,000 patients included, 566 were vaccinated, 171 were unvaccinated, and 263 had unknown vaccination status”. Lines 255

Comments #2:

line 252-253 - “The proportion of positive cases was higher among unvaccinated subjects (19.3%) compared with vaccinated subjects (8.3%)...” - replace subjects → persons

Author’s response:  

Agreed! The term “subjects” has been replaced with “persons”. Please take a look at Lines 256-257

Comments #3:

In my opinion, the “Limitations” section is unnecessary. All that is needed is to add a paragraph in the “Materials and Methods” section that would begin with the words “Limitations of our study are related to ....”

Author’s response:

We thank the reviewer for this valuable suggestion. Following this recommendation, we have removed the dedicated “Limitations” section and incorporated a concise statement on study limitations into the Materials and Methods section. Lines 139-143

 

Author Response File: Author Response.pdf