Progress report by unit: March to August 2002

t{ WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE ONCHOCERCIASIS CONTROL PROGRAMME IN WEST AFRICA PROGRAMME DE LUTTE CONTRE L'ONCHOCERCOSE EN AFRIQUE DE L'OUEST EXPERT ADVISORY COMMITTEE Twenty-third Session Ouagadougou. 23 - 27 September 2002 EAC23.1 Original :French PROGRESS REPORT BY UNIT (March to August 2002) Part I = Part 2 = Part 3 = Vector Control Planning, Evaluation and Transfer Adminis tration and support serttices Page2toll Page l2 to 26 Page 27 to 29 t T a2 PART 1 VECTOR CONTROL 3SALIBNT POINTS OF VECTOR CONTROL ACTIVITIES IN 2OO2 HYDROLOGY AND AERIAL OPERATIONS 1. Hydrology Rainfall was not homogeneous in the rvhole of the Programme area in 2002.In the Eastern zone, the rains were early this year compared to last year. Thus, the quantities of rains recorded in March and May are higher than those of the same months of 2001. From January to May, only February had no rains. In the Western Zone, a delay was observed in the resumption of the rains. This delay affected florvs during April and May 2002 in the majority of the basins except for the Niandan basin which had rains in time. In almost the whole of the river basins of the Western Zone, the fall in the water level of the hydrological year (2001-2002), compared with that of 2000-2001, was less marked until the fifteenth week of 2002, due to the positive hydrous results of the last season. This year, due to the reduction in the larvicide coverage the hydrometric network was also reduced by almost 28yo.It is now composed of 8l limnimetric stations 34 of which are equipped with beacons. 2. Aerial contract and flights hours The year 2002 marks the end of the last four-year contract signed with the Evergreen Helicopter Company (EHI). In view of the activities to be carried out in 2002 following the suspension of aerial larviciding in several basins in the Programme area, the air fleet was reduced from five to three helicopters, and from 3001.6 guaranteed hours to 1999.2 hours. Like the previous years, the concerted management of flight hours in 2001 in the two Zones made it possible to limit the expenditure in flight hours to the guaranteed hours envisaged for this pulpose; thus of a total of 3001.6 hours guaranteed to the company,3001.7 hours were ictually used for the treatments. The maintenance of the helicopters was satisfactory in 2OOl. Engine failures reduced from 30 to 22% compared to the total breakdowns, and radio breakdowns from l0 to 6Yo. No breakdown of batteries was noted. In spite of this good perforrnance, particular attention must be given to the spraying system of and the pumps for kerosene and insecticide whose breakdowns are on a considerable increaieithese breakdowns have increased from 7 to 25oh for the spraying systems and 0 to 28%o for the insecticide and kerosene pumps. The situation seemed to be well controlled for the first semester of 2002 as only two breakdowns were noted. 3. Use of the larvicides For the same larvicide coverage area, insecticide consumption in 2001 reduced by 6% compared to that of 2000. It must also be noted that the biological insecticides were favoured during the Lrvicide treatments.Thistendencycontinuedin2002; thequantityof B.t H-14usedaccounts forg6yoof the overall larvicide consumption during the first half of the year. 44. Product Losses The sustained effort of the VCU teams, the populations and the administrative authorities in the management of the kerosene and insecticide depots made it possible to reduce considerably the losses of products, thus passing from2,4o/o loss of total stock in 2000 to l.5oh in 2001. These results could have been much better this year, had it not been the loss of products caused by the poor quality of packing and/or covers of the barrels (pyraclofos, phoxim, etofenprox, permethrine), and the ageing of stocks (carbosulfan). On the whole thefts, leakage and contamination cost the Prograrlme, US$69 582 in 2001, against US$134 890 in 2000; that is, a reduction of US$65 308 (48.5%). No kerosene and insecticide loss was recorded in the Programme area from January to June 2002. RESULTS OF THE ENTOMOLOGICAL EVALUATION A) WESTERN ZONE The results from January to June 2002, compared with those of the same period of 2001, show a certain upward trend of the partial annual transmission potentials. However for the moment, the highest value of transmission of O. volvulus is 66 and relates to Fifa where nearly 70%o of the parasites found are different from O. volvulus. The Middle Niger in Mali: The ground larviciding as well as the distribution of the ivermectin will continue in this basin until the end of December 2002. Animal filaria occupy a significant place (84%) in the transmission and generally mask the downward trends of the ATPs in this basin. Nevertheless, the first half of 2002 is marked by the absence of infection on the Faya and the Dylamba. At Tienfala, the partial ATP is 16 both for the transmission of O. volvulus and that of all the parasites. The Sassandra in COte d'Ivoire and in Guinea Conakry Larviciding was definitively stopped at the end of December 2001 on the Upper Sassandra in C6te d'Ivoire. The reduction of the crude ATP there was higher than 95 % in 2001 on the five monitoring points. Trends have been on the decline since 1991 and the savana ATPs lower than 100 since 1993 (except at Vialadougou where this ATP was 147 in 2000). This exceptional transmission was only a false alarm as no infected female was recorded there in 2001 (crude ATP : 0). Larviciding was stopped on December 31, 2001 on the Upper Sassandra in Guinea Conakry. The reduction of the crude ATP there varied between 89 and 100 % on the Upper Bafing and Upper Bagb6. The savana ATP has remained lower than 100 since 1993 on all the five entomological monitoring points (savana ATP: 0 on all the capturing points in 2001). 1 2. 53 Sankarani and Milo in Guinea Conakry In the basins of Sankarani and Milo, the reduction of the crude ATPs varied from 78 to 100 o/o onall the thirteen (13) entomological monitoring points. Transmission has been dropping steadily since 1990 and savana ATPs have been lower than 100 since 1993. No transmission of O. volvulus was recorded in 2001 on all the capturing points of the basins of Sankarani and Milo. Larviciding was stopped here on December 31,2001. Niandan in Guinea Conakry Larviciding is being maintained in this basin until the end of December2002 due to its role as a barrier between the untreated zone and that still under treatment. The reduction of the crude ATPs varied between 97 and 100% in 2001. The savana ATPs have remained lower than 100 on all the seven (7) monitoring points since 1993. In 2001 , only the capturing point of Sansambaya presented savana ATPs reaching 28. Upper Niger-Mafou in Guinea Conakry Larviciding will continue in this basin until the end of December 2002. The reduction of the crude ATPs varied between 87 and 100 % and the trends have been on the decline since the beginning of the combined treatments of larviciding and ivermectin in 1989 (except in Balandougou, Ser6koroba and Yalawa). The resumption of the transmission on the Mafou since 1996 is due mainly to forest flies (savana ATP lower than 100). However, at Yalawa, savana ATP above 100 were observed in 1996 and 1997. The specific actions implemented made it possible to obtain good results with savana ATPs of 35 in 1999 and 2000. No transmission of O. volvulus was recorded in Yalawa in 2001. The partial ATP of O. volvulrzs is lower than 100 for first half of the year of 2002. Tinkisso in Guinea Conakry Larviciding and specific actions will continue in this basin until the end of Decemb er 2002. The trends of crude ATPs are falling, with a reduction from97 to 100 oh.The rise in the transmission since 1995 seems localised around Fifa where the savana ATP went up to 510 in 1998. The specific action implemented made it possible to again obtain good results in 1999. The ATP of O. volvulus by the savana species in 2001 was 2l in Lab6ro,42 in Konden, and 7l in Fifa. This year, the transmission was intense in the first six months with partial ATPs of 66 in Fifa and 63 in Lab6ro. It is zero for the moment in Konden. B) EASTERN ZONE In this zone, the excellent results recorded on the basins of Mono and Sio in Togo, and the tributaries of the Volta Lake in Ghana and Togo, both on the entomological level since the establishment of the extensions in February 1988 (ATP lower than 100 for nearly l0 years) and on the epidemiological level, made it possible for the final suspension of larviciding in these basins on December 31, 2001. The difficulties met relate especially to the basins of the Pru in Ghana and the tributaries of Oti in Togo and in Benin on which a particular stress is laid in this document. 