Annual internal technical review meeting: Ouagadougou, 15-19 January 1990

\\,', -' , 'i) 2 ^,41 \ryORLD HEALTH ORGANIZATION ONCHOCERCIASIS CONTROL PROGRAMME IN WEST AFRICA Annual Internal Technical Review Meeting Ouagadougou, 15-19 January 1990 Document OCP/DIR/89/xxx Table of Contents I TNTRODUCTTON ........... I 2 LATEST RESULTS ON IVERMECTIN 2.1 Coverage and adverse reactions after three treatment rounds 2.2 Microfilarial reduction and repopulation ............... 2.3 Observed effect on transmission .......... 2.4 Predicted long term effect on transmission and parasite reservoir 2.5 Disease prevention 2.6 Further research 3 DIAGNOSTIC TOOLS AND TRANSMISSION STUDIES 3.1 Identification of O.volvulus strains 3.2 Differentiation of O.volvulus and animal Onchocerca L3s 3.3 Diagnosis of new infections 3.4 Vector feeding and Transmission Experiments .. 3.5 Diagnostic tools for the vector complex ...........:. 4 EPIDEMIOLOGICAL MODELLING 5 ORIGINAL OCP AREA 5.1 Report on larviciding in 1989 5.2 Criteria for stopping larviciding ............... 5.3 Latest Entomological results 5.4 Latest Epidemiological Results 5.5 \Yhere and when to stop larviciding 5.6 Entomological evaluation during two years after cessation of larviciding ....... l5 5.7 Effect of Vector Control on Animal Onchocerciasis ........... ........... l5 6 DEVOLUTION t5 7 FURTHER RESEARCH FOR OPERATIONS IN THE EXTENSION AREAS 7.1 Epidemiological mapping and ophthalmological patterns 7.2 Distribution of vector species 7.3 Role of different vector species 8 OPERATIONS IN THE EXTENSION AREAS 8.1 Results and plans for the \#estern extension 8.2 Results and plans for the south-eastern extension .... 8.3 Evaluation of the impact of vector control 8.4 Plan for large scale ivermectin distribution 9 BRTEFING ON INTRA-UNIT RESEARCH ACTIVITIES 9. I Insecticide research 9.2 Insecticide susceptibiliry testing 9.3 Optimization of larviciding operations 9.4 Ecological monitoring 9.5 Socio-economic studies ........................ I I I 2 4 4 5 6 6 7 7 8 9 ll 2 2 2 2 4 5 7 7 I 8 l9 ... l9 ... 20 ... 2l 1',' 22 22 23 23 23 24 IO DATA ANALYSE AND COMPUTER SUPPORT 24 I I MISCELLANEOUS 25 12 RECOMMENDATIONS ................. 26 Appendix A. List of participants 27 Appendix B. List of receut OCP publications ......... 28 1 INTRODUCTION In his opening address the Director urged the participants to concentrate their efforts on an«l limit their discussions to technical matters. They should, however, note at the same time that technical considerations are associated with political and budgetary implications. The participants should therefore bear these limitations in mind in any recommendations they woutd make. The CAM then briefed the meeting on the deliberations of the lOth JPC meeting held on 4-7 December 1989 in the Hague. The chairman noted that the lengthy agenda would only be covered satisfactorily if those findings dealt with in the 1989 Annual OCP Research Meeting were not repeated. In addition, participants were requested to restrict to a minimum the background information presented at the introduction of each section. In order to reflect more accurately the nature of this, and earlier, meetings, it was agreed that the title be changed from Research Meeting to the Annual Internal Technical Review Meeting. 2 TATEST RE,SULTS ON TVERMECTIN 2,1 coverage and adverse reactions after three treatment rounds Approximately 116,250 people in the OCP area were treated with ivermectin in 1989: 70,000 by the OCP, 14,000 by Lunsar Hospital in Sierra Leone arnd32,250 by national teams in the Western Extension. Since 1989, monitoring has been limited to 36 hours, during which period only serious reactions have been recorded. Out of the approximately l16,250 people who have now been treated with ivermectin in the OCP area in 1989 only one case of asthma in a known asthmatic was reported by Lunsar hospital. Two cases of severe dizziness were recorded by the OCp. Only the case of asthma needed treatment and it responded promptly to one injection of aminophyllin. OCP coverage levels had remained high at second and subsequent treatments. In the Niandan river basin (Guinea), the number of people treated rose from lO,OO0 to 14,000 during the second treatment, due, it is believed, to the community's confidence in the beneficial effect of the drug.The third rounds of treatment of the Asubende and Milo foci have been completed. Coverage has remained around the initial 60% level, falling by only about l% between each successive treatment. The coverage of the most infected villages has either remained unchanged or has improved over time but a substantial reduction in coverage was registered in the lowest infected villages in both areas. 