Summary report of the OCP/TDR meeting on the impact of ivermectin on onchocerciasis transmission: held at the dep. of public health, Erasmus University Rotterdam, Rotterdam, the Netherlands 3-5 October 2001

IWO RLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ONCHOCERCIASIS CONTROL PROGRAMME IN WEST AFRICA PROGRAMME DE LUTTE CONTRE L'ONCHOCERCOSE EN AFzuQUE DE L'OUEST EXPERT ADVISORY COMMITTEE Ad hoc Session Ouasadousou. I I - l5 March 2002 EAC.AD.2 Original: English October 2001 Summary Report of the OCP/TDR meeting on the impact of ivermectin on onchocerciasis transmission Held at the Dept. of Public Health, Erasmus University Rotterdam, Rotterdam, The Netherlands 3-5 October 2001 Summary Report of the OCP/TDR meeting on the impact of ivermectin on onchocerciasis transmission Held at the Dept. of Public Health, Erasmus University Rotterdam Rotterdam, The Netherlands 3-5 October 2001 SumnrarvJ A conrprehcnsive analysis has been undertaken of available dala on the impact of more than a decade o1- ivermectin treatment on onchocerciasis inf-ection and transmission. Relevant entomological ar-rd epidemiological data from 15 river basins in the OCP and one basin in Cameroot-t rvere reviewed. In all of these river basins, ivermectin treatment has been extremely successlul in eliminating onchocerciasis as a public health problent. However, elimination of transmission has proven more difficult. In some basins significant transmission is still ongoing alter 10-12 1'ears of ivermectin treatment. In other basins. transurission may have been interrupted but this needs to be confirmed by in-depth evaluations. In one meso-endemic basin, where 20 rounds of treatment had reduced the prevalence of infection to levels as low as2-3oh, lltere rvas significant recrudescence of infection within a 1'eu, years after interruption of irertrlcctitr treatment. The implications of these findings lbr tl-re fbasibility of elimination of otlchocerciasis transmission by ivermectin treatment are being investigated further in computer sirnulation studies. I ntrod uction 'l'hc ivennectin trials tlrat were undertaken a clccadc ago denronstrated the eff-ectiveness o1' ivcrtlccLitr treatment for morbidity' control. 'l-ransnrission trials also showed that ntass trealment rvith ivcrnrectin resulted in a major reductiorr in transmrssion in Africa. However. alier thc first thrcc rounds of treatment there slill remained a signillcant level of transmission. Simulation nrodels that were calibrated using these early trial data predicted that interruption o1- transnrission by ivermectin treatment alone would bc diffrcult to achieve and that ivermectin trcutmcnt needed to be planncd lbr a pcriocl o1' clecacles. Hence. ivermectir-t treatnlent pr'ogrilnnles werc established u,ith a lonr.l tinre liantc in ntind. the exact duration to bc rlctct'tlined rlu thc basis o1'lirrthcr cvaluatior-r on thc long-ternt impact of rnass lreatment ou trirnsnrission and tlie parasitc rcservoir. Ivermcctin has now been in operational use fbr more than a decade, and the question o1'the rcquired duration of treatment is receiving renewed attention. During the meetings of the Joint Prograrnme Committee of the Onchocerciasis Control Programme in West Africa (OCP) and the .loint Action Forum of the African Programme for Onchocerciasis Control (APOC), held in Yaounde in December 2000. this question was also raised. It was noted that the nrain cxperience with large-scale ivennectin treatment o\/er a long period of time in Africa was in the OCP. It was recommended, therefore. to undertake an in-depth analysis of the relevant OCP data. and to update on the basis of the results the ONCHOSIM model predictions of the long ternr itnpact of ivermectin treatment on onchocerciasis transmission and of the feasibility of onchocerciasis elirnination witli il'ermectin treatment alone. Llarll' this year, this process u,as started. A detailed analysis plan was developed during the annual internal operational research meeting of tlie OCP in March 2001. and the Centre fbr Decisior-r Sciences in Tropical Disease Control o1' tlie E,rasmus University Rotterdam was ct'rnlracted to undertake the analvsis ar-rd the corresponding ONCHOSIM simulations. The data analvsis has now been completed and the results were discussed during an OCP/TDR s1'ronsored r-neeting of onchocerciasis experts that was held fiom 3-5 October 2001 at the Ilrasrnus University Rotterdam. the Netherlands. A summary of the results on the long tenr iurpact of ivermeclin treatment on onchocerciasis transnrission and the rnain conclusions of the niceting are reported in tliis document. A cor-nplete report of the analysis will be available shortly. Ir-r the mean time, the second phase of the rvork has started. This will involve a re-calibration of the ONCHOSIM model on the basis of the observed epidemiological trends in the diff'erent river basins. and updated predictions of tlie l'easibility of elirnir-ration of Onchocerca volvultts lu ndcr d if ferent operational scenarirts. Restrlts [)trling discussions uith O('[) and \\'ll0 stafl. l4 arcas liom w,itl-rin the OCI) programr-nc wcrc sclcctecl on the basis o1-tlieir liistorl,of ivcrntectin treatment. Areas that only had larviciding clonc rtr were under ivernrectin treatment fbr a too short period were not selected. Variation in thc epic'lemiological background and treatrnent historlr was also important in selecting these arcas. One area fiorn outside OCP *'as includecl in acldition. namely Vina Valley in Cameroon. 