Report: experts consultative meeting on alternative treatment strategies for the acceleraton of the elimination of onchocerciasis and lymphatic filariasis in ares requiring intensified interventions, Ouagadougou, 6-7 September 2014

World Health Organization Report Experts Consultative Meeting Treatment Strategies for the e Eliminat and Lymphatic ntensifiedFilari a'.aurnng ! interventions Ouagadorryou, S-Z Sefrember 2Ot4 African Programme for Onchocerciasis Control (APOC) on Alternative Experts Group on Alternative Treatment strategies (ATS) 1. Dr Michel Boussinesq (chair) 2. Professor Samuel Wanji 3. Dr Nana-Kwadwo Biritwum 4. Dr Louise Alice Kelly-HoPe 5. Dr Annette Kuesel 6. Mr. Thomson Luroni Lakwo 7. DrJan H.F. Remme Page 1 of 30 Executive Summary The APOC guided control of onchocerciasis in Africa has largely been through annual community directed treatment with ivermectin (CDTI). By the end of 20L2, over 100.8 million people in 184,560 communities were receiving ivermectin and in areas where CDTI has been ongoing for many years, CDTI has eliminated onchocerciasis as a public health and socio-economic problem. ln Senegal and Mali, t5-L7 years of annual CDTI eliminated onchocerciasis infection and interrupted transmission. Epidemiological evaluations conducted subsequently by APOC and the countries in 55 CDTI project areas suggest that the reduction in onchocerciasis prevalence achieved in 84% of these areas is consistent with CDTI being able to eliminate onchocerciasis. This mounting evidence motivated JAF to endorse a shift in APOC objectives from control to elimination of onchocerciasis in at least 80% of endemic countries in Africa by 2025. TCC36 and JAF19 advised that alternative treatment strategies (ATS) are needed to accelerate progr€ss towards elimination in areas in which progress using annual CDTI is slower than necessary for elimination by 2025. APOC was advised by JAF to scale up the implementation of ATS in 2g3'4/t5. Global elimination of lymphatic filariasis (LF) is targeted for 202A. The strategy is annual mass drug administration (MDA)with albendezole ectin or,diethylcsrhsm azin e for iasis'r&o'endem icity wh ich prevents implementation of the standard strategy,and req To address gaps and challenges for imphmenta consultative meeting in Ouagadougou, Burkin prerequisites for implementation of ATS for POC management convened a 5-7th September 2014 on the s and LF. The expert group discussed identification and categorization of areas requging ATS, ways to strengthen the impact of annual CDTI, options for ATS and selegtion of the most appropriate ATS, and operational research required to irr$orm successftd implementation of ATS. Three categories of onchocerciasis ends*nic areas requiring ATS were identified: areas with onchocerciasis pre-control endemicity forwhich modelling suggests that annual CDTI cannot eliminate onchocerciaEis, areas which will.not achieve elimination by 2025 because CDTI started late relative to the number{if years required to achieve elimination, and areas with poor progress tswards elimination after lOyears of CDTI. The last category was subcategorized by the operational or epidemiological characteristics contributing to the poor progress. Both mass drug administration based and test and treat' based ATS were reviewed for their suitability to address the reason(s) preventing elimination of LF by 2020 and onchocerciasis by 2025. This included development of algorithms for 'test and treat' ATS for hypo and hyper-endemic areas for onchocerciasis, loiasis and LF. Next steps and challenges to be addressed were identified. Operational research studies are needed to identify how to address different factors critical for successful implementation of ATS. The critical factors to be investigated can be informed by the operational research studies which formed the basis for successful implementation of CDTI and the experience of countries which have implemented bi-annual CDTI. It was concluded that ATS offer an opportunity to accelerate progress towards elimination of onchocerciasis and LF. Successful implementation requires proper understanding of field scenarios, challenges and requirements, full commitment at all levels of the health care Page 2 of 30 2 5 years. Progress in Africa is less than required partly dse system, availability of the required diagnostic/intervention tools and the necessary competencies on all health care system levels. The main recommendations for future actions are as follows: o ln areas of unsatisfactory epidemiological results, the country should conduct a situation analysis and develop a roadmap to address the obstacles identified. o Clear guidelines for programme managers and health workers for effective and efficient implementation of bi-annual CDTI and other ATS need to be issued. o There is need to define pre-control endemicity thresholds above which elimination of onchocerciasis with annual treatment with ivermectin would be difficult to achieve and ATS need to be implemented. o ln areas with high onchocerciasis prevalence where annual CDTI has been conducted for 15-20 years but progress does not suggest thd transmission will be interrupted by 2025, the group recommended that, as per previous TCC advice, managerial issues be addressed in priority and that use of mobile teams, bi-annual CDTI and vector control be considered (as well as treatment with moxidectin Qr flubendazole when these become available). o To scale up implementation of LF control, areag,'which can implementthe standard treatment and those which require ATS and the most Sppropriate ATS need to be identified. o To guide decisions on ATS implementation, infqrmation on the cost and cost- effectiveness of different ATS and ATS vs. annudl€DTl needs to be generated. The report was shared with TCCS9 whlch endsrsed it as a good basis for the roadmap with recom m endations for fu rth er hprovemant' "'-il:. Page 3 of 30 Table of Contents 1 lntroduction !.7 Onchocerciasiselimination L.2 Lymphatic Filariasis elimination 1.3 Alternativetreatmentstrategies 1.3.1 Definition of Alternative Treatment Strategies L.3.2 TCC recommendations on intensification of interventions and the im plementation of Alternative Treatment Strategies L.4 Characteristics of onchocerciasis endemic areas that may require ATS to achieve elimination bV 2025 1.5 Characteristics of LF endemic areas that may require ATS to achieve elimination of LF by 2020 1.6 Gaps and Challenges for implementation of Alternative Treatment Strategies 2 Objectives of the Consultative meeting on ATS :. 3 Meeting outcome ' i 3.1 Algorithm for identification of CDTI project areas.rt!uiringAfs 3.1.1 Category 1 areas qualiffing for ATS:,llejects with very high pre-control endemicity and/or vector competen'ib for which modelling predicts that onchocerciasls elimination cannot bgachieved with CDTI alone 3.7.2 Category 2 areas qualifying for ATS: Projects which started CDT| late relative to the number of years of CDTI required to achieve elimination and whiih will not reach elimination by 2025 for that reason alone 3.1.3 Category 3 arem qualifying for ATS: Areas with poor progress towards elimination of onchocerciasis and/or LF 3.7.4 Projects qualifying for more than one of the categories 3.2 Algorithm for identifying LF endemic areas requiring ATS 3.3 Alternative treatment strategies and tools 3.3.1 ATS based on mass drug administration with ivermectin 3.3.1.1 Annual ivermectin MDA by mobile teams 3.3.L.2 BiannualCDT| 3.3.2 MDA with drugs currently in development 3.3.2.L Moxidectin 3.3.2.2 Flubendazole 3.3.3 'Test and treat strategies' 3.3.4 ATS for different categories of areas requiring ATS 7 7 7 8 8 8 8 9 9 10 10 10 11 L2 72 13 13 13 L4 L4 74 L4 1.5 16 16 t7 Page 4 of 30 3.3.5 Algorithms for selection of ATS by co-endemicity of onchocerciasis, Loiasis and LF 3.3.6 