Dear Prof. Wanji,

Thank you very much for submitting your manuscript "Observations on the hydrologic network and dynamics of onchocerciasis transmission within nine months following a mass drug administration campaign with ivermectin in the Mbam river drainage, a site with persistent transmission in Cameroon" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.  

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. 

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Wilma A. Stolk, Ph.D.

Guest Editor

PLOS Neglected Tropical Diseases

Jaap van Hellemond

Deputy Editor

PLOS Neglected Tropical Diseases

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Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: The methods were presented

Reviewer #2: 1. The objectives are clearly articulated

2. The study design is consistent with expected standard

3.The population is clearly described and appropriate

4. The sample size is sufficient

5. Statistical analysis is correct to support the conclusion

6. There are no concerns about ethical or regulatory requirement

Reviewer #3: The methods are articulated well and the hypothesis is clearly stated

The study design is appropriate

The population is clearly decribed

The sample size is sufficient

The statistics is fine

There are no concerns about ethical or regulatory requirements

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: The analysis is fine

Reviewer #2: Presentation of the result is satisfactory and consistent with expected standard. However, the results of the revised manuscript should factor in the geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone

Reviewer #3: The analyses presents matches the plan

The results are clearly presented

Tables and Figures are sufficient

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: The conclusion if fine

Reviewer #2: 1There is need for the introduction of the geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone and its impact on the dynamics of Onchocerca volvulus infection in the black flies in the conclusion.

2. The authors discussed how these data can be helpful to advance our understanding of the topic under study

3. The public health relevance of the study was addresses

Reviewer #3: The conclusion support the data presented

The limitations are fine

The author does describe how this data can advance entomology

The public health significance is discussed

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: Minor Revision

Reviewer #2: 1. Title: The title is good, relevant and operational but I suggest that it can be made smarter by reframing as “Hydrologic network and onchocerciasis transmission post ivermectin MDA campaign in the Mbam river drainage, Cameroon”

2. Abstract; Consistent with expected standard but the following corrections on RED can be effected to add advantage to it:

Introduction: The impact of large scale Mass Drug Adminstration (MDA) of ivermectin on Simulium damnosum, which transmits the parasite Onchocerca volvulus is of great importance for onchocerciasis control programmes. We investigated the impact of MDA of ivermectin on entomological indices and also verify if there are hydrologic network factors that could have favoured the transmission of onchocerciasis in this area and contribute to the persistence of disease. We compared three independent techniques to detect Onchocerca larvae in blackflies and also analyzed the hydrologic network within 9 months post-MDA of ivermectin.

Method: Methodology is consistent with expected standard and the experimental design is satisfactory.

Results: Satisfactory but the underlisted correction should be effected:

� Line 49: We used human landing collection method (previously called human bait) to collect 22,274 adult female Simulium flies from Mba River System. Of this number, 9,134 were dissected while 129 pools constituted for

Conclusion: Satisfactory but the under listed corrections should be effected:

� Line 56: Results from fly dissection (Microscopy), real-time PCR and LAMP revealed the same trends

� Key words: Mbam river drainage, MDA Ivermectin Simulium, biting rate, infection rate

2. Introduction: The under listed corrections should be effected:

� Line 82-83: Onchocerciasis is a parasitic disease caused by Onchocerca volvulus, transmitted by the bite of an infective female

� Line 92: The control/elimination of onchocerciasis today relies on ivermectin (Mectizan®) mass drug administration

� Line 95: programmes. Mectizan® has been donated free of charge by Merck and Co.

� Line 96/97: Whitehouse Station, NJ since 1987. Ivermectin must be repeatedly given once a year for more than 15 years (with at least 60% geographical and chemotherapeutic coverage of MDA) to successfully achieve the elimination of onchocerciasis by the year 2030

� Line 128/129: Following the adoption of IVM-MDA as a control/eliminaltion strategy in Cameroon, it has been demonstrated that the Community Directed Treatment with Ivermectin (CDTI) project of Central Region at the level of Bafia had limited impact on

� Line 134: Delete (or Mf are not being cleared in the treated individuals)

� Line 137: vector capacity and efficiency of Simulium damnusum for the transmission of onchocerciasis in this area and

� Lines 139-145: Should be reframed to reflect the objectives of the study not the procedure of study

3. STUDY AREA: Effect the following correction:

� Lines 170-177: The geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone should be included

� Line 181: Collection of Simulium flies by human landing method

� Lines 207 – 272 covering the following should be reframed and summarized.

(i) Genomic DNA extraction from pools of Simulium flies,

(ii) (ii) Detection of O. volvulus in pool-DNA of blackfly using colorimetric O-150 LAMP and

(iii) Detection of O. volvulus / O. ochengi in pool-DNA of blackfly using real-time PCR

4. RESULT: Presentation of the result is satisfactory and consistent with expected standard. However, the results of the revised manuscript should factor in the geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone

5. DISCUSSION: The result of this study is well discussed but the absence of the data on the impact of geographical and chemotherapeutic coverage of the MDA in the past 15 years on the transmission zone should be taken into consideration.

