A community-based vector control intervention “Slash and Clear” implemented in two onchocerciasis-endemic foci in South Sudan

PLOS Neglected Tropical Diseases

Dear Dr. Colebunders,

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Kind regards,

Adly M.M. Abd-Alla, Prof asso.

Section Editor

PLOS Neglected Tropical Diseases

Adly Abd-Alla

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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Reviewers' Comments:

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: I believe the hypothesis is clear and that the study design appropriate to the challenging setting the authors worked in.

I am not a statistician so I would defer any opinion on the methodology to someone better qualified to judge. I am concerned that the ethical issues around human landing catches are not articulated and there is no reference to this aspect of the study. The oncho community are seeking to find alternative approaches to the issue and this needs to be referred to

Reviewer #2: • Line.111. What was the approximate distance between the study and control sites? The figures are not titled and are rather blurred, but in Figure 1, it looks as if the study site was flanked by the control sites; if this was the case can the authors comment on whether the interventions at the study site could have contaminated the findings at the control sites?

• Lines 150-151: The sentence “Prospections in the two rivers (Naam and Yei) were conducted by experienced technical staff,…” could be reworded for clarity. The word “prospected” usually applies to the search for mineral deposits. For example: The rivers Naam and Yei were surveyed by experienced technical staff,…”. Lines 153, 180, 238, 415, Table 1: “prospections” could be replaced by “surveys”.

• Lines 240-241: can the authors give a figure for the number of remaining sites along the River Naam? Table 1 suggests there were four.

Reviewer #3: THe authors need to review the indicators used to calculate the reduction rate (% exchange rate)

Reviewer #4: Yes, the objectives of the study were clearly articulated and testable. The study design was not entirely clear, if it was a case-control or before-after intervention.

Reviewer #5: The objectives of the study are not clearly articulated with a clear testable hypothesis.

A comparison is made between the baseline Monthly Biting Rate and the subsequent MBR for 14 months. It is difficult to imagine that this Slash and Clear could have an impact on the subsequent MBR during 14 months.

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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: Yes analysis matches plan.

Results well presented.

Good quality figures and Tables.

Reviewer #2: • Table 2. The heading for the last column should be Daily Mean Biting Rate (DBR).

• Figure 3. Does the figure show clearly an evening rise in biting rates at Tawa (Lines 268 – 269)? This is not clear from the figure.

• Lines 305 – 307. How confident are the authors about the reliability of the log transformed data on mean biting rates on the Naam River?

Reviewer #3: See the document attached

Reviewer #4: Yes

Reviewer #5: The results are well clearly and completely presented, but these results are based on hypotheses that does not take into consideration the biology of the Simulium and breeding sites.

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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: Conclusions supported by data presented.

Limitations described.

Authors have a firm grasp of the implications of the study

Public health as well as programmatic relevance addressed

Reviewer #2: • Lines 343, 424. Can the authors explain what is meant by emboldened rocks?

• Lines 359-361. It is not clear from this sentence whether the Tawa and Boro sites are located in savannah regions. Could the authors clarify?

• Lines 366 – 368. Can the authors provide evidence in support of the negative effect of high temperatures on black fly breeding behaviour, even in the more stable forested areas?

Reviewer #3: Yes

Reviewer #4: Yes, however, the main results which is the impact of the S&C should standout clear and undiluted.

Reviewer #5: The conclusion is supported by the data presented, but it could not be otherwise. Having one round of Slash and Clear, it is absolutely normal there is no impact on Monthly Biting Rate during a period of 14 months.

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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: See below

Reviewer #2: • The paper could be streamlined in terms of language and punctuation, for better flow of the narrative. It would have been helpful for a native English speaker to have reviewed the text before submission.

• Lines 84, 196, 451, 460: AMREF Health Africa should be Amref Health Africa. Amref is no longer an acronym after the name change of the organization.

• It is quite hard to match the figures to the text since none of the figures are titled. In addition, they appear to be rather blurred.