Algorithms for decisions on intervention strategy for LF elimination 3.4 Areas of operational research related to ATS 3.5 Next steps 3.6 Challenges 3.7 Conclusions 3.8 Recommendations 4 TCC 39 Comments on the proposed road map for ATS 5 References 6 Annex 6.L List of participants 6.2 List of countries predicted by the CSA working group on elinrination to achieve national onchocerciasis elimination by 2020 6.3 Provisional Agenda for lnformal consuttative m ee$ngg-n ATS Table of Tables and Fifures Table 1 Alternative treatlrpnt stfttegies for'dlf,ferent c*egories of areas requiring ATS Table 2 ATS for areas qualifuine for ATS hy co-endemicity of onchocerciasis, Loiasis (>2O% microfilariae pranalgnce (>4O% RAPLOA) and LF Figure 1 f$gorithm for dqtermining eO& project areas qualifying for ATS Figure 2 Algorithm for decisq{Lmaking ln onchocerciasis hyperendemic areas with Loa loa microfilaria prevalenre of >2Oa/6 (RAPLOA >4Oo/ol in the presence of LF Figure 3 Algorithm for decision mdking in onchocerciasis hypoendemic areas with Loa loa microfilaria prevalence of >20% (RAPLOA >40%l in areas known not to be LF endemic Figure 4 Algorithm for dpeision making in onchocerciasis hypoendemic areas with Loa loa microfilaria prevalence of >2O% (RAPLOA >40%l in the presence of LF Algorithm for mapping and deciding on intervention strategy for LF elimination Figure 5 18 22 23 24 24 24 25 25 26 28 28 29 30 L7 22 LL 19 20 2L 23 Page 5 of 30 Abbreviations ATS Alternative Treatment strategy ALB Albendazole APOC African Programme for Onchocerciasis Control A-WOL compound Antibiotic effective against Wolbachia CDTI Annual Community Directed Treatment with lvermectin CMFL Community Microfilaria Load CNTD Center for Neglected Tropical Disease aCDTM AnnualCommunity Treatment witftMoxid bCDTM B ian n ua Com m un itv Di with Moxidectin DEC Diethylcarbamtzine DNDi Drugfor Neglecte 6Dise ases initietive DOLF ,Death to s project to optimize MDA for nd to study the impact of MDAel m nation of LF a as rs a for LF on Soil Tra nsm itted CSA Committee of Sponsoring Agency Eliminati rking GroupEWG JAF Joint Action Forum IVM lvermectin LF Lymphatic Filariasis MDA Mass Drug Administration NTD Neglected Tropical Diseases TCC Tech nical Consu ltative Comm ittee SAE Severe Adverse Event WHO World Health Organization Page 6 of 30 L lntroduction 1.1 Onchocerciasis elimination The African Programme for Onchocerciasis Control (APOC) was launched in December 1995 to establish, in collaboration with the Ministries of Health and non-governmental organisations in onchocerciasis endemic countries within its mandate, sustainable systems for ivermectin distribution in onchocerciasis meso- and hyperendemic areas. The strategy for ivermectin distribution is annual community directed treatment with ivermectin of the eligible population (annual CDTI). The objective of sustainable CDTI was to eliminate onchocerciasis as a public health and socio-economic problem' By the end of 20L2, over 100.8 million people in 184,560 communities were receiving ivermectin and in the vast majority of areas where CDTI has been ongoing for many years, APOC and the countries have achieved their objective of eliminating onchocerciasis as a public health and socio-economic problem. A study initiated in 2005 in two hyperendemic foci in Mali and Senegal showed that 15-17 years of annual CDTI had led to eliminatiort of onchocerciasis infection and interruption of parasite transmission [1,2]. Encouraged by these results and the Joint Action Forum (JAF), APOC developed in 20L0 a 'Conceptual and Qperatiqld Framework'f91, Onchocerciasis Elimination with lvermectin Treatrnent' [3]. Betsfieen 2008 And,?013, 55 eDTl project areas underwent the 'Phase La' epidemiobg.tc.l evaluatlsns aOe$i,iiding to this framework [4,5]. ln g4% of these areas, progress was as pr€dicted or €ven better, supporting the conclusion from the study in Mali and,,sen9qal that anligal CDTI can lead to interruption of O. volvulus transmission. The 2010 Mid-tenn Evaluation.'@ort submttted to JRr 15 on APoc clearly stated that there is mounting widencethat indeed.#ter years of tfAatrnent onchocerciasis may just be about to be etimiaated in Africa. Given this evidence the'report said it may be premature to close ApOC as planned by 20L5. JAF16 requested the Committee of Sponsoring Agencies (CSA) to provide advice for considera& by JAF 17 on the Future of APOC.CSA created three advisory groflps amgEigst *n,.6.'.the CSA Advisory Group on Elimination. This group did a detailed analpi{gf:,**mectln treatraant history and reviewed progress towards elimination of onchocerciasig,i,gfection and interruption of transmission using the current tools in APoc projects. These resutB were used to predict for each project when ivermectin treatment can be safely stopped. Tlia.eSA working group elimination estimated that no country will be ready to achieve eliminatbn by 2015. Some foci within some countries will be able to stop treatment. The group predicted that 23 African countries (see Annex, section 5.2) may achieve national onchocerciasis elimination by 2020, i.e' can stop treatment in the last onchocerciasis endemic focus to be followed by 3 years of post-treatment surveillance' L.2 LymphaticFilariasiselimination Global elimination of lymphatic filariasis s targeted for 2020. The strategy is preventive chemotherapy through annual mass drug administration (MDA) with albendazole plus ivermectin (in countries where onchocerciasis is endemic) or diethylcarbamazine (in other countries) for z 5 years. progress towards achieving this goal in Africa is less than originally planned due to the fact that mapping of LF prevalence has not been completed in all countries and that a number of LF endemic areas are loiasis co-endemic which prevents Page 7 of 30 implementation of either of the two MDA strategies due to the severe and serious reactions to ivermectin or diethylcarbamazine that can occur in Loa /oo infected people [6]. 1.3 Alternative treatment strategies To achieve elimination of onchocerciasis in 23 African countries bV 2O2O and in at least 80% of onchocerciasis endemic African countries by 2025, the reduction in transmission has to be accelerated through intensified interventions in areas in which data available to date suggests that onchocerciasis will not be eliminated within these time frames with CDTI. Progress towards elimination of onchocerciasis with CDTI depends on the treatment coverage which has in some areas been less than required. Acceleration of the reduction in transmission can thus be achieved either by increasing treatment coverage or by using other treatment strategies. To achieve elimination of LF in LF-Loiasis co-endemic o6llptries byZO2O requires preventive chemotherapy to be initiated. ln 2072 WHO recomrncnded twice yearly albendazole treatment, combined with vector control activities, as the provisional strategy for interruption of LF transmission in Loiasis co.endemic areas without onchocerciasis [7]. The rationale for this recommendation is awaitingthe&sults from the $trdies conducted in the Republic of Congo and in DRC (DOLF studies). ' 1.3.1 Definition of Alternative Trcatment Strat€i,er ..r, Considering that the APOC treatment strategy is arlnual CDTI, any other treatment strategy is defined as an 'alternativ€ tre-atment strEtegy' (ATS). The treatment strategy for LF dlmlnation is aRnual ma$:administration with ivermectin or diethylcarbamazine plus albendazole. S$t gther rtreatrnent strategy is consequently an 'alternative treatment strategy'. 