4 5 6 61. Pru The captures started in 1978 while the larviciding and the distribution of the ivermectin started only rn 1988. We thus have l0 years of data of pre-control on this basin. The black fly population is made up almost exclusively of savana species of S. dantnosut?l. A very intense transmission (ATP:3330) was recorded in 1978. The identification by DNA probe of the parasites collected from January 1993 to December 2000 showed that 2Oo/o of these parasites are forest O.volvulus ;48% of savana O.volvultts and32o/o of other parasites. Larviciding was suspended from the 33'd week in 1988 and 1989 for studies of xenodiagnosis and the impact of the ivermectin on the transmission. From 1990, lower Pru was treated up to 2002 with the ,.u.n OCP larvicides used in rotation. In the dry season ground larviciding is implemented. The reinforcement of prospecting teams and ground larviciding allowed for a suspension of the aerial larviciding for 26 weeks in 2002 against 13 for the same period of 2000 and 2001 . Although having decreased to a significant degree, the annual transmission potential oscillates around the tolerance level of 100, more precisely between 63 and 189 from 1997 to 2001. The situation basically did not improve in spite of the stringent measures put in place in 1996 / 1997 (extension of the larviciding coverage, accompaniment of the pilots, increased monitoring of the tributaries, intensification of the prospecting and ground larviciding). The corrected ATP from January to December 2001 is 140. For the first six months of 2002, the ATP for O. volvulus is seven' 2. Tributaries of Oti (Kara-K6ran-M6) Captures have been going on since 1976 in 07 points on K6ran, 04 points on Kara, and in 06 points on M6. The vector species seen from January 1994 to July 1997 are primarily: - on K6ran - Kara -M6 98 o% savana,02 o/o forest 84 o/o savana, 16 %o forest 52 o/o savana, 48 o/o forest The transmission there is due mainly (92%) to the savana females and 8 oh to the forest females. The identification by DNA probes of the parasites collected on K6ran, Kara, MO from January 1993 to July 1997 indicates that approximately 72o/o of the larvae are O. volvulus (ll % of forest O. volvulus and 6lYo of savana O. volvulus) and the remaining 28 o/o are not O volvulus o K6ran, Kara, M6 (tributaries of Oti) have been regularly treated by air since 1977 to date. In 1993, the larviciding which also started in 1977 on Oti (main river) was suspended following the good entomological and epidemiological results recorded. The suspension also concerned the lower K6ran and the lower Kara. o In 1997, following the poor entomological results recorded in May - June, special measures were taken to increase the effectiveness of control operations. These actions consisted primarily of : i) intensification of the ground larviciding in support of air treatments; ii) increase in the larvicide coverage by the inclusion of the lower K6ran and lower Kara and their confluence with Oti. iii) treating the main Oti before the increase in water level for four to six weeks. iv) reinforcing the treatments of Upper Ou6m6 which could be the source of the blackflies re-colonising the upper K6ran and the Kara. , 7The analysis of the entomological results shows that the annual transmission potential on these rivers started reducing significantly only from 1988, date at which larviciding began in the south-eastern extension. Beside the exceptionally high transmission recorded in 1997, the situation on these river basins is as follows: - on the lower K6ran, the crude ATPs which was around 1500 before the beginning of the operations were reduced by almost 90%o and even more if one takes into account the results of these last two years where the transmission is below the tolerance level (77 and 7 in 2000 at the tri'o catching points (Titira and Tapounde), which were the most affected, and 72 and 28 in 2001). The partial crude ATPs for the first six months of 2002 are 14 at Titira and 40 at Tapound6, thus by far lower than the tolerance level; - on Kara and M6, the situation in terms of transmission of the human onchocerciasis is well controlled since 1994 with O. volvulus ATP of below the tolerance level. The blackfly densities during the first six months of 2002 were everywhere lower than those of the same period of the previous years. Nevertheless on the M6, an increase in population was recorded during the last weeks of May and June. Generally, even if the entomological results improved on the Pru and the tributaries of Oti compared to that which prevailed before the beginning of the operations, the current situation of the transmission on M6 which is to be seen in relation with the cessation of larviciding of the eastern tributaries of Lake Volta requires great caution. It is therefore important to maintain the pressure for a few more years to ensure the elimination of the parasite reservoir in these zones and thus avoid a premafure resurgence of the disease. Ou6m6/0kpara The situation is satisfactory on the upper Ou6m6 with an annual transmission potential below the tolerance level at all the points visited. On the other hand on the lower Ou6m6, even if the situation is satisfactory in Atcherigb6 and Aguigadji with ATP below the tolerance level, the O. volvulus ATP remains higher than 100 in Mb6t6koukou. The same situation prevails in Kaboua and Djabata. OPERATIONAL RESEARCH Blackfly Movements and identification of vectors and parasites Generally, the data collected during 200112002 are of a particular importance as they mark the end of activities undertaken relentlessly for three decades, and emphasise the main trends to be considered for a suitable planning of the operations necessary for the maintenance of the achievements of the Programme. Within the framework of the actions initiated by VCU for a detailed analysis of these trends, a particular accent was put on the study of blackfly movements, a phenomenon which could, in some cases, compromise the effectiveness of the activities for the maintenance of the achievements, particularly in the river basins harbouring alternatively balckfly populations of various origins. This refers in fact to the basins of the zone of transition forest-savana characterised by the presence of savana species of S. damnosum s.l. some of which are involved in migratory movements from the 3 I 8south-west towards the north-east at the beginning of the raining season and in the opposite direction at the beginning of dry season. Due to the seasonal nature and the magnitude of these movements, it is important to stress that not all the foci concerned benefited from the activities of the Programme for the length of time necessary for the stop of the transmission. Even if such a situation relates only to Sierra Leone, it could be alarming insofaias the research undertaken in 1988/1989 on re-invasion showed that the North of this country is regularly affected by the blackfly migrations as evoked above. Besides, these observations are in agreement with the data recently recorded within the framework of special studies mainly based on the cytotaxonomic and molecular biology (microsatellites) techniques oi identification. In iact, these studies, still in progress, show that the S. sirbanum populations are actually implied in the great movements covering the river basins of Mali and Guinea. These migrant populalioni of S. sirbaium could well come from non decontaminated areas of the North of Sierra L.br., due to the proximity of this foci, and its geographic position in relation to those of Guinea and Mali (South-westA{ord-east axis). To verify this assumption, of many samples collected in 2002, simultaneously in the river basins of North Sierra Leone (Seli and Kabi-Mongo of Guinea (upper Niger/Iv1afou, Milo and Niandan) and of Mali (Baoule) are currently being analysed by the DNA laboratory of O-CP in collaboration with the IRD of Monfpellier. The iarvae samples will also be analysed in collaboration with a specialist in cytotaxonomy from the "Noguchi Memorial Institute for Medical Research " in Accra. Similarly, the infectivity of flies in the north of Sierra Leone between December 2001 and June 2002 were compared with that which prevailed there in 1996. Only six (6) infectious females were captured in Yirafilaia and Kaba Ferry. The identifications carried out by the DNA probes indicated five females carrying savana O volvulus and one female infected by larvae of animal origin. In 1996, at the same period record was made of 22 infectious females at the points of Musaia, Yirafilaia and Arfanya. No infectious fly was found at the time of the study 2002 at points Musaia and Arfanya. Samples collection in connection with the blackfly movement study are also in progress in the Eastern Zone. The analyses of these samples will undoubtedly make it possible to appreciate the magnitude of the blackfly movements on the iouth-west/north-east axis covering the basins of Pru in Ghana, the tributaries of Oti in Togo and those of the Niger in Benin. For these studies and for routine entomological evaluation, the molecular biology laboratory continued to ensure the identification of the parasites collected by the entomological network to enable the correction of the transmission parameters. The infecting larvae of 291 infectious females collected in the zones under larviciding, were thus identified during the 2000-2001 entomological year. The females carrying parasites of animal origin accounted for 7\Yo. The zones having a high rate of human parasites are the special intervention zones. The partial results obtained up to June 2002 is identical to what was observed for the previous period. A particular stress was laid on the treatment of the infections coming from the specific intervention zones. The identification of parasites also related to parasites coming from the APOC countries. 