'l'hc l-5 arcas citn bc cliviclcc'l into three categurics dcpcndir-rg on thc cornbination o1- conl.rol lt)casLll'cs taken. uilutelv arcas that had ivcrnrcctin clistribution only. arcas that hacl iverntcctiu 2 treatment after vector control, and areas that had ivermectin distribution and vector control in parallel. Epidemiological data (prevalence and community microfilarial load, CMFL) and entomological data (annual biting rate, ABR, and crude annual transmission potential, ATP) were taken from the OCP databases as available in June 2001. Areas that had ivermectin distribution only (A) Gambia (Mako). This basin is situated completely in the savannah area in the eastern part of Senegal and the northeastern part of Guinea Conakry. The area is entomologically relatively isolated. Only savannah vectors were present, mostly S. sirbanunr. The area was hypo/meso endemic before onchocerciasis control with pre-control CMFL values > 30 mf/s in only two survey villages, and prevalences from 60-800%. However, these data were collected during a prolonged period of very severe drought that affected the area at that time, and data from before the drought indicate a much higher endemicity. Entomological studies were carried out for only two years in preparation of treatment. These studies showed ABRs around 15000, and highly variable ATPs around 3000. DNA probe identification of onchocercal larvae from flies collected during 1986-1992 showed 23o/o savannah strains of O. volvulus and 77o/o non- vohulus parasites (mostly O. ochengi). Experimental larviciding was carried out in 1989 for 20 weeks during the rainy season. Large-scale ivermectin treatment started in 1989, with a 6- monthly treatment schedule. The epidemiological indicators prevalence and CMFL show a dramatic decline in this area to very low values, although prevalence seems still a bit hanging in a few villages. This suggests that the parasite reservoir is nearly close to suppression. The entomological data is very limited. However, there is some very recent pool screening data wherein no infective flies have been detected. Therapeutic treatment coverage was high (around 80%). Factors that may have influenced results are: l) there is important human migration from south to north and west, and 2) there is evidence that the increasing human population may have changed the environment in some places significantly affecting transmission. These results suggest that ivermectin treatment may have interrupted transmission in this area. However, this needs to be proven by more proper detailed entomological studtes withfull dissection offlies. If interuuption of transmission is confirmed in these studies, it should be considered to stop treatment after afew more years (when the prevalence in all villages has fallen close to zero), while still keeping the surrounding areas under control, and observe whether transmtssion remains interrupted. Further activities recommended for this basin are a reanalysis of existing records with a view to incidence, and getting a better insight in geographical coverage by maktng a complete map. (8, C) Rio Corubal, Rio Geba. The main part of these two basins is situated in Guinea Bissau, very close to the Rio Gambia, Mako focus (A). Rio Corubal used to be a meso-endemic area with pre-control CMFL levels mostly < 30 mfls, and prevalences varying from almost zero to 80%. Rio Geba had a very low pre-control endemicity, with CMFL < 5 mfls and prevalence varying from almost zero to 30oh. Vector control has never been done in these areas, but some capturing and dissection has been done for a period of two years in Rio Geba (1989-1990) and four years in Rio Corubal (1989-1992). DNA probe examinations of parasites in 46 infective flies from 1993 to 2000 showed 6.5% O. volvulus and 93.5o/o non-O. volvulus.In Rio Corubal, 3-monthly ivermectin treatment started in 1991, but this came to an end in 1996 because of civil strife in the area. In Rio Geba, 6-monthly ivermectin treatment was started in 1989. 