1'.g.2 TCC tucommend*lons on intensification of interventions and the imptementation d Alternative Treatment Strategles During its 36th session in March'2013 [8]; TCC made the following recommendations on intensification of intervention and irnplementation of ATS: (i) lntensification of interventldns should include timely provision of information of evoluotian results to national project officiols, provision of additionol financiol resources, improving CDTI ond considerotion of other strotegies such os inmeasing tredtment frequency ond vector control in specific settings;(ii) Progrommes should resolve coveroge issues before considering increasing mass treotment frequency(iii) lncreosing mass treotment frequency should be considered if elimination connot be ochieved before 2022 by increosing moss treatment coveroge(iv) Progrommes thot increase moss treotment frequency should moke sure to mointain high treotment coveroge. 1.4 Characteristics of onchocerciasis endemic areas that may require ATS to achieve elimination by 2025 Based on the data acquired by APOC and the countries, as well as the predictions of the CSA Working Group on elimination, onchocerciasis endemic areas which may require ATS to achieve elimination by 2025 have one or more of the following characteristics: Page 8 of 30 (a) co-endemicity of onchocerciasis and loiasis, (b) very high pre-control levels of infection, (c) late start of treatment relative to the level of pre-control endemicity, (d) prevalence of infection recorded in recent epidemiological surveys higher than consistent with elimination through CDTI by 2020 or 2025, (e) past or present civil unrest which made or makes implementation of CDTI with the required treatment coverage impossible, (f) presence of individuals with parasites whose response to the embryostatic effect of ivermectin is less than currently regarded as 'typical' or 'optimal'. These "sub-optimal responses" or "atypical responses" need to be addressed by an ATS if there is evidence of selection and preferential transmission of O.:u,alvulus with "suboptimal response" that could jeopardize elimination. 1.5 Characteristics of LF endemic areas that may require ATS to achieve elimination of LF bY 2020 LF endemic areas which may require ATS to achieve elimination by 2O20 have one or more of the following characteristics: (a) co-endemicity of LF and loiosis, (b) high level of endemicity relative to.the effectivenesg of ivermectin-albendazole MDA (c) late start of MDA r€mive to the 'effectiveness of ivermectin-albendazole MDA or biann ual treatment wi& albendazole (d) past or present civil unrest which made or taakes implementation of MDA with the re q u i red freq u en-cy a n d treatfrant cove raep'. t4passi b I e o r u n I i ke ly' l.G CapF and Ct@lenges fuf implementation of Alternative Treatment $trategies There are {nany gaps to fill and challe a ltern ative traatm entstrategies. These i n cl ,ri i@s to overcome for the implementation of ude: 1) Guidelines andalgorithms for the identification of areas that should implement ATS 2l Guidelines and el,forithms for the identification of the most suitable ATS for a particular area 3) Diagnostic tools for the implementation of ATS which are not mass treatment based, notably simple accurate and rapid screening tests to identify people with onchocerciasis andlor lymphatic filariasis and/or high intensity of infection with Loa loo. 4l Assessment of the feasibility of implementation of ATS which are not mass-treatment based and require identification of those who should or should not be treated with a particular drug based on their infections and who have other characteristics that put them at risk of adverse reactions to the treatment (pregnancy, nursing). 5) Availability of financial and personnel resources per year and overall to elimination. A study in Ghana showed that annual CDTI in Wench District cost USD O.4O/person treated/year (excluding CDDs' time) and that biannual CDTI increased these by 50-60% [9]. Katabarwa et al. [10]have reported similar finding even though they reported that the cost reduced drastically for larger districts (>40 OOO people). Biannual MDA for Page 9 of 30 Lymphatic filariasis in West Africa was estimated to cost around 63% more per year than annual treatment [11]. No information is available on the personnel and financial resources required to implement ATS which are not MDA based. Hence the feasibility of implementation of such strategies remains to be evaluated. 2 Objectives of the Consultative meetint on ATS Cognizant of these gaps and challenges and in view of the recommendations of TCC36 and JAF 19, APOC management convened a meeting of experts from 6th to 7th September 2OL4 in Ouagadougou, Burkina Faso to discuss how to operationalize implementation of ATS and to discuss prerequisites for piloting of alternative treatment strategies in 2015. The meeting was asked to: o Develop algorithms for identification of areas where ATS is required o Determine appropriate ATS for each area requiring ATS for onchocerciasis, LF or onchocerciasis and LF o ldentify appropriate areas for pilotingATS during the period 20L4-20L5 for oncho/LF o ldentify what type of operational rese'ff€h ralated to ATS needs to be conducted. o Report to TCC39 and JAF the outcome of the expeft group meeting. .,:t:o Publish the outcome of this meeting in an open accesqJqurnal. 3 Meeting outcome 3.1 Algorithm for identification of,e0il projettrareas requiring ATS The characteristics of CDTI pror$. areas list€d in section 1.4 will impact the decision on whether ATS is required and which ATS is apprcpriate. Teking into account challenges to CDTI implementation and factors impacting eBfi effectiveness and selection of the appropriate ATS, the group developed the algorithtn shown in Figure 1. The algorithm groups Page 10 of 30 Does modelling predict that onchocerciasis elimination would be very difficult with annual CDTI? NoYes Considering pre-control endemicity/vector competency and start of CDTI, does modelling predict that elimination can be reached by 2020 or 2025 with CDTI Category 1 area qualifying for ATS YesNo Does the area have any operational or epidemiological characteristics other than late start relative to pre-controlendemicity/vector competcncy which prevents reaching elimination by 2020 or 2025 with CDTI YesNo Category 3 area qualifying for ATS C.tegory 2 area qualifying for ATS Operational or epldcmiological characteristics Has CDTI been implemented with :80% treatment coverage? NoYes Category 3H.rea: Poor geognPhlc and/or treatment@uenge due to 3b lnfrastructure/programmatic issues !k Opentlonal challenSes 3d Loa loa cc.endemicltY CateSory 2b area qualifying for ATS Cat€8ory 3a areal tndMduals with parasltes with genotype conferring 'atypical' response to ivermectan Cetegory 2. area qualifying for ATS CDTI ect areas into three main ca ies for decisions on ATS CDrII:lmriect at€so qualrying for ATSFigure 1 Algorithm for determining 3.1.1 dbe Th of Ad Projects with very high pre-control endemicity ce for modelling predicts that onchocerciasis ieve with annual CDTI alone the values of the pre-control parameters (prevalence eters, etc.) above which foci belong to this category. A similar question mightbe posed for LF elimination with the standard MDA strategy. High pre-control endemicity is always associated with high vector abundance andcompetency. lnformation on the vector competency / vector capacity to transmit the parasite when low skin microfilariae levels have been reached, is not available for all species in APOC countries and needs to be generated. projects likely to belong to this category are the North CDTI project (Vina Valley), most of the districts in the Center L,2and 3 projects (Mbam region), Littoral 1, South West l and 2 and Western projects (the latter being on track according to simulations by Onchosim) in Cameroon and Taraba and Kogi CDTI projects in Nigeria. APOC management will generate a list of CDTI projects in this category after consultation with the modellers. Page 11 of 30 3.L.2 Category 2 areas qualifying for ATS: Projects which started CDTI late relative to the number of years of CDTI required to achieve elimination and which will not reach elimination by 2025 for that reason alone This category includes project areas of any level of pre-control infection prevalence for which modelling (ONCHOSIM or EpiONCHO) predict elimination can be achieved with CDTI, but not by 2025 even when CDTI is implemented with >80% treatment coverage. CDTI projects in this category include some in Ethiopia, C6te d'lvoire, Tanzania, and Uganda and most likely several in DRC as well as the South Sudan project. An analysis of all CDTI project areas for the anticipated year of elimination based on ONCHOSIM modelling has been conducted previously. APOC management will review this analysis to update the list of CDTI projects not anticipated to reach elimination by 2025 solely based on pre-control endemicity relative to CSll start (i.e. not because the project areas have any of the characteristics described in s$!