Onchocerciasis Control: Vision for the Future from a Ghanian perspective

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Open AcceMeeting reportOnchocerciasis Control: Vision for the Future from a Ghanian perspectiveMark J Taylor*1, Kwablah Awadzi2, María-Gloria Basáñez3, Nana Biritwum4, Daniel Boakye5, Boakye Boatin6, Moses Bockarie7, Thomas S Churcher3, Alex Debrah8, Geoffrey Edwards1, Achim Hoerauf9, Sabine Mand9, Graham Matthews10, Mike Osei-Atweneboana11, Roger K Prichard11, Samuel Wanji12 and Ohene Adjei8
Address: 1Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK, 2Onchocerciasis Chemotherapy Research Centre (OCRC), Hohoe Hospital, Hohoe, Ghana, 3Department of Infectious Disease Epidemiology, Imperial College, London, UK, 4Lymphatic Filariasis Elimination Programme, Health Research Unit, Ghana Health Service, Accra, Ghana, 5Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Accra, Ghana, 6TDR, World Health Organisation, Geneva, Switzerland, 7Centre for Neglected Tropical Diseases (incorporating the Lymphatic Filariasis Support Centre), Liverpool School of Tropical Medicine, Liverpool, UK, 8Kumasi Centre for Collaborative Research (KCCR), Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana, 9Institute for Medical Microbiology, Immunology & Parasitology, University of Bonn, Bonn, Germany, 10Department of Biological Sciences, Imperial College of Science, Technology and Medicine, London, UK, 11Institute of Parasitology, McGill University, Québec, Canada and 12Research Foundation for Tropical Diseases and the Environment (REFOTDE), Buea, Cameroon

Email: Mark J Taylor* - [email protected]; Kwablah Awadzi - [email protected]; María-Gloria Basáñez - [email protected]; Nana Biritwum - [email protected]; Daniel Boakye - [email protected]; Boakye Boatin - [email protected]; Moses Bockarie - [email protected]; Thomas S Churcher - [email protected]; Alex Debrah - [email protected]; Geoffrey Edwards - [email protected]; Achim Hoerauf - [email protected]; Sabine Mand - [email protected]; Graham Matthews - [email protected]; Mike Osei-Atweneboana - [email protected]; Roger K Prichard - [email protected]; Samuel Wanji - [email protected]; Ohene Adjei - [email protected]

* Corresponding author

AbstractSince 1987 onchocerciasis control has relied on the donation of ivermectin (Mectizan®, Merck &Co., Inc.) through the Mectizan Donation Programme. Recently, concern has been raised over theappearance of suboptimal responses to ivermectin in Ghana – highlighting the potential threat ofthe development of resistance to ivermectin. This report summarises a meeting held in Ghana toset the research agenda for future onchocerciasis control. The aim of this workshop was to definethe research priorities for alternative drug and treatment regimes and control strategies to treatpopulations with existing evidence of suboptimal responsiveness and define research priorities forfuture control strategies in the event of the development of widespread ivermectin resistance.

IntroductionSince 1987 onchocerciasis control has relied on the dona-tion of ivermectin (Mectizan®, Merck & Co., Inc.) through

the Mectizan Donation Programme (MDP). This pro-gramme is rightly regarded as a model paradigm for masstreatment control programmes [1]. The 20th anniversary

Published: 21 January 2009

Parasites & Vectors 2009, 2:7 doi:10.1186/1756-3305-2-7

Received: 15 January 2009Accepted: 21 January 2009

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of MDP was an opportunity to reflect on the successes theprogramme has achieved [2]. As the African Programmefor Onchocerciasis Control (APOC) enters the phasing-out period of the programme (2008–2015) a number ofongoing and future challenges face the sustained deliveryof onchocerciasis control by national programmes. Whileattention on the problems presented by 'fragile states',poor primary health care systems and co-infection withLoa loa are evident [2-4] – the role and priorities forresearch activities to address complementary and alterna-tive control strategies have received less attention. This isparticularly important in view of the conclusion thatonchocerciasis in Africa cannot be eliminated with exist-ing tools [5]. To address this issue a meeting was held inGhana in April 2008. The aim of this meeting was toreview the current status of onchocerciasis control inGhana in light of evidence of poor-responsiveness to iver-mectin, define the research priorities for alternative drugand treatment regimes and control strategies to treat pop-ulations with existing evidence of suboptimal responsive-ness and define research priorities for future controlstrategies in the event of the development of widespreadivermectin resistance.

