Informal consultation on elimination of onchocerciasis transmission with current tools: "shrinking the map"

a wHo/APOC/MG/09. t @ Copyright African Programme for Onchocerciasis Control (WHO/APOC), 2009. All rights reserved. Publications of the WHO/APOC enjoy copyright protection in accordance with the Universal copyright Convention. Any use of infor- mâtion in this document should be accompanied by acknowledgement of WHO/APOC as the source. For rights of reproduction or translation in part or in toto, application should be made to the office of APOC Director, WHO/APOC, 01 B.P. 549 Ouagadougou, Burkina Faso, dirapocponcho.afro.who.int. WHO/APOC welcomes such applications. Graphic design: Lisa Schwarb / layout: Sabine de Jonckheere / Photographers: Hannah Brown, Andy Crump, Peter Williams Ir-{ Ft:t I;: l,l ft r_ rlr-1 H 5 U LTtlTIrl H'-l H ELII{Ir'{ fiTIil f'{ |] F I] ft [H']'::EE:':If15I5 T F;fi H = I-IIE:=II:I T.{ [.IIT H'] U I-I I*] E T.{T Tr_l rl L:= If'{ * f [':Ir]n *:=HF;It{}';.It{t_; THE tlftF * OUAGADOUGOU, BURKINA TASO 25 - 27 FEBRUARY 2OO9 Tfi f:t*t rl f r_.'] f"{î{ f{T::; Executive summary lntroduction and rationale Opening Def initions ELI MI NATION OF ONCHOCERC!ASIS TRANSMISS!ON ZONE 10 10 12 Session 1: Elimination with ivermectin: state of the art Elimination in the Americas, current evidence/ critical issues - Frank Richards Etimination in Africa, current evidence/ critical issues' Hans Remme 13 13 14 Session 2: Predictors of elimination with ivermectin Long term impact of ivermectin treatment on survival and reproductivity of the parasite - Kwablah Awadzi Long term impact of ivermectin treatment on survival and reproductivity of the parasite - Ed Cupp Model predictions of elimination : strategies, assessment and critical factors - Hans Peter Duerr & Wilma Stolk 16 16 16 17 Session 3: Spatial issues in Elimination Vector migration and vector/parasite complexes, human migration issues ' Frank Walsh Vector migration and vector/ parasite complexes, human migration issues - Daniel Boakye Target areas /populations for ivermectin treatment and non'treatment areas - Mounkaila Noma, Hans Remme and Frank Richards 20 21 22 Session 4: Assessing infection and transmission Onchocerciasis: old and new diagnostic procedures - Iom Unnasch Diagnostic tools, evaluation and post treatment surveillance strategies' Laurent Toe 24 25 Session 5: Twice yearly vs. annual treatment with ivermectin Session 6: Conclusions and Recommendations State of the art of elimination of onchocerciasis transmission with current tools in Africa and identification of favourable and unfavourable factors, assessment of feasibility of elimination in different parts of the continent ACTION PO!NTS FOR MOVING FORWARD TO ELIMINATION RESEARCH NEEDS AND PRIORITIES 31 31 32 34 Acknowledgements References Appendix l: Agenda of the meeting Appendix ll: List of participants 42 1+€=ÿ .=!.::tf ./ - :, .-./ -,ti*{ tr':-iËt-'llTTllt: .t UHT,I fiF::J The African Programme for Onchocerciasis Control (APOC)was initiated in 1995 with the objective "to establish effective and self- sustainable, community-directed ivermectin treatment throughout the endemic areas in the geographic scope of the Programme, and, if possible, in selected and isolated foci to eradicate the vector by using environ- mentally safe methods'i The attainment of this objective is expected to contribute towards the elimination of onchocerciasis as a disease of public health and socio- economic importance throughout Africa and to improving the welfare of its people. APOC's objective reflects expectations of the effectiveness of available control strategies. Since vector eradication was not thought to be feasible, except in some selected and isolated foci, ivermectin mass treatment has been defined as the primary control strategy in most of the Programme area. lvermectin effectively kills the microfi- lariae that cause the severe manifestations of the disease, but has limited impact on adult worms. Regular re-treatment is therefore required durlng the life span of adult worms. Consequently, annual mass treatment with ivermectin reduces but does not halt transmission during the first years of intervention. lt was therefore concluded that mass treatment needed to be con- tinued for a very long time. APOC/TDR supported research showed Community Directed Ïeatment with lvermectin (CDTI) to be a feasible and effective mechanism for sustained ivermectin delivery. The question of whether transmission of the parasite could eventually be eliminated and mass ivermectin treatment be stopped remained u nanswered. However, recently evidence became available from Senegal and Mali, showing that it is possible to eliminate the disease in some settings in Africa. This led APOC to adopt as one of the new objectives for the phasing out period (2008-2015) "to determine when and where ivermectin treatment can be safely stopped and to provide guidance to countries on preparing to stop ivermectin treatment where feasible'1 To refine APOC's strategy in moving towards the elimination of onchocerciasis, an informal consultation of experts in various onchocer- ciasls related fields were invited to a meeting in Ouagadougou titled " informal consul- tation on elimination of onchocerciasis transmission with current tools in africa ". This meeting was organised by the African Programme for Onchocerciasis Control (APOC), in collaboration with The Bill & Melinda Gates Foundation and Mectizan Donation Programme. The objectives of the meeting were: l. To review the state-of-the-art of elimina tron of onchocerciasis transmission with current tools in Africa, and to predict the feasibillty of elimination in different parts of the continent. 2. To identify critical issues for the feasibility and optimal strategies of elimination in different epidemiological settings. 3. To identify research needs and priorities to answer key challenges related to elimi- nation of onchocercrasis Elimination was defined as the reduction of infection and transmission to the extent that interventions can be stopped, but post intervention surveillance is still necessary. The meeting concluded that the Mali/ Senegal study has provided convincrng evrdence that elimination of onchocerciasis is possible in Africa with current tools, which is supported by promising results from other countries. However, evidence is still insuf- ficient to define the precise circumstances under which elimination is or is not feasible and the interventions required to achieve this goal. ln particular, there is still a lack of rnformation from forest areas, a major part of APOC's target zone. The feasibility of elimination and efforts required to achieve this goal depend on the following factors: 1. Local circumstances: seasonal transmission, extent of hyperendemic areas and maxr- mum endemicity level before the start of interventions, extent of transmission zones, level of onchocerciasis transmission in surrounding areas (includlng currently u ntreated low-endemic areas), vectorial capacity, immigrating flies, human migra- tion, and accessibility. 2. Operational factors: geographic cover- age, therapeutic coverage, years of iver- mectin distribution, number of treatment rounds provided per year. 3. Local obstacles to treatment: Politlcal i nsta bility/ co nfltct, Loa /oa co-endemrcity A framework to assess the potential for elimination in different parts of the conti- nent was agreed. The meeting concluded that it will be dif- ficult to achieve elimination in the whole of Africa. Therefore, APOC should proceed gradually, targeting elimrnation where it is considered feasible. A critical evaluation of the epidemiological and operational situa- tion in countries is required, before adopting the goal of elimination. This is particularly important, because a shift in strategy may require programmatic changes that can have far reaching implications for communi- ties who play a leading role in the control programme. Action points for moving forward to elimination include: l. Generation of more empirical evidence on the feasibility of elimination and req u i red interventions u nder different circumstances 2. Development of guidelines for countries on what has to be done to achieve, prove and maintarn elimination of onchocerciasis infection and transmission. 3. Reviewing target areas for mass treatment and delineation of transmission zones. 4. Defining what has been accomplished in project areas to date and preparing projects for elimination where feasible. 5. Continue investments in development of better tools for onchocerciasrs elimination, including: a. tools to kill or sterilize vlable adult WOTMS; b. diagnostic tools for measuring the presence and number of parasites in the human host, particularly viable adult worms. 6. Examination of the opportunitres of linking with LF elimination.o:ï"*r.t Based on this list, research needs and prorities were defined. They are listed in this report. If'{TI-'.: t-t tr Ul:: TIüH iif'{tt I-'.: r-rTIuf'{iiLt The African Programme for Onchocerciasis Control (APOC)was initiated in 1995 with the objective "to establish effective and self- sustainable, community-directed ivermectin treatment throughout the endemic areas in the geographic scope of the Programme, and, if possible, in selected and isolated foci to eradicate the vector by using environmen- tally safe methods ". The attainment of this objective is expected to contribute towards the elimination of onchocerciasis as a disease of public health and socio-economic impor- tance throughout Africa and to improving the welfare of its people. APOC's objective reflects expectations of the effectiveness of available control strategies. Since vector eradication was not thought to be feasible or cost-effective, except in some selected and isolated foci, ivermectin mass treatment has been chosen as the primary control strategy in most of the Programme area. lvermectin effectively kills the microfi- lariae that cause the severe manifestations of the disease, but has limited impact on adult worms. Regular re-treatment is therefore required during the life span of adult worms to clear the infection entirely. Consequently, annual mass treatment with ivermectin reduces but does not halt transmission during the first years of intervention. lt was therefore concluded that mass treatment needed to be continued for a very long time. APOC's research showed Community Directed Treatment with lvermectin (CDTI)to be a feasible and effective mechanism for sustained ivermectin delivery. Whether transmission of the parasite could eventually be eliminated and mass ivermectin treatment stopped was not known. At a conference on the eradicability of onchocerciasis in Atlanta in 2002, it was concluded that onchocerciasis is not eradicable worldwide using current tools due to the major barriers in Africa (Dadzie et al.2003). However, in most, if not all, of the Americas, and possibly Yemen and some sites in Africa, elimination of onchocerciasis transmission was thought to be feasible using current tools. Since then, the Pan American Health Organi- sation has resolved to eliminate onchocercia- sis in the Americas and the Onchocerciasis Elimination programme of the Americas (OEPA) was established in 1992 to undertake this. OEPA has made steady progress and in several sites onchocerciasis transmission appears to have been stopped (Sauerbrey 2008). ln 2008, PAHO adopted a new resolution calling for elimination of morbidity from onchocerciasis and interruption of transmission by the year 2012. Evidence that it is possible to eliminate the disease in some settings in Africa with iver- mectin treatment alone has recently emerged from Senegal and Mali (Diawara et al. 2009), and is supported by promising findings from Guinea Bissau and Kaduna State in Nigeria. This led APOC to include an additional objec- tive, namely to develop the evidence base on when and where ivermectin treatment can be stopped, and provide guidance to countries on how to prepare for and evaluate cessation of treatment where feasible ( APOC 2008). This was approved by APOC's governing body, the Joint Action Forum, in December 2008. To shape APOC's strategy in moving towards the elimination of onchocerciasis, an informal consultation of experts in various onchocerciasis related fields were invited to the meeting, on which we report here, titled "informal consul- tation on elimination of onchocerciasis transmission with current tools in africa " (Ouagadougou, Burkina Faso, 25-27 February 2009). This meeting was organised by the African Programme for Onchocerciasis Control (APOC), in collaboration with The Bill & Melinda Gates Foundation and Mectizan Donation Programme. The agenda of the meeting and list of participants are included as appendices. The objectives of the meeting were: 1. To review the state-of-the-art of elimination of onchocerciasis transmission with current tools in Africa, and to predict the feasibility of elimination in different parts of the continent. 