$rn 3.1.3). Furthermore, APOC management will contact the modellers from lmperial Nlege to see whether they can provide the input needed to complement thg ONCHOSIM motl€$ing based anticipated year of elimination with Ep|ONCHO modelling ptedistsd year of elimination and the modellers from Rotterdam regarding refining ONCHOSTM to tEke into accsunt different blackfly '.' species and their competencies. ,i. . The group noted that the decision on the appropriate AT}$iild$$distinguish between two subcategories in terms of project performance: a. projects with "good" performan.",Il&th"rapeutic coverage >BOyo, b. projects with "poor" resutts, i,e. therape$tic coverage far below 80%. ATS implementation in the latter will be rnoFe tha{lenglng than in the former and may require a diffurent approach. .r,. 3.1.3 Cffiory 3 areas Qurlifying forATS: Areas with poor progress towards elimination of onchocerciasis andlw [F Areas with poor progress towards elimination of onchocerciasis were defined as those areas where Phase ta 4ldemiological evahations or research studies have indicated higher prevalence of infestion than expected based on ONCHOSIM. The group noted that poor progress towards elimination of onchocerciasis and/or LF can be attributed to a number"iif,factors. Consequently and as per previous recommendations of TCC, these areas need to be evaluated for the reasons contributing to the poor progress. This evaluation needs to include assessment and verification of the extent of geographic and/or therapeutic coverage reported, examination of the reasons for verified poor coverage and identification of other factors, notably 'atypical responders' and Loo loo co- endemicity. Based on these evaluations, the areas should be categorized into four subcategories: a. Areas with individuals with a response of the parasite to the embryostatic effect of IVM considered "atypical", referred to in the literature as "suboptimal response", Areas with poor geographic and/or treatment coverage due to: b. lnfrastructure and programmatic issues: weak health system, poor management, poor monitoring, poor partnership, poor training, human resource issues, CDD motivation Page 12 of 30 and attrition, low number of CDD/CDD overload, poor community mobilization and ownership,, c. Non-programmatic reasons unrelated to the target population: difficult access (including nomadic populations), shortage of drug(s), conflict and civil unrest, d. Reasons related to the target population: fear of SAEs in areas co-endemicfor Loo loa. The group noted that the contributing factors have to be addressed by all stakeholders since some of them are outside the mandate of the project. For instance, a weak health system has a number of key players whose support and involvement for onchocerciasis and LF control needs to be assured to make ATS, which is much more challenging to implement than CDTI, feasible. 3.1.4 Projects qualifying for more than one of the categories A project can belong to 2 or 3 of the categories. ln that case the decision on the appropriate ATS is particularly difficult. Examples are the Mbam district area in Center 3 project and the Littoral 1 project in Cameroon where prevalences are sti}l high after L5-20 years of treatment and where multiple factors contribute to the poor rcsults: High transmission, infrastructure and programmatic issues and 1*ypical' responses. 3.2 Algorithm for identifying LF endemh areas requiring ATS The algorithm for the appropriate control strategy deydsped in collaboration between WHO-APOC and CNTD is provided in secthn 3.3.6 artd'FiS{ire 5. 3.3 Alternativetreetiuantstrategiwandtools lmplementation and upscaling of AT$irequires proper guidance to countries on the choice and implementation of ATS and availab@ gf Ste.necessary resources to ensure that implementation does not encountef.lny obstacles. l$I5 comes as a 'new product' (strategy) i nto the'market', a n d succegofu I i m plet.nentation req u i res o propr sensitization fur concerned projects including high level advocacy for acceptability o improveS.Deffqrmance monitoring on the health system and community level, o intensifyirfE the mobilisation, training, supervision, ... campaigns, o timely availability.of the drugs and other tools required o treatment at a tima relative to transmission patterns that ensures optimal impact. ATS were categorized into the following groups: a) mass drug administration with ivermectin or albendazole b) mass drug administration with drugs currently in development c) Test-and-treat (T&T) algorithms d) vector control Page 13 of 30 3.3.1 ATS based on mass drug administration with ivermectin 3.3.1.1 Annual ivermectin MDA by mobile teams ln some circumstances where CDTI failed to reach the necessary geographic or therapeutic coverage, the group proposed the use of mobile teams e.g. in Category 3c areas with non- programmatic issues. 3.3.1.2 BiannualCDT! The group reviewed the experience of bi-annual treatment from Ghana and Uganda where this strategy was adopted in 2009 and 2007, respectively. The rationale for adopting this strategy was poor geographic and therapeutic coverage and the fact that annual treatment had not interrupted transmission despite many years of treatment. The group also considered the results of ONCHOSIM modelling presented to TCC which concluded that biannual CDTI is not a cost-effective ttBthod for compensating for low treatment coverage with annual CDTI [8]. Hence, biannualeDTl was defined by the group as 'Treating the same person twice a year with the aim of act**erating the elimination of microfilariae in the body''. The group proposed the following set of indicators to help kth (i) proportion of people who took tVM once only d(ii) proportion of people who took IVM once on g second round,(iii) proportion of people who too*.IVM du The Ghana experience concluded that bi-annual rounds. improved coverage but that thisCDTI has required commitmgnt of partners and governfiGftt; The lespns learnt that need to be taken into account in all aneas adopting bCDTI to accela&,progress towards elimination are: (a) Absolute need to ensure sustained health education, mobilization and appropriate supelision to achieve the treatment coverage required, (b) Special efforts to address the challenges for maintaining treatment cycles in a migratory population need*o be implemented (c) Timely release of funds at the natisnal and district level is critical to allow adherence to the timeline for implementation of activities (d) Timely availability of ivermectin and other supplies (e) Resources for timely retrieval and verification of treatment coverage data to identify actions required to improve bCDTI implementation. The results of modelling of the relative impact of increasing CDTI treatment coverage vs. introducing bCDTI [8] and the results of recent modelling of the importance of the timing of annual CDTI for the number of years required to elimination in areas with seasonal transmission (see section 3.3.2.1) should be taken into account when deciding on bCDTI as ATS. 3.3.2 MDA with drugs currently in development Two drugs (moxidectin, flubendazole) are currently under development which have potential to be suitable for MDA based ATS. Page 14 of 30 The group also considered Anti-Wolbachia treatments. Doxycycline cannot be considered for MDA due to the need to exclude pregnant women and children <8 years, considerations of risk-benefit in nursing women and the long treatment course. The A-WOL consortium is progressing rapidly with clinical studies of other antibiotics (e.g. minocycline) and discovery of antibiotics with potential to be effective with a 3-day regimen to transition them to clinical development [12]. It was emphasized that introduction of new drugs into MDA requires appropriate surveillance to ensure that any safety and tolerability issues, not encountered during clinical studies are detected, treatment for potential adverse reactions is available and, if applicable, the suitability of the new drugs for MDA is re-assessed. 