The Molecular Epidemiology of Enterovirus in a Birth Cohort in Nepal

Round 1

Reviewer 1 Report

In this study Shrestha et al aimed to investigates the prevalence of NPEV in stool samples from children below the age of 3 in Nepal. Within the small cohort, the authors look at the seasonality of NPEV and diarrhea as well as genotypes the PCR positive samples which revealed predominantly serotypes of EV-B species such as coxsackieviruses and echoviruses. While the manuscript is logically and clear presented, I have several comments:

 

Line 27: Keywords: I am not sure why the authors added numbers to the keywords.

Line 31: According to the ICTV rules, the virus family name should always be written in front of the virus family. -> family Picornaviridae

Line 34 and Line 40. The authors use poliomyelitis or polio-myelitis. The authors should use one spelling consistently

Line 46: I also would add CV-A24 as a serotype causing hemorrhagic conjunctivitis. 

Line35 and 47. Hand, foot and mouth disease and hand foot and mouth disease. Authors should use one term consistently. 

Line 67: double spacing in front of The

Line 102 see comment at Line 31

Line 139: NPEV is should be NPEVs are 

Line 155: Throughout the discussion the authors should carefully evaluate the singular and plural of EVs and NPEVs. Often the authors use the singular form EV/NPEV even though the plural form EVs/NPEVs is required. 

Line 159 The prevalence of EV -> The prevalence of EVs

Line 167: Can the authors speculate more on the discrepancy on these studies? Is the different peak pattern due to the sample size?

Line 207: In my opinion the authors should tune down their argument that NPEV are the etiological agent of diarrhea in children. I would re-phrase it more carefully since EV RNA will always be found in stool. I am not sure that their data support the hypothesis that indeed these enteroviruses cause diarrhea pathologically. I agree that it is paradox that even though the primary replication site of most of EV is the GI tract, however enteric manifestations such as vomiting and diarrhea are rare. One idea could be to discuss the knowns of the pathology more in the discussion. 

 

 

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Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Dear Editor,

 

Thank you for allowing me to review the manuscript "Enterovirus in a Birth Cohort in Nepal" by Shrestha et al. Upon careful evaluation, several areas require revision in order to enhance the clarity, scientific rigor, and overall quality of the article.

 

Title: I would suggest revising the title better to reflect the scope and focus of the study.

 

Abstract: The abstract should be revised to provide a concise and clear summary of the main objectives and findings of the study. It should also clearly state the research gap or problem the study aims to address.

 

Introduction: While the introduction starts well by emphasizing the importance of enteroviruses and citing the efforts of the World Health Organization (WHO), it would benefit from further elaboration on the significance of the research gap addressed in the study. Specifically, the authors should highlight the potential impacts of implementing a non-polio enterovirus (NPEV) surveillance program in Nepal.

 

Study population and data collection: The manuscript should include information on the study type. Additionally, it would be valuable to provide additional details regarding the sample size, inclusion and exclusion criteria, and the representativeness of the cohort.

 

Real-Time RT-PCR of EV: Specifying the highly conserved region within the Picornaviridae family targeted for NPEV typing (types A to D) is recommended.

 

Discussion: The authors discussed the prevalence of diarrhea and compared it with other studies. In the second paragraph, they discussed the potential clinical implications of the identified serotypes. However, I suggest including another paragraph directly relating the current findings of enterovirus infection to the studied population. This would enrich the manuscript and discussion. For example, it would be valuable to discuss the impact of the hygiene theory and the benefits of early exposure to EV in infected individuals, as discussed  [ref: 10.18544/PEDM-20.03.0008, 10.1002/rmv.639, 10.4161/isl.21570]. Furthermore, it would be worthwhile to explore the correlation of these findings with the current incidence of autoimmune diseases, including type 1 diabetes, in Nepal. Some regions have overlooked this relationship, which may be the case in Nepal [ref: 10.1007/s00125-011-2305-3, 10.1136/bmj.d35, 10.1038/s41574-022-00688-1, 10.3390/microorganisms8101458].

 

Conclusion: The manuscript should conclude with a clear summary of the main findings and their significance. This will help readers understand the key takeaways from the study.

 

References: There are two instances where references are numbered incorrectly and must be corrected.

 

Addressing these points will significantly enhance the quality and readability of the manuscript. I firmly believe that with the necessary revisions, this article can potentially make a valuable contribution to the field. I eagerly await the revised version for further evaluation.

Understandable

Author Response

Please see the attachment. 

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

The authors responded well to my comments. I suggest adding the study design to the title.