The current status of onchocerciasis control in GhanaIn Ghana, onchocerciasis is endemic in 9 out of 10regions. About 3204 communities from 66 districts areendemic in these regions. Some 247 of these communitiesin Brong Ahafo and Ashanti regions have been designatedas Special Intervention Zones (SIZ), which are areas ofhyperendemicity, within the Pru River basin that serve asthe focus of Community-Directed Treatment with Iver-mectin (CDTI). The total at risk population for onchocer-ciasis is about 3.2 million.

Ivermectin distribution in Ghana started with the use ofmobile teams in 1987, with CDTI introduced in 1998.Since the devolution of onchocerciasis control from theformer-OCP (Onchocerciasis Control Programme) toGhana (under APOC), the national programme has beenmonitoring recrudescence through entomological andepidemiological surveillance activities. Ivermectin treat-ment started in lymphatic filariasis and onchocerciasis co-endemic areas in 2001 and has undergone a gradual up-scaling to cover 61 endemic districts by 2005. From 2002to 2007 3.4 million people were treated through CDTIwith coverage ranging from 48.4 to 79.1%. Since 2006onchocerciasis control has been implemented in the con-text of the Neglected Tropical Diseases Control Pro-gramme (NTDCP). Implementation of NTDCP started inApril 2007 on a pilot basis in 5 regions of Ghana.

Results from the entomological and epidemiological sur-veillance activities have indicated fly infectivity levels andinfection in humans that require improved programme

attention. Results of surveys done in 2005, indicated highinfectivity rates of 1.82 per 1000 parous flies, from theAsubende site within the Pru River basin. In 2006 resultsagain showed high infectivity rates of 0.556 – 1.01 per1000 parous flies from sites within the White Volta, Kul-pawn, Anum and Pra River basins. Fly nuisance was signif-icantly high in each of the surveyed sites.

In 2004 epidemiological surveys showed a microfilariapositive prevalence of 8.9% with 13 out of the 18 villagessurveyed having prevalence of more than 5%. About 2.8%and 0.75% had visual impairment and total blindnessrespectively. About 9 of the 24 communities surveyed in2006 had prevalence rates above 5% with the highestfocus found in 3 sites in the Asante Akim district inAshanti region. Community microfilarial load (CMFL)ranged from 0.56 – 2.89 mf per skin snip. A site within thePru River basin produced CMFL of 0.98, which is abovethe threshold of 0.5 while results of other communitieswere below this threshold.

A number of factors may contribute to the trends observedfrom entomological and epidemiological surveys, includ-ing CDTI coverage, individual compliance and the possi-bility that the efficacy of ivermectin is compromised.

Evidence for poor responsiveness and resistance to ivermectinEvidence for Sub-optimal Responses to IvermectinSuboptimal response (SOR) of Onchocerca volvulus to iver-mectin is manifested by responses that are incompatiblewith previous experience with multiple treatments. Criti-cal to this definition is incontrovertible evidence of theconsumption by the subject of the number of treatmentsunder consideration. Additional factors are parasite expo-sure to adequate concentrations of ivermectin and controlfor the effects of ongoing transmission. SOR is usually sus-pected when the prevalence of and/or the intensity ofinfection by skin microfilariae are higher than expectedand is confirmed by direct examination of the adultworms. Multiple treatments with ivermectin have markedeffects on embryogenesis [6]. Quantitative estimates haveranged from an irreversible decline in microfilarial pro-duction of ~30% per treatment [7], a reduction in the pro-ductivity index of 83% [8] to arrest of development at thesingle cell stage [9]. Thus when the factors listed above aretaken into account, the presence of normal reproductiveactivity in female worms exposed to multiple treatmentsis incompatible with a normal response.

An open case control hospital based study [10] enrolled21 microfilaridermic and 7 amicrofilaridermic subjectsfrom two river basins in Ghana with little risk of ongoingtransmission and with documented consumption of ≥ 9ivermectin treatments, and also 14 microfilaridermic iver-



mectin naïve subjects from a focus of continuing trans-mission. Detailed clinical ophthalmological andlaboratory examinations were done. Ivermectin 150 μg/kgwas then administered. A pharmacokinetic componentdetermined drug exposure. Skin snipping and fly feedingwere done before and at days 8, 90 and 365. Embryo-grams from adult female worms were examined at day 90.The study determined that the significant microfilarider-mias despite multiple treatments with ivermectin weremainly attributable to the non-response of the adultfemale worms and not to inadequate drug exposure orother factors. This was confirmed in a 30-month followup study [11]. Microfilariae in general remained sensitiveto ivermectin.