2. Follow-up of blackfly sensitivity to insecticides Due to the strict application of the restrictive measures recommended for optimum results of the insecticide rotation strategy, the risks of appearance or intensification of resistance to organo- phosphorus are considerably minimised at this period of end of the Programme. In addition to the tests carried out within the framework of the routine monitoring, this period is also marked by the continuation of the investigations initiated in 1999-2000 to evaluate the sensitivity of the blackfly 9populations in the river basins where vector control activities were stopped after several years of intensive larvicide treatments. In the Western Zone, these investigations showed that on the majority of the rivers no longer under larviciding for at least five years, the sensitivity of the blackfly populations has been generally normal to temephos and phoxim, and intermediary to pyraclofos. The weakest level of sensitivity were observed at Markala-barrier on the Niger (NN300) where resistance to the pyraclofos became obvious. Concerning the basins on which the treatments were recently stopped (Sankarani and Milo in Guinea), the larval populations show generally a normal sensitivity to phoxim and intermediary to the other trvo organo-phosphorus. Data collected on the rivers under larvicide treatment indicate a case of resistance to temephos on the Niandan in Bagou6 (ND500). The analysis of the results of cytotaxonomic identification revealed that the larvae having tolerated the strongest concentrations of temephos (1,25 and 2,5 ppm) belong primarily to the S. damnosum s.s. species (approximately 44 oh), whereas the lowest levels of sensitivity to pyraclofos are observed in the S. sirbanum which constitutes approximately 72o/o of the larvae living or dying at 0,078 ppm. It must be pointed out that among these less sensitive larvae appear a considerable proportion of S. damnosunt s.s. / ,S. sirbanum hybrids (respectively 26 % and 1 I o/o of the larvae having tolerated the strong amounts of temephos and pyraclofos) In the Eastern Zone, no case of resistance to organo-phosphorus was encountered during the last three years (2000,2001 and2002). The cytotaxonomic identifications seem to show the same trends as in Western Zone, i.e. the more or less pronounced sensitivity of the savana species (5. sirbanun and S. damnosunt s.s.) be it temephos or pyraclofos. 3. Transfer activities: training and recycling of the nationals Within the framework of operational research at VCU, the main activities undertaken during this last decade is intended to prepare for the post-OCP. In fact the technicians and the national teams are implicated more and more in the planning and/or the implementation of the entomological research activities. They also take part in special sessions of training, in order to improve individual performances and to reinforce the operational capacity of the countries which will be taking on entomological activities soon. Thus, since 1998, VCU research teams have ensured the training of national entomologists capable not only to plan and supervise the residual activities, but also to analyse the data collected, interpret the results and make the decisions essential for the maintenance of the achievements of onchocerciasis control. The training currently going on relates to the third generation of entomologists made up of l4 trainees from six OCP countries (Benin, Guinea, Mali, Niger, Sierra Leone and Togo), and of one APOC country (the DRC). This will change the total number of entomologists trained by the VCU research team to 37, including32 OCP countries as indicated in the table below. 10 National entomologists trained by OCP - Current Status Countrv Number of entomologists TOTALS (envisaged)1998 Bouak6 2001 Odienn6 2002 Odienn6 (in progress) Benin I 1 I 2 Burkina Faso 1 ., 0 3 Cdte d'Ivoire I I 0 2 Ghana ) I 0 3 Guinea 1 0 ) 1 Guinea -Bissau I I 0 7 Mali 1 0 ) I Niger I 0 I I Senegal I I 0 2 Sierra Leone I I ) ) Togo I 3 I 4 DRC (APOC) 0 0 5 5 TOTALS t2 11 t4 37 4 Collaboration with external institutions Within the framework of the blackfly migration studies, relationship was established with the department of parasitology of the "Noguchi Memorial Institute for Medical Research", Achimota, Ghana, for cytotaxonomic identification of vectors. For this same study, the OCP laboratory collaborated with that of the IRD (ex-ORSTOM) of Montpellier to carry out the identification of vectors by microsatellites. In the collaboration which continues this year, the role of the IRD consists primarily of the supply of starters for the microsatellites, quality controls and assistance in the analysis and the interpretation of data. The IRD also contributes to the training of the laboratory staff, bearing the cost of the stay of technicians in its facilities at Montpellier. Collaboration also continued with Dr. T.R. Unnasch's laboratory at the Division of Geographic Medicine, University of Alabama (UAB), Birmingham. The UAB carried out the quality control of the identifications of parasites and vectors by traditional techniques (DNA probes, Heteroduplex). The past year was particularly marked by the conception of a new data-processing programme for the analysis of data obtained by the pool screening technique. This programme enables a link with the results of routine dissections. The molecular biology laboratory of the Programme was also involved in the collection of nodules and the preparation of DNA for research works on resistance to ivermectin. Furthernore, the laboratory took part in the preparation and the use of the DEC patch test for epidemiological evaluation. It also l1 contribute to the development of the immunological test of Prof. Weil by undertaking evaluation missions in OCP and APOC countries. In the field of hydrobiology, collaboration continued with institutes (Water Research Institute, Achimota, Ghana; "Centre national de recherche agronomique", Bouak6, C6te d'Ivoire), and national team for onchocerciasis control in Guinea. Exchanges are also maintained with the IRD and the World Bank in the field of the environmental activities in general. 7 t2 PART 2 PLANNING, EVALUATION AND TRANSFER 13 DrsrRrBUTIoN oF TvERMECTIN (MECTIzAI\ t ) axo EPIDEMIOLOGICAL ACTIVITIES L IYERMECTIN TREATMENT l. The implementation of the CDTI is now effective in almost all the eligible basins of the programme area. Socio-political disturbances somehow disrupted the installation of CDTI in Cote d'Ivoire in 1999. The situation was the same in Sierra Leone and Guinea Bissau until 2000 due to internal conflicts. Distribution activities have since resumed in these two countries. Z. ln z112,like the previous years, the treatments were carried out in all the hyper and meso- end'emic foci of the eligible basins. CDTI is used in the northern part of the Western extension of the programme area in Guinea Mali and Senegal as the only strategy for onchocerciasis control. It is also "ppii.a in certain parts of the original Programme Area. This is the case of the basins of the Dienkoa, th" Bougorriba and the Black votta (Mouhoun) in the district of Bati6 in Burkina Faso, the basins of the Oti-iendjari, the Sota Alibori in Benin, the Oti and its tributaries in Togo, the basins of the Sissili, the Kulpawn-Uote and the lower Black Volta in Ghana the basins of the Como6, the N'Zi/Bandama, the Sasiandra and the Marahou6 in C6te d'Ivoire as well as the basins of the Kank6laba the Bagod and the Baoul6 in Mali. The majority of these basins and that of the Gambia in the Senegal have undergone two annual treatnents up to now. All the other basins are treated only once ayear. Fig. 1: Zones of large-scale ivermectin treatment in the Programme Area in 2002 't ( I{ inffala at extandoE F bduDlnffiM[:.:.:.3 zrn€d.rraffi& O.igin.l Proe?.hm. .t . bound.ryJ Lihtlc airc initi.l. Naffonrl bo0ndr.i.r / Fronllids OCP bound.r (odrin.l. dto. eulh.m and totl oado daidon boundary) umtt OcP (.ir. iolli.l.. .ftndod ou.d. d.l .l onoho€.€o dc loiao E--:l Effi FY6 Fbdbrulffipr- fqE.Girolrd.dhdEiEdtaffi 2.6 A ,o,|l h.fuG 6t bd.ffiruma&c t4 3. OCP has always given technical and financial assistance to the Participating Countries. A vast mobilisation and public awareness campaign of the decision-makers, health workers and the communities concerned with the CDTI made it possible to obtain their adhesion to the process' Decision-makers at all levels are targeted by this sensitisation which is carried out by the health workers. 4. The training of the health workers at the peripheral level was undertaken in all the eligible districts for CDTI. The health workers thus trained by the national teams proceeded in their turn with the training of the Community Distributors (CD). Almost all the villages under treatment have Community Distributors carrying out the distribution of the ivermectin in their respective localities. These distributors are chosen by the communities which decide themselves the moment as well as mode of the distribution. The communities organise themselves to guarantee the regular supply of ivermectin for their village. They provide in most cases the material necessary for treatment (book, measuring gauge, etc.). 5. To consolidate the implementation of the CDTI, the training and recycling of the Community distributors and health workeis are organised each year by the national teams with the technical and financial support of the OCP and NGO partners. These training/recycling based on the deficiencies recorded duiing the supervisions or evaluations, initially consists in training the trainers among which doctors and chief .rurrir of the health centres of the zones concerned with the distribution. These in their turn train the Community distributors. 6. 1n2002 more than 5,316 Community distributors were trained in Sierra Leone for example and more 300 in Guinea Bissau. To date, on the whole, approximately 500 district chief medical officers, more than 3,500 technicians/nurses and other health workers, more than 60,000 Community distributors have benefited from a training/recycling on the implementation of the CDTI in the various countries since the starting of this strategy. 