3 Prevalence and CMFL in Rio Corubal show very favourable trends, reaching values close to zero in 1997, when ivermectin was no longer distributed. However, recently collected data strongly suggests that at least in some villages prevalence is increasing again from 2-3o/o in 1996 to values between l2o/o and 36% in 2001. ABR (around 15000) and ATP (around 500) were not extremely high, and seem compatible with a meso-endemic situation. Therapeutic coverage increased from around 60% at the start of the program to around 80% in 1996. Prevalence and CMFL in Rio Geba went down to values near zero in 1997, when the last available epidemiological data was collected. ABR (range 0-6000) and ATP (range 0-200) were quite low. Baseline ABR values may have been underestimated because of the period of severe drought in which they were measured. Therapeutic coverage was good (80%). Despite the limited data available, it seen$ that in Rio Geba onchocerciasis is now eliminated. It is unclear whether this is the result of ivermectin treatment or whether onchocerciasis would have died out by itself in this low endemic area. Rio Corubal seems very similar to River Gambia, but later follow-up shows evidence of significant recrudescence. This seems especially alarming after about 20 rounds of ivermectin treatments in a not very endemic situation. No specific further activities were recommended for the Rio Geba. For Rio Corubal it was recommended to l) construct a good map of geographical coverage, 2) investigate whether what happened in this basin can be explatned with the curuent Onchosim paranxeterisation, or whether a new parameterisqtion is needed, 3) do a careful check of all individual records, and (maybe) 4) have a look at the possible development of ivermectin res is t anc e. (D, E, F, G) Faleme, Bafing, Bakoye, Baoule. These are very similar basins located across the borders between Mali, Senegal, and Guinea in the western extension area. The Faleme is a very complex river system with many tributaries. Vector control was planned for this area based on data collected in the 60's and 70's that indicated high endemicity. The whole area was badly affected by drought in the 70's and 80's. Subsequently, in epidemiological surveys carried out before the start of the western extension (when ivermectin was not yet available) an endemicity much lower than expected was found, and especially the blinding form disappeared from the north of the area. Annual ivermectin treatment was introduced in these four basins in 1989. Studies done in 2000, using DNA probe identification of parasites, found 21% O. volvulus savannah strain in the Falema basin, no O. volvulas savannah strain in the Bafing basin, l2o/o in the Bakoye basin, and 39o/o in the Baoule basin. These are all mostly meso-endemic foci, with pre-control prevalences around 60% (range l0- 80%) and CMFL values around 10 mf/s, with a small number of villages with higher values up to 60 mf/s on the Bafing, Bakoye, and Baoule. Epidemiological indicators show very favourable trends in all areas, with CMFL reaching values near zero in 2001 and prevalences coming down under l0%. Entomological data is only available for a short period between 1985 and 1990, with the exception of one capture point on the Bafing for which there is data up to 2000. ABR with values around 10000 was not very high, although there were a few places with values up to 50000. Now the period of drought is over, the entomological parameters may resemble those of the 60's and 70's. Therapeutic coverage was good with values about 80%. Geographical coverage, however, may not have been very good because these are areas far from urban centres with bad roads that make communication and treatment difficult. 4 From the point of view of morbidity control the whole area lool<s very good, and onchocerciasrs rs no longer a public health problem. The latest epidemtological results are similar to those for the Gambia basin in spite of the different treatment interval (annual vs 6-monthly). The lack of recent entomological data makes it impossible to state whether transmtssion has been interuupted. Stopping ivermecttn distribution is, however, not indtcatedfor the moment because prevalences are still close to 10% in some villages. Recommended further activities are I) construct good maps of geographic coverage, and 2) perform a special entomological study on transmisston in a site that has a pre-control endemicity and a curuent situation comparable to Gambia. (Cameroon) Vina Valley. This is the only basin outside OCP that is discussed in this report. It runs from the east to the west in the centre of Cameroon in a sudano savannah region close to the borders with Chad and the Central African Republic. The area along the river Vina is very isolated. The villages are all on the main road, which runs from east to west, roughly parallel to the river. Where the road approaches the river closely, there is a yery high hyperendemicity, with CMFL's in excess of 200 or 300 mf/s. About 50% of the adult population have eye lesions. Pre-control ABR increased from 24250 at the upstream part of the river (Mbeing) to 47450 downstream at Touboro. Pre-control ATP also increased in the downstream direction from 1055 at Mbeing to 4190 at Touboro. Just over % to about 3h of the infective larvae were O. volvulus. The Centre Pasteur started annual ivermectin treatment in 1987 in the most eastern part of the area. This area was expanded twice in 1988 to cover the whole basin. Since 1995 all north Cameroon is treated with ivermectin. The area is now part of APOC. Factors that have to be taken