In a two phase epidemiological study [12], 2501 individ-uals were randomly selected from 19 onchocerciasisendemic communities located in 3 river basins in Ghana.Very stringent criteria were met by the communities anddetailed investigations provided incontrovertible evi-dence of the consumption of 6–18 rounds of ivermectinby the participants; one other community was ivermectinnaïve. The microfilaria prevalence and community micro-filarial load ranged from 2.2% to 51.8%, and 0.06 micro-filariae per snip to 2.85 microfilariae per snip,respectively. Assessment of skin microfilariae 30 days after150 μg/kg of ivermectin treatment showed 100% clear-ance in more than 99% of subjects. However, re-snippingof 342 initially skin snip positive participants from 10communities at days 90 and 180 during the second phaserevealed an usually high repopulation rate at day 90 thatwas confirmed at day 180 in 4 out of 10 communities.This finding suggests that the adult female worms had notresponded to the known suppressive effects of the multi-ple treatments of ivermectin administered previously.

The Ghana studies (either conducted with little risk ofnew infections [10,11] or with ongoing transmission[12]) yielded similar results and demonstrate that iver-mectin remains a potent microfilaricide but that non-responsive female adults may be present in some commu-nities. This is also suggested by the much more rapidreturn of skin microfilariae at 4–6 months in a subgroupof subjects treated with a single dose of ivermectin and liv-ing in a non-endemic area [13].

Genetic evidence of resistance to ivermectinDrug resistance has been defined as a loss of the normalresponse to treatment and is heritable [14]. Ivermectinaffects both the microfilariae, removing them from theskin, and the adult worms, inhibiting their reproductionfor many weeks. Because of these various and prolongedeffects, and because ivermectin activity involves hostimmunity, it is not reliable to assess efficacy in vitro. Phe-notypic assessment of resistance needs to consider both

skin microfilarial loads (repopulation of the skin bymicrofilariae), and worm fertility (by embryogram). Ameta-analysis was conducted of both these outcomes aftersingle-dose ivermectin following a systematic review ofearly clinical and field trials and fitted a mathematicalmodel to the data [15]. Results were compared with thoseobtained in a study of 10 repeatedly treated communitiesin Ghana (with >10 annual treatments) [12]. This studyindicated continued high microfilaricidal activity of iver-mectin but suggested that inhibition of reproduction byadult worms was impaired in some repeatedly treatedcommunities in contrast to an ivermectin-naïve commu-nity. Subsequent repopulation of skin by microfilariaewas faster than expected even after considering the inter-study variability of the (also ivermectin-naïve) meta-anal-ysis. A model for repopulation rates was fitted to micro-filarial temporal profiles after treatment for each personexamined in one of the communities (treated for 10 years)to quantify the level of inter-individual variability in par-asitological response. Ivermectin resistance is common inveterinary parasites and has a genetic basis associated withselection on ATP-binding cassette (ABC) transporters (e.g.P-glycoproteins) and β-tubulin. Onchocerca volvulus sam-ples from communities in Ghana and Cameroon thathave received many treatments have been found to havesignificant changes in similar genes (β-tubulin, P-glyco-proteins and other ABC transporters) compared withworms isolated from treatment-naïve subjects or the samesubjects prior to treatment [16,17]. These genetic changesshould be useful markers for ivermectin resistance moni-toring. Genetic and parasitological data can be integratedinto mathematical models to assess the epidemiologicalconsequences of anthelmintic resistance, identify optimalhost characteristics and parasitic stages to sample, andassist in the development of intervention strategies todelay or manage resistance.

Alternative Chemotherapy, drug discovery and developmentAntibiotic therapyNew and alternative treatments for filariasis are thereforeurgently needed. The break-through of using antibiotics totarget the bacterial symbiont of the parasite has identifieda novel treatment and target that offers a superior thera-peutic alternative to current anthelminthic drugs [18-21].The rationale for this novel treatment is the antibiotic tar-geting of Wolbachia – a bacterial endosymbiont of filarialparasites essential for worm development, fertility andsurvival and inducer of inflammatory disease pathogene-sis. A series of field trials against onchocerciasis and lym-phatic filariasis have demonstrated that 4–8 week coursesof the antibiotic doxycycline deplete the bacteria andresult in the long-term sterility and most importantlydeath of adult worms [18-21].