2. To identify critical issues for the feasibility and optimal strategies of elimination in d ifferent epidemiolog ica I setti n gs. 3. To identify research needs and priorities to answer key challenges related to elimination of onchocerciasis. :eæ tr!fr.*æ I The meeting started with nostalgic reminiscing about the history of onchocerciasis control and initiation of APOC. Many of the meeting participants played a significant role in these efforts, defining strategy, implementing the activities and evaluating progress. There have been debates about the path to follow, but the innovative approach of CDTI as pioneered by APOC has proven to be successful. The important role of Merck & Co. lnc. in this success, with their unprecedented drug donation and commitment, is acknowledged, as is the emerging role of the Bill and Melinda Gates Foundation in defining a way forward. Recent studies in Mali and Senegal now show that the CDTi approach can even lead to elimi- nation in specific foci. These successes need to be celebrated and built on. With the renewed focus on neglected tropical diseases as well as significant funding and goodwill, there is now a unique opportunity to take these advances forward and explore new tools and strategies. The main challenge for the future is to " shrink the map" of onchocerciasis prevalence in Africa, by eliminating onchocerciasis transmis- sion where possible. Participants were invited to explore the options available to advance control and eliminate onchocerciasis in an open, scientific discussion. GI t&, 3 d : !'l :::l T'EFIHITII-]T.{ The APOC Governing Body, the Joint Action Forum, during its meeting in December 2008, requested that the informal consultation clearly define what is meant by elimination. The participants therefore discussed this question at length and arrived at the following definition of onchocerciasis elimination. ELIMINATION OF ONCHOCERC!ASIS: Short definition: Reduction of O.volvulus infection and trans- mission to the extent that interventions can be stopped, but post intervention surveil- lance is still necessary. 0perational definition : Defining when interventions can be stopped is a challenge, and in practice the stop-decision always needs to be evaluated afterwards. Therefore, operationa lly, elimination req ui res achieving the following steps: . Interventions have reduced O.volvulus infection and transmission below the point where the parasite population is believed to be irreversibly moving to its demise/ extinction in a defined geographicalarea; . lnterventions have been stopped; . Post intervention surveillance for an appropriate period has demonstrated no recrudescence of transmission to a level suggesting recovery of the O. volvulus population; . Additional surveillance is still necessary for timely detection of recurrent infection, if a risk of reintroduction of infection from other areas remains. Theoretical basis for these def initions: ln the above definitions, the term intervention refers to the active measures implemented to reduce the parasite population in previously endemic areas. For APOC, this currently includes (annual) mass ivermectin treatment and, in isolated foci, vector control. The term surveillance is used to describe the activities to ensure that the infection transmission has stopped and that there are no new infections. Both definitions are based on the ideas of the lnternational Taskforce for Disease Eradication (ITFDE) and Dahlem Workshop on the Eradication of lnfectious Diseases in 1997, which defined elimination of infection theoretically as "a reduction to zero of the incidence of infection caused by a specific agent in a defined geographic area as a result of deliberate efforts; continued measures to prevent reestablishment of transmission are required " (Dowdle & Hopkins 1998). The continued need for measures to prevent reestablishment relates to the local nature of the concept: there remains a risk of reintro- duction of infection from outside. The operational definition of onchocerciasis elimination reflects current thinking about the impact of interventions, as illustrated in Figure 1. Basically, we distinguish 4 phases in elimination programmes, which differ with respect to transmission and needs for interventions/ surveillance. . Phase 1 - lnterventions lead to a reduction in transmission and parasite numbers, but transmission still continues. lf interventions are continued successfully, both measures will decline and at some point remaining transmission may be zeto or negligible (1't arrow). This achievement is conditional on continued interventions. . Phase 2 -Transmission in this phase is negligible or zero, as long as interventions are continued. ln this phase, the adult worm parasite population shows an accelerated decrease due to natural or treatment-induced death of old worms without replenishment. This phase ends if the adult worm population is reduced to such low levels that it will move irreversibly to its demise/extinction, even without further interventions (2nd arrow). ln modelling terms: the parasite density is brought below its breakpoint. .t Phase 3 - Parasite numbers are now so low that any residual transmission is insufficient for the parasite population to survive: possibly remaining parasites have too low a chance of successful reproduction and eventually the parasite population becomes extinct. Intervention measures have been stopped. Post-intervention surveillance is required, to check that the parasite population and transmission do not recover after stopping the interventions. lf post-intervention surveillance confi rms the continued absence of transmission, we say that elimination is achieved (3'd arrow).The Transmision suppressed lo nql[ible levels Adult wom population Phase'l Phase 2 WHO guidelines suggested using a period of at least 3 years (WHO. 2001). . Phase 4 - After achieving elimination, a routine surveillance system should be esta- blished for timely detection of the possible reintroduction of infection from other areas where the i nfection stil I occurs. Theoretically, this phase continues until global eradication is achieved. We deliberately attributed no time scale to the different phases, acknowledging that their duration depends on chosen control strategies (vector control, mass treatment, or a combi- nation) and local circumstances. Adult worm population reduced to such low le{ebthat it is irreversibly moving to iB demise / extindion Transmirsion lnterYention Surrelllance onooino Negligible, conditional on continued inteflention A(tive iniervention, aimed at reducing worm burden ortransmission (mas treatment and/or vertor control) Monitodng & ev-aluation ofprogrss Phare 3 Phase 4 (lmversibly approaching) rerodueloinsuffdentor Zem abrent adult womt Surveillance for timely Adive surverllan(eto'*"';-:.":'-.:- * dete<tim of a possible Dt00l eltmmatDn reintrodudion of infedion Figure 1. Schematic representation of the phases in programmes for elimination of onchocerciasis transmission, in relation to the theoretical fall-off of the adult worm population and annual trans- mission potential (ATP). Arrows mark major achievements, which indicate the transition between phases and changes in required interventions or surveillance activities as described. TRANSMISSION ZONE A geographical area, where transmission of O.volvulus occurs by locally breeding vectors. This zone can be regarded as a natural ecological and epidemiological unit for interventions. A transmission zone can be'open'or'closed', depending on whether there is migration of (possibly infected)flies or humans to and from neighbouring areas. Complete closure may rarely occur in real life. For practical purposes, we define closed transmission zones as those where in- or out-migration of infected humans or flies is a relatively rare event that normally has little impact on the transmission dynamics. To achieve elimination in closed transmission zones, interventions can be restricted to the transm ission zone itself. Howeve r, post-i nter- vention surveillance is still necessary if there is a risk of reintroduction of infection from out- side. To eliminate onchocerciasis from open transmission zones, interventions are also needed in the source-areas of infected flies and humans. lt will therefore be important to define transmission zones and determine whether these are closed or open systems. :l E:l:l I ü f'{ I : r: LI t'{ I r{ ItIEI-,lf'l f r-:TII{: =TËTE t_lF iiTIIH I..IITH THË r'rl-':T Eliminat*mm ün thm America§, current nvidence / criticai issr,r#s * lran[q f,?ichards . The Onchocerciasis Elimination Programme of the Americas (OEPA) aims to eliminate onchocerciasis from the Americas by ivermectin mass treatment given twice per year with a goal of reaching >85 o/o eligible population coverage. It is thought that onchocerciasis was taken to the Americas from Africa. Yet, the epide- miology of onchocerciasis in the Americas has some unique features: it is limited to specific foci, relatively static and most of the American vectors are not as efficient as those in Africa. lf elimination is to occur, interventions (such as treatment coverage) need to be sufficient over a specified time period OEPA uses a 2x per year ivermectin treat- ment regimen, because this is thought to keep transmission at negligible levels throughout the whole year and to reduce the adult worm lifespan. Epidemiological and entomological data should be monitored in sentinel areas: ' Population based surveys are important - Transmission should be measured by looking at infection rates in children ATP thresholds are important (Breakpoint / Rs concept) OEPA's criteria for certification of elimina- tion are based on those published by WHO in 2001 (2001), but the OEPA steering committee made some modifications based on operational, statistical, cost and programmatic considerations. These criteria distinguish between elimination of morbidity and transmission. - Elimination of morbidity: . Prevalence of microfilarioe (mf ) in the corneo or onterior eye chamber <1 ÿo - Elimination of transmission: . OCP standard of L3 in flies <0.05 %o (0.1 % in parous flies); . ATP lower thon 5-20 L3 per season; . Absence of detectable infection in school children and antibody prevalence of <0.1 o/o. . Based on current guidelines, a sufficiently long post treatment surveillance period (at least 3 years byWHO guidelines (2001)) is required to declare elimination. . Progress towards elimination of onchocer- ciasis in the Americas is traced by documen- ting how many of the 13 foci have reached phase 2, 3 and 4 in the elimination process (see Figure l):6 are in phase 3 ("interrup- tion of transmission") and 1 other has par- tially met the criteria for this phase; t has reached phase 2 ("suppression of transmis- sion ") and the remaining 5 foci are still in phase 'l . The " problem " clusters are located in Venezuela and Brazil.These results can be summarized in a tabular form, sorting the foci by phase and using colour codes for the achieved phases (" Onchocerciasis flag "). This categorization or"flag"is now also being used in the Ugandan programme for elimination. . NB. WHO certifies country notToci'for elimination. Following progress in foci is an important step towards elimination, but certification of elimination can only occur at the national level when all foci have been eliminated. External technical assistance is usually required. " WHO guidelines should be used'in princi- ple'but may have to be modified.They are useful for guiding the declaration of elimi- nation, but must be constantly re-evaluated given country and programmatic require- ments / realities. . The new PAHO resolution about onchocer- ciasis elimination, which was adopted in 2008, now explicitly includes a timeframe for elimination: elimination of (new) ocular morbidity and interruption of transmission is to be achieved by 2012. The feasibility of using entomological mea- sures such as ATP for monitoring & evaluation and for certifying elimination was discussed because of the problems in catching and counting flies. Current methods, based on landing catches, are expensive and have increasing ethical concerns. There is a need for a new efficient trap to capture flies that will solve the ethical dilemma of using current methods. Elimination in Africa, current evidence / critica I issues - Hans Remme . The Onchocerciasis Control Program in West Africa (OCP) has successfully eliminated onchocerciasis by vector control from most of the original OCP area, and this achie- vement has been well-documented. An important publication in a French language journal (Agoua et a|.1995) gave the results of epidemiological and entomological stu- dies after 1 4 years of vector control. ln 18 catching points pre-control infectivity rates that ranged from 60 - 90 per 1 000 parous females had decreased to less than 1 per 1000; levels at which recrudescence was thought to be most unlikely.These results validated the cessation of larviciding at the time. . When OCP stopped vector control, preva- lence of infection and transmission were not 0, but transmission was below thres- hold levels required to stop transmission of disease.This shows that it is not necessary to bring transmission down to zero. . Whilst the criteria used by OCP were gene- rally validated, recrudescence of infection along the River Bougouriba at the time demonstrated a situation where evaluations had failed to detect residual transmission along an affluent where a new dam had created new breeding sites. . The example of OCP showed that (local) elimination is feasible in Africa by vector control. Whether this can be achieved by ivermectin treatment remained uncertain. It was therefore agreed to carry out a study to test the feasibility of elimination in 3 foci in Mali and Senegal, where ivermectin mass treatment was started in the late eighties and remained the only control strategy. Two foci had annual treatment; the other had 6-monthly treatment. . The results from this study showed that whilst prevalence varied it had been above 700lo in many villages prior to the intervention: - After 15 to 17 years of ivermectin treat- ment, the infection and transmission levels were below postulated thresholds for elimination (Prevalence of mf < 1 o/o in 90o/o of villages and < 5 % in all villages; Rate of flies with L3 in the head < 0.5 per 1000 flies) - Treatment was therefore stopped in test areas of 5 to 8 villages in each focus. Evaluations 1.5 to 2 years after the last treatment showed no infected persons and no infected blackflies in the test areas Hence the study provided the first empirical evidence that elimination of onchocerciasis with ivermectin treatment is feasible in endemic foci in Africa. ' ln Guinea Bissau, civil conflict interrupted the MDA program and provided a natural experiment in which the impact of just 6 annual ivermectin treatments could be evaluated. Epidemiological and entomolo- gical evaluations undertaken 12 years after the last treatment round in the River Geba focus showed that onchocerciasis had been eliminated. lt is not clear if this was a result of ivermectin alone or whether other fac- tors also played a role as the area was only hypoendemic before the start of control, and the epidemiological situation may have been unstable. ln summary, there is now evidence from Senegal, Mali and Guinea Bissau that elimination is possible within defined geographical areas. " ln addition, there are promising data from two foci in Kaduna State in Nigeria, which were meso endemic before the start of control and in which, after 16-19 years of ivermectin treatment the prevalence of mf has reduced to zero. . Based on the positive findings from the above studies, the Joint Action Forum has adopted a new objective for APOC, namely to determine when and where ivermectin treatment can be stopped and to provide guidance to countries on preparing to stop ivermectin treatment where feasible (APOC 2008). . lssues remaining to be addressed are: Elimination thresholds - stopping criteria . Does infection / transmission need to be 0 to stop treatment ? . lf not, what levelis occeptable in whot e pi de m i ol og i ca I sit u oti o n, con si d e r i n g the risk of recrudescence 7 . How do we measure the relevant level of infection (indicators, tools, strotegies; cross-sectionol or trends) ? Recrudescence . What is the risk of recrudescence for different indicator levels ? . How mony years after stopping treot- ment is recrudescence still possible ? . Whot are the dynomics of recrudescence 7 . How to detect recrudescence in time (tools, proctical surveillance strotegies / early worning) ? Other endemic areas in Africa: . Whot is the feasibility, timeframe for other vector porasite complexes / endemicity levels ? . To what extent are eliminotion prospects influenced by spatiol factors (vector re i nvo si on, d i sto n ce fo ctors, cove ro çl e patterns, human migrotion, etc.) Alternative i ntervention strategies : . Treatment frequencies, 1-monthly vs. yearly treotment . Vector control . Endpoint strategies Some of these issues were discussed in later sessions, focusing on the question: how confident are we that elimination strategies working in one area will also work in others? . Besides the successes shown in OCP, there was also the temporary setback in Bougouriba. Targeted studies in this area showed that new breeding sites had deve- loped there, causing the recrudescence, which was successfully addressed before the closure of OCP. This highlighted the need for continued environmental evalua- tions so that opportunities for re-infestation can be identified and controlled. " For ivermectin mass treatment program- mes it is also important to understand whether few remaining infected individuals after mass treatment can pose a threat to elimination. Are there "super spreaders "for onchocerciasis ? t. .t t-l F E LI i{ I r.{ i:t TI r_r r.{ Long term impact of ivermectin treatment on survival and reproductivity of the parasite * Kwablah Awadzi . lvermectin is a powerful microfilaricidal drug. lt is also thought to affect adult worms in two ways: - Effects on vitality of adult female worms; - Effects on reproductive activity of the parasite. . ln general, ivermectin is considered very effective. However, some findings suggest that ivermectin is not always that effective, for example: - Persistentmlcrofilaridermiasdespite multiple treatments; - Suboptimal response of adult female worms: . Non status embryostoticus; . Non serial embryostoticus. - Putative development of resistance; - Putative loss of ability to sequestrate mf in utero. There were lengthy discussions on possible explanations for these observations. . Based on his studies, Dr. Awadzi categorized the female worm responses to ivermectin as follows: - Category 1 : Female worm fully responsive; - Category 2: Female worm response partial or incomplete; - Category 3: Female worm is not responsive. . ln conclusion: there is general agreement on the complete microfilaricidal effects of iver- mectin.There is also an effect on longevity or fertility of (female) adult worms. Some studies suggest that some adult worms are not responsive or only partially responsive to treatment, but there was debate regar- ding the explanation for such findings. F F; E tr i '::T ':' F.:5 [.] IT H Il,l E I.] l,l E ITI H I l.l.II . r. t I il ?-t . It I t-. The discussion highlighted two issues. Firstly, further evidence of poor response to ivermectin treatment needs to be collected. lmplications for elimination need to be assessed and plans for how to respond need to be defined. Sec- ondly, the search for other drugs with good macrofilaricidal effects should continue. Long term impact of ivermectin treatment on survival and reproductivity of the parasite - Ed Cupp . This presentation summarized the results of several clinical trials, done in the Americas to investigate how treatment frequency affects its impact (Cupp & Cupp 2005). . These trials compared the following three treatment regimens: - monthly treatment for a period of 4, 8 or 12 months - single dose vs.4 6-monthly doses - 3-monthly treatment . Other evaluations concerned the impact of repetitive comm unity-wide ivermecti n treatment in Guatemala (Cupp etal. 20(N) . Main conclusions from these studies: - lvermectin has activity against the adult worm when used sequentially (e.9.2 or 4x per year), reducing the number of both male and female worms found in nodules; - Exposure lo2x/yt ivermectin treatment over a 6 year period (1995-2001) signi- ficantly reduced the numbers of males per nodule (p<0.0001)compared to his- torical controls and significantly altered reproductive status in surviving females producing microfi lariae (p<0.0001 ). . An important consideration for using multiple treatments per year is to suppress transmission, so that new L3 larvae are not formed and incidence of new infections is prevented. The increased effect on male and female adult worms also benefits elimination efforts. . The above unpublished studies suggest that the effect of 5 years of 6-monthly ivermectin treatment is greater than that of 12-13 years interrupted transmission by vector control. There was some debate aboutthe interpretation of data and the added effect on adult worms. The data from Duke may still be available at John Hopkins University for reanalysis. There are no studies that explicitly compare the effect of once yearly vs. twice yearly treatment. Model predictions of elimination : strateqies, assessment and critical factors - Hans Pefer Duerr & Wilma Stolk Dr. Duerr explained theoretical thinking about elimination vs. persistence of oncho- cerciasis infection and discussed some im- portant concepts. See also (Duen etal. 2005) - A persistence curve shows how the parasite density (e.9. measured by ATP, CFML, mf prevalence, number of adult worms) depends on the annual biting rate of the black fly vector and what happens under the influence of interventions. - With a constant biting rate, the parasite density will (move to, or) remain in a stable equilibrium, which depends on the biting rate.ln general, a higher biting rate will result in a higher equilibrium level, but tends to a maximum. - Vector control reduces the biting rate. lf the annual biting rate is brought below a threshold, called the threshold biting rate, parasites cannot effectively repro- duce because there are too few flies to transmit infection from one person to another. lf annual biting rates remain below this threshold, the parasite popu- lation will decline and eventually move towards extinction. - Repeated ivermectin mass treatment reduces the parasite density in