3.3.2.t Moxidectin Moxidectin completed Phase 3 clinical development [8]. WHO has recently concluded an agreement with Medicines Development for Global Health (MDL), an Australian Not-for- Profit organisation, which aims to register moxidectin for onchocerciasis and also develop it for LF and scabies. tn the Phase 2 study [13], a single dose of I mB Moxidectin resuhed in skin microfilariae levels which were for 12 months lower than the lowest levels achieved *er ivermectin treatment. The superiority of 8 mg moxidectin was confirmt$,in a larger study conducted in Ghana, Liberia and DRC [8]. . ,,i' The results of EpiONCHO modelling of the Phase 2 StttdY data conducted by H. Turner, M. Walker and MG Basanez (tmperial College London)were reviewed. The modelling compared the effect of annual corrrmunity direct_ed treatment with 8 mg moxidectin (aCDTM), biannual treatment.with ivermectin $eDTl|,and:annual treatment with ivermectin (aCDTl) on time and in-cou*f*. costs (based on costs for aCDTI vs bCDTI from Ghana) to reaching the proposed:operatidnf,l'threshol'dt for interruption of treatment (pOTTlS, [3]) in different epidemir;figgfcal and contrd,,prograrY&e settings (pre-control endemicity, control history, treatmgnt coverage). The resultlgf the modelling suggest that: o The:1g{ycti$r.in numbei:Of years of treatment to reach pOTTIS relative to aCDTI is similar wtth aCDTM and bCDTI o Since , i"*nA treatment/year increases in-country costs/year relative to a single treatment/year, an aCDTM strategy results in significant cost savings for countries. o Time to pOTTIS with bCDTI and aCDTM is similarly sensitive to treatment coverage, butwith aCDTM hightreatment coverage needsto be achieved onlyonce a year, not twice a year. The modelling also compared the effect of the timing of aCDTI and aCDTM relative to transmission season patterns on years to pOTTlS. The results showed that timing of aCDTM relative to peak transmission season does not significantly impact time to reach pOTTlS, while suboptimal timing of aCDTI increases the number of years of aCDTI required until treatment can be stopped significantly. There are no data on the effect of moxidectin on Loo loo microfilariae from animal models. The effect of moxidectin on O. volvulus microfilariae suggests that moxidectin will not be suitable for MDA in Loo /oo co-endemic areas since it is likely to result in adverse reactions like those seen after ivermectin treatment' Page 15 of 30 3.3.2.2 Flubendazole An oral formulation [14] of flubendazole is under development (DNDi-Drugs for Neglected Diseases initiative [DNDi], Michigan State University, Johnson & Johnson) and expected to enter Phase 1 studies in 2015. Data from a clinical study in O. volvulus infected participants with an injectable formulation [15] as well as data from animal models suggest that even only a single dose of flubendazole is cidal to a significant proportion of macrofilariae. The data also suggest that flubendazole is not microfilaricidal. This makes flubendazole a very promising candidate for MDA, especially in Loo /oo co-endemic areas, even if its safety profile should require 'selective MDA' based on sex and/or age [16]. 3.3.3 'Test and treat strategies' A 'test and treat strategy' (T&T) was defined as any strategy that requires diagnosis of infection and/or contra-indications to treatment before a decision on whom to treat with what regimen. This strategy deviates from APOC's community directed intervention approach in several ways: 1) lt is not mass-drug administration based 2) Some diagnostic tests cannot be administered by gDDr and require at a minimum extensive training of community health workais while others will require administration by health care workers. ...:i3) The drugs used may have a safety profile no(lbnsistent with distribution by CDDs requiring involvement of personnel wtth specific skills and experience. 4) For some drugs, monitoring of ther.apeutk covotege will require more resources than monitoring of compliance with CDTI since it will require monitoring of compliance with >1dose regirnens. For each T&T, a series of questions needs to be answered before implementation is planned L. Who needs to be tested t2. Which infection is to be tested'for? 3. Which contra-indications other than infections need to be tested for? 4. Which tests are to be used? 5. Who can conduct these tests? 5. Who will be treated? 7. What drug regimen is the most suitable for which subpopulation? 8. What resources are required for successful implementation. All of these requirements imply that prerequisites for successful implementation of T&T include and go significantly beyond those for successful implementation of bCDTI outlined in section 3.3.7.2. Prior to implementation of T&T, the feasibility of implementation needs to be examined, operational research to determine critical factors for successful implementation needs to be conducted and the timely availability of all required resources needs to be assured. Page 16 of 30 3.3.4 ATS for different categories of areas requiring ATS Table L summarizes the proposed ATS by category of area qualifying for ATS. Table 1 Alternative treatment strategies for different categories of areas requiring ATS ExamplesAhernatlve strategy or actionCategory of area quallfylng for ATS Foci in Cameroon Vina Valley, DRC etc. . Vector control (ground larviciding) if possible PLUS + LLIN if LF present o Residual prevalence too high for T&T r Ensure availability of resources for bCDTI o bCDTI r (aCDTM when moxidectin becomes available) o (Flubendazole if available in time) o Residual prevalence compatible with T&T (to be defined) and elimination not feasible with other ATS o Assess feasibility of T&T o T&T: Test for O$$HO and treat ONCHO posit individual with A,-WOL compound + IVM ive Category 1: Modelling predicts that Onchocerciasis will be difficult to achieve with CDTI alone. (no Loiasis) lrlew areas in Ethiopia, Uganda, C6te d'lvoire etc. o (aCDTM when moxidectin becoqtqs available) o (Flubendazole if available in tinre) (ground larvi ciding),if :Possibo Vector control le PLUS + LLIN if LF present r bCDTI <80%)will lization to necessary DTI relative Category 2: Late start of CDTI relative to pre-control endemicitY and time required to achieve elimination with annual CDTI No too co-endemicitY stics which prevent reaching elimination by 2O2O orcategory 3: OPorational or 2025w No Loa loo I if feasible (ground larviciding for o T&T (drug to be discussed) o (possibly aCDTM when moxidectin becomes available) r (Flubendazole, if available in time) a a ONCH if LF present) Category 3a Confirmed p,resence of individuals with'afypicaf response (no loo lwco- endemicity) Mbamo Correct the weaknesses and enhance