7. The supervision and the foltow-up of the distribution are carried out by the central level and the decentralised teams supported by the OCP. These supervisions and follow-ups organised by levels have made it possible to better install the system and to familiarise the various actors with the principles undeilying the CDTI. In most of the countries, the activities of follow-up and supervision of itre principal actors were somehow regularly carried out in order to minimise the errors and to provide the iorefront actors with the needed support. Today these activities are organised and carried out by the health workers of the peripheral health centres of the zones under CDTL AT the end of each treatment they are charged with the collection of the data of each village and the preparation of a report addressed to the district chief medical officers. The serious side effects recorded by the distributors are referred to the closest health workers for action. 8. As in the past, partner NGOs provided the Participating Countries with technical, material and financial support in the implementation of CDTI, particularly, in the supervision, organisation of the annual reviews, follow-up, training/recycling of health workers and Community Distributors. The partner NGOs are among others Sight Savers Intemational in Mali, Guinea, Ghana and Togo; the brganization for the Prevention of Blindness (OPC) in Mali, Guinea and Senegal; Helen Keller Wotawiae (formerly Helen Keller International or HKI) which continue to assist certain countries like Burkina Faso, COte d'Ivoire, and Mali in the field of oncho IEC and collaborate with the latter in the implementation of several activities contributing to the promotion of CDTI. 15 9. Ivermectin figures on the list of the essential drugs of the various countries. Currently the drug is ordered directly from the Mectizan Donation Programme (MDP) by the countries eicept Guinea Bissau which started direct ordering this year. The orders are directly received by the countries themselves with the support of the WHO or the UNICEF Representations in the countries. These orders are integrated in their usual channels of drug distribution. Annual reports from the village up to the level of the national team are prepared at the end of each treatment. 10. Efforts continued and intensified in view of the improvement of the treatment coverage. The emphasis was laid on the need for treating all the eligible villages and at least 65 % of theirpopulation each year. Active inspections made it possible to detect the majority of the villages and hamlets which escaped the treatment. It was the case in the basin of the Pru for example where inspection by helicopter and on the ground was carried out. I l. More than 7,500,000 people in nearly 25,000 villages were treated with ivermectin in line with the CDTI method. The geographic coverage varies from country to country and from one district to another. It goes from 50 to I 00 Yo with an average of 7 5 o/o. The therapeutic coverage varies from 60 to 81 % and the average is about 7l o/o (table. I ). It is to be noted that the analysis of the performances by village makes it possible to detect the villages that have not received treatment and especially those with weak therapeutic coverage. Meetings of reinforcement or complementary treatment are then organised to improve the coverage in these villages. 12. To identify certain socio-demographic factors underlying the unsatisfactory entomo- epidemiological situation on the Upper K6ran in Togo, the Upper Niger-Mafou and the Tinkisso in Guinea, the Pru in Ghana, the Koumongou in Benin, and to propose solutions, sfudies were carried out on these basins in 2001 and2002. The research results showed a weak accessibility of these zones, and a significant migratory flows of the populations. Although these studies showed the effective installation of the CDTI in all these basins, efforts still remain for the improvement of the coverage, especially with regard to the control of the treatment of the migrants. 13. The problem of report writing by illiterate distributors is a handicap to the system of collection and analysis of treatment data. To find a solution to this thorny problem, a study on a "Pictorial Form" designed accordingly, was undertaken in June 2002 in Senegal. The study showed the potential use of this form as support for the preparation of reports by the illiterate distributors after treatment. This form which will be used by the national teams will have to take account the socio-cultural specificity of each country, even of each community. Country Number of villages to be treated Envisaged Treated Geographical coYerage o//o Population Listed Treated Therapeutic coverage Burkina Faso COte d'lvoire Guinee Mali Senegal Togo 346 1,350 7,478 3,508 483 4,587 346 839 7,320 2,992 472 3,203 r00 % 62% 98% 82% 98% 70% 172,342 584,300 2,455,457 1,562,444 127,422 1,785,3 l3 120,468 375,000 1,989,850 1,246,167 t}l,719 1,206,193 70% 64% 8t% 80% 80% 67% Total 17,752 15,072 85 0/, 6,687,278 5,039,397 75 0h l6 Table l: Ivermectin treatment in the Programme area in 2002 (partial results) II. EPIDEMIOLOGICAL EVALUATIONS l. As with the CDTI, with the help of the teams trained by the OCP in collaboration with national coordinations for several years, the epidemiological evaluations were, as in the past, carried out satisfactorily in2002. These activities are carried out mainly by the decentralised teams of the regions or the districts in each country, with the technical support from the central organ and the logistical and financial support of OCP. They took place mainly in the original area and in the extensions of the Programme. In some countries (Sierra Leone for example), OCP provided once again its technical assistance in order to complete the training of the national teams, carry out the quality control of the epidemiological surveillance or to ensure their readiness to carry out these activities independently after OCP. The epidemiological surveillance allows for the verification of the epidemiological situation of onchocerciasis in the original area where larviciding is no longer canied out. In the extensions zones (western and south-eastern), in certain particular zones of the original area subjected to ivermectin distribution or combined with larviciding, they also constitute an element for the assessment of the impact of the activities undertaken. 2. From January to September 2002,498 villages were evaluated in 9 Participating Countries including Sierra Leone. These evaluations were carried out in the original area as well as in the extension zones. They involved 60 villages in Benin, 1l in Burkina Faso, 22inCdte d'Ivoire, 125 in Guinea, 106 in Mali, 12 inNiger,2l in Senegal,60 in Sierra Leone and 81 in Togo. The traditional skin-snip biopsy which allows for the assessment of prevalence, the intensity of the infection and the appearance of new possible infections was used. The new infections are infections occurring in children of less than five years who did not receive ivermectin treatment, or in individuals who had been found negative before during two consecutive evaluations. In addition to the skin-snip biopsy, the large-scale test with the Diethyl-carbamazine (DEC patch test) continued in some endemic villages. The epidemiological evaluations of 2002 will complete the cross-evaluation started in 1997. They will make it possible to have sufficient data illustrating a general view and an evolution of the general epidemiological situation in the Programme area before it comes to an end. They will be used as comparative data between the current situation and the pre-control situation in the various zones of the Programme. Figure 2 shows the epidemiological map of the Programme area between September 2000 and September 2002. ) a17 Figure 2 : Prevalence of onchocerciasis in villages evaluated in2002 Epidemiological Surveillance in the original Programme Area 3. More than 160 sentinel villages in the original Programme area were evaluated by the national teams in 2002 in Benin, Burkina Faso, C6te d'Ivoire, Ghana" Mali, Niger and Togo. The results are generally excellent in the majority of these basins under epidemiological surveillance. The prevalence is around 0%ointhe majority of the villages. In Benin, the prevalence passed from 59% to l.l yo on the Niger and its tributaries. The same applies to several basins where the epidemiological situation was particularly alarming at the beginning of the Programme. It is the case for example of Koutayagou ,iltuge in the basin-of the Oti-Pendjari where the last prevalence of 83.60/o (CMFL 29.8) in 1977 passed to 5.7o/o (CMFL O.t2), of the Sarmaga village in the Ou6me basin with a prevalence of 82,6(Cfvfff 34.44) in 1978 and of 7 % (ClvtrL 0,2) at the last evaluation in 2000. The maximum prevalence observed on the Red Volta in 2002 is 7.4Yo with a CMFL of 0,14 (in Saro). [n the basins which remain under ivermectin treatment like those of the Oti/Pendjari and tributaries, the prevalence observed in the villages evaluated in20}2 range from 0%o to 4.9o/o. The trends are excellent in the other basins of the original area in Benin as on the Sota/Alibori, the Niger, and the M6krou where the prevalences have been nil in all the villages evaluated these last years, including 2002. On the i<ournorgou on the other hand, the situation is not yet as expected. One notes prevalences of around 3 4%o in certain communities. PIfYAI.E|CE C XIC*OfI-AEAC TI YI.L'GES EYTLIAIET IEIEI2T.2M ll OC? PnEUlfEaCE fl ICROflrxfS lEs uaLrGa;EYlllIStrXf 2I- 212 AL!G? o o o 3 0 -5 5.ti6 t6 t-40 tr) 140 ''lt , ,--,- fudd Ltr OCP (f! nbh,.daslo.B or..l, r.d aqdErc@&tq&) oriqild Prqtmnc G hrt hry rlfic d?r ru ori,ld r{ wlddn cd srhdn arEltn c br.bry 18 4. In Togo, in spite of a remarkable fall in the prevalences in a greater part of the original area (g2.7% preialence, Cvrpf- 17.78 and 2.3 prevalence, CMFL 0.03 in 2000 in Landa Pozanda), the epidemiological data are not fully satisfactory on the Oti and its tributaries (88.5 prevalence, CMFL 36.62 in 1976 and,Zl.7Yo prevalence, CMFL 0.9 in 2001 in Titira, Bagan from 65.7 to 2.6 %)- 5. In the villages evaluated in Burkina Faso in 2002, the prevalences are_lower than 5 o/o on all the basins compared to more than 80% (98.8%, in Dangoudougou on Leraba/Comoe in 1978, 0% since 1994) in certain basins at the beginning of the Programme. The incidences are almost nil just as the microfilarial load of the communities. Larvicide treatments were stopped in the basin of the Dienkoa in 2001 due to the excellent results obtained there, after 12 years of combined larviciding and ivermectin treatment. In the BougouribalBlack Volta basin, the highest prevalences observed in 2001 were of 6.6Yo atMouvielo, and7.9o/o at Salibor, with almost no microfilarial loads. 