humans (e.9. measured by CMFL, mf prevalence, number of adult worms), and therefore the density in flies (e.9. measured by the ATP), and number of new infections. Below a threshold parasite densiry called the breakpoint, the mating probability and chance of successful reproduction bec6me too low: the number of new infections introduced into the human population is too low to maintain the worm jiopulation. Without any further intervention, the parasite population will move to extinction.The breakpoint density depends on the annual biting rate (ABR): the higher the ABR, the lower the breakpoint. Mass ivermectin treatment can lead to elimination if the parasite density is brought below the breakpoint.This theory explains why it is not necessary to reduce the parasite density to zero to achieve elimination: it is sufficient to bring it below its breakpoints.lf control stops before the breakpoint is reached, recrudescence occurs and the parasite density will move back towards its equilibrium level. The breakpoint level depends on the ABR: the higher the ABR, the lower the breakpoint. ln areas with high ABR, longer or more intensive interventions will be required, because the initial parasite density is higher and reproductive capacity at low parasite density is also higher.ln areas with very high biting rates, the standard mass treatment approach may not be sufficient to reach the breakpoint. Additional measures may be required, such as extra efforts to increase the coverage, more frequent mass treatment, or addition of vector control. Challenges for APOC: - ldentifu adequate and feasible diagnos- tics for monitoring parasite density, infection intensiry and prevalence. - Determining the breakpoint curve. - Defining setting-specific control require- ments (e.9. additional vector control in areas with very high ABR) Dr. Stolk mentioned that the modelling groups in Rotterdam,Tuebingen and lmperial College London are allworking on estimating breakpoints.This presentation summarized results obtained with the ONCHOSIM simulation model (Plaisier et a\.1990). Estimates of the coverage and number of treatment rounds required to achieve elimination in different settings have already been published (Winnen et ol. 2002). ln summary: 'I 0 rounds of annual ivermectin mass treatment with 65 o/o coverage are usually not sufficient to achieve elimina- tion in a village with pre-control CMFL = 30. The elimination probability is about 5 o/o. The elimination probability increases with increasing duration of the mass treatment programme, but >20 annual treatments are required for >= 9Oo/o probability of elimination Factors that determine the required duration of mass treatment are: . Local tronsmission conditions, including the : . Pre-control endemicity level (which mainly depends on fly density/ABR) . Heterogeneity in exposure betvveen individuols (leading tovoriobility in the porosite densities) . Prog rom matic factors, i ncludi ng coverage, extent of systematic non-com- pliance, frequency of treatment (NB. the required durotion of moss treotment is obout halved, when treatment is given 6-monthly instead of annuolly) Efforts are ongoing to estimate " break- points " (see above) and define criteria for determining when to stop mass ivermectin treatment in different situations. ONCHOSIM determines the outcomes of a mass treatment programme by chance processes. The same intervention applied in areas with similar transmission conditions may sometimes lead to elimi- nation and sometimes to recrudescence. The probability of elimination can be related to the remaining parasite density after the last treatment round, here measured by CMFL or mf prevalence. The table shows rough estimates of the levels to which CMLF and mf prevalence must be reduced to achieve >90% probability of elimination : @H Meso-endemic areas (simulated with the fol- lowing mean pre-control o:. Bolo values: CMFL 30 mfls, mf mf /s prevalence 520lo) Hyper-endemic areas (sim- *::iJ::::::,::,:i:: -,;], 30,.cmfl about 70 mf /s, mf prevalence 75 7o) Note that the'breakpoint' levels depend on the pre-control endemicity (influenced by biting rate, exposure heterogeneity, and other local factors) and the risk of failure that is still considered acceptable. All estimates presented are subject to uncertainties, e.g. about : . Effects of ivermectin . Densiÿ dependence in different processes of the transmission cycle - Heterogeneity in exposure Model predictions remain to be validated, using the available data on trends in infection prevalence/CMFL during (and preferably after!) long term ivermectin treatment. Key issues raised in discussion: . Breakpoints should be determined for diffe- rent indicators of parasite density in human or vector populations, e.g. measured by ATB CFML, mf prevalence, number of adult worms.This is particularly important, because skin snipping is no longer popular and is increasingly considered to be unethical. . We need to understand the correlations between different infection indicators in situations close to elimination. . There is already substantial data available that can be used for model validation and there may be opportunities to collect new data. ' Statistical approaches (instead of mathema- tical modelling) can also help to determine how the infection prevalence/CMFL after treatment depends on programmatic factors. This requires the availability of many data. It could be useful to bring all available data together

.t I t.r. It . t. t I il H 3: 5I'fiTIfiL I5:::UE:j II.{ TLII{IHfiTII:'H Vector miqration and vector lparasito complexes, human miqration issues * Frank Walsh - Before OCB the entomologists knew that S. domnosum flies were migrating. Yet the extent of the problem was not anticipated. . Major problems occurred in the Leraba and White Volta basin, where infection recommenced with the start of the rainy season. After many studies, entomologists were convinced that the programme was working well, but that the flies were coming from outside (mainly from the southwest). When vector control was extended in a southwestern direction, the problems in the core areas disappeared. . Lesson learned: for control measures to be effective, the source areas of migrating flies need to be included in the intervention zone. . Vector migration may explain the fact that the severest onchocerciasis foci were not on permanent rivers, but on the temporary ones.When there are many immigrant (older) flies, the parous rates in an invaded area are higher. Normally around 500/o, but in invaded areas it can be 70to 8oo/o. lf infected in source area, they arrive with mature L3 larvae (higher infectivity rate). . We now know that individual flies can move distances of 300-600 km.This is common in savanna flies(Simulium dam- nosum s.s., S. sovonnum), but not in forest flies (which live in a favourable ecological environment and have no reason to move). . This has implications for APOC: - ln northern savanna areas, APOC would need to work on a large scale concurrently, because of immigrant flies: treatments are needed both in the areas where the flies come from and those where they fly to. - lt would be beneficial to start in the source area of flies and to provide mass treatment just prior to the migration period.This has large benefits for the areas where the flies go to, in particular where treatment is given only yearly. But this may not be feasible in practice, because other factors co-determine when communities provide treatment. APOC also operates in isolated transmission zones. - Simulium neavel must be considered separately.These flies live and breed in pockets offorest.They don't have the tendency to move up to air streams for travelling long distances.They are really isolated. ln areas like this we do not have to worry about control in surrounding areas (as was necessary in the northern savannas). 5. neavei flies are very effective vectors: they are extremely anthropophilic flies with a long lifespan, and obligatorily breed on certain species of crabs. For elimination, vector control would be very cost-effective in this type of area. - lsolated S. damnosum foci are generally large. There have been foci in which the vector was eliminated by vector control, even in areas with S. domnosum s.s.as the main vector. Conclusion: if elimination is the objective, it is important to consider whether the " transmission zone " (see definitions) is open or closed. Key points from discussion: . Reflecting on the success regarding S. neovei elimination: must we always go for vector elimination or would a period ofvector control be sufficient for oncho- cerciasis eliminatlon ? ls there a need for vector control in APOC's elimination efforts ? What is the impact of fly and human migra- tion between Nigeria and Benin ? We have fly movement, maybe dispersion of flies from Nigeria to Benin in July-Sept every year. This has been reported by people from the Kara basin and is currently under investigation by APOC/MDSC. Migration is an important issue for trans- mission and elimination. We need to understand: infectivity of migrant flies distances covered and establishment of viable colonies - vector species and their distribution . availability of suitable breeding sites Bi-directional migrations due to seasonal changes. Migration patterns of major savanna subs- pecies are understood, e.g. S. domnosum distribution in rainy and dry season; during the dry season, flies are found much further south S. sirbanum - in the rainy season flies move up north; in the dry season they are found much further south. Breeding sites may often contain several species. The vectorial capacity of these species can differ. ln isolated transmission zones, vector control attempts focus on removing the main vector, but other minor vectors (with different breeding sites and behaviour) may remain and become more important in transmission. Although savanna vectors are better at transmitting savanna parasites, they can also transmit forest parasites and vice versa. Unpublished results of feeding experi- ments, carried out with 5. sonctipauli, were presented. Key points from discussion: Model predictions suggest that imported infections (e.9. via migrating flies) are an important factor for the success of elimination predictions. We have many data on transmission from OCP and OEPA, but few from APOC, because APOC was originally set up as a morbidity control programme. However, when consi- dering elimination we have different data requirements, which need to be listed and will include data on vector migration. Project areas are not strictly based on (closed) transmission zones. Sometimes only part of a transmission zone may be covered by a project, while another part is not covered, (e.9. because it is in another country).This is problematic for achieving interruption of transmission. iæ:r::f -:;..,, -:]*;lpt 3aT-r: "riGë . Remote sensing could help to identify bree- ding sites and dispersion areas for different vector species. . When APOC succeeds in introducing treat- ment in all areas, then the importance of migrating flies is limited, because immi- grant flies will no longer be heavily infected. However, maintaining high treatment cove- rage is not always possible (e.9. in conflict areas). Moreover, even low infection rates in immigrant flies may threaten elimination. Target areas / populations for ivermectin treatment and non-treatment areas - Mounkafla Noma, Hans Remrne f,nd Frdn k Richards . At the beginning of the APOC programme, the key questions were; - What is the magnitude and distribution of the disease? - Where is ivermectin mass treatment needed ? - Who is in need of ivermectin mass treatment? . Data was not available at the time to answer these questions in APOC areas. Therefore a WHO Expert Committee on Onchocerciasis Control was set up to make estimates. . lt was then decided to do Rapid Epide- miological Mapping for Onchocerciasis (REMO) rather than using techniques such as skin snips for practical and ethical reasons. . The principles of REMO (outlined in Noma et a/. 