A series of field trials on onchocerciasis in Ghana beganwith a regimen of daily treatment with 100 mg doxycy-cline for 6 weeks, followed by ivermectin 4 months later,which resulted in depletion of Wolbachia and femaleworm sterility for 18 months in all worms except for a fewthat were acquired after doxycycline treatment [21-23].The data allowed the conclusion that this effect was due todoxycycline alone [22]. In a more recent, placebo control-led trial, treatment with a daily dose of 200 mg, either for4 or 6 weeks (again followed by ivermectin), also lead tosterility of female worms and more importantly to a mac-rofilaricidal effect of 50 or 60%, respectively, observed at21–27 months after treatment [24]. If one subtractedthose worms that had been newly acquired in the intervalafter doxycycline treatment, the macrofilaricidal ratewould have been approximately 10% higher. The propor-tion of dead female worms in ivermectin-only treatedpatients who had received placebo instead of doxycyclineremained at levels equivalent to those found in onchocer-comas from untreated patients (around 15%). The macro-filaricidal effect of doxycycline appears to take >1 year tomanifest accounting for the lack of this activity in earlierreports. In support of this, another study using 100 mg/day of doxycycline for 5 weeks (without ivermectin) alsoled to sterility and a 50% macrofilaricidal effect after 21–27 months [25].

The 'slow-kill' outcome of doxycycline therapy has severaladvantages including the elimination of the inflammatoryinducing bacteria [26,27] and avoidance of potentialadverse reactions to nematode products associated with arapid-kill as observed in loiasis co-infection [3].

The current major obstacles to the use of antibiotic ther-apy in control of filariasis is the length of treatment,which is considered to be logistically incompatible withthe community-directed treatment strategies used forfilariasis control and contraindication for children >9 andpregnancy. Shorter regimes using combinations of exist-ing antibiotics effective against Wolbachia require testingto establish the minimum effective regime for integrationinto existing control programmes to meet the program-matic aims of eliminating filariasis or be used in morerestricted situations, such as during the 'mop-up' phaseand the end of programmes, in the event of the emergenceof resistance or poor responsiveness to existing drugs or inindividuals co-infected with Loa loa and at risk of severeadverse reactions to ivermectin. Definition of the minimaleffective regime will also provide an important advance inthe treatment options for individual cases outside of con-trolled areas.

In the case of communities co-infected with L. loa; the riskof severe adverse events following ivermectin therapy inindividuals with high intensity of L. loa microfilaraemia

precludes the use of ivermectin in many of the forestedregions of APOC. The use of doxycycline in these commu-nities has been determined in two trials in Cameroon. 1)A placebo-controlled trial of doxycycline with or withoutivermectin in areas of low loaisis co-endemicity, and 2) atrial of community-directed delivery of doxycycline alonein communities with high prevalence of loaisis. The out-come of these trials, which is currently under analysis,should reveal the suitability of these approaches as analternative therapy for onchocerciasis in areas of loiasisco-endemicity.

Anti-Wolbachia (A-WOL) Drug Discovery and DevelopmentIn an attempt to translate Anti-Wolbachia therapy into apublic health tool the A-WOL consortium has been estab-lished through funding from the Bill and Melinda GatesFoundation to find new drugs active against Wolbachiathat improve upon existing antibiotic therapy.

The principal goal is the establishment of anti-symbioticchemotherapy directed against Wolbachia compatible withmass drug administration (MDA) programmes for humanfilariasis. The expected health outcome would be an alter-native treatment for human filariasis to ensure that thelong-term goals of global elimination of the public healthproblems are achieved. A secondary goal is the establish-ment of anti-symbiotic chemotherapy suitable for a morerestricted use, planned for an interim phase in which there isyet no drug or drug combination available that is compatiblewith MDA usage. For example, in the event of the emer-gence of drug-resistance to existing treatment in limitedpopulations or as an alternative for communities co-endemic for loiasis.