6. In C6te d'Ivoire the prevalence rates which were higher than 60% before the beginning of the operations are today globally between 0 and 5% although the evaluations carried out in 2000 and 2001 showed a suspicious ii.ra o.r the Upper-Nzi, in the villages of Namayeredougou (6.7%) and Kobadara (9.2%) and on the white Bandama in2002 (8.8% at Nagoungokaha). 7. In Niger the epidemiological situation remains excellent. The epidemiological evaluation carried out in 2002 in25 villages in the various basins showed zero prevalences' g. In Ghana, the epidemiological results are excellent with zero prevalences in the villages evaluated in the basin ofihe Sissili and the Red Volta. on the other hand, the epidemiological situation continues to be unsatisfactory in the basins of the Black volta (14.3%), the Daka (13.7%-15.1%) the Kulpawn/M ole (27.5%o) and the pru (more than 20%; prevalence). However, the trends are on the whole downward compared to the previous results. Suitable alrangements accompanied by a reinforced follow-up u.. i, progress iniollaboration with the national team to improve the geographic coverage of the villages andthe therapeutic coverage of the populations under ivermectin treatment. Epidemiological Evaluations in the extension areas of the Programme g. In the southern extension in C6te d'Ivoire, the prevalence rates which ranged between 20 and more than 3O%o are today of about 5o/o and 15% maximum since the installation of the CDTI in this zone in 1994. The epidlmiological results are satisfactory in the Sassandra basin which remained under seasonal larviciding combined with ivermectin distribution until 2001. Larvicide treatment was stopped in this basin in December 2001. Prevalences vary from 0% to 6.3%o and the microfilarial loads ur*rd zero. On the Como6 and the Marahou6 the results are also good. The same goes for the villages evaluated in the basins of the N'Zi and the Bandama. 10. After more than four years of cessation of ivermectin distribution, an epidemiological evaluation was carried out in June 200i in Guinea Bissau, in the basins of the Rio Geba and the Rio Corubal. The prevalence is nil in the lZ villages evaluated in the basin of the fuo Geba. In the basin of the fuo 'Corubal the prevalences are mostly nil or very close to 0o/o with the exception of the Cobuncara village with a prevalence of 35.6% (56.7;'/0 in 1990 and 10.8% in 1997), Cuatche with a prevalence of 23-6%o (22.3% in 1990 and Z,ZYo in 1997), and Queue with a prevalence of 11.8% (57.3% in 1990 and l'7Yo in 1997). Investigations are on course for a better understanding and confirm these results. 11. In Guinea, pre-control prevalence of infection was between43 %o and 88% before control but currently ranges beween 0 lo and 10% in most of the communities due to the strategy of combined a I19 vector control and ivermectin treatment. However in the basin of the Milo, an epidemiological evaluation carried out in January 2002 gave a prevalence of 29.2 % (Badala village). This point deserves a continuous attention as much as the Kaba basin where the prevalences vary from 0% to 19.3%. The situation is excellent on the Bakoye with prevalences from 0% to 2.1%o. Prevalence also ranges from 0% to2.8Yo on the Niandan, 0o/oto l.5ohon the Tinkisso,0o/oto7.9o/o on the Niger, 15.7% on the Niger/Mafou, and }oh to 2o/o on the Sankarani. 12. In the basins under ivermectin distribution alone in Guinea, the results are excellent. The prevalences and the CMFL are nil in almost all the surveyed villages. Thus, they go from 0% to 1.6%o in the villages in the Bafing basin that were evaluated in 2002. The trend was identical in the villages surveyed in 2001 in this basin. The epidemiological situation is also satisfactory in the basin of the Koulountou-Kolilba and the Kolent6. A village of the Koulountou basin presents however a prevalence of 21.1% (CMFL 1.07). All things considered, in Guinea, the epidemiological situation has seen a remarkable improvement but vigilance must be maintained in certain points of some basins like the Milo, the Koulountou, the Niger/Mafou etc. 13. In Senegal, simple epidemiological evaluations undertaken in May 2002 in 25 villages of the basins of the Fal6m6 and the Gambia that have had ivermectin treatment alone since 1988 showed excellent results. The prevalences vary from lYo to 6.9% (Guemedie, basin of the Fal6m6). Of l8 villages evaluated in the basin of the Gambia in 2002, prevalences are nil everywhere except in the village of Ossounkala 1.3 o/o,in Bamboya (l%) and T6p6r6 Diantou (0.4%). All the infections were noted in old persons of more than 20 years. No new infection was observed in these basins. 14. In the basins of the south-eastem extension in Togo and in Benin still under combined larviciding and ivermectin distribution, the epidemiological evaluations carried out showed satisfactory epidemiological trends on all the basins. In Togo, the basins show prevalences lower than 5%o and almost zero microfilarial loads, except in the specific intervention zone (SIZ) of the K6ran, Kara and MO basins, where the epidemiological situation is not completely satisfactory. All the villages show a drastic regression of theirprevalence compared to the beginning of the control (Tokpo from 85.1 to 2.5 %). In 54 villages evaluated out of 65 in the southern extension (that is 88 %) prevalence was lower than 5 o/o. Of 60 villages evaluated in Benin, 52 (87 %) had prevalences between 0 and 5 oh. The prevalence decreased from71%o to ll oh on the Okpara, 72.4% to 1.8 % on the Zou. On the Mono and the Ou6m6, in spite of prevalences around 20%o to 30 % observed in certain villages, a downward trend was noted. The Community Microfilarial Loads (CMFL) are almost nil in almost all the evaluated villages. 15. An epidemiological evaluation was carried out in July 2002 in 60 villages in the main basins of the north of Sierra Leone by the national team in spite of the difficulties of the ground. Technical, financial and logistics support was provided by OCP. The situation is obviously alarming. The following prevalences were noted in the survey :19.8% (CMFL 0.61) in Mafuri in the Mabole basin and 73.3Yo in Kotor (CMFL 9.4) in the Kaba basin. The prevalence at the last evaluation in this village (Kotor) in 1996 was 34.7o/o with a CMFL of 2.13. In addition to the epidemiological studies, the current situation of the onchocerciasis in the country deserves additional survey, such as a thorough entomological investigation and socio-demographic studies to consider the best actions to be taken. 20 16. The epidemiological situation saw a certain improvement in the specific intervention zones (Guinea, Togo). The epidemiological trends are declining but sustained attention and energetic actions must be considered for these zones both on the entomological level as on the epidemiological level and the distribution of the ivermectin. The attention to these zones must not overshadow that for the other basins such as the Ou6m6 and the Okpara, the Milo, etc. where some foci are noted to have relatively unsatisfactory results. Sierra Leone constitutes a special entity deserving a particular consideration. Ophthalmological evaluations 17. Ophthalmological evaluations were undertaken in the villages of the lower Como6 in C6te d'Ivoire from February to March 2OOZ and in villages of Benin in December 2001 in the basin of the Ou6m6, the Zo\ the Okpara in order to measure the impact of control on the ocular lesions of onchocercal patients in these zones. The results are encouraging just like those from previous evaluations these last years in other basins of the Programme. One notes a remarkable regression of the interior eye lesions though there remains on the other hand a stabilisation of those of the posterior lesion. No ocular macrofilarae was detected and there were no new cases of blindness from onchocerciasis. III. BIOSTATISTICS AND INFORMATION SYSTEM l. In view of the forthcoming closure of the Programme in December2002, the Biostatistics and Information System sub-unit (BIS) continued and intensified the transfer of the data-processing tools (equipment, programmes, data bases and user-guides) to the Participating Countries. To this end a workshop was organised this year which brought together the data processing specialists, the managers of data bases and epidemiologists, to make an exhaustive diagnosis of the problems involved in the applications and the corresponding data bases. Thus, the programmes of consultation and analysis of entomo-epidemiological data were re-examined in detail and were improved. The interfaces and the menus were also amended in order to facilitate their use, the data banks audited and supplemented, and user-guides updated. The sub-unit continued the entering and validation of the entomological and epidemiological data, the data-processing assistance within the Programme by the maintenance of the various equipment and source prograrnmes, that of the local area network and the associated services like the Internet and the electronic mail. This assistance also relates to the continued training in data processing, the management of the various data banks and their safeguard. 