into account when interpreting the results are l) that there are herdsmen migrating into the country from the north with their cattle, and 2) that from 1985 on the area was invaded by refugees from Chad, who settled close to the river and were thus subjected to high infection rates. Prevalence dropped from 80% in 198711988 to just over 20Yo in 199611997, after 10 years of ivermectin treatment. CMFL dropped from just below 50 mf/s in 198711988 to values very near zero in 199611997. ABR's were quite variable over the years with values between 10000 to 70000 in the period 1987-2001. Crude ATP was also quite variable and remained on a fairly high level (range 1030-2171). ATP due to O. volvulus. however, dropped from l22l in 1987 to values between 504 and 29,wh1le ATP due to O. ochengiremained on roughly the same but quite variable level around 600 with high peaks in 1996-1998 (1529) and in 2000 (1416). Herdsmen moving around the area might explain the variability in ATP due to O. ochengi. Geographic coverage was very high because all villages are on the main road. Therapeutic coverage was not so good, varying from 42%o to 760/o in one evaluated village along the river. No coverage data is available after 1994, but it is likely that values have remained approximately the same. The main conclusion is that there was a signtficant decrease in transmission due to 12 years of ivermectin treatment but certainly no interruption. Recommendations made for further actions to be taken for this basin include a continuation of fly-catching for the next one or two years, and an effort to get more detailed treatment coverage data. Area that had ivermectin treatment after vector control (N) Bougouriba. The Bougouriba is a tributary of the Black Volta river, and is located in the south-western part of Burkina Faso, just on the border with Ghana. It is in the Sudano-Guinean 5 savannah zone with forest galleries. The area has non-permanent medium sized rivers. The savannah vector species is predominant. The pre-control sifuation before 1974 was very highly endemic, with an ABR of more than 6000, an ATP > 600, a prevalence of 83.7% (at Mouvielo), and a blindness rate of ll.6%. There was regular larviciding done on the main river and on important tributaries during the period 1975-1990. On some tributaries, and in particular on the Naimo, larviciding stopped in 1987. There was a complete cessation of larviciding in 1990, when the usual evaluation sites indicated good results or good trends in the previous two years. In the period I976-1991, there was an organised installation of populations in the basin by the govemment, in particular in the Naimo area. These migrants modified the environment and thereby created new artificial breeding sites. At the time when it was decided to stop larviciding, this new situation was not known. Prevalence went down from around 80% in 1975 to low, but still not zero values in 1990. CMFL went down from very high values in some villages (> 90 mf/s) to values close to zero in 1990. In 1992, post-control entomological data tumed out not satisfactory at Batie on the Bambassou river, a tributary of the Black Volta, very close to the Bougouriba.ln 1994, newly infected children were found with an incidence > 1.8o/o in some villages. In 1996, after this bad situation had been discovered, large scale ivermectin treatment was started in the Bougouriba basin for the purpose of recrudescence control. A 4-monthly treatment schedule was adopted. Therapeutic coverage was quite good (70-80%). Geographic coverage left much to be desired because it is not exactly known how many villages are to be treated, and, because after an initial strong effort to get a good coverage, the number of villages treated dropped from around 180 to values below 100 after 1998. Some ground larviciding was done to protect the population of a village on the Naimo, at the breeding sites created by this population. After cessation of vector control in 1990, ABR rose to very high levels ranging from 30000 to 70000, and ATP rose to over 400 in one catching site in 1998. Because of the frequent ivermectin treatment schedule, very little epidemiological follow-up is available after 1996. Prevalence rose to values around 20oh in some villages in 1996, but, in the few villages for which data is available, it was below 10% in 2000. CMFL remained near zero in all but a few newly included villages. There are some pool screening results from 2000 based on a limited number of flies caught by the local population. These rather uncertain results indicate that the situation is improving. This is a very problematic area in which post-vector control recrudescence is going on, which went much faster than was anticipated from model simulations. Top priority here is to gather more entomological data on large numbers of Jlies to determine whether or not transmission has been interrupted. Also, there has to be a much better understanding of the geographical coverage, preferably in theform of a map. Areas that had ivermectin and vector