2000) are : - Division of the country into zones - Selection of communities to be surveyed by zones - Rapid epidemiological assessment of endemicity in the selected communities (by nodule palpation of 50 adult males) . REMO was used to delineate the population at high risk of contracting onchocerciasis, where ivermectin would be needed. lt also gives some indication of pre-control preva- lence and intensity of infection, which can be related to other infection indicators (e.9. blindness, low vision, itch) to get estimates ofthe pre-control burden ofdisease and potential impact of APOC. Dr. Remme's presentation focussed on the question of whether treatment zones need to be expanded to include hypo-endemic zones. REMO aimed to delineate hyper- and meso-endemic areas, where treatment would be required. Hypo-endemic areas would in principle not be mass treated, but passive treatment should be stimulated. lf hypo-endemic villages were surrounded by villages with higher endemicity, they were also included in the target area for mass treatment. ln practice, the boundaries of treatment target areas were not always clear and administrative boundaries also played a role in defining them. ln discussing whether treatment is required in currently untreated hypo-endemic zones, it is useful to distinguish two types of hypo- endemicity: ' First we can have hypo-endemic tails of transmission zones : in most trans- mission zones, the infection is greatest at the river and declines with increasing distance from the river. Hypo-endemic areas here represent the " tail " of the transmission zone.The hyper- or meso- endemic core area is already included in the treatment programme.lt is hypothe- sized that hypo-endemic tail areas only exist because of incoming infections from the core-area and that infection would disappear from this area once the infection in the core is successfully controlled. - Second, there may be independent hypo-endemic areas that are self-per- petuating and will not disappear unless control happens in that specific area. Dr. Richards observed that the rationale for not treating in "true " hypo-endemic areas will have to be re-visited for an elimina- tion strategy (the current policy of passive treatment is not widely implemented).To prevent re-introduction of infection into treatment areas from hypo-endemic areas, )È=Ë\ §- the latter would also have to be treated. Thus, a new transmission map for Africa is needed including hypo-endemic areas in target areas for treatment. Group discussions focussed on the following issues: . The term"hypo-endemicity"was introdu- ced because of its operational consequence: there was no need for mass treatment in low-endemic areas for morbidity control programmes. ln the context of elimination programmes, the term does not function anymore, because it has no operational consequence. There was a consensus at this meeting to abandon the term. . ln elimination the term transmission zone becomes more relevant than a distinction ;\ between hyper- meso- and hypo-endemic areas.The challenge is to define the geogra- phical area needed to move from control to elimination; i.e. is this equivalent to that for control or is it more ? lf it is more, by how much ? The methods to define and delineate transmission zones are not clear. This is an operational research issue.The delineation will be difficult as there is little data outside the treatment areas to guide the expansion. REMO data will probably be of limited use, because of the high risk of false-positivity in low endemic areas and limited sensitivity to detect low intensity infections. The issue of Loo loa presence in hypo- endemic areas and the risk/benefits of treating with ivermectin need to be kept in view. r \L- FtI : "I§' .t E:]:]Ir-r f{ If'{FEr_:TIr_r ti iiH ff ::; ::; F:::;5I lJ t-; T l--l n f .| :J l"l I::; 5I t-t l{ ftncn0rei"ciasis : *[d anc :leUi [] I a,qft ,:S.r iC pfOCeCL.ii-eS " f,on,- Lln,t*sii; . An ideal test for monitoring for elimination needs to have the following characteristics. High specificity High sensitivity High throughput lnexpensive Field based (i.e. no cold chain etc) . One complicating factor that needs to be kept in view is the existence of O. ochengi: a very similar cattle parasite, transmitted by the same vector, often impossible to distin- guish morphologically and whose presence can cause false estimates. ln areas where these coincide, an assay must be able to distinguish these two Onchocerca species. , O. volvulus only exists in 2 hosts - in humans and black flies - and there are ad- vantages and disadvantages of monitoring in either: The importance of high specificity cannot be stressed enough : in low-prevalence situations, it is extremely important to have high speci- ficity in detecting rare events. Low specificity implies many false-positives, particularly in low-prevalence situations. . Not only the choice of test, but also sampling methods are critical in certifying elimination. The more negative observations accu- mulated, the stronger the conclusion of an absence of transmission will be => negative results are valuable Sampling CANNOT be confined to a sin- gle time frame or single area if one seeks to prove absence; Always calculate confi dence intervals : all sampling is associated with sampling errors and that must always be considered! UIc o E Sentinel population will potentially sample thousands of vectors per year monitoring methods are simple, inexpensive and well documented lmmediate indication of transmission levels lnfection process is inefficient Long pre-patent period ln areas under control infected flies are often rare Large numbers of flies need to be screened to detect transmission "l I ::l i: I li:jt:h l: i r:, t i), : ::, ,[1,,, ,il ! i] "; ii-: r: J I i g i:;u-; r rf ai r-n+.-it s[,J I r r, [fi fr ;,r r]{:u: :.,i I rlT U, tt [,t,1,1, J- AUf ,f,,r':, fl i*e . Many diagnostic tools have been developed for onchocerciasis: Epidemiological tools for measuring infeaion levels in humans & eorly detection Entomological tools for measuring transmission levels & early detection of recrudescence of infection: Parasitology of infection in humans: Parasitology Serology (antibody detection) DNA Tests DEC skin patch test The methods used to evaluate the impact of vector control on infection and transmis- sion in the OCP were: skin snip surveys undertaken every three years in sentinel villages in order to assess the incidence and trends in prevalence of mf fly collection at selected catching points near major breeding sites in each river, and the dissection of the flies for para- sites in order to estimate vector density and transmission indicators, i.e. annual biting rates, annual transmission poten- tials and vector infectivity rates For post intervention surveillance, the following strategy may be considered: Entomological surveillance: detection of areas at risk of recrudescence of trans- mission Skin Biopsy Nodule Palpation Tricock 1 Tricock 2 c27 ov 16 Ov 3.6 Ov 9.4 o-1s0 PCR Scratch PCR "OCP TEST" LTS Fly dissection Fly poolscreening . Method: pool screening . Periodicity: every j years in surveillonce sites . lndicator: infectivity rote Epidemiological surveillance : detection of new infections . Methods: . Skin biopsy . DECpatchtest - Periodicity: every 3 yeors in surveillance sites - lndicotor: prevalence ond incidence Comparison of available diagnostic techniques skin snip Nodule palpation snip PCR scratch PCR DEC patch Ov'I6 ELISA ->.l000/o moderate ->100 o/o ->i 00 o/o variable ->1000/o Low ->100 o/o Low Low ->]000/o ->100 o/o variable + 600/o Low ->1000/o Key points from discussion . High specificity is really crucial for surveillance, because even with 990lo s pecificiÿ we will pick up many false positives in our surveillance exercise.This is posing large problems for lymphatic filariasis elimination programmes. By (separately!) applying two different types of tests, we may be able to improve the specificity, if we require both tests to be positive for taking action. . There was discussion about the recom- mendation to implement pool screening, because there have been large problems in the past: Fly densiÿ is often low, making it difficult to catch sufficient fly numbers for reliable estimation of infectivity rates. ln such situations, vector infectivity is also not a good indicator of transmission intensity. The Pool Screen software, developed for analyzing pool screen data, has been adjusted to better deal with such situations: it does not only calculate infectivity rates, but also the ABR and ATP. The latter is a better indicator of transmission than infectivity rate alone: a high infectivity rate is not problematic as long as the ATP is low. low low low high low high There were practical problems with respect to transportation of flies and lab capacity, but these have been overcome or can be overcome with additional investments. Fly catching (still based on human landing) continues to pose a problem. There is a need for an efficient trap. A trap should probably have the following characteristics: CO2 can be used as a first attractant; when the fly is close, a visual attractant is needed to bring the fly towards the trap; a biochemical attrac- tant is needed to elicit a landing respon- se. ln the past, there were problems with identifuing attractants, but biochemical methods have improved and trap deve- lopment might succeed now. Another question related to the use of pool screening concerns the stage of infection that should be detected: should we aim for detection of L3 or is it better to detect any stage of infection ? Because infection rates are usually much higher than infectiviÿ rates, the sensitiviÿ of the tests improves when you examine flies for any infection stage. There was also discussion about the pos- sible use of the OVl6 antibody test in the hish low field field lab lab field lab field lab low low high high low medium medium varies no 7?7? yesflvdissection pool screen PCR African context. OVl6 is successfully used in OEPA. lt is expected that the test will also work for the African species of oncho- cerciasis, although there is some uncer- tainty about the specificity (in particular for distinguishing O.volvulus and O. ochengi exposure). There have been experiments with a card format test, which can be easily used in the field without requiring ELISA. An unpu- blished validation study with the card test conducted in 2001 showed: - sensitivity 80% in mf positives; - 7 % of OCP personnel were positive; - ln uncontrolled areas, children are frequently found positive ; however, positivity either does not occur or is infrequent in this age group after interruption of transmission ; - The correlation between mf prevalence and the OV16 card test positive is not too bad. Some practical problems remain: - problemswithexpirydates; - components are still patented; - the card test was never marketed, because of uncertain benefits. Significant investments would be required to (re) develop a card test for large scale use in APOC. Experience with the card test for antigen detection of LF is not promising. . There was discussion about recommenda- tions for the type of diagnostic test to be used in post-treatment surveillance. There are a number of candidate tests each of which has it advantages and disadvantages. An assessment is necessary of what needs to be done to bring these tests into practice. This should include: - Furthervalidation of the DEC patch test; - Development of traps for fly catching, to enable large-scale implementation of pool screening with PCR; - Development of a rapid format card test for detection of OVl 6 antibody, with sufficient sensitivity and specificity. r_' l_ r_' r_' l I l r.J L -r-l tlr-. . t t . t ' t I L t I . I I lrl t t lt f'J hi I I Ël Ti;'i:àTt'1 Ëf'lTttttl I !.