mobilization, monitoring, etc o AND THEN bCDTI (with Albendazole if LF present) . Vector control if feasible (ground larviciding for ONCHO + LLIN if LF Present) o (aCDTM when moxidectin becomes available) o (Flubendazole, if available in time) Category 3b lnfrastructure / managerial weaknesses/issues (no Loo /oo co-endemicity) o Mobile team based MDA if acceptable o Vector control if feasible (ground larviciding for ONCHO + LLIN if LF Present) o bCDTI (+Albendazole if LF present) o (aCDTM when moxidectin becomes available) Flubendazole, if available in time)o( Category 3c Other operational challenges (e.g. nomadic poPulation, difficult access to endemic areas, civil conflict) (no Loa loa co-endemicity) Page 17 of 30 Category of area quallfylng for ATS Alternative strategy or action Examples Category 3d. Operational and epidemiological characteristics which prevent reaching elimination by 2020 or 2025 with CDTI: Loo loo prevalence > 2OYo (RAPLOA>4O%) Meso. or hyperendemic areas After >15 yrs of CDTI, >15% oncho mf prevalence (thresholds to be discussed) o T&T o See algorithms in section 3.3.5 Most CDTI areas with high too prevalence in Cameroon (Littoral, West and SW) Nodule prevalence <20Yo or other data indicating onchocerciasis hypoendemicity o T&T o See algorithms in section 3.3.5 Onchocerciasis hypoendemic areas without CDTI LF MDA for elimination o T&T o See algorithms in section 3.3.5 3.3.5 Algorithms for selection of ATS by co emicity of onckmerciasis, Loiasis and [F The group developed algorithms for the decision on tll€:choice of AT$,for areEls in which ATS is indicated based on Loo /oo co-endemicity, considert*g three different epidemiological scenarios: 1. Onchocerciasis meso- or hyperendemic, LF prerra$rce requlrhg LF control, Loo loo microfilariae prevalencE >20o/o (RAPLOA >4Oo/ol (eee Figure 2). 2. Onchocerciasis hypo-endemicity, no lymphatic filariasis, Loo loo microfilariae prevalence >2O% (RAPLOA >4096) {see Figure 3) 3. Onchocerciasis hypoendemicity, LF prcvatsnce requiring LF control, Loo loo m i crofi la ri a e p revale n c e >2W6 { RA P LOA > 40o/ol (se e F i gu re 4) These algorithms considered a$endazold'and ivermectin, vector control as well as well as the possibility to use drugs such as doxycycline, moxidectin, and flubendazole . Test and treat scenarios summarized in Table 2 take into account only drugs that are donated or commercially available. Page 18 of 30 Figure 2 Algorithm for decision making for biannual treatment in onchocerciasis hyperendemic areas with Loa loa microfilaria prevalence of >20o/o (RAPIOA >4O%l in the presence of LF A lgorithm 1: HyPer endemic for ONCHO + Loase + LF Test oncho \ sJsK L No-Yes + (T",,f llo/tTEtllTest L oasis Test L oasis Doxy +(AlbX2 ) (Arbx2 ) No-Yes + Test loasis Page 19 of 30 \ K lvM+Alb Figure 3 Algorithm for decision making in onchocerciasis hypoendemic areas with Loa loa microfilaria prevalence of >20% (RAPLOA >4O%l in areas known not to be LF endemic Test Oncho Test Loa J OR Yes + No- OR Test toa Nlt Dory No tvM Ntt tvM illt J Yes + Dony ilo Yes + No I I IJ Yes + Do,.y Test Oncho Test Oncho Yes + Page 20 of 30 \ t\ t\ No- IVM Figure 4 Algorithm for decision making in onchocerciasis hypoendemic areas with Loa loa microfilaria prevalence of >2O% (RAPLOA >4O%l in the presence of tF (All will receive ArB) Test loa Test oncho &rF Table 2 summarizes LF. strategies by co-endemicity of onchocerciasis, Loiasis and Yes + No- Yes + to either Dony No- to both I Page 21 of 30 IVM +AtB Oncho- cerclasis* Loalsis*r tF Standard treatment stratety Treatment in areas requiring ATS Example Meso/Hyp er No No CDTI . Vector control (ground larviciding) if possible PLUS + LLIN if LF present o Residual prevalence too high for T&T o bCDTI o (aCDTM when moxidectin becomes available) o (Flubendazole if available in time) o Residual prevalence compatible with T&T (to be defined) and elimination not feasible with other ATS o T&T: Test for ONCIIO and treat ONCHO positive indMdualwith A- WOLcompound + IVM Vina valley Meso/Hyp er Yes No CDTI T: Treat + u Treat Lo n Meso/Hyp er No Yes IVM+ALB Bi-annual treatment with IVM+ALB Meso/Hyp er Yes Yes T&T: Test for Loiasi$ Treat LOlasis + with A-WOL compound Treat Lolas-is - with IMV+ALB No No Yes IVM+ALB bCDTI No Yes Yes ALB X2 Biannual AtB (+LtlN if feasible) No Yes No None .None Hypo Yes No Ncne See Figure 3 Hypo No Yes rVM+ALg Biannual ALB (+LLIN if feasible) Hypo Yes Yes ALB X2 + test oncho : See Figure 4 Table 2 ATS for areas qualifying for ATS by co-endemicity of onchocerciasis, Loiasis l>2Wo microfilariae prevalence l>4O% RAPTOA) and LF ** Loo /oo prevalence>20% (RAPLOA>4O%) Loiasis +: people with >8100 mf /mL Loiasis -, people with <8100 mf/ml provisionally, consideration may be given to asking people with i8100 mflml but <30 000 mflml for their preference following information on risks and benefits of the different treatrnent options 3.3.6 Algorithms for decisions on intervention strategy for LF elimination Plans for scalinB up twice yearly treatment with Albendazole and vector control for LF elimination in 10 countries in sub-Saharan Africa are being developed by CNTD in collaboration with WHO. The plan is based on collation of data from various sources, incorporation of Loa loo and CDTI project area maps provided by APOC; coding data on endemicity and intervention for each country and developing summary sheets for each country. The algorithm developed (Figure 5) takes into account the need for ATS where LF is co- endemic with too /oo. What remains to be done to enable the algorithm to be used, is to Page 22 of 30 IVM+ALB identifywhich LF endemic areas require intensified interventions. The relevance of this plan and collaborative consultations between WHO-APOC and CNTD for scale up of control of LF, including use of ATS in Loa loa co-endemic areas was recognized. Figure 5 Algorithm for mapping and deciding on intervention strategy for LF elimination START Has LF been mapped No - orLF historical - evldence? Yes ls oncho endemic with CDTi priority? No MDA required as LF not endemic Standard MDA required as no LF/loa loa co-endemicitY Ahernative strategY req uired as no history of MDA implementatlon Alternative strategl, required as no evidence of high coverage of ivermectin to avert risk of SAEs Atternative strateSly required as covefttges rate not high enough to avert SAEs / or SAEs rePorted Standard mapplng tct / Mt Mlcro- mapplng Mf Determine evidence of vector control incl. bed net/LLIN distributlon network Determine coveraSe rates and identify high risk areas and subgroups During MDA identify previous noncomPllant individuals and elther monltor/prepare lor SAEs, use Test & Treat or simply wlthhold ivermectin J Yes Yes Yes MappinS required as no data available ls Loa loa endemlc? Yes ]s there evidence of No , LF infection? No Actlon + Actlon + Actlon Actlon + Are ivermectih cov€role lls andreportson + SAEs available? Yes Have coverage rates been high (>8O%) with No Yes Standard MDA required if there is no evidence of clustering of low coverage areas or noncomPliant subgroups at risk 3.4 Areas of operational research related to ATS Research studies need to be designed to determine critical factors for successful implementation of ATS and allow to fill the gaps and address the challenges listed in section Page 23 of 30 No No 1.6. The type of critical factors to be investigated can be informed by the operational research studies which formed the basis for successful implementation of CDTI in APOC countries and the experience of countries which have implemented bCDTl. Furthermore, cost and cost-effectiveness studies need to be conducted. 