control in parallel (H) Tienfala. This is a highly endemic area, situated in southern Mali on the river Niger, just on the border of the original Programme e area in Mali and the western extension. Aerial larviciding started in 1977 in the dry season, but was suspended in the rainy season because of very high river discharges. No larviciding was done from 1911 until1985, and from 1986 until 6 1993 aerial and ground treatment were used, but there were also periods in which treatment was suspended. From 1994up to now only ground larviciding was used. Because of the huge size of the complex of breeding sites vector control is extremely difficult here, and the objective of larviciding was more to protect the people on the riverbanks against nuisance. Ivermectin treatment started in 1987. This was also an area of extensive nodulectomy that was stopped in 1988. The trend in prevalence was very good with pre-ivermectin control levels varying from l0% to 80% to values below L)o/o in 2000. The trend in CMFL is similarly good, with pre-control levels going down from 30-70 mf/s to near zero values reached around 1995. ABR was generally high and very variable (range from 0 to > 70000). ATP was below 1000 with a few exceptional years with higher values. The percentage of O. volvulus strain varied considerably between sites (5% to 32%) as determined in 2001, and, correspondingly, the ATP involving only O. volvulus was very low and in accordance with the epidemiological data. Therapeutic coverage rose from 60%in 1988 to 80% in 1998. The dramatic decline in parasite loads in this holo-endemic focus is illustrative of very good morbtdity control. It is unclear what the relative contributions of vector control and tvermectin distribution have been. But as the pattern of decline in epidemiological parameters was similar to that observed in basins were only iverntectin distribution was used, and as the main part of the improvement seems to have occurred after the introduction of ivermectin treatment, it seems plausible that the contributton of ivermectin was most important. Aside from this, it should be noted that there might have been an tmportant contribution of nodulectomy. (I) Bui Gorge. This area is located in Ghana on the lower Black Volta. The limit of the focus is not clearly defined to the south. Most of the flies in this area are savannah flies. Aerial treatment started in 1975 and stopped on 3l December 1996, after 22 years. Annual ivermectin treatment started in 1987. Prevalence went down from around 60% in 1980 to values around 10-20% in 1997-2001. First CMFL values available were from 1980 and were not extremely high (range 5-25 mf/s), indicating that 5 years of larviciding might have had an effect. ABR was very variable and decreased from values in the range 10000-20000 in 1975 to rather low values in the period 1980-1985 and then increased again to be in the range 10000-20000 in 1996 with an occasional extremely high value (> 50000). Crude ATP declined from values around 1000 in 1975 to low values in 1996 (around 100). Therapeutic coverage increased from 50% in 1987 to > 80% in 1997 . Many factors complicate the interpretation of these findings. In the first place, this area is the largest non-stop breeding site in the program. There is a continuous string of breeding sites from Tagadi in the north to Tain-Aboi in the south, and, consequently, this is a very difficult area to control. Then, there has been some nodulectomy done in a few places, but this does not seem to have had much effect. There is also evidence of human migration to and from the south and south-east. There has been some effect of larviciding, but 22 years of vector control has not brought transmtssion under control. Ivermectin distribution has improved the epidemiologtcal parameters but has also not interrupted transmission. (J) Titira / Koupergou. This is a meso- to hyperendemic area located in the eastern part of the program in Togo. The core area consists of the Oti, Keran, Kara, and Mo river basins. It is a mountainous area with many huge breeding sites in the rainy season. Most of the flies are of the 7 savannah species. Thousands of golddiggers migrate during the dry season from Ghana, Togo, Benin, and Nigeria to the Keran. There are also possible migrants from the south of Togo. Larviciding started in 1977, but results were poor until in 1987 larviciding in the south was started. Aerial treatment was suspended from 1993 until 1996 on the Oti, Keran and Kara rivers. Annual ivermectin distribution started in 1988. Prevalence came down from very high values (between 50o/o and 90%) in 1977 to still high values (range: 0-50%) in 2000. CMFL has declined substantially from values around 30 mf/s to very low values, but is in some places not yet zero. ABR has risen considerably in recent years to values around 15000, but this observation was based on data from two capture points only, that had high values throughout the whole period. Crude ATP came down from values around 1000 in some villages to much lower values, but