Reviewer #3: Minor revisions

Reviewer #4: Accepted with minor revision

Reviewer #5: (No Response)

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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 an important paper in the context of the potential approaches to controlling blackflies using the Slash and Clear (S&C) method by reducing the vegetation substrate in blackfly breeding sites which has been used in other settings. I feel that the authors need to emphasise the rationale that vector control is an important adjunct to the overall objective of elimination of onchocerciasis in Africa in combination with ivermectin MDA. The effectiveness of vector control (using insecticide) in certain settings needs to be expressed (eg Bioko, Uganda foci) assuming they are isolated which the sites studied in South Sudan are not. However, the study does show that the challenges of this approach really cannot be used and/or sustained over the vast areas of oncho endemicity placing in doubt the likelihood that S&C can be used at the necessary scale. This needs to be contextualised as the feasibility of insecticide is also a major challenge for environmental, cost and sustainability reasons. I would encourage the authors to add a paragraph raising these issues. Essentially, if WHO targets for oncho elimination are to be reached on the scale required in the diverse oncho geographies then vector control, however desirable, is not likely to have a meaningful role.

Reviewer #2: This study is limited by the single slash and clear intervention at each site, and the follow up over a relatively short period of time, giving inconclusive results. The authors themselves state (P443 – 446) that “repeated implementation of this intervention with the right timing (towards the end of the dry season and throughout the rainy season) could be effective in reducing Simulium biting rates in endemic communities”. Although the paper provides some interesting information, it would be considerably strengthened if data could be collected over several interventions and over a longer period of time. In addition, the distance between control and study sites is not provided (they appear to be quite close on the maps), so it is hard to know how much the interventions could have impacted the control sites.

Reviewer #3: This paper, whose data present a trial of physical control of onchocerciasis vectors, is very important. These data allow us to further explore the contours associated with the implementation of this black fly control strategy to eliminate onchocerciasis in endemic areas. However, the data presented in this paper suggest that a single round of S&C cannot impact MBR in the medium or long-term. The success of this strategy requires repeated rounds of S&C implementation each year with the right timing to sustainably decrease black fly biting rates.

Reviewer #4: This is a great work especially as slash and clear has not been overly exploited as a vector control tool. However, I had a bit of concern especially with the study design. It was unclear to me if this was a case control study or an intervention study (before-after).

Secondly, in the abstract, I think the results and conclusion do not emphasize the purpose of the work. From my understand, the study was to assess the impact of the community-based vector control S&C. The other results such as the BR being higher in one season than the other, etc., are more secondary outcomes but they overshadowed the rationale behind the study. I think the main objective should stand out esp. in the abstract. This was however elaborated in the author summary.

Reviewer #5: This paper by Thomson Luroni Lakwo et al. is a contribution of the experimentation of the impact of the Slash and Clear strategy on the control and elimination of onchocerciasis. This strategy has shown a significant reduction in the Simulium Monthly Biting Rate where it was implemented. In this study by Thomson Luroni Lakwo et al, a unique round of Slash and clear was conducted and the impact evaluated throughout the following 14 months, with the evaluation of the percentage change relative to baseline Monthly Biting Rates (MBR). Considering the cycle of Simulium damnosum around a month and the cycle of the vegetation along the fast-flowing rivers that grows after one month or so, one wonders what the hypothesis was, in hoping the one round Slash and clear could have a significant impact on Simulium daily or monthly biting rate throughout the following 14 months. Whatever the analyses are, or the model, it is difficult to conceive that one round of Slash and clear could have impact on Simulium Monthly Biting Rate and hence an impact on onchocerciasis transmission.

The results of this study are trouble message concerning this environmentally friendly vector control strategy. Even if the reduction of the biting rate in some experiments is modest, it remains that this strategy induced in most cases a significant reduction of the biting rates, with monthly or two monthly Slash and clear. Nobody can imagine that one round of Slash and Clear can impact either the biting rate or the onchocerciasis transmission.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes:  Philippe Bienvenu Nwane

Reviewer #4: No

Reviewer #5: No

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Reproducibility:

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Dear Dr Colebunders,

We are pleased to inform you that your manuscript 'A community-based vector control intervention “Slash and Clear” implemented in two onchocerciasis-endemic foci in South Sudan' 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,

Adly M.M. Abd-Alla, Prof asso.