2.2 Microfilarial reduction and repopulation 2.2.1. Endemic /oci in the extension areas Reductions of 96%-99% in skin microfilarial (mf) loads in treated patients were observed in allbut one of the trials in the extension arel§. In the Mako focus in Senegal, mf loads appeared to have fallen by less than 90% one week post-treatment but the follow-up skin snips were probably taken too soon after treatment to show the true decrease. The effect of ivermectin and the subsequent repopulation of mf coutd clearly be seen by comparing mf loads in those treated once or twice with those who had escaped treatment. Even after two treatments in the Asubende trial, mf were repopulating the skin at a much faster rate than that observed in the clinical trials.Howgvsl' there was some indication that mf loads had increased more slowly after the second treatment round in persons treated twice as compared to those who had been treated for the firsttime during the second round. Further follow-up was recommended for this focus where the collaboration of the population remains excellent. -1- ') 2.2.2. The Dienkoa /ocus In the Dienkoa focus, where there has been a relapse of transmission during the vector control period, a very different trend was observed. Two months after the first treatment the mean mf load in treated persons had fallen by more than 99% but fifteen months after treatment, and just before the second treatment round, the mean had risen till above the pre-treatment level. The most remarkable finding was that four months after the second treatment the mean mf load had reduced by 27% only. More detailed results showed that a considerable number of skin snip negatives had become positive after treatment. Furthermore, mf repopulation was faster in those with low mf loads its compared to those with high loads. Due to the implications of this very recent finding, all steps in data recording, processing and analyzing will be rigorously checked and a sample of tablets will be sent to MSD for potency checking. Unless an error or other problem is uncovered, it may need to be concluded that the second treatment occurred at a time when many worms were still pre-patent and, possibly, that ivermectin is for some unknown reason less effective in new infections. If it takes approximately 2 years from inoculation of L3 larvae into the human body till the moment that the offspring of the resulting adult worms have reached a sufficient density in the human host to be detectable in skin snips, then the relatively heavy transmission in June-July 1987 may have been responsible for the significant incidence of patent infections in the summer of 1989. It was stressed that the epidemiological situation in the Dienkoa focus, where between 35% and 45% of the first line population was still skin snip positive at the start of the trial, is not comparable with a recrudescence situation where worm loads would start virtually from zero and the worms' reproductive rate would be limited by the difficulty of finding a mate. Furthermore, pre-treatment mf loads were low, with all CMFL's being below 4 mf/s, and there is as yet no question of a public health problem in this focus. 2.3 Observed effect on transmisslon 2.3.1 . Asubende Transmission data for three annual ivermectin treatments have now been collected. Differences in biting and parous rates between years and some instability in the infection rates after ivermectin treatment complicated the comparisons. However, the overall pattern in 1989 was basically similar to that in previous years (Fig.l). One year after the second treatment round, the vector infection levels had again increased to over 50% of the pre-ivermectin levels of 1987. The rates for L3 larvae were even higher than those before the first treatment in 1987, but this could partly be attributed to the high parous rates in 1989. Also the third treatment resulted in a major decline in vector infection levels but the infection rates fell more slowly than after previous treatments. During December 1989 there was a sudden change in the vector population when the daily biting rate (DBR) fell from values of over 150 to less than 30 bites per man per day. During the first week of January 1990 the DBR started rising again and stabilized around values of 200 bites per man per day. The estimation of the reduction of vector infection levels after the third ivermectin treatment round will, therefore, have to await the full entomological results for January 1990. From an operational point of view the results for the year following the second treatment were the same as for the first post treatment year, and it was again concluded that without vector control the ATP would have been in excess of 1000, a level of transmission which is unacceptably high. From February 1990, the Asubende focus will be subjected to year-round vector control. JFig.1: Vector infection levels in Asubende Chrnges following ivermecUn distribution (, , a o aÀ ooo oÀ U a aJ oâ az 320 300 280 260 210 2ZO 200 r80 t60 t,10 r20 100 80 60 {0 z0 0 04-Sep 03-Nov O2-Jc-u 02-Mu 1987 1986 02-Nov I 9BB 0 I -Jan I 989 l3-Sep l2-Nov I 989 I I -Jan l 990 - Ll2 larvae L3 larvae 2.3.2. Milo Infection rates in over 10,000 parous flies collected at a capture point in the centre of the treated area in January-March l98E and 1989 were compared by staining to determine the