-.*tt t lt,-tt ! F :l Ë fr I;'l :J l..l ':; l.,l ITH Il.l F:F: I-1 tl::TIf'i Shifting the focus from control to elimination may have programmatic and strategic consequences. An important issue is the frequency of treatment: willyearly treatment be sufficlent to achieve elimination ? OEPA, which from the start aimed for elimination, has chosen to provlde treatment 6-monthly. The Mali / Senegal study (see session 1) shows that elimination can be achieved by yearly mass treatment if contin- ued for a long time. Results from Kaduna also support this, but the strategy may not be optimal. Data from Cameroon and Uganda suggest that a once yearly treatment regimen over 10 - 12 years will fail to disrupt transmission (Kata ba rwa et a l. 2OO8). H istol og ica I eva I uation of nodules in worms between 1993 and 2005 showed an initial ivermectin effect - but the live female worms persisted. Better effects may be achieved by twice yearly treatment. Advantages and disadvantages of shifting to twice yearly treatment are listed below. Advantages of twice yearly treatment: 1. Leads to a more sustained reduction in skin mf densities in treated individuals 2. Multiple treatments per year will result in a stronger reduction in live and reproductive adult worms in nodules 3. May help to increase the proportion of people that is treated at least once per year 4. May speed up the achievement of the point at which transmission is negligible or zero, as long as the intervention continues (see definition section: " suppression of transmission ") 5. May reduce time needed to achieve elimi- nation, therefore easier to proclaim an end- point and proclaim success in elimination. Heightens programme focus on shifting to elimination 6. May reduce the risk of resistance spreading in the worm-population Disadvantages: 1. Will lead to a change in the CDTI philosophy in which communities decide when to treat 2. Distribution times will be necessarily more controlled from central level 3. When transmission intensity reaches low levels after several years of mass treatment, the extra benefit of twice yearly treatment may be limited 4. Extra costs involved 5. May put extra strains on communities and volunteers 6. Retraining of community volunteers and others involved 7. Logistics in country 8. More ivermectin needed Discussion: - There is general agreement that the time needed for elimination is shorter with six monthly treatment, although it is not certain whether a 2x higher frequency of treatment results in 2x shorter required duration. Some argued that it may reduce the required duration to 6-7 years, but such a statement cannot be generalized. Data from the River Gambia/Mako focus, where large-scale 6-monthly ivermecti n treatment has taken place since 1 989, suggests that mf prevalence fell rapidly after the first few treatments, but was still 10-200/o after 6-7; additional treatments did not always lead to further decline. Nonetheless, mf preva- lence was usually lower than in river basins with yearly treatment. Data: (Borsboom et ol.2003). . Rapid success is important if APOC wants to move towards elimination, particularly because of the limited timeframe of APOC (closure in 2015). Additional evidence of feasibility of elimination will be needed to provide guidelines to countries on when they can shift their goal towards elimination and what needs to be done to achieve the new goal. lt may also strengthen the commitment from policyma kers, prog ra mme managers, donors, etc. Some questions remain regarding the reduction in transmission and time needed for elimination that would be achieved by increasing the treatment frequency. But there is potential for a significant benefit of such a change for elimination programmes, given the effect on adult worm burden, the potential win in time, the psychological effect reaching defined targets earlier, and the potential reduction in risk of resistance emergence. Because of the programmatic implications, programmatic changes should not suddenly be implemented in all countries. Critical evaluation of the epidemiological and pro- grammatic situation in each country should precede a decision on strategic changes. Expected advantages should be balanced against the efficiency of increasing the frequency. For example, in mature pro- grammes with long standing ivermectin treatment the added impact of increasing the frequency may be rather limited and not worth the extra expense.The same is true for low-endemic areas, where good results can be expected with annual treatment. But in new programmes with hyperendemicity, it may be efficient to start directly with 6-monthly treatment. The recommendation is to move on gradually, checking carefully where increased frequency would be beneficial and evaluating the impact of programmatic changes. Annual treatment should, for the time being, be maintained in settings as below: Mature projects which show good progress towards elimination ; Countries unable to scale up to good annual coverage: they should use current resources to scale up annual treatment. - Low-endemic areas, which are cur- rently not selected for CDTI, where good results can be expected with annual treatment Twice yearly treatment should be considered in the following settings: ln younger projects, if evaluation studies and / or targeted research projects sug- gest that the total period of mass treat- ment can be reduced by increasing the frequency and if 6-monthly treatment seems programmatical ly feasible ; ln other projects with good coverage, but poor epidemiological results; ln isolated transmission areas; For mopping up in areas with breaks in good coverage; ln areas where there is a sub-optimal response to ivermectin, suggesting possible emerging resistance. i tIr| ':, ffiffiffiflil .,, .*ml, ti+ut.üff qr It Ë r.J t': mtatt s*' T r-r *. tr trl L l_. 1_l I'l I'i r-' i-r t'l r-' I I I 'r:T i-i l'l ':: ltH I tlt;"{'-" State of the art of elimination of onchocerciasis transmission with current tools in Africa and identification of favourable and unfavourable factors, assessment of feasibility of elimination in different parts of the continent The Mali/Senegal study provided convincing evidence that elimination of onchocerciasis is indeed possible in Africa with current tools. Reports from other regions (Guinea Bissau, Nigeria) further support this conclusion. Evidence is still insufficient to define the precise circumstances under which elimination is feasible and the interventions required to achieve this goal. ln particular, we still lack information from forest areas, which form a large part of APOC's target zone. The feasibility of elimination and efforts required to achieve this goal depend on the following factors: The actual prediction of the feasibility of elimination per country is a challenging task, which requires a system to score countries on each of these factors and weight the different factors to arrive at a summary measure for fea- sibility. This requires good knowledge of the situations in different parts of Africa. Detailed scoring of countries or areas falls beyond the scope of the meeting, but we can draw some preliminary conclusions : ' Co-endemicity with Loa loo and / or conflict situations are challenges to effective imple- mentation of mass treatment; prospects for elimination are currently poor in some countries with these problems. . However, although elimination would be difficult to achieve in the whole of Africa, local elimination may be possible in geo- graphically defined areas and shrinking of the current onchocerciasis regional map is feasible. ' For other countries, the feasibility of elimination primarily depends on local circumstances and operational factors listed above. Extent of transmission zones Presence and extent of hyperendemic areas Maximum endemicity level before start the start of interventions Level of transmission in surrounding areas (including currently untreated low-endemic areas) Vectorial capacity Seasonal transmission lmmigrating flies Human migration Accessibility of the endemic area Geographic coverage Therapeutic coverage Frequency of treatment Years of ivermectin distribution Political instability / confl ict Loa loa co-endemicity ACTION POINTS FOR MOVING FORWARD TO ELIM INAT ION The following action points must be considered in order to move towards elimination: 1. Generation of more empirical evidence on the feasibility of elimination and required interventions under different circumstances. This is important to motivate countries and donors and to advise countries on rein- forcement of control measures or adjustment ofthe strategy. 2. Development of guidelines for countries on what has to be done to achieve, prove and maintain elimination of onchocerciasis infection and transmission. Guidelines should be developed from empirical data and can be supported by simulation mod- elling. Guidelines are needed for: a. Programmatic changes required to achieve elimination, depending on local circumstances (e.9. moving from yearly to 6-monthly treatment). b. Available guidelines for deciding when to stop and confirmation of elimination should be refined for use in APOC and tested /validated in the field. c. Routine surveillance after elimination, for timely detection and suppression of possible reintroduction of infection. 3. Redefine the target areas for mass treat- ment and delineate transmission zones. a. Redefinition of target areas is required, because low endemic areas are currently not targeted for treatment. Treatment is necessary in areas with self-sustainable low level transmission. Extension of mass treatment into areas, which are low-endemic because of a constant influx of infection from neighbouring areas, should also be considered. b. lt is important to determine where transmission zones extend into neigh- bouring project areas or across national borders, to coordinate interventions throughout the zone to achieve elimination goals. 4. Define what has been accomplished in project areas to date and prepare projects for elimination where feasible. This includes: a. documentation of the epidemiological situation in each project area; b. an assessment of the feasibility of elimi- nation (e.9. not possible, feasible on long term, feasible on relatively short term) ; c. where feasible: define the elimination strategy and target areas for initiating elimination with a clear workplan, defined endpoints, and monitoring and evaluation plan; d. in partnership with the MoH and endemic communities, initiate elimina- tion plans in targeted countries. All data collected should be used to modify the elimination strategy as appropriate. 5. Continue investments in development of better tools for onchocerciasis elimination, including: a. tools to kill or sterilize viable adult worms: although it is shown that repeated mass ivermectin treatment can be sufficient to achieve elimination, availability of a macrofilaricidal drug would make it much easier to achieve that goal. b. diagnostic tools for measuring the pres- ence and number of parasites in the human host, particularly viable adult worms. There still is a need for better, cheaper or more specific diagnostic tests to measure parasite numbers and transmission. 6. Examination of the opportunities for linking wlth LF elimination programmes. LF programmes aim to distribute ivermectin (in combination with albendazole) to a large part of the African population. Activities of both programmes need to be coordi- nated to optimize their implementation. 7. Establish a regular update mechanism for feedback on the above action items, such as an annual review of elimination pros- pects and status, to ensure engagement with key operational stakeholders and reporting on progression towards goals.