3.5 Next steps To move the implementation of ATS to the next level, the following activities have to be undertaken: o Categorization of all APOC projects into the three categories identified by the expert group o Discussions with modellers on criteria and areas with pre-control endemicity levels for which elimination of onchocerciasis with annual CDTI would be very difficult (Category 1 areas) o Development of protocols for evaluating the resourCes needed for implementation of different ATS, as well as their comparative cost effectlvgness o Evaluation of the feasibility of vectori&ontrol by ground terviciding in areas requiring ATS o Development of guidelines and indicatorsfor proeess and impact of @, o Face to face meeting of experts 3.5 Challenges lmplementation of the propose_! AfS willfequire o Availability of DEC pat{h t€&&r large seah testingfor patent O. volvulus infection ; o Completion of research on and availability of diagnostic for identifying individuals with >8L00 Loa loa mflmlblood; o Availability of diagnostics for identification of 'atypical responses' and results of research aimed at determining whether parasites with 'atypical responses' are preferentially transmitted and could jeopardize achieving elimination with CDTI ; o Cost and operational constraints for doxycycline large scale use; o Design, funding and conduct of operational research required to identify critical factors for successful implementation of ATS, in particular T&T strategies. Some of the challenges that countries will encounter when implementing ATS will be eliminated or reduced by o Availability of moxidectin and flubendazole; o Availability of other A-WOL compounds with safety profiles and treatment regimens more suitable than those of doxycycline for large scale use; 3.7 Conclusions o ATS offer an opportunity for accelerating elimination of onchocerciasis and LF where needed. o Successful implementation of ATS requires proper understanding of field scenarios, understanding of the challenges and requirements and commitment at all levels of the health care system involved, availability of the required diagnostic/intervention tools and the necessary competencies and resources on all health care system levels. Page 24 of 30 o Availability of clear and simple algorithms is a prerequisite for scale up of Test and treat strategies in Loa loa endemic areas. o Bi-annual treatment with ivermectin is capable of accelerating onchocerciasis elimination when implementation time lines are adhered to and there is commitment by the government and partners. o Development of a protocol to assess feasibility and cost effectiveness of ATS and operational research are critical for scale up of ATS implementation. 3.8 Recommendations o ln areas of unsatisfactory epidemiological results, the country should conduct a situation analysis and develop a roadmap to address the obstacles identified. o Clear guidelines for programme managers and health workers for effective and efficient implementation of bi-annual CDTI and other ATS need to be issued. o There is need to define pre-control endemicity thresholds above which elimination of onchocerciasis with annual treatment with ivermeetin ,.would be very difficult to achieve and ATS need to be implemented, o ln areas with high onchocerciasis preva{€ne where CDTI has been conducted for 15- 20 years but progress does not suggest that transmission will be interrupted by 2025, the group recommended that, as per previous TCC advice, mafiagerial issues be addressed in priority and that use of mobile teams;;,bCDTl and vector control be considered (as well as treatment with moxidectin or flubendazole when these become available). . Suspending CDTI to conduct surveys to establish the impacts of treatment on onchocerciasis prevalence mlgfit have a negative impact beyond onchocerciasis, therefore APOC managqrnent needs to srfkiatty inform Ministry of Health top management oft€epective couatries when su*lgtrrveys are planned. o To scale up implenrcRtation of 'LF control, areas which can implement the standard trgatment and those \ildiqh require ATS and the most appropriate ATS need to be identified. o To guide deeisions on ATS implementation, information on the cost and cost- effectivdiiesf pf different ATS and ATS vs. CDTI needs to be generated. 4 TCC 39 Comtmnts on the proposed basis for a road map for ATS The recommendations of the group were presented to TCC39; the Experts Group was commended for the impressive work done. TCC raised a number of critical issues to improve the implementation of ATS. TCC members underscored the need for conducting situation analysis in poorly performing projects to better understand the determinants for poor performance which could include political, decentralization, data flow, etc; and this should be incorporated in the modelling framework. Members of TCC wondered whether APOC management and countries are prepared for this strategy given the pertinent issues of in-country capacity building and other issues related to systematic non-compliance is some projects. These issues should be identified and incorporated into the framework for PENDA which should include issues of high level Page 25 of 30 advocacy, visits to problematic countries, cost of ATS and how it can be piloted in some countries. Thegroup's suggestions were endorsed by TCC39 with the following recommendations:- o ln order to ropidly scole up ATS to countries, DEC potch Test and Moxidectin should be made ovailoble. o Guidelines for identificotion of atypical responses to IVM should be developed ond incorporated in the ATS document. o ln scoling up ATS to countries, TCC members observed that Albendozole monotheropy for LF control should be odministered in conjunction with integroted vector control to creote impoct. o As Doxycycline hos been proposed for use in test ont treat strotegy, TCC recommended thot thot cleor guidelines for the dninistrotion of this drug should be developed to toke care of children under 7 yeors ok{ pregnant women os this sub- group may be difficult to identify. o TCC further recommended thot the wtcome o! these discussions on A,?5 should be disseminated to Nationol Coordinotors in the prq@g meeting in November 2014 ond some messoge sent ta coun To enoble effective scole up of.ATS, this projects so os toa ond feosibility of 5 ReferenceS, infegrOtgd vector oddress the issue of use of use of cords to verify treotment ,ril., . R, BiisS'Y, Doumbia K, Goita SF, Konate !1. Diawara I Traore MQ, Badji F, To€ L,Mounkoro K, Sarr MD, Seck A Touree S, Remme JH (2009) Feasibility of onchocerciasis elimination wlth ivermeetin treatment in endemic foci in Africa: first evidence from studies in Mali and senegal. PLos Negl Trop Dis 3: e49l. 2. TraoretO, Sarr MD, Badji A, Bissan y, Diawara L, Doumbia K, Goita SF, Konate L, Mounkoro K, Seck AF, Toe L, Toure S, Remme JH (2OL2l Proof-of-principle of onchocerciasis elimination with ivermectin treatment in endemic foci in Africa: final results of a study in Mali and Senegal. PLoS Negl Trop Dis 6: e1825. tO.137Lfiournal.pntd.OOO182s ldoil; PNTD-D-L2-0066o tpill. 3. African Programme for Onchocerciasis Control (APOC) (2010) Conceptual and Operational Framework of Onchocerciasis Elimination wtih lvermectin Treatment. wHo/APOCA4c/l0.1. 4. Tekle AH, Elhassan E, lsiyaku S, Amazigo UV, Bush S, Noma M, Cousens S, Abiose A, Remme JH l2}72l lmpact of long-term treatment of onchocerciasis with ivermectin in Kaduna State, Nigeria: first evidence of the potential for elimination in the operational area of the African Programme for Onchocerciasis Control. Parasit Vectors 5:28. 17s6-330s-s-28 [p i i] ; 1 0.LL86 / L7 s6-330s-5-28 [doi]. 5. African Programme for Onchocerciasis Control (APOC) (2OL4l Report of the 39th session of the technical consultative committee (TCC), September 20L4. Page 26 of 30 6. Boussinesq M, Gardon J, Gardon-Wendel N, Chippaux JP (2003) Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon. Filaria J 2 Suppl 1: 54. LO.Lt86 / 747 s-2883-2-S 1-S4 [d o i] ; 1475-2883-2-5 1-Sa I p i i ] . 