In order to achieve these goals A-WOL has identified fourmajor objectives to address the discovery and develop-ment of new drugs and regimes against Wolbachia (seeAppendix 1). The strategy is intended to cover; 1) the opti-mization of regimes of drugs with known activity againstWolbachia (doxycycline and rifampicin, [28,29]) for inte-gration into existing MDA programmes within 5 years, 2)the evaluation of anti-Wolbachia drugs already licensed forhuman use, which could enter control programmedeployment without the need for extended toxicity andregulatory processes and 3) the identification of noveldrugs and compounds identified through high-through-put screening and target discovery to provide a portfolioof lead candidates in a product pipeline, which could beused in future control and treatment approaches.

Progress during the first 12 months of the programmeincludes the discovery of novel tetracyclines withimproved in vitro and in vivo efficacy to doxycycline, novelclasses of antibiotic and other drugs active against Wol-



bachia and validated targets for novel drug design, whichprovide encouragement that the goals of the programmewill be achieved.

WHO-TDR: Anthelminthic Drug Discovery and DevelopmentDrug discovery and development activities for onchocer-ciasis continue under the TDR helminth drug initiative.Drugs from a variety of sources are screened againstOnchocerca lienalis microfilariae and O. gutturosa adultmale worms in vitro and O. lienalis microfilariae in mice.Hits from these screens are then tested against Brugiapahangi in jirds and dogs. From 2006/7 some 5000 com-pounds have been screened in vitro producing ~100 com-pounds for follow-up and around 6 lead compounds foroptimization. In addition, cyclooctadepsipeptides such asemodepside, show species-dependent activity againstfilarial nematodes. Variability in sensitivity to larval andadult stages is reported for Acanthocheilonema viteae, L. sig-modontis and B. malayi [30], but it remains an effectivemicrofilaricide in all three species [31].

Another drug being developed for control programme useis moxidectin (Wyeth). A partnership between endemiccountries, APOC, TDR and Wyeth is undertaking thedevelopment required to determine whether moxidectinhas the efficacy and safety not only to eliminate onchocer-ciasis as a public health problem but to eradicateonchocerciasis. The development has progressed throughstudies in healthy volunteers to an ongoing Phase II hos-pital-based trial of up to 192 O. volvulus infected subjectswhich will complete the 18 months efficacy follow up atthe end of 2009. Based on the safety and microfilaricidalefficacy data obtained in this trial to date, initiation of alarge phase III trial is planned. This will be followed by astudy to determine a safe dose in children before applica-tion for regulatory agency approval. Data from commu-nity studies on safety, efficacy and effect on transmissionwill be obtained before an expert meeting to assesswhether moxidectin can be recommended for use in con-trol programmes by 2014.

Vector ControlVector control was a major component of the onchocer-ciasis control programme (OCP) and was based on rou-tine aerial application of larvicides over a period of morethan 14 years. This is an expensive method of treating theriver, but was considered essential due to the vast areawithin the project. Since OCP was completed, vector con-trol has not been considered feasible or cost-effective inthe APOC countries, except for a few small isolated foci in'special intervention zones' (SIZ).

In Ghana, vector control has virtually ceased, except forlimited activities associated with the Bui Dam construc-

tion, but in Cameroon, temephos has been applied acrossthe full width of the Sanaga river, at selected sites usinglocal boats. Three applications were made ideally at 7 dayintervals, with adult blackflies monitored on Perspexsheets covered with a sticky substance, to determine whena subsequent series of larvicide treatments should beapplied to keep adult fly populations below a threshold.Other insecticides used in a rotation will be needed tominimise the risk of resistance. Dosage applied was calcu-lated according to WHO recommendations.

These control operations were required where areas oftropical rain forest along the Nyong and Sanaga riverswere de-populated due to the high incidence of onchocer-ciasis and the constant irritation caused by the bites of thevector Simulium spp. The latter affects people's skin andprevents working a full day, so agricultural production hasdeclined. The severity of black flies is considered to haveincreased and this may be partly due to hydroelectricschemes along the Sanaga River.

So far larval control has been confined to major rapids onthe Sanaga, but to treat narrower rivers, larvicide could beapplied using motorised hydraulic knapsack sprayers fit-ted with boomless nozzles to project the insecticide acrossthe river.