6. CONCLUSION: There is need for the introduction of the geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone and its impact on the dynamics of Onchocerca volvulus infection in the black flies in the conclusion.

7. REFERENCES: The authors demonstrated an in-depth knowledge of the field of study and also made due acknowledgement of existing information. However, there are minor collections that should be effected:

(a) The biological names in reference numbers 20, 25, 30, 35, 36 and 38 should be in Italics

(b) Reference 32 should re-written to be consistent with the expected format.

8. OBSERVATIONS

(a) This study has made original contributions to scientific knowledge by bringing to focus the impact of hydrologic network/characteristics of transmission zone and other factors on onchocerciasis transmission post-mass MDA of ivermectin

(b) The introduction of the geographical and chemotherapeutic coverage of the MDA in the past 15 years of the transmission zone and its impact on the dynamics of Onchocerca volvulus infection in the black flies is going to add value to the work.

9. RECOMMENDATIONS

(a) The manuscript should be accepted for publication but NOT in its present form

(b) The corrections pointed out should be effected before publications, especially the introduction of the treatment coverage (both geographical and chemotherapeutic coverage) of the MDA in the past 15 years of the transmission zone and its impact on the dynamics of Onchocerca volvulus infection

Thanks for inviting me to serve and contribute.

Please accept the continued assurances of my highest esteem and regards.

Prof. B. E. B. Nwoke

Reviewer #3: Here are my views….

36..Impact of large scale ivermectin MDA on s. damnosum……. This is as though Ivermectin had direct impact on s. damnosum…In that sense, there would be need to have entomological proof. Instead, it would be….Impact of large scale ivermectin MDA on active onchocerciasis transmission. Your investigations were based on the presence of O. Volvulus lavae in the fly, and rather not the physical health of the fly.

65.. The presence of parasite strains that respond sub-optimally to an approved drug….With regular ivermectin MDA, its known that host parasite load is significantly reduced and consistent ivermectin MDA can cut oncho transmission even amidst abundance of s. damnosum biting….So,. ivermectin is not sub-optimally effective against microfilaria……..To dispute ivermectin, investigate and show proof of community compliance to ivermectin uptake.

69... The hydrologic network factors that could have favored abundance vector breeding and contributed to the persistence of disease transmission were also examined within the study period….I think what you exactly did here was a study of the mbam river drainage system.

92.. The control of onchocerciasis today relies on ivermectin mass drug administration (IVM-MDA) to at risk populations in endemic countries….If this is true then ivermectin is not sub-optimally effective against micro filaria

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Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: This is a well thought out study

Reviewer #2: (a) The manuscript should be accepted for publication but NOT in its present form

(b) The corrections pointed out should be effected before publications, especially the introduction of the treatment coverage (both geographical and chemotherapeutic coverage) of the MDA in the past 15 years of the transmission zone and its impact on the dynamics of Onchocerca volvulus infection

Reviewer #3: The paper is fine. Its significance is important in terms of implementing larval control for this vector

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Reviewer #1: Yes: Moses Katabarwa

Reviewer #2: Yes: Prof. Bertram Ekejiuba Bright NWOKE

Reviewer #3: No

Figure Files:

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Reproducibility:

To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plosntds/s/submission-guidelines#loc-materials-and-methods

Attachments

Attachment

Submitted filename: PNTD-D-20-01257 - Mbam River Drainage review.docx

Attachment

Submitted filename: MANUSCRIPT REVIEW FOR PLOS NEGLECTED TROPICAL DISEASES.doc

Dear Prof. Wanji,

Thank you very much for submitting your manuscript "The Mbam drainage system and onchocerciasis transmission post ivermectin Mass Drug Administration (MDA) campaign, Cameroon" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. Thank you for addressing their comments. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the editorial recommendations listed below.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.  

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript. 

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Wilma A. Stolk, Ph.D.

Associate Editor

PLOS Neglected Tropical Diseases

Jaap van Hellemond

Deputy Editor

PLOS Neglected Tropical Diseases

***********************

Editorial suggestions (line numbers refer to the clean version of revision 1)

1) References 3 and 5 are no longer available online. Please replace by more up to date references.

2) Abstract, line 37: make clear that this work is done in the Mbam river system area

3) Methods, study area, lines 164-166: clarify how coverage was calculated in this case. If I am correct, you are referring to reported coverage levels, expressed as number treated out of the total population. Ref 24 also highlights that survey coverage estimates are considerably lower than the reported ones. This should be acknowledged. Check whether similar changes are required in the concluding paragraph of the paper.

Figure 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. 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 us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plosntds/s/submission-guidelines#loc-materials-and-methods

Dear Prof. Wanji,

We are pleased to inform you that your manuscript 'The Mbam drainage system and onchocerciasis transmission post ivermectin Mass Drug Administration (MDA) campaign, Cameroon' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Wilma A. Stolk, Ph.D.

Associate Editor

PLOS Neglected Tropical Diseases

Jaap van Hellemond

Deputy Editor

PLOS Neglected Tropical Diseases

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