effect of rhe November 1988 ivermectin delivery on transmission. Although biting rates were higher in 1989, parous rates were sufficiently similar to allow direct comparisons of infection levels. The proportion of flies with early (Lt/L) stages fell by only l0%-1506 and, although the proporrion of flies with all L3s fell by over 3006, no significant change in infective fly and infective larval indices was observed. Eighty-five head L3s had a mean length of 775 microns (compared to 612 microns for O. volvulus from Ouadaba along the R. Gambia in Guinea) and 39o/o of these were over 800 microns in length. This suggests that animal Onchocerca species obscured the potential effect of ivermectin on transmission in this focus. This stretch of the Milo is now subject to full scale annual larviciding and only routine entomological and epidemiological monitoring is planned. 2.3.3. Bui This study was designed to investigate the additional impact of mass ivermectin treatment in the Bui Gorge, an area where vector control has not been sufficient to interrupt transmission. Ivermectin was delivered in August 1987, July 1988 and June 1989. A high level of vector control on the Black volta itself was maintained throughout and all flies were assumed to have invaded from elsewhere' When the periods after long distance fly movement (mid-August onwards) are compared, the transmission of head L3s was reducedby 76%-78% in 1987 and by 85%-92ÿ0, in both lggg and 1989. Reductions of 80%-84% were even recorded in June-July, when some reinvasion from other river basins to the south-west might have occurred. Comparisons with previous years suggest that, without ivermectin, the I989 ATP of 128 might have been 5-6 times greater. However, a true perspective of ivermectin's additional role in lowering transmission in this focus is limited because of our uncertainty of the flies' origin (which may vary from year to year causing transmission to fluctuate naturally). Mf loadi in the Bui area and, almost certainly, the flies' Ivermectlo Ivermectin v Ivcrmcctln Y i iÉ i:l i ri o Êt o o 4sources, have been falling steadily since control began despite the fact that transmission control has been incomplete. The natural decline in mf loads must have added to the reduction in transmission during the trial. 2.3.4. Dienkoa This focus of onchocerciasis on the Dienkoa River in South-western Burkina Faso was only sporadically controlled in 1980-1985. Infection levels have increased in recent years and the OCP has made a detailed study over the last three years to determine to \rhat extent ivermectin can reduce transmission. The Dienkoa focus was treated with ivermectin for the second time in early July 1989 (the first treatment had been in early April 1988 and the focus has also been treared in November 1989). May-September infection rates in the three years were compared. A high proportion of the target population was treated (64%). Assessments of changes in transmission levels were hindered by considerable differences in biting and parous rates between years. Infections withLl/L2 stages were chosen for comparison because these are least affected by fly age. Not more than 25% reductions in transmission occurred in the first four months after the first treatment in April 1988. The July 1989 treatment coincided with low biting and parous rates but infection levels in the mid-July to end of September periods were shown to have fallen by nearly 600/o compared to the month before treatment. However, transmission levels remained at least as high as in previous years suggesting that ivermectin had only succeeded in stabilising and not reducing transmission in this focus. Such a result is hardly surprising once the rate of mf repopulation (see section 2.2) is taken into account. 2.4 Predicted long term effect on transmission and paraslte reservoir In the model the effect of ivermectin has been quantified using the results from the community trial in Asubende which has yielded the most extensive longitudinal skin snip data after ivermectin treatment and the best data on transmission. The observed trends in skin mf loads and in vector infection levels during the two years after the start of ivermectin treatment were similar to those predicted by the model. The latest field observations for the Asubende focus provide therefore further support for the modelling conclusion that Iarge scale ivermectin treatment alone cannot achieve the progressive elimination of the parasite reservoir in endemic areas in the West African savanna. The major uncertainties in predicting the long term impact of ivermectin treatment concern the mf repopulation dynamics following treatment and the cumulative effect of repeated treatment on mf production. A revised version of the model has been received which allows a more realistic simulation of the repopulation process. The revised model is currently being tested and quantified, but it is not expected that the modifications will affect the major modelling conclusions. It was recommended that the model predictions continue to be tested and refined when more data on the long term effect of ivermectin treatment become available. 