remained still above 100. Only in the last two years there may be an improvement in ATP. It is unclear as to what extend this improvement is attributable to vector control or to ivermectin treatment. Therapeutic coverage was reported to be good (80%) with equally high geographic coverage (96%), but it was noted that this evaluation was made only in static.villages and did not include the migrants. Furthermore, distribution of ivermectin is very difficult in this mountainous area. This casts doubt whether geographic coverage is really good enough. It is clear that there is still a problem in this area. The entomological data suggests that there may be improvement in the last two years. The epidemiological data are far front satisfoctory, and there is still significant transmission going on. Recommended further activities are l) to perform a study of the various Jly populations using micro satellites and 2) to perform a study of the fficts of population ntovetnent with special reference to the impact of iverntectin on transmission. (K) Milo / Sankarani. The Milo and Sankarani basins are located in the eastem part of Guinea Conakry, and while the Milo is entirely within Guinea, a small part of the Sankarani extends to Cote d'Ivoire. The medium and lower parts of the basins are in the sudano-guinean zone. The lower parts are mountainous with more vegetation. Maximum discharge is reached in September/October. The human population is engaged in agro-pastoral activities, fishing, and mining activities (diamond and gold) the latter mainly during the dry season. These used to be hypo to hyperendemic areas with pre-control prevalence ranging from 4.4Yo to 88.1%o in villages evaluated from 1985 to 1987. There is much migration of flies in these basins. In the lower Milo basin there is a predominance of savannah vectors throughout the year, in the medium part there is a predominance of savannah vectors in the dry season and of forest vectors in the rainy season, and in the upper part forest vectors are predominant throughout the year. In the lower part of the Sankarani basin there is a predominance of savannah vectors throughout the year, while in the medium and upper parts savannah vectors predominate during the dry season, and forest vectors during the rainy season. In the Milo basin, anti-reinvasion and experimental larviciding was done in 1987 and 1988. Full-scale larviciding started in 1989, as was large-scale ivermectin treatment. In the Sankarani basin anti-reinvasion and experimental larviciding was done from 1984 until 1988. In 1989, full-scale larviciding and ivermectin treatment was started. The proportions of parasite strains in infective flies from 1993 to 2000 on the Milo were 52o/o O. volvulus savannah, 14% O. volvulus forest, and32o/o non-O. volvulus (35 infective flies). On the Sankarani, these proportions were 47%o O. volvulus savannah, ll% O. volvulus forest, and 42o/o non-O. volvulus (36 infective flies). Prevalence went down from very high values around 80% in 1985 to values < l0o/o but not yet zero in 2001. There was an enorrnous pre-control heterogeneity in CMFL values ranging from < 10 mf/s to 70 mf/s. CMFL went down to values very near zero from 1993 onwards. ABR was 8 very high (around 10000 in 1985) and increased to around 20000 in 2000, with extremely high values (> 50000) occurring in some villages. These high values may be the result of reinvasion or of treatment failures. The rise in ABR may be partially explained by the suspension of larviciding in the northern part of the OCP program. ATP values were more favourable, and went down from values between 100 and 2000 in 1984 to below 100 in 2000. Therapeutic coverage went down from 75o/o in 1989 to around 20oh in 1997, which can be explained by the fact that only positives were treated. There seems to be no information on geographical coverage. There are good trends in the epidemiological data in these basins. The entomological data seems consistent with this, despite the high ABR's in some places. The only logical conclusiott seen$ to be that this is the result of the additional ffict of ivermectin treatment. It is recontmended as a further action to stop vector control in a good basin in 2002 and implement very good monttoring. This will allow OCP to test whether the strategy of 12 years of combined vector control and ivermectin treutment is tndeed sufJicient to eliminate the risk of transmission. (L) Asubende. This is a hyperendemic focus located in the eastern part of the southern extension on the Pru river in Ghana. There is a continuous string of breeding sites along the river with the village Asubende in the centre. Larviciding started in the southern extension in 1988. On the Pru in 1988 and 1989, it was suspended in the rainy season, because of xenodiagnostic studies and because of studies of the impact of ivermectin on transmission. From 1990 until now the lower part of the Pru river was normally treated. From 1994 until 2000 almost all flies caught were of the savannah strain. Very few flies were forest