7. World Health Organization (2012) Provisional strategy for interruption lymphatic filariasis transmission in loiasis-endemic countries. Report of the meeting on lymphatic filariasis, malaria and integrated vector management, Accra, Ghana, March 2OL2' 5139 PCT ua=1 8. African Programme for Onchocerciasis Control (APOC) (2013) Report of the thirty-sixth session of the technical consultative committee, Ouagadougou, 11-15 March 2OL3.http:/ vww.who.int noc/about/structure ?6 Final Report 170513.Odf. g. Turner HC, Walker M, Churcher TS, Osei-Atweneboana MY, Biritwum NK, Hop kins A, Prichard RK, Basanez MG (2014) Reaching the Loadon Declaration on Neglected Tropical Diseases Goals for Onchocerciasis; An Economic Ewluation of lncreasing the Frequency of lvermectin Treatment in Afr ica. Oin lnfect Dis . ci u467 [pi i] ; 1.0. 10S/ cid I ciu467 ldoil 10. Katabarwa MN, Habomugisha P, Richards Jr. (2002) lmplementing Slatko BE, Ward SA (2014) Anti-Wolbachia laricides for onchocerciasis and lymphatic com mu nity-directed treatment ocerciasis in Uganda (1997-2000): an evaluation. Ann 11. Stolk W QA, de Vlas SJ, Fischer PU, Weil GJ, Goldman AS (2013) Modeling the impact an ian nual mass drug administration for accelerated elimination of lymp rnal.pntt{;000 Negl Trop Dis 7: e1984 tO.L37Lfiou 198a [doiJ;P piil. 72. Taylo drug diseovery and lpiil;10 A, Townson S, : safe macrofi r erauf d filariasis. Parasitol L4tt 7L9-L27. s0031182013001108 L il 13. Randomized, K, Opoku NO, Attah SK, Lazdins-Helds J, Kuesel AC (2OL4l A ding-Dose, lvermectin-Controlled, Double-Blind Study of Moxidectin in rca volvulus lnfection. PLoS Negl Trop Dis 8: e2953 t0.l37Lfiournal.pntd 3 [doi];PNTD-D-13-00311 [Pii] L4. Ceballos L, Mackenzie C, Geary T, Alvarez L, Lanusse C (2014) Exploring the potential of flubendazole in filariasis control: evaluation of the systemic exposure for different pharmaceutical preparations. PLoS Negl Trop Dis 8: e2838. LO.L37 Lfiou rn al. pntd.0002838 [doi] ; P NTD-D-13-01792 [pi i]. 15. Mackenzie CD, Geary TG (2011) Flubendazole: a candidate macrofilaricide for lymphatic filariasis and onchocerciasis field programs. Expert Rev Anti lnfect Ther 9: 497-50t. L6. Longo M, Zanoncelli S, Messina M, Scandale l, Mackenzie C, Geary T, Marsh K, Lindley D, Mazue G lz1L4l ln vivo preliminary investigations of the effects of the benzimidazole anthelmintic drug flubendazole on rat embryos and fetuses. Reprod Toxicol 49C: 33-42. 50890-6238(14)OO11O-5 [pii];10.1015/j.reprotox.2014.06'009 [doi]' Page 27 of 30 6 Annex 6.1 List of participants 1. Dr Chris Ngenda MWIKISA, Programme Manager a.i., WHO/APOC, 01 P.O. Box 549, Ouagadougou, Burkina Faso, Te!: +226 50 34 29 53 - E-mail: mwikisac@who.int 2. Mrs. Christellv BADILA TCHITEMBO, Programme Manager, Sightsavers C6te d'lvoire/Burkina & CT WHO/APOC for C6te d'lvoire, Ouagadougou, Burkina Faso - Tel: 226 7 6 9921 20 - E-m a i I : cba d i la @ sishtsavers.ors 3. Dr Nana-Kwadwo BIRITWUM (participant by skype), Programme Manager, Neglected Tropical Diseases Programme (NTD), Ghana Health Service, P.O. Box MB-190, Accra, Ghana Tel: +233 20 8232286 - +1 260755 38869 E-mail: nanakwadwo. biritwu m@gma il.com 4. Prof Daniel BOAKYE, Technical officer/Entomology, wHo/Apoc, 01 p.o. Box 549, Ouagadougou 0L, Burkina Faso - Tel: +226 50 34 29 53 - E-mail: boakved@who.inU vawo bad i e i (ova hoo.co. u k 5. Dr Michel BOUSSINESQ, lnstitut de Rec Mr-233, Tel:911 Avenue Agropolis BP 64501, 34394 +33 675 139 151- E-mail: michel.boussinesq@ird.fr 6, Dr Grace FOBI, Chief of the Sustainable Drug Tel: +225 50 34 n APOC, P.O. Box 549, Ouagadougou, Burkina Faso, 29 ail : 7. Dr Louise Alice KELLY-HOPE, Senior P me r, Centre for Neglected Tropic Diseases, Liverpool School of tctn ), Pembroke Place, Liverpool L3 5QA, United m- 1 3336 - Mobile: +aa (0) 790768 7600 - E-mail: Lo le D6ve loppement (lRDl, U Cedex ,5, Stance D 8. Dr Annette KUESEL (partici Development and Evaludtion skype), Moxidectin Project Manager, Drug (BLG O/TDR, CH-1211 Geneva, Switzerland - Tel: 4L22-79L-L541- Mobi E-mail: kuesela@who.int 9. Mr. Thomson Luroni Entomologist, National Onchocerciasis Conttrol Programme tllOCP) Secretariat, Mlnistry of Health, P.O. Box 7272, Kampala, Uganda - Mobile: +256 772 438 311- Landline: +256 4L425t 927 - E-mai!: tlakwo@email.com L0. Mr lssaka Niandou YACOUBA, lso, wHo/APoc, 01 p.o. Box 549 ouagadougou 01, Burkina Faso - Tel: +226 50 34 29 53 - E-mail: niandouv@who.int 11. Dr Asiedu Dacosta ODAME, Programme Officer (Oncho), Neglected Tropical Diseases Control Programme, Disease Control & Prevention Department, Ghana Health Service, P.o. Box MB 190, Accra, Ghana - Tel: (office): +233302 66 22 232 - Mobile: +233 244 7 6L 357 ; +233 27 2 894 226 - E-ma il: odame 1 hoo.com L2.Dr Jan H.F. REMME (participant by mail), 120 Rue des Campanules 0120 Ornex, France Tel: +33 645457404 - E-mail: hansremme@smail.com L3. Dr Franck Paul SINTONDJI, Technical Advisor APOC/NTDs, WHO Country Office, Ndjamena, Tchad GPN: 34036 Mobile: +23s 66 46 06 59 E-mail: sintondiip@who.int Page 28 of 30 14. Mr Tendainashe SIWOMBE, lTO, WHO/APOC, 01 BP 549 Ouagadougou 01, Burkina Faso -Tel: +226503429 53 - E-mail: siwombet@who.int 15. Dr Frangois SOBELA, Health System Specialist, Sustainable Drug Distribution Unit & Chief a.i. of the Epidemiology and Vector Elimination Unit, WHO/APOC, P.O. Box 549, Ouagadougou, Burkina Faso, Tel: +22650342953 - E-mail : sobelaf@who.int 15. Dr Afework Hailemarian TEKLE, EPl1, WHOIAPOC, P.O. Box 549 Ouagadougou 01, Burkina Faso - Tel: +226 50 34 29 53 - E-mail teklea@ who.int L7.Dr Laurent TOE, Temporary Adviser, WHOAPOC, 01 P.O. Box 549, Ouagadougou 01, Burkina Faso - Tel: +226 50 34 29 53 - E-mail: toel@who.int; ltoe@hotmail.com 18. Prof. Samuel WANJI, Head of Department of Microbiology and Parasitology, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon - Tel: +237 77 724384; +237 77 679 282- E-mail: swanii hoo.fr: samwandii@gfnail.com 19. Mr Honorat Zour6, Biostatistician lnformation Mapping,{BtM), WHO/APOC, 01 P.O' Box 549 ouagadougou 01, Burkina Faso - Teh+226 50 34 29 53 - E-mail zoureh o.int 6.2 List of countries predicted by ttre C$4, working group on elimination to achieve national onchocerciasis eltminatloft by 7O2O :' Page 29 of 30 a6.3 ProvisionalAgenda forconsultative meeting on ATS Experts Consultations on APOC's roadmap on alternative treatment strategies for accelerating elimination of oncho/LF in problem areas. Ouaeadousou, 05-07 September 2014 PROVISIONAT AGENDA 1. Opening (Dr Chris Mwikisa) 2. Adoption of the Agenda (Dr Chris Mwikisa) Strategic and technical issues Alternative treatment strategies: Update from research (Drs Boussinesq, Dr wanji) APOC Road map on alternative treatment strategies for accelerating elimination in problem areas (Dr Grace Fobi) Countries' Experience in biannual treatment with IVM (Or Thompson Lakwo, Mr Odame) Countries Experience in Test and treat(Drs Boussinesq, Dr,Wanji) Opportunity for using Moxidectin as analleraative treatment{Er Annette Kuesel} Operationalising Alternative Treatment $trate6ies in Problem areas (Most appr6priate strategy for accelerating elimination in tlreproblem areas such as Centre e&al Littoral projects in Cameroon; Gabon etc) (Dr Hans Remme) o Areas for piloting alternative treatment strateBbs during the period 2074-2015 (Dr Hans Remme) o Algorithms fior decision making{or implementation of ATS (Dr Samuel Wanji, Dr Kelly Hope) o Field guidelines(Ilr o Key indieators of protess and im pson Lakwo, Mr Odame and Dr Michel Bouseinesq) Areas of operations research related to ATS (Dr Samuel Wanji) Results of epidemiological,and entomological evaluation with focus on projects with concern (Afewo*/Boa kye) Next stepl{gr Grace Fobi)Conclusions and recommendations to TCC39 (Dr Grace Fobi) Closure of the session (Dr Chris Mwikisa) t 3. 4. 5. 6. 7. 8. 9. 10. 7L. 72. Page 30 of 30