2. The update of the various data banks by the information collected on the parasite, the vector and ivermectin treatment was undertaken. A particular effort was made for the collection from the countries of more than 500 epidemiological evaluation files for the entry and the update of the data bases. In the same way the bank of the data available on CDTI from 1987 to 2002 initially entered by the countries were checked and used by OCP. In sum, a detailed attention was given, within the framework of the updating of the data banks, to routine analyses of ophthalmological and epidemiological data, as well as data on the distribution of ivermectin and those of the socio- demographic studies carried out in the basins of the Tinkisso/lvlafou (Guinea), the Kara/I(6ran/M6 (Togo), the Pru (Ghana) and the Koumongou (Benin). 3. With the support of an ophthalmologist and a statistician, a new bank was initiated made up of the ophthalmological data from 1914 to 2002. This bank comprises the data of 239 villages with more than one hundred ophthalmological indicators. The thorough analysis of this data bank allowed the drafting of a detailed document on the evolution of ocular parasitism, blindness and the ocular lesions. o a2l 4. With the collaboration of the University of Rotterdam OCP undertook the filing and the conservation of all the data of the Programme in the form of "simple rectangular files" independent of the formats of current software (VisualBasic, dBase, Access...). These data collected since nearly 30 years with an operational and scientific aim, will play a dominant role in future for the control of onchocerciasis, public health and research activities. Each data bank was documented and referred in detail by specifying the goals, the history, the method of collection, the forms, the operations used, coding, the data base, the calculated data, the definition, the mode and the formulas of calculation. 5. Within the framework of the filing and conservation of the Programme's data, a specific data base was conceived for the exhaustive census of the people having worked for OCP from 1974 to 2002: OCP personnel, personnel of the Participating Countries, consultants, Coordinators, hydrologists, national hydrobiologists and entomologists, members of the Ecological Group (EG), members of the Expert Advisory Committee (EAC). This historical bank will certainly be used as reference bank for future research. 6. With an aim of reinforcing the operational capacities of the Participating Countries of the Programme for the data management, the Programme equipped national coordinations, some districts and sub-sectors of each country with very powerful computer equipment. The development of the capacities in the use of computer equipment was reinforced. Training sessions were organised for the national teams to enable them peruse, enter, validate and analyse the data collected during epidemiological evaluations or ivermectin treatments. For an optimal transfer of competence, these trainings concerned three technicians of each country: the agent in charge of epidemiology, the entomologist and the data processing specialist or the statistician. This is a thorough training of trainers on NewEpicros, VCUDataManager and HealthMapper applications. The objective of this training is the appropriation by all the participants of the various input tools, of consultation and integrated analysis of epidemiological, entomological data and of ivermectin treatment. Data processing specialists or statisticians were associated in this training with an aim of constituting a team of resource persons capable of effectively solving problems inherent in the use of the transferred applications. Finally the modules on the management of the data were finalised. 7. The Programme gave a special attention during the training of the technicians to the operational tool for integrated spatial analysis of the data collected within the general framework of onchocerciasis control (epidemiology, entomology, ivermectin, hydrology and hydrobiology) namely, the HealthMapper software, developed by the HealthMap unit of WHO in Geneva in collaboration with OCP. This simple and practical module for the decision makers and the technicians of the Participating Countries is of an additional value to the traditional method of data analysis. 8. The Web site of the Programme is functional. That of the Library /Documentation centre, accessible only in-house, is also operational for consultation on bibliographical references and technical documents of the OCP and APOC Programmes. For a popularisation of this information in the Participating Countries, this site was transcribed on CD-ROMs in the form of multimedia documents. 9. The local area network of the Prograrrrme was consolidated by the replacement of certain equipment and the information processing system protected with powerful anti virus. The process of a reinforced protection of the bulky scientific data from external attacks is completed. The OCP assistant storekeepers were trained in computerised management of stocks. Generally, the competence in data processing of OCP/APOC personnel was reinforced and a special assistance was provided to 22 WHO/AFRO for the development of an application, and to the WHO representations of Burkina Faso and C6te d'Ivoire for accounting (imprest) and stock management. IV. ACTIVITIES OF THE LIBRARY/DOCUMENTATION CENTRE For 28 years OCP has undertaken intensive and varied activities which have constituted during all its existence, an impressive memory made of statistical reports and complete series of documents relating to the meetings of the statutory bodies and others. The whole of this immense source of information is available at the Library/Documentation centre. A project on the treatment of the technical documents and files of OCP and APOC was initiated in September 1999 in order to place their respective data on an electronic medium. The major concern underlying this initiative is to guarantee the conservation, the classification, the access and fast consultation; to diffuse some references selected by the means of Internet; to engrave on CD-ROM the bibliographical references and the complete text of the scientific publications (published articles or scientific reviews, personalised reports and some anonymous reports) produced by the two Programmes. 1. Inventory Inventory at the OCP Headquarters in Ouagadougou: this operation was carried out in all the units in 2002. The personnel of the documentation centre went to all the offices to help prune those documents in duplicate, the drafts and other documents judged of less importance by the occupants of these offices. The inventory and the transfer were also undertaken in the operational bases. 2. Transfer of the administrative documents The arrangement, the transfer and the storage of all the significant administrative files of OCP were carried out. 3. Scanning of documents and entering of bibliographical references All the documents relating to statutory meetings were scanned. CD-ROMs were prepared, multiplied and distributed to the national coordinators. The technical reports of the Vector Control Unit, and those of the Planning, Evaluation and Transfer Unit were also scanned. Their bibliographical references were entered in the documentary software BiblioMaker. A provisional version is already available on Intranet. The bibliographical references of the book "Twenty years of Onchocerciasis Control" were entered and its articles scanned. They are also available on CD-ROM. 4. User Services For the period covered by this report, the Library saw an intense visit of the external users (OCP/APOC Experts and Consultants, Students of the School of Public Health and the Faculty of Health Science, secondary and primary school pupils) thus a great demand for bibliographies, articles and information documents. I 23 5. Relationships with other institutions The Library maintains a good collaboration with the documentation units of the Agencies of the United Nations and other International Organizations based in Burkina Faso. The Library is member of the Association of Health Information Libraries in Africa (AHILA). It practises the interlibrary lending. 