RESEARCH NEEDS AND PRIORITIES APOC should proceed with the above action points to move towards elimination where feasible. Yet, to ensure programmatic success, research is needed on the following issues. Ad 1. Generation of more empirical evidence on the feasibility of elimination and reguired interventions under different circumstances. '1. Create a database for the available data on the long-term effects of mass ivermectin treatment on various indicators of onchocerciasis infection. Update it when new data becomes available. Conduct statistical and model-based analysis of the above data to obtain a better understanding of the relationship between characteristics of interventions, local circumstances, and infection levels after mass treatment and of how variables can be modified to increase elimination probabilities. 2. Select pilot projects, in which the strategy will be changed for elimination, aiming to provide additional examples of successful elimination. Select project areas that are presumed to be closest to achieving elimination and which cover different epidemiological settings. lf necessary, reinforce/ intensify control efforts to make sure that criteria for stopping treatment are reached before 2012,so that elimination can be confirmed before APOC's closure in 2015. 3. Start operational research in the demon- stration / pilot project areas to address the many strategic questions and remaining uncertainties: a. Test the feasibility of existing or adjusted guidelines for stopping treatment and confirmation of elimi- nation in different epidemiological settings. b. Validate the endpoints for post-inter- vention surveillance in different epide- miological settings, using 3 years as a starting point and - where possible - 3 or more years later, to reconfirm that the infection has not been reintroduced (particularly where the system is "open " (see def initions section). c. Comparative assessment of the value of the available diagnostic tests and sampling strategies in the field for each of the following tasks: i. Monitoring & evoluotion in the end stage of mass treatment proqrom mes ii. Decision to stop interventions iii. Confrrm elimination iv. Routine su rveillo nce d. Define the optimal treatment regimen for different transmission areas, including the need and feasibility of increasing frequency of treatment to a 6-monthly interval or making other adjustments to the treatment strategy (e.9. addition of vector control), for earlier achievement of elimination. This should include an assessment of the implications of these changes at the community level and the possibilities for countries to maintain these programmes after APOC's closure (if still needed). e. Assess the extent of systematic non- compliance, the existence of non-treated villages or hamlets, the implications for successful elimination and the necessary strategies to address these issues. f. ldentify individuals who still carry infec- tion after long term mass treatment and examine the reasons for their persistent infection (e.9. systematic non-com- pliance, migration, poor response to treatment) and develop other possible treatment strategies. g. Evaluate the hypotheses that treat- ment in hyper- and mesoendemic core areas of a river basin will also cause elimination in surrounding, untreated low-endemic areas, without extending treatment into these areas. Perform targeted studies in areas where people have a poor response to treatment, to examine whether it is caused by resist- ance and test possible solutions to deal with this problem. 4. Ad 2. Development of guidelines on what has to be done to achieve, prove and maintain elimination of onchocerciasis infection and transmission 1. Define the optimal use of diagnostics and criteria for measuring transmission and population of adult worms using, for: a. Delineating transmission zones b. Deciding when to stop in different epi- demiological settings c. Confirming absence of transmission d. Post-elimination surveillance This can include combinations of a rapid/ cheap screening test (e.9. DEC patch test) with other tests for confirmation. The WHO guidelines should be used as starting point and adjusted where appropriate. 2. Assess, and if necessary improve, the validity of model predictions of the effects of long- term mass treatment on transmission and parasite density, using available data on the long-term effects of mass ivermectin treat- ment on various indicators of onchocerciasis infection (see recommendation 1). ldentify key uncertainties for which better data are still needed to refine and improve the models. 3. Use suitable simulations models for a systematic assessment and comparison of the expected outcomes of elimination programmes, varying with respect to duration, coverage and other operational factors), under different epidemiological circumstances: a. To estimate breakpoints of transmission with the different indicators of infection (e.9. mf prevalence, CMFL, DEC patch test, or outcomes of PCR-based screen- ing of pools of flies). b. To assess the importance of incoming infection via human migration or fly movements and determine cost-effective approaches to prevent recrudescence. c. To assess the potential benefits ofchang- ing the frequency of mass treatment from yearly to 6-monthly or other changes in the intervention, if implemented from the start of mass treatment or after varying periods of annual mass treatment. d. To assess the need for and potential benefits of extending mass ivermectin treatment into the low-endemic zones that border the areas currently selected for mass treatment. e. To assess the efforts required to elimi- nate onchocerciasis in transmission zones with only low-level transmission (no meso- or hyperendemic core), which are currently not considered for iver- mectin mass treatment. f. To estimate the risk of failure to achieve elimination within a reasonable time frame, in relation to the diagnostics and criteria used to stop mass treatment and confirm elimination. g. To assess the speed of recrudescence in case of failure to achieve elimination and determine cost-effective approaches for post-elimination surveillance h. To assess the need for programmatic changes in areas with LF elimination programmes Ad 3. Reviewing target areas for mass treatment and delineation of transmission zones 1. Redefining target areas for mass treatment: a. ldentifying areas for which there are no data and therefore no treatment, and areas of insufficient data. b. Assess the usefulness and validity of existing REMO data for redefining target areas for mass treatment. c. Define how currently available diag- nostic tools can best be used to deter- mine areas with low-level transmission, including the 'tail'-areas of the already defined project zones and independent low-endemic areas that have previously not been considered for mass treatment. 2. Develop methods for delineation of transmission zones in the field, e.g. based on ecological, entomological, or parasito- logical findings or results of the DEC patch or OV 16 antibody tests. Take into consid- eration specific circumstances, e.g. with respect to human migration or the presence of breeding sites in the direct environment. o: oo N- tr f e, o lrl lL l-N I ulN a Ad 4. Defining what has been accomplished in project areas to date and preparing projects for elimination where feasible (no specific research activities related to this action point) Ad 5. Development of better tools for achieving elimination. This includes: 1. Continue the investment in research for a macrofilaricidal drug. 2. Test the accuracy and usefulness ofdifferent diagnostics for determining when to stop treatment or confirming elimination. a. Validation of diagnostic tests for detection of low-level infection at the individual level, with particular attention to specifi- city (including DEC patch tests, mf skin snip, and perhaps the OVl6 antibody test, particularly in children) b. Determine the accuracy of and correla- tion between the outcomes of avail- able methods for detecting low level transmission and parasite density, via a systematic comparison of all methods in different epidemiological settings. This should include methods based on the DEC patch test, mf skin snip, OV '16 and PCR screening of pools of flies. Specific attention is needed for the OV 16 antibody test, considering the current uncertainty about its usefulness and the high investments still needed to develop a rapid format test. 3. Further development of modern diagnostic tests that appear to be useful in different phases of the elimination programme (monitoring & evaluation, defining when to stop, confirm elimination, post-elimination surveillance) a. For entomological monitoring: i. new fly traps, to trop parous flies ii. looking into ways to improve the efficiency of PCR tests and upscaling the throughput. b. Rapid format OV 16 antibody test (card test or dipstick), if additional studies show it to be an accurate and useful tool for determining when to stop treatment or to confirm elimination. c. New diagnostic tool to detect viable adult worms and /or fertile female worms. Ad 6. Examination of the opportunities of linking with LF elimination programmes .l . Overlap in target areas, with particular attention to the low-endemic areas where APOC has not yet started its operations. 2. Study the added benef it of albendazole treatments with onchocerciasis control. 3. Study the possibilities, need and cost- effectiveness of changing the strategy to synchronize time schedules of LF and onchocerciasis elimination programmes. ::1,: ":: " oo o N É, , É, E lrJll F N I n N a We,would like to thank Dr Uche Amazigo, Director of APOC for initiating this meeting; Dr Julie Jacobson of the Bill and Melinda Gates Foundation and Dr Adrian Hopkins, Director, Mectizan Donation Programme, for their invaluable contributions in the planning and orclanisation of the meeting. We are also very gratefulto Professor Homei- da, University of Technology, Khartoum, for Ch,riring the meeting and the rapporteurs - Professor Wilma Stolk and Dr Chikwe lhekweazu for their excellent work. Those who co-facilitated the organisation of this meeting, in particular, Drs Laurent Yameogo, Mounkaila Noma, Stephen Leak and Mr H. Zoure are gratefully acknowledged. We would especially like to thank Ms Emily Wright of the Bill and Melinda Gates Foundation, Miss Joni Lawrence of the Mectizan Donation Programme for their active support and Mr Y. Aholou and Mrs P. Mensah of APOC for making necessary administrative and travel arrangements. This meeting was funded by co-financed by the African Programme for Onchocerciasis Programme (APOC), the Bill and Melinda Gates Foundation and the Mectizan Donation Programme. ffilro' $r rr r t ! I r t r.E t 'r-!