flies (<1%). In the period January 1993 until December 2000 the proportions of flies infected with the various parasite strains were: 48% O. volvulus savannah, 20% O. volvulus forest, and 32oh non O. volvulus. Annual ivermectin treatment was started in 1987. There were favourable trends in the epidemiological data. Prevalence went down from > 90oh in 1987 to 20-35o/o in 1997. CMFL declined from very high values around 75 mf/s to very low but not yet zero values in 1997. The ABR was very variable over the years with maximum values above 40000 in 1978 and 1999, and minimum values around 500 in 1986 and in the period 199l-1994. ATP dropped from values above 3000 in 1978 to values around 200 in about 1991, and remained at that level until 2000. Therapeutic coverage was high (> 80% in 1977). Geographic coverage was good. A new recent evaluation resulted in a therapeutic coverage of 760/o, and a geographic coverage of 80%. It is not clear what happened in this area. Entomological studies indicated that there was little impact from vectors coming from outside. There is some evidence of people from outside coming to this area, but it is not known where these people come from. An important point is how effective vector control has been here. At the moment, the biting rate is similar to pre- control values. There are therefore quite some vectors around. The entomological data clearly indicate that there is still significant transmission gotng on. It is therefore impossible to stop ivermectin treatment. The parasite population and prevalence are declining nicely but slowly, and this is probably consistent with significant transmission in addition to treatment. It is dfficult to determine what effect ivermectin has on transmission. (M) Dienkoa. This is a quite limited but severely affected focus, located in the south-western part of Burkina Faso near the border with Mali. It is on the upper part of the Black Volta river 9 and in the sudano-guinean zone with perennial mcdium sized rivers and savannah vector species. The area is very fertile and characterised by intensive migration and numerous hamlets. Before control started, it was a hyperendemic focus with an ABR of more than 9000, an ATP of 1200, a prevalence of 68% (Pendie), a rather low CMFL of 13.9 mf/s, and a blindness rate of 2.8%. Larviciding started in L916. There were difficulties in selecting good catching sites representative of the epidemiological situation. The regularly visited sites were changed with time and the network was restructured in 1978/1979. New good sites were selected in 1985, 1986 and 1988, and three of these were regularly visited from 1986 onwards. From 1979 to 1989, larviciding was very difficult, and was done irregularly. This resulted in a resumption of transmission and the detection of a number of newly infected children in 1983 and 1985. No larviciding was done in the period 1987-1988 because of studies on the impact of ivermectin on transmission. Ivermectin distribution started in 1988 with mobile treatment, and was switched to CBTI in 1996, and finally to CDTL Systematic and widespread ground larviciding was started in 1990, because of the poor results and new infections found, and because some catching points indicated that transmission was still going on. Better epidemiological results were obtained from 1994 up to now. Over the whole period, prevalence went down from high values in 1975 (around 60%) to values near zero in 2000. CMFL ranged from less than l0 mf/s to just over 30 mf/s at the start, and went down to values near zero around 1993, after which this level was maintained. ABR went down after the start of the Programme in 1974 from values around 2000-4000 to quite low levels, with a sudden increase in 1986 when larviciding was stopped. When vector control was resumed it went down again, but in some places problems with high values remained. ATP followed the same pattern, and was generally low during the period of vector control, but with a recent small rise in one village. Geographic coverage was very poor at the start of ivermectin treatment (about 5 villages treated) but gradually improved until it was over 60 treated villages from 1997 on, but with a serious relapse in 2000 (31 villages). Therapeutic coverage was 50% at the start in 1988 and rose to 85o/o in 2000. The situation in this basin is very complex, involving many factors outside vector control and iverntectin treatment. It is therefore not particularly well suited to answer the main questions posed in this report. With all the changes tn catching sites, poor geographical coverage, migration, and so on, the impact of ivermecttn on transmission is very dfficult to ascertain. r0 Conclusions The main results in the l5 study areas are given in Table 1, where for each basin the impact of ivermectin on four aspects of the disease problem have been summarised. The first of these aspects is its impact on the intensity of infection as measured by the Community Microfilarial Load (CMFL). The CMFL is an index of the public health importance