6. Dissemination of information With the aim of having the important documents of the Programme in electronic form a project on the "data-processing of technical documents" was initiated. This action aims at an easier dissemination and information sharing on OCP and APOC with the researchers and other recipients. V. BRIEFING PAPER: MACROFIL / FILARIASIS R&D 1. Clinical studies l.l A survey carried out in two onchocerciasis endemic foci in Ghana (Asubende in the Pru River basin and Bui in the lower part of the Black Volta) in 1997 by the OCP, revealed individuals with persistent, significant microfilaridermia. Both foci had been under prolonged vector control and had received multiple treatments with ivermectin. As a working definition, individuals with : or > 10 mf/snip after 9 or more treatments with ivermectin were labelled as "non-responders"; individuals who were skin snip negative after similar exposure were termed "responders". The pathogenesis of non- response could be failure or inadequate drug intake, sub optimal drug exposure, adverse interactions, patient factors, parasite resistance and possibly other factors. An open, case control study was set up to investigate the phenomenon. This involved the OCRC at Hohoe, The Division of Oncho Control of the Ministry of Health Ghana, The Noguchi Memorial Institute for Medical Research of the University of Ghana. The aims of the study were to investigate whether the microfilaria and /or the adult female worrns of Onchocerca volvulus in non responders to multiple treatments have developed resistance to ivermectin and provide characterised parasite material to aid the development of tools to detect such resistance. The individuals were studied at the OCRC: History of drug intake was confirmed and reclassified on the basis of skin snip findings Underlying disease or adverse interaction with other drugs excluded Re challenged with ivermectin and a pharmacokinetic study conducted Determined the sensitivity of microfilariae at day 8 (% reduction on initial counts, vector mf uptake and development on fly feeding) Determined the sensitivity of adult worms at days 90 and or 364 (embryograms, skin microfi lari ae, fly feeding) Parasite material saved for future probing for markers of ivermectin resistance. From the OCP data base 16 cases ("non responders") were matched with 12 responders from the same foci and 14 individuals from an area (Todzi basin) without previous ivermectin distribution ("ivermectin naive") or vector control. After re examination of the cases and the responders there were 21 cases andT responders. 24 The study will be completed by end of August 2002 and the results will be reported at the EAC23 1.2 combinations Due to the fact that the LF elimination programme could be viewed in some areas as a coordinated programme with the Onchocerciasis Control Programmes, it was recognised that additional clinical ituai.r addressing the PK, safety and efficacy of ivermectin or DEC + albendazole were warranted. Three studies were initiated: l.Z.l Albendazole *ivermectin safety, efficacy in LF and intestinal helminthes study in Pemba Island (Dr. M. Dahoma). 1000 subjects including LF positive. The treatment phase of this study has been completed. The data analysis is ongoing and results are expected by Decembet 2002. 1.2.2 Albendazole + DEC, pharmacokinetics, safety study (Dr. K. Shenoy) This study has been terminated and has provided PK data indicating that there are no drug interactions between albendazole + DEC. 1.2.3 Alb+DEC safety, efficacy and PK (Dr. N. Kshirsagar) 1400 subjects from a LF endemic region in India have been treated, the one year follow up (night mf, scrotal and ICE card test evaluation) has been concluded. The study was extended to study the effect of a second treatment and is expected to be finalized (two year follow-up) in September 2002. 1.3 Moxidectin Moxidectin is a veterinarian product that TDR scientists investigated for its effect on filarial wolrns showing that it has a better profile than ivermectin. The pharmaceutical company WYETH has conducted clinical, technical and regulatory activities to define if moxidectin can be assessed in Onchocerca volvulus patients. The results from the studies that WYETH has conducted have allowed defining the dose range to be used in future efficacy and safety studies. The consultations with UK and French drug regulatory authorities regarding the suitability to evaluate moxidectin in patients as well as the suitaUltity of the clinical development strategy was welcomed and endorsed. Current activities have been focused on the strategy and design of the Phase II study to be conducted in OCRC, this was finalized during a recent meeting at WYETH (August 20-21,2002). For this study to be implemented a "Clinical Transfer Agreement" must be negotiated befween WYETH and WHO. It is expected that this agreement will be finalized by 3'd quarter 2002 and the study could be initiated in October- November 2002.It will include 193 patients with different levels of microfiladermia and eye disease, will compare several doses of ivermectin against several doses of moxidectin addressing safety and efficacy with a follow-up of l8 months. The results of this study will serve as the Go/noGo for future phase iIt studies that will have to be conducted at several sites / countries. The search for these sites was initiated during a recent meeting of APOC with the National Onchocerciasis Coordinators in Abuja, Nigeria. 2. Pre-clinical research activities 2.1 Ivermectin resistance detection tool In June 1999 a WHO sponsored meeting entitled "Ivermectin Resistance in Onchocerca volvulus: Tools To Detect It" was held at APOC/OCP headquarters, Ouagadougou. This workshop concluded + a25 that it was feasible to develop a PCR-based assay to detect ivermectin resistance or shifts in the allele frequencies at loci that may serve as markers for ivermectin resistance in O. volvulus. Two focused teams were formed, one in West Africa undertaking fieldwork and one international group (The Product Development Team) undertaking laboratory studies. During the first year of the project the identification of ivermectin resistance candidate genes associated with ivermectin resistance in Haemonchus contortus and C. elegans was completed in order to identify genes likely to be associated with ivermectin resistance in O. vohulus. In the second year, candidate O. volvulus genes, based on experience in H. contortus and C. elegans, from "unseletted" (untreated areas) and "IVM exposed" populations were examined for polymorphism and a short list of marker genes and their alleles were determined. The IVM exposed Onchocerca came from people who had received at least six treatments with IVM. In addition to the examination of candidate IVM- resistance genes, the onchocerca EST database was examined for all sequences in which there was evidence of polymorphism and a number of polymorphic ESTs were identified. In the past year, analysis of differences in polymorphism between the unselected and IVM exposed worms for both the candidate resistance genes and ESTs that showed polymorphism con tinued. Three candidate genes had Nodules have been collected from more regions, so that it can be determined whether differences in polymorphism can be attributed to treatment history or to geographical source of collection. This analysis of polymorphism in the identified genes, using the material collected from a wider range of regions has continued. At the same time, two rapid PCR based assays have been developed foi monitoring the frequency of resistance-associated alleles of one of the identified marker g.n.i in O. volvulus. Other genes showing polymorphic differences, between untreated and treated populations of O. volvulus, will be further evaluated and if shown to be reliable markers of ivermectin resistance in all regions from which worms have been collected, they will be developed into PCR based assays to dletect ivermectin resistance. So far one of the marker genes shows a strong positive correlation between the frequency of a particular allele and microfilaria count after ivermeitin treatment. At the end of the fourth year a robust PCR assay to detect allelic changes in O. volvulus candidate genes in microfilaria will have been completed and assessed on a large number of O. volvulus samples f.orn ,.u.ral regions in Africa. At this stage the assay should be ready for surveillance monitoringin the field. This piject will contribute to the sustained control of O. volvulus through developmint of an assay to detect ivermectin resistance before resistance genes become widespiead in the parasite populaiion. Early warning of resistance development will allow alternative control measures to be introduced to eliminate the resistance genes before they spread. 2.2 Optimization of DEC skin patch test Based on discussions with LTS Lohman Therapie-Systems AG, a German Company with expertise in transdermal drug delivery systems their expertise was assessed and an agreement to perform work(APW) was established. This work has yielded 3 patch prototypes. On the basis of the results of a short term stability study one of the formulations that were prepared have been selected. The selected formulation is the most stable one, but nevertheless there was seen a slight decrease of the drug content over the time. This decrease is very likely because some of the drug evaporated out of the edges of the patches into the pouch material (the citrate has to be converted into the free base in situ during the manufacturing process and that the free base is a liquid at room temperature). Degradation products which could explain the loss of drug have not been seen and in aged patches higiher drug concentrations were found in the center of the patch compared to the peripheral rim. In order to minimize the losses, during the production of the clinical iamples u -o.. inert primary packaging material will be used. The anticipated production date is the second week in Septem-ber 20:02, wheieby 26 the patches can be released until middle of November. At this point the clinical studies could be initiated. 