-FFr?Fl!t African Programme for Onchocerciasis Control (APOC) (2008). Addendum for the plan of action and budget 2008-2015. Ouagadougou, African Programme for Onchocerciasis Control (APOC), World Health Organization. Agoua H, Alley ES, Hougard JM, Akpoboua KL, Boatin B and Sékétéli A (1995). Études entomologiques de post-traitement dans le programme de lutte contre lbnchocercose en Afrique de l'Ouest. Porasite2:281-288. Borsboom GJ, Boatin BA, Nagelkerke NJ, Agoua H, Akpoboua KL, Alley EW, Bissan Y Renz A, Yameogo L, Remme JH and Habbema JD (2003). lmpact of ivermectin on onchocer- ciasis transmission: assessing the empirical evidence that repeated ivermectin mass treatments may lead to elimination/eradication in West-Afric a. Filaria J 2 : 8. Cupp EW (1992).Treatment of onchocerciasis with ivermectin in Central America. Porasitology TodayS:211-214. Cupp EW, Duke Bo, Mackenzie CD Guzman JR, Vieira JC, Mendez-Galvan J, Castro J, Richards F, Sauerbrey M, Dominguez A, Eversole RR and Cupp MS (2004). The effects of long-term community level treatment with ivermectin (Mectizan) on adult Onchocerca volvulus in Latin America.Am JTrop Med Hyg71:602-607. Cupp EW and Cupp MS (2005).lmpact of ivermectin community-level treatments on elimination of adult Onchocerca volvulus when individuals receive multiple treatments per year. Am J Trop Med Hyg 73 : 1 159-1 161. Dadzie Y Neira M and Hopkins D (2003). Final report of the Conference on the eradicability of Onchocerciasis. Filorio J 2:2. Diawara L, Traore MO, Badji A, Bissan Y Doumbia K, Goita SF, Konate L, Mounkoro K, Sarr MD Seck AF, Toe L, Toure S and Remme JHF (2009) Feasibility of onchocerciasis elimi- nation with ivermectin treatment in endemic foci in Africa: first evidence from studies in Mali and Senegal. PLoS NeglectedTropical Diseases 3: e497. Dowdle WR and Hopkins DR, Eds. (1998). Ihe eradicotion of infectious diseases. Report of the Dahlem Workshop on the eradication of infectious diseases, Berlin, Morch 16-22, 1997. Series. Chichester, John Wiley & Sons Ltd. Duerr HP, Dietz K and Eichner M (2005). Determinants of the eradicability of filarial infections : a conceptual approach. Trends Porositol 21 : 88-96. Katabarwa M, Eyamba A, Habomugisha P, Lakwo I Ekobo S, Kamgno J, Kuete I NdyomugyenyiR, Onapa A, Salifou M, Ntep M and Richards FO (2008). Aftera decade of annual dose of mass ivermectin treatment in Cameroon and Uganda, onchocerciasis transmission continues. Trop Med lnt Health 13:1196-1203. Plaisier AB Van Oortmarssen GJ, Habbema JD, Remme J and Alley ES (1990). ONCHOSIM: A model and computer simulation program for the transmission and control of onchocer- ciasis. Computer Methods and Progroms in Biomedicine3l:43-56. Noma M, Nwoke BE, Nutall l, Tambala PA, Enyong P, Namsenmo A, Remme J, Amazigo UV Kale OO and Seketeli A (2002). Rapid epidemiological mapping of onchocerciasis (REMO): its application by the African Programme for Onchocerciasis Control (APOC). AnnTrop Med Parasitol96 Suppl 1 : 529-39. Osei-Atweneboana MY Eng JK, Boakye DA, Gyapong JO and Prichard RK (2007). Preva- lence and intensity of Onchocerco volvulus infection and efficacy of ivermectin in en- demic communities in Ghana: a two-phase epidemiological study. Lancèt ?69 : 2021 -2029. Sauerbrey M (2008).The Onchocerciasis Elimi- nation Program forthe Americas (OEPA).Ann Trop Med ParasitollO2: Suppl 1 :25-29. WHO (2001). Certification of elimination of hu- man onchocerciasis: criteria and procedures, guidelines. Geneva, World Health Organization. Winnen M, Plaisier AP, Alley ES, Nagelkerke NJ, van Oortmarssen G, Boatin BA and Habbema JD (2002). Can ivermectin mass treatments eliminate onchocerciasis in Africa ? BullWorld Health Organ 80 : 384-391. l- --r -..- t , t t UI L I'' t- }-l I-r T r..' T t§fi ilr: THt HtETIIirl Objectives of the meeting : 1. To review the state-of-the-art of elimination of onchocerciasis transmission with current tools in Africa, and to predict the feasibility of elimination in different parts of the continent. 2. To identify critical issues for the feasibility and optimal strategies of elimination in different epidemiological settings. 3. To identify research needs and priorities to answer key challenges related to elimination of transmission. DAY I - Wednesday 25 February 2OO9 O9:00-12:40 Welcome Remarks by: . Director, APOC, Dr Uche Amazigo . WHO Representative in Burkina Faso Opening Remarks by: . Dr Julie Jacobson, Bill & Melinda Gates Foundation . Dr Adrian Hopkins, the Mectizan Donation Programme ' Professor M. Homeida, Chair of the meeting lntroduction of participants ELIMINATION WITH IVERMECTIN : STATE OF THE ART (i) Elimination of Onchocerciasis in the Americas, current evidence/critical issues - Drs Fronk Richard (1 1mi n) / Mou ricio So uerbrey (l 0 mi n) (ii) Elimination in Africa, current evidence/ critical issues - Drs Hans Remme('l1min)/ Rich o rd N dyo m u gyenyi (1 0 mi n) Tea Break Discussion on presentations (i) and (ii) Summary of key issues Lunch Break 09:00-09:30 09:30-09:50 09:50-10:10 10:10-10:40 10:40-12:10 12:10-12:40 12:40-15:00 DAY I - Wednesday 25 February 2OO9 15:OO-18:10 09:00-12:30 (i) Long term impact of ivermectin treatment on survival and reproductivity of the parasite - Drs Kwabla Awodzi(10min)and Ed Cupp (11min) (ii) Model predictions of elimination: strategies, assessment and critical factors - joint presentation by Dr Wilma Stolk (10 min) and Hans-Peter Duerr (11min) Discussion on Presentations (i) and (ii) Tea Break Discussion on presentations (i) and (ii) (cont d) Summary of key issues l5:00{5:20 15:20{5:40 15:40-16:30 16:30-17:00 17:OO-17:40 17:40{810 09:00-09:20 09:20-09:40 09:40{0:30 10:30-11:00 '11:00-11:40 11:40-12:10 12:40-15:00 (i) Vector migration and vector/parasite complexes, human migration issues - Drs FrankWolsh (10min)/ DanielBookye ('10 min) (ii) Target areas/populations for ivermectin treatment and non-treated areas - Drs Mounkaila Noma (10 min) / Hans Remme (10 min) / Frank Richards (10 min) Discussion on Presentations (i)and (ii) Tea Break Discussion on presentations (i) and (ii) (cont d) Summary of key issues Lunch Break DAY ll - Thursday 26 February 2OO9 15:OO-17:15 (i) Diagnostic tools, evaluation and post treatment surveillance strategies - DrTom Unnasch (10 min)/ LaurentToe (10 min) (ii) Discussions Tea Break Summary of key issues Dinner 15:00{5:20 15:20-16:05 16:05{6:35 16:3517:05 19:O0 - 21:00 DAY lll - Friday 27 February 2009 O8:3O-13:00 (i) lntroduction by the Chair (ii) Presentation of key issues - Rapporteurs (iii) Conclusion and recommendations Tea Break (iv) Conclusion and recommendations (Cont d) Closure 08:30-08:35 08:35-08:50 08:50{0:30 10:30-1'l:00 11:00{3:00 13:00 , ) I I iif'F'f f'{tt I:,.i II: I_ I::;T Il f' I-, n l-'.tT I t_:I F fi f'{ T H 1. Prnl'" /\rrl*rnike ABIG5[ P.O. Box 29771,Secretariat Main Office, lbadan, Oyo State, Nigeria fel:234-2-7517329 or 234-8037865702 Fax:1-509-5628212 E-mail : adenikeabioseo@yahoo.com 2. Prof,Oladele B*ni;*rnin AKO{UN Parasite and Tropical Health, Federal University of Technology, Yola, Nigeria Tel: (234) 75 627281 Mobile : (234) 8037 220460 E-mail : akoguno6yahoo.com 3. *r Ucl"re Vq+r(}firta AMAZICS Director, African Programme for On- chocerciasis Control (APOC), N' 1473, Avenue Naba Zombr6,01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226) 50342277 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : dirapoc@oncho.afro.who.int 4. Dr t4h,\roi[.iinl"] AllI/\ilZi Clinician, P.O. Box 2018 Mamprobi, Ghana Tel: +233-21-40-22-50 Fax;+233-21-668871 or + 233-21-93-522-111 E-mail : awadzi@ghana.com ; ayodelel3@live.co.uk 5. Prof. Darrir:i 8O"fi,l{\'[: Head, Parasitology Department, Noguchi Memorial lnstitute for Medical Research, P.O. Box 1G581, Legon, Accra, Ghana Mobile: +233266237 365 E-mail : dboakye6noguchi.mimcom.org or yawbadjei@ya hoo.co.u k 6. Llr Josrpir Dossoi.r aATRAYf Zone des Ambassades, parcelle J,03 BP 2503, Cotonou, R6publique du B6nin Tel : (00229) 97188144 Fax : (00229) 21 33 64 06 E-mail : jcatraye@basp96.org 7. Dr Er1 Wayn* (tlPP Entomologist/ Geneticist Tel:270-296-1559 E-mail : cuppedd@auburn.edu 8. ["]r h{;*ris l}eter DUERtt I nstitut fuer Medizinische Biometrie, Universitaet Tuebingen, Westbahnhofstr. 55, 7 207 O f ubingen, Germa ny Tel : ++49 (0) 7071 29 78259 9. Fax: ++49 (0) 7071 29 5075 E-mail : hans-peterduen@uni-tuebingen.de Mr. Pau[[JlMl Communication Officer. African Programme for Onchocerciasis Control (APOC), N' 1473, Avenue Naba Zombr6, 01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226) s03429 53 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : ejimep@oncho.afro.who.int Dr $r act l$BI Community Ownership and Partner- ship Officer, African Programme for Onchocerciasis Control (APOC), N' 1473, Avenue Naba Zombr6,01 BP 549, Ouagadougou 01, Burkina Faso Tel: (226) 503429 53 Fax: (226) 503428 75 or 50 3436 47 E-mail : fobig@oncho.afro.who.int l!4s. f{attralie GARON Senior Development Officer, Western and Central Africa Regional Program, Geographic Programmes Branch, Canadian lnternational Development Agency, 200 Promenade du Portage, Gatineau (Qu6bec), Canada KiA 0G4 Tel: +819-994-7088 Fax: +819-997-5453 E-mail : nathalie.garon@acdi-cida.gc.ca prr.rf, " f\i'iit t'uclt"t tt HOI'4 E I DA. Professor of Medicine and Therapeutics, President, University of Medical Sciences & Technology, P.O. Box 12810, El Riyad, Khartoum, Republic of Sudan Tel:(00249) 183224762 Fax: (00249) 183224799 E-mail : homeidam@umst-edu.org or amst33@hotmail.com t.rr Adrian HOPKIN5 Director, Mectizan' Donation Program, 325 Swanton Way, Decatur, GA-30030, USA fel: +404-371-1460 Fax: +404-371-1138 E-mail : ahopkinsqtaskforce.org llr rl."f rikwr,r tt'lUlKWtl\Zu Consultant Regional Epidemiologist, South East of England, 7h Floor, Holborn Gate,330 High Holborn, London WClVPP, United Kingdom 10. 11. 12. 13, Tel: +442077592856, (PA +442077592842) Mobile: +447961993056 E-mail : chikwe.ihekweazu@gmail.com Dr "jult* .,[A(ffm$ffhl Bill & Melinda Gates Foundation, Seattle, USA E-mail : JulieJacobson@gatesfu undation.org Dr Annette Christiarre KU[$[1. Scientist, TDR, World Health Organization (WHO),20 Avenue Appia, Ch-121'1, Geneva 27, Switzerland Tel:+41 22791-1871 Fax:+41 22791-4774 E-mail : kuesela@who.int Dr Stepherr t FAK Technical Officer, African Programme for Onchocerciasis Control (APOC), N' 1473, Avenue Naba Zombr6,01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226) 50 34 29 53 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : leaks@oncho.afro.who.int MI. \'.i( { iu[)d f,JIANDOU lnformation System Officer, African Programme for Onchocerciasis Control (APOC), N" 1473, Avenue Naba Zombr6, 01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226) so342953 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : niandouy@oncho.afro.who.int *r ful*lrrrkaila NCMA Chief Epidemiology and Vector Elimina- tion Unit, African Programme for Onchocerciasis Control (APOC), N" 1473, Avenue Naba Zombr6,01 BP 549, Ouagadougou 01, Burkina Faso Tel: (226) 503429 53 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : nomam@oncho.afro.who.int Dr K*nneth Nnafi rr li {)$:}l.\f,iA Faculty of Science, Department of Zoology, University of Uyo, Nigeria E-mail : nkopara@yahoo.com llr Hans REMME, Epidemiologist, 120 Rue des Campanules,0120 Ornex, France Tel:+33 645457404 E-mail : hansremme@gmai!.com fltr Fr.rn]< t{lCHAHiiS Director, RiverBlindness Program, One Copenhill, 453 Freedom Parkway, Atlanta, GA 3O3OZ USA Tel : +770-488 -4511 / 4502 direct Fax: +770-488-4527 E-mail : frich@1 @cdc.gov []u \fl/iflmrn A" 5T*l-K Department of Public Health, Erasmus MC University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands Tel:+31 107043730 (dir)+31 10 7038460 (secretary) Fax: +3110 7038474 E-mail : w.stolk@erasmusmc.nl Dr Laurent T0E Head of Molecular Biology Laboratory, Multi Diseases Surveillance Center (MDSC), N'1473, Avenue Naba Zombr{,01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226)50342953 Fax:(226)503428 75 or50 343647 E-mail : toel@oncho.afro.who.int Dr Tlrornas R. UNNASCH Molecular Biologist/ Diagnostics, Global lnfectious Diseases Research Program, Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Blvd., Suite 304, Tampa, FL 33612, Florida, USA Tel : 00i -813-974-0507 Fax: 001 -81 3-974-0992 Cell:001 205-807-2505 E-mail : tunnasch@health.usf.edu ffir fl:rank W/\t 5H Chairman, Uganda Onchocerciasis Elimination,80 Arwdel Road, Lytham St. Annes, Lancashire FY8 lBN, Great Britain Tel: +44 1253737765 E-mail : frank@walsh.me.uk ["ll r {.";r u r *r+t YAME0GO Coordinator Director's Office, African Programme for Onchocerciasis Control (APOC), N' 1473, Avenue Naba Zombr6, 01 BP 549, Ouagadougou 01, Burkina Faso Tel:(226) 50342953 Fax:(226) 50 3428 75 or50 343647 E-mail : yameogol@oncho.afro.who.int fuir. Honorat Gustavq lSLlnt Responsible Biostatistics and Mapping, African Prog ramme for Onchocerciasis Control (APOC), N'1473, Avenue Naba Zombr6,0'l BP 549, Ouagadougou 01, Burkina Faso Tel: (226) 503429 53 Fax: (226) 50 34 28 75 or 50 34 36 47 E-mail : zoureh@oncho.afro.who.int 23. 15. 16. 20. 21. 24. 17. 25. 18. 26. 27. 22. 28.