Achievements and challenges of lymphatic filariasis elimination in Sierra Leone

Background Lymphatic filariasis (LF) is targeted for elimination in Sierra Leone. Epidemiological coverage of mass drug administration (MDA) with ivermectin and albendazole had been reported >65% in all 12 districts annually. Eight districts qualified to implement transmission assessment survey (TAS) in 2013 but were deferred until 2017 due to the Ebola outbreak (2014–2016). In 2017, four districts qualified for conducting a repeat pre-TAS after completing three more rounds of MDA and the final two districts were also eligible to implement a pre-TAS. Methodology/Principal findings For TAS, eight districts were surveyed as four evaluation units (EU). A school-based survey was conducted in children aged 6–7 years from 30 clusters per EU. For pre-TAS, one sentinel and one spot check site per district (with 2 spot check sites in Bombali) were selected and 300–350 persons aged 5 years and above were selected. For both surveys, finger prick blood samples were tested using the Filariasis Test Strips (FTS). For TAS, 7,143 children aged 6–7 years were surveyed across four EUs, and positives were found in three EUs, all below the critical cut-off value for each EU. For the repeat pre-TAS/pre-TAS, 3,994 persons over five years of age were surveyed. The Western Area Urban had FTS prevalence of 0.7% in two sites and qualified for TAS, while other five districts had sites with antigenemia prevalence >2%: 9.1–25.9% in Bombali, 7.5–19.4% in Koinadugu, 6.1–2.9% in Kailahun, 1.3–2.3% in Kenema and 1.7% - 3.7% in Western Area Rural. Conclusions/Significance Eight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination.

look at differences between the population sources, and the impact this has on achieving the necessary programmatic MDA coverage. Response: The accuracy of denominators is a longstanding issue in endemic countries. The purpose of using different sets of denominators was to evaluate the treatment coverage as effective or ineffective against the WHO recommended minimum thresholds, not to compare the different denominators. Please see the response above.
In the ethical approval section of the methods, it states that 'participants identities were protected by collecting, recording and analyzing data such that participants remained anonymous'. However, when detailing where the data can be found, the authors state that 'data is available with certain restrictions due to the patients personal information contained in the data.' Response: Thanks for pointing this out. The language in the Ethics section is revised.
The results section is very limited, with just over a page of results presented. The results presented are not clear or completely presented. For example, when presenting the MDA coverage results by district -the author refers to districts reporting ineffective coverage 'on a total of 5 of 6 occasions'. From the map presented in Figure 2 -it is not clear what the cluster represents -is it the location of the household of the positive case or the school? It would be interesting to understand the clustering effect of TAS positive cases -from how many schools did the 7 FTS positive cases identified in Kono and Tonkolili come from? Was information collected during the TAS to determine if these positive individual took the MDA? If so, what were the reasons for not taking MDA? How does the LF programme intend to use these results to plan further surveillance activities. Response: The TAS survey here was a school-based cluster survey as described in the Methods. Each cluster represents a school surveyed. We have conducted the clustering analysis using the Spatial Autocorrelation (Moran's Index) in ArcGIS. This is added to the results.
The title of the paper is 'achievements and challenges of LF elimination in Sierra Leone' yet no reference is given to Sierra Leone's achievements and challenges towards the second pillar of the GPELF: morbidity management and disability prevention for lymphodema and hydrocele patients. Response: We appreciate this valuable comment. We have added this in the Discussion as a critical challenge for Sierra Leone.
In the discussion, the authors present their 'program observation' to justify potential reasons why the five districts failed pre-TAS, and four districts failed the pre-TAS twice. This is anecdotal evidence and it is not clear how these conclusions have been reached.
Response: These are discussions on potential reasons, not conclusion on the reasons of pre-TAS failure. The exact reasons are hard to know in a national program. Only when you consider all potential reasons and start to address these in programming, can the program evolve and achieve the program goals. There is only one "program observation" cited in the coverage discussion. We believe such discussions are justified.
This paper presents the output of the LF programme in Sierra Leone including MDA coverage, TAS survey results, and pre-TAS results. This data presented is not novel and the authors do not conduct any further analysis to explore reasons for pre-TAS failure, other than anecdotal evidence presented in the discussion. Response: We do not agree with the Reviewer on this comment. The paper presents the outcome of a national LF elimination program and discuss the challenges to achieve the program goal. Only through transparent dissemination and discussion of the program achievements and challenges the national programs are facing, can we learn from each other and overcome the challenges to achieve the global goal of elimination of LF. Every country experience is valuable in the cause. This is not a pure research.

Reviewer #2:
This manuscript is well written and reports important outcomes that are highly relevant to the NTD community. The study design and methodology are appropriate for the research question. However, the narrative could be better structured to enhance its impact. Response: Thanks for this comment.