3. Drug discovery activities For the identification of new drug leads for Filariases the group of TDR Drug Discovery addresses filariases in the context of a multi-parasite drug discovery approach. 3.1 Grant renewals :Two key research grants in the drug discovery are currently being supported through MACROFIL 3.1.1 M. Kron (Michigan State University, USA) is using a rational, target-based approach to search for inhibitors of B. malayi asparagine tRNA synthetase. Sixteen hits from a high-throughput screen of a large diverse library are being followed up by synthesis and testing of analogues. Two of six tested hits were toxic to cultured adult worms at25 micromolar concentration, but structure optimisation and analogue selection, based on the enzyme's three-dimensional structure, are expected to improve this activity. In addition, a unique lysyl tRNA synthetase from Wolbachia has been expressed, in preparation for a high-throughput screen on this new potential drug target. 3.1.2 C. Behm (Australian National University) used RNA interference (RNAi) to validate trehalose- 6-phosphate synthase and two trehalase isoforms as potential new drug targets in C. elegans. Other enzymes are now being investigated as potential targets. 3.2 Compoundevaluation 3.2.1 Tibotec. Screening of about 9000 compounds in Tibotec's T. colubriformis in vitro larval development test produced about 60 confirmed hits. All of these except 8 are from BioSPECS. Compounds that are available in sufficient amount and whose structures are promising will be sent to S. Townson for further evaluation against O. gutturosa. 3.2.2 S. Townson, Detailed study of many available antibiotics by S. Townson (Northwick Park Institute for Medical Research; London, UK) suggested that minocycline was the most promising candidate for further progression. An agreement for evaluation of a large series of novel tetracyclines is under negotiation with Paratek (Boston, MA, USA). Also, about 800 non-antibiotic compounds (mostly from GSK, selected around pharmacophores with known or likely anti-filarial activity) were evaluated for activity against adult O. gutturosa worrns in culture. About 30 were further evaluated for activity against microfilaria in mice. Analogues of the most promising active compounds have been requested for further studies including antibiotics, pharmacophore-selected compounds from GSK, and potentially teracyclines. 3.2.3 A focused collection of 220 additional compounds, selected around pharmacophores with known or likely anti-filarial activity, has been purchased from Olivia (Princeton, NJ, USA) and is now being evaluated by S. Townson. 3.2.4 A diverse compound library of over 10000 compounds will be screened for activity against C. elegans in two assay systems that are being developed by Cambria Biosciences (Bedford, MA, USA): one assay detects changes in nematode nuclear functions, and the other targets enzymes in the worrn's protein secretion pathway. I J 27 PART 3 ADMINISTRATION AND SUPPORT SERVICES a28 ADMINISTRATION AND SUPPORT SERVICES Objectives, organisation and operation l. The Administration and Finance Unit ensures support for the operational, technical and scientific units. Within the framework of the approved budgets, it manages the human, financial, and material resources of the Programme, based on a structure of four distinct services: Personnel, Budget and Finance, Transport and Telecommunications, Supply and Maintenance of equipment and material. In addition, the unit also extends its services to APOC. Closing of OCP 2. By way of orientation for the closure and to allow for the best decisions in each field, the Regional Director of WHO for Africa set up a tripartite working group made up of staff members of the Regional office for Africa (AFRO), OCP and APOC under the chairmanship of AFRO. The group met twice in Ouagadougou in 2001 and for the last in May 2002. The group, charged with making recommendations to the Regional Director for final decision, deliberated on the cessation of operations and the best to make of the existing assets and structures in Ouagadougou and in the field. Also, all aspects of the human resource were reviewed. Finally the group underlined the need for an estimated budget covering the period from lst January to 31st March 2003 for the activities to be carried out by some staff, for the final closure of all the administrative and technical files of OCP. Taking account of the requirements of the Programme, the good administrative and financial order and the framework traced by the working group, the Administration and Finance Unit has taken or envisaged a series of measures summarised in the paragraphs below. Budget and finance 3. The budget for 2002, approved at the twenty-second session of the Joint Programrne Committee held in Washington D.C. in December 2001,, amounts to US$ 12 266 000; 17% Iess compared to the budget approved for 2001, in accordance with the Progress Report of the Programme as it draws to an end and vector control activities are reduced. The number of bank accounts managed by the Budget and Finance section is progressively decreasing: at August 2002 there remained about 12 accounts in eight countries. Personnel 4. A progressive disengagement of the personnel, started about ten years ago is being accelerated. The major stage was in 1993, with the passage of a great number of personnel from WHO status to special services contracts which are cheaper and closer to the national conditions of employment. The tendency continues, and in addition measures are taken to replace vacant positions only with temporary or short term contracts. As of lst August 2002 248 people were employed by OCP, of which 79 under WHO/OCP contracts and 169 under other types of contracts, in particular special service contracts. 29 5. As the Programme comes to an end, OCP endeavours to orient the personnel explaining the rights of each one, supported in this by efforts of the WHO/AFRO Regional Director in the search for employment from other organisations. Concretely, discussions are underway for part of the personnel, in line with the qualification of each one, to be taken on by the organizations which will continue to work directly in the field of onchocerciasis (APOC, the team for the special intervention zone after OCP), or working within a vaster health framework (MDSC, WHO Representations). Some measures for further training complementary to those already implemented by the OCP in the past, are taken in particular in the fields of secretariat, documentation, data processing, laboratory, training and courses in techniques of telecommunications, training and sensitising of drivers and mechanics to the maintenance of the vehicle fleet. In addition to the quality of work reinforced by OCP, the training acquired constitutes an asset for the staff members in particular in their search for employment. Supply and Services 6. This sector deals with the management of the assets of the Programme and other diverse services. Concerning the assets of the Programme, the work now consists of the management of purchases, stocks, as well as the liquidation of obsolete or surplus articles. Purchases are made either locally or at the international level through the central Supply Service of the WHO Headquarters. The purchases of vehicles and major equipment have completely ceased and the purchases of insecticides considerably decreased. In view of the closure of the Programme, all the inventories of fixed and movable assets were re-examined in detail. Transport and telecommunications 7. This service is responsible for a vehicle fleet and a telecommunications network which have always constituted the essential and indispensable elements to the work of the Programme. The fleet has gone through a progressive reduction these last years as the Programme draws to a close and the resumption of its activities by the countries. It still comprises 151 vehicles, of which 91o% four-wheel drives made available to the national teams for vector control activities and epidemiological surveillance. 8. The Programme has a central garage in Ouagadougou, entirely equipped for maintenance and repairs of vehicles and is equipped with the qualified personnel for this purpose. This garage also includes a central store of spare parts which supplies four satellite stores on the field. Available stocks have made it possible to avoid a great immobilisation of vehicles. The purchase of parts have ceased since last year, and a cleansing of surplus stocks continues. In addition, the service manages five fuel tanks of a total capacity of almost 60 000 litres. 9. The vehicles in good condition at the end of the Programme will be distributed among the countries on the one hand, and the organizations concerned on the other: APOC, the special intervention teams after OCP, the AFRO MDSC and WHO Representations. A formula is being elaborated for the maintenance of the garage and its components by the various parties. 10. The telecommunications network comprises 45 radios/teleprinters installed throughout the Programme area and a maintenance and repairs network in Ouagadougou. Here again, a formula is being studied for the maintenance of the whole network and the workshop for the benefit of health work in West Africa. t