Section Editor

PLOS Neglected Tropical Diseases

Adly Abd-Alla

Section Editor

PLOS Neglected Tropical Diseases

Shaden Kamhawi

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-4304-636XX

Paul Brindley

co-Editor-in-Chief

PLOS Neglected Tropical Diseases

orcid.org/0000-0003-1765-0002

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1) Thank you for including an Ethics Statement for your study. Please include:

i) A statement that formal consent was obtained (must state whether verbal/written) OR the reason consent was not obtained (e.g. anonymity). NOTE: If child participants, the statement must declare that formal consent was obtained from the parent/guardian.].

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3) Some material included in your submission may be copyrighted. According to PLOSu2019s copyright policy, authors who use figures or other material (e.g., graphics, clipart, maps) from another author or copyright holder must demonstrate or obtain permission to publish this material under the Creative Commons Attribution 4.0 International (CC BY 4.0) License used by PLOS journals. Please closely review the details of PLOSu2019s copyright requirements here: PLOS Licenses and Copyright. If you need to request permissions from a copyright holder, you may use PLOS's Copyright Content Permission form.

Please respond directly to this email and provide any known details concerning your material's license terms and permissions required for reuse, even if you have not yet obtained copyright permissions or are unsure of your material's copyright compatibility. Once you have responded and addressed all other outstanding technical requirements, you may resubmit your manuscript within Editorial Manager. 

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i) Figures 1, and 2. Please (a) provide a direct link to the base layer of the map (i.e., the country or region border shape) and ensure this is also included in the figure legend; and (b) provide a link to the terms of use / license information for the base layer image or shapefile. We cannot publish proprietary or copyrighted maps (e.g. Google Maps, Mapquest) and the terms of use for your map base layer must be compatible with our CC BY 4.0 license.

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If your map was obtained from a copyrighted source please amend the figure so that the base map used is from an openly available source. Alternatively, please provide explicit written permission from the copyright holder granting you the right to publish the material under our CC BY 4.0 license.

If you are unsure whether you can use a map or not, please do reach out and we will be able to help you. The following websites are good examples of where you can source open access or public domain maps:

* U.S. Geological Survey (USGS) - All maps are in the public domain. (http://www.usgs.gov)

* PlaniGlobe - All maps are published under a Creative Commons license so please cite u201cPlaniGlobe, http://www.planiglobe.com, CC BY 2.0u201d in the image credit after the caption. (http://www.planiglobe.com/?lang=enl)

* Natural Earth - All maps are public domain. (http://www.naturalearthdata.com/about/terms-of-use/).

4) Please amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

1) State the initials, alongside each funding source, of each author to receive each grant. For example: "This work was supported by the National Institutes of Health (####### to AM; ###### to CJ) and the National Science Foundation (###### to AM)."

2) State what role the funders took in the study. If the funders had no role in your study, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

3) If any authors received a salary from any of your funders, please state which authors and which funders..

If you did not receive any funding for this study, please simply state: u201cThe authors received no specific funding for this work.u201d

5) Please ensure that the funders and grant numbers match between the Financial Disclosure field and the Funding Information tab in your submission form. Note that the funders must be provided in the same order in both places as well. Currently, the Financial Disclosure states there was no funding received.

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

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

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

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

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

-Were correct statistical analysis used to support conclusions? Yes

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

Reviewer #4: (No Response)

**********

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: -Does the analysis presented match the analysis plan? Yes

-Are the results clearly and completely presented? Yes

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

Reviewer #4: (No Response)

**********

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: -Are the conclusions supported by the data presented? Yes

-Are the limitations of analysis clearly described? Yes

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

-Is public health relevance addressed? Yes

Reviewer #4: (No Response)

**********

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: No

Reviewer #4: (No Response)

**********

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: I am satisfied by the extensive revisions the authors have undertaken following review.

Reviewer #4: (No Response)

**********

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.

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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 #1: No

Reviewer #4: No

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