Major comment
The title does not project the value of progressive outcomes that will transition to elimination of LF in Sierra Leone. This manuscript could be the first of three papers in a series titled 'Towards Elimination of LF in Sierra Leone as suggested below: I.
Towards elimination of LF in Sierra Leone 1: Cross border challenges II.
Towards elimination of LF in Sierra Leone 2: MDA to eliminate LF during public health emergencies III.
Towards elimination of EL in Sierra Leone 3: Interruption of LF transmission nationwide The 'conclusions/significance' section in the abstract ties in well with the suggested title for the first series: 'Eight districts in Sierra Leone have successfully passed TAS1 and stopped MDA, with one more district qualified for conducting TAS1, a significant progress towards LF elimination. However, great challenges exist in eliminating LF from the whole country with repeated failure of pre-TAS in border districts. Effort needs to be intensified to achieve LF elimination. The references to carrying out MDA during the Ebola epidemic should be expanded into a long-awaited story of the contribution of the CDDs in the containment of Ebola in Sierra Leone. This should be a separate paper that explores the following questions: Why were TAS surveys stopped during the Ebola epidemic? How did CDDs contribute to contact tracing and MDA for malaria? What led to the reduced CDD motivation after the Ebola epidemic? It is clear that the data and information to address these questions are available. Response: Thanks for this suggestion. We did think about going this way before we drafted the paper, but looking at the data we have, we decided to combine into one paper as separately the data would not have justified either papers for PLoS NTDs (Reviewer #1 already criticized the limited data in this paper). But certainly, the third paper will be considered when Sierra Leone achieved interruption of LF nationwide.

Introduction
Paragraph 1, Line 3: replace 'due to' with 'manifested as'. Paragraph 2, line 1. Why start with 2014? I would limit this to figures for 2017.

Response: Done and revised.
Ethical approval Crosscheck that approval was obtained from MOHS Research and Ethics Committee and not the National Ethics Committee. Response: Thanks. Correct.

Reviewer #3:
The topic of the paper is very interesting and important since countries are facing challenges with transmission assessment surveys in some of the settings Response: Thanks for the comment.
Following comments are from the attached document.
Transmission assessment surveys for lymphatic filariasis are recommended by the World Health Organization (WHO) as a mean to evaluate the impact of mass drug administration on the transmission of the infection. This topic is important since countries endemic for lymphatic filariasis do fail these assessments in some settings for a few reasons. I liked reading your paper and I am happy to share few comments Response: Thanks for the comment and glad you liked this paper.

INTRODUCTION.
Th introduction section is straight to the point and ends well with a clear aim of the paper which is to present the results of surveys conducted in the context of their mass drug administration and discuss related challenges. However, I do have some minor comments on few sentences in this section. 1. The first comment is on the use of abbreviation or acronyms. I suggest writing in full the word followed by the abbreviations and acronyms in bracket for the first time and next time just use the acronyms and abbreviations. For example, in the following sentence, "WHO recommends that 5-6 rounds of effective annual MDA be conducted to eliminate LF transmission., I suggest the following "The World Health Organization (WHO) recommends be conducted to interrupt the transmission of LF ". Response: Thank you. This has been checked and addressed throughout the paper.
2. You mentioned in the following sentence the ineffectiveness of CDTI: "In 2010 a distribution strategy based upon immunization campaign was introduced in the remaining districts Western area urban and rural due to the ineffectiveness of the CDTI." First, I am wondering what you mean by infectiveness of CDTI. I guess you are referring to challenges related to the implementation of CDTI in urban areas compared to rural areas. Secondly, I think this statement does not match with the reference provided which refers to high coverage of MDA of lymphatic filariasis which is in contradiction with the effectiveness of CDTI. Could you please look at this? Response: Your assumption was correct. It is the approach using CDDs was not effective. We have revised the description as follows: "In 2009, the CDTI plus albendazole approach using CDDs in the remaining 2 districts Western Area Urban and Rural was found to be ineffectual in these urban/rapidly urbanizing settings attaining only 29% epidemiological coverage. So, in 2010 a distribution strategy based upon a five day-immunization campaign was introduced implemented by paid community health workers/trainee health workers [12]." Methods 3. On this section, I think there is a need having a brief introduction for this section. Could you please present in one or two sentences the methods used in your paper? Response: As the details are given in each method sections, it is unnecessary to have introduction sentences at the beginning of the Section. We decided not to add.
4. I think the first two headings of your methods section "mass drug administration" and "epidemiological and programmatic coverage assessments" could be brought back to the introduction. In the revised introduction section, you can briefly mention what was done in terms of Mass drug administration and treatment coverage. Since you clearly mentioned that epidemiological and programmatic surveys were published previously, this support also the suggestion of mentioning what was done in terms of epidemiological and programmatic coverage assessments in the introduction section. Response: Agreed. Most of these two sections have been moved and modified to fit into the Introduction. However, as the coverage data were presented in the Results, we therefore added a subheading as "MDA coverage data collection" to describe how these data were collected. We moved the calculation of coverage to the Data analysis section.
5. You used in these section, the following acronyms/abbreviations CHWs"; "re-pre-TAS", "NTDP ", "MOHS ", "s" . "hr"? What does each of them stand for? Please kindly refer to my comment on the use of acronyms and abbreviations (comment #1). Response: Please refer to the response to Comment #1 above. The abbreviations are now clearly defined. "s", "min" and "h" are standard abbreviations for time, but these are now made in full.