of the disease, and onchocerciasis is considered a public health problem when the CMFL exceeds 5-10 mf/s. The second is its impact on prevalence of infection. The third aspect concerns whether or not ivermectin distribution has intemrpted transmission. The fourth and last aspect is whether elimination of the parasite has been achieved to the extent that control can be stopped without risking renewed transmission. All evidence from these study areas clearly shows that ivermectin treatment has been everywhere extremely successful in controlling onchocerciasis as a public health problem. CMFL values are everywhere zero or very near zero, and prevalence of infection is generally quite low. The difficult questions are coming up when intemrption of transmission is considered. There are some areas where it is certain that transmission is still going on after 10-12 years of ivermectin treatment. There are also a few areas where transmission may have been intemrpted, but there are still many uncertainties, and further monitoring and research is required to remove all doubt. There is also an important step from the third to the fourth column of Table 1, because stopping ivermectin distribution when low levels of infection, and low but not yet zero prevalences are attained may result in very serious problems. This is illustrated by the results from the Rio Corubal area where the latest data show a serious and unexpected recrudescence. So, even if intemtption of transmission has been achieved for some time, if the parasite reservoir is not entirely eliminated, it is a big question whether ivermectin treatment can really be stopped. A final point is noted regarding the frequency of ivermectin distribution. As far as elimination of onchocerciasis as a public health problem is concerned, annual treatment has done it and there is no need for shorter treatment intervals. The question was raised whether annual treatment should continue or that less frequent schedules should be considered, because when intemrption turns out to be impossible, treatment should be maintained for a long time. However, implementing other treatment schedules, and especially less frequent ones, may have important operational consequences as well as implications for the development of ivermectin resistance. This should be further investigated, e.g. by incorporating ivermectin resistance in the simulation models. 11 Table 1: Impact of ivermectin distribution on four aspects of onchocerciasis infection and transmission. River Basin Intervention strategy Impact of ivermectin treatment (Status in 2001) CMFL rc 0 (PH problem eliminated) Prevalence of infcction very low (< 107.) Transmission interrupted (R, ongoing) Elimination (control ceascd) Ivermectin only: R. Gambia (A) Ivm. 6-monthly since I 989 ? R. Corubal (B) (up to 1996) Ivm. 3-monthly l99l- t996 , R. Corubal(B) (from 1996 onwards) No ivm. treatment since 1996 ,, Increasing prevalence Transmission ongoing R. Geba (C) Ivm. 6-monthly since 1989 and no treatment since 1996 ,| , R. Faleme (D), R. Bafing (E), R. Bakoye (F), R. Baoule (G) Annual ivm. since 1989 , Vina Valley (Cameroon) Annual ivm. since 1 987 Prev. mf =20%o in 1999 Transmission ongoing Ivermectin treatment after vector control: Bougouriba (N) Ivm. 4-monthly sincet996 Transmission ongolng lvermectin + vector control: Tienfala (H) Annual ivm. since 1987, and (ground) larv. since 1977 ,, BuiGorge (I) Annual ivm. since 1987 (3-monthly from 1994-1996), and larv. from 1975-1996 Prev. mf up to 55% in I 998 , Titira / Koupergou (J) Ivm. annual since 1988, and larv. since t977 Prev. mf up ro 50% in l 998 Transmission ongoing Milo / Sankarani (K) Annual ivm. since I989, and larv. since r 989 Asubende (L) Annual ivm. since 1987, and larv. since r990 Transmission ongoing Dienkoa (M) Ivm. since 1988, and larv. since 1976 (with intemlptions) t2 Annex I Figure 1: Location of the 14 study areas orubal (B (E) ba Gurnga Legend: ..\ i i..._.) G_u rh da 500 Burkrna Faso Ortgtnal Ptogtam Area Tltlra/Ko u p Ghana BulGorg 'irl '.1 Foiesl Exlenston nkarani (K)(' Srerr_a Leonc o ,sto IV oast 0 250 kilometers Study Area -t;--'. . ----r OCP Boundary (original and western, southern,t-----l and forest extension boundaries) ffi NationalBoundary Sene0al R..Ga Ilil ako !: Nrgcr(D) la (H) D lenkoa bal' i lc)---,r Baou le 13 jI .! Annex 2 List of participants. Chair EAC Chair TCC: Erasmus University Rotterdam: Imperial College UK IRD: University of Ttibingen WHO/AFRO: WHO/CPE : WHO/OCP WHO/TDR World Bank Mectizan Donation Programme (MDP): Dr Mary Alleman OEPA (Ecuador): Dr Tamara Mancero Prof Abiose Adenike Prof M. Homeida Gerard J.J.M. Borsboom (rapporteur) Prof J. Dik F. Habbema Dr Nico J.D. Nagelkerke Dr Gerrit J. van Oortmarssen (rapporteur) Dr Maria-Gloria Bas6frez Dr Jean-Marc Hougard, IRD/Montpellier Dr Bernard Philippon, IRD/Paris Dr Alfons Renz Dr E.W. Soumbey Alley (rapporteur) Dr Marc Karam Dr Hyacinthe Agoua Dr L.K.B. Akpoboua (rapporteur) Dr Yiriba Bissan Dr Boakye A. Boatin Dr Laurent Yameogo Dr Hans Remme Dr Bernard Liese l4