To minimise treatment of rivers, research is need to deter-mine whether adult blackflies can be lured by an attract-ant to insecticide treated screens as used in tsetse control,and whether insecticide treated over-garments or bandanaat the wrists and ankles could reduce the impact of theflies on field workers. Further research is needed toimprove monitoring and establish thresholds that deter-mine when control is needed.

In Ghana on-going transmission shows that operationalresearch remains critical to sustain gains of the OCP andimprove onchocerciasis control. A closely monitored area-wide blackfly management programme could signifi-cantly reduce the populations of blackflies, and thus allowagricultural productivity to increase in West Africa. Byintegrating vector management with drug treatment, sucha programme could lead to better use of the drugs by thoseaffected by onchocerciasis. However, capacity building isneeded to increase local knowledge of vector ecology,sampling procedures and control techniques.

ConclusionThe outcome of the meeting was a list of priorities forresearch (Appendix 2). Some of these areas are ongoingand funded, but a number of important areas requireadditional support and renewed effort. Failure to graspthe importance and urgency of addressing these activitiesruns the serious risk of undoing much of the benefits and



achievements of past and current control programmes. Aunanimous outcome was the belief that, where possible,this research should be undertaken by African scientistswithin endemic countries. Sufficient capacity buildingand funding for such activities are urgently required if theaims of the Yaoundé declaration [32] are to be realisedand the future control of onchocerciasis is to be secured.

Competing interestsThe authors declare that they have no competing interests.

Authors' contributionsMT compiled the report from contributions to each sec-tion written by each of the other authors. All authorsapproved the final draft of the report.

Appendix 1A-WOL has four main objectives:

1) Regime Refinement – To address this we will carry outtwo phase II field trials in Ghana on O. volvulus and W.bancrofti to test combinations of doxycycline withrifampicin at low doses to achieve shorter regimens todefine the optimal regime using drugs already licensed forhuman use.

2) Assay development – To develop Wolbachia-cell lineassays compatible with combinational high throughputscreening (cHTS) technologies and as a novel tool toscreen existing and novel compounds for anti-symbioticactivity.

3) Library Screening – To screen novel derivatives of tetra-cycline (TC), large diversity libraries (~100 K compounds)and combinations of existing drugs against Wolbachia.

4) Target Discovery – To identify targets and inhibitors ofkey enzymatic and metabolic pathways predicted fromWolbachia genomic annotation. To use bioinformatics toidentify the 'essential gene set' of Wolbachia and multi-step computational approaches to identify potential drugtargets and develop a surrogate screening system in E. coli.To use aptamer technology to identify inhibitors of noveldrug targets to incorporate into HTS.

Appendix 2Research prioritiesMapping responsiveness to ivermectinInformation on the extent and geographical range of iver-mectin responsiveness is needed through:

- Spatial and longitudinal monitoring of epidemiological,parasitological, vector and clinical responses

- Investigation of parasite genetics in relation to drug sus-ceptibility and the development of genetic markers toquantify connectivity between parasite populations

Alternative/complementary/combined control strategies- Improved integration of existing strategies of chemother-apy and vector control

- Re-evaluation of control strategies for drugs with macro-filaricidal or permanent sterilizing activity

- Continue development of macrofilaricidal drugs andapproaches to deplete the parasites of Wolbachia endo-symbionts

Diagnostic tools- To develop specific, rapid and less invasive tools toimprove mapping and provide prospective tools to definecontrol programme endpoint

Vector control- Evaluate new methods of blackfly trapping for monitor-ing and to reduce fly density

- Optimizing techniques to apply larviciding

- Develop research on blackfly attractants, reducinghuman-vector contact, improved knowledge of vector-parasite combinations

- Consider role of Community-directed activities for vec-tor control

Quantitative population biology / Mathematical modellingTo assist in the planning of activities for:

- Identification and optimisation of indicator groups (inthe area of diagnostics and programme monitoring)

- Monitoring of resistance (detection and quantificationof genetic markers)

- Exploring different control scenarios, combinations ofcontrol measures, timings of applications, etc. that canalso delay spread of drug resistance

- Vector biology, quantification of vector competence, vec-tor population dynamics, insecticide resistance

Capacity building in all the areas above

AcknowledgementsFunding for the meeting was provided by the Ghana-UK initiative of the Royal Society UK and a Bill and Melinda Gates Foundation grant awarded to the Liverpool School of Tropical Medicine in support of the A-WOL



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Onchocerciasis Control: Vision for the Future from a Ghanian perspective

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