2.5 Disease prevention At Asubende, twelve months after two rounds of ivermectin treatment at one year intervals, ocular microfilarial loads have declined to levels which appear safe and pose little risk of provoking the development of onchocercal eye lesions (Fig.2). Early lesions of the anterior segment of the eye continue to regress and in particular the incidence of iridocyclitis has been reduced to virtually nil. Lesions of the posterior segment have remained stable. Though the analysis has not been completed, clinical impressions indicate that subjects who still carry high ocular microfilarial loads are those who have not benefited from two ivermectin treatments. It is noteworthy that two epileptics with advanced eye lesions and very high ocular microfilarial loads who had not been treated with ivermectin because of the exclusion criteria, have gone blind. The contrast between the deterioration of eye disease noted in those who have not been treated with ivermectin, because 5Fig.2: Mean ocular microfilarial Ioads in Asubende ch s afLer ivermecLin treaLmentll0 100 90 BO 70 60 50 40 30 20 l0 0 4 8121620 Number of months after first treatment z4 of the exclusion criteria, and the improvement or stabilisation of the eye lesions in those who have benefited from two rounds of ivermectin treatment, would suggest a review of the exclusion criteria to enable maximum availability of benefit to all. Furthermore, and contrary to impressionsgained one year after the first round of ivermectin treatment, it now appears that treatment at yearly intervals could also be advocated in such holo-endemic areas. These very gratifying results suggest that the role of ivermectin in the prevention of disease may be even greater than hitherto demonstrated. 2,6 Further research It was concluded that the OCP now had sufficient information on the effect of ivermectin on transmission in an endemic disease situation (Asubende) and in a focus (Dienkoa) where the disease had relapsed due to a localized failure of vector control. Both foci will, from lst February, be subject to the full I4 years of vector control, Asubende as part of the Southern Extension and the Dienkoa by ground treatment organised by local communities once the OCp itself leaves the area. Transmission at both foci will be monitored only on a routine basis since every attempt will be made to maintain vector populations at very low levels. The Asubende focus will continue to be treated annually with ivermectin and cohorts followed as long as possible. Mf loads in the Dienkoa focus will be monitored to find out how the situation evolves. The OCP still needs to determine the degree to which ivermectin can control transmission in a true recrudescence focus, what critical threshold should be reached before ivermectin delivery should be undertaken, and the best dosage frequency to achieve control. Such a focus has yet tàbe found in the OCP. The explosive build-up of parasite populations, as found in the Dienkoa area, needs to be studiedfurther to determine whether ivermectin does have a reduced efficacy where a very young wormpopulation is involved. Immunodiagnosis will be conducted longitudinally in this focus io helpdetect new infections and determine the effect of ivermectin. ihe modet needs to modified toincorporate the possibility that ivermectin effectiveness and mf repopulation are dependent of q) 6 ù) 4 i)! I G)i.À o C) à0 0)() l< oÀ 0 ta.-----__-- MFAC DMFC 6worm age, and it should subsequently be used in the analysis of follow-up data from the Dienkoa focus. A somewhat similar population is found amongst Chadian refugees who have settled in hyperendemic foci in Northern Cameroon. It was recommended that TDR be requested to consider supporting an ivermectin trial in that focus to study the impact of ivermectin in new infections. It was recommended that the OCP study the movement of the human population in areas where ivermectin coverage is critical to the Programme. The ophthalmological findings in the Asubende trial indicate that annual treatment is sufficient to control blinding disease in endemic areas. \Yhere the disease dynamics are different, such as in recrudescence situations, the frequency of ivermectin treatment may have to be increased to catch infections very soon after the pre-patent stage and provide some control of transmission. It was recommended that the OCP contact MSD to determine the minimum safe interval between treatments. It was noted that spectacular improvement had been observed on lesions of the anterior segment of the eye, notably sclerosing keratitis, which could only be demonstrated objectively using photography. This has not hitherto been possible but it is planned to upgrade the existing photographic equipment of the OCP to enable the documentation of important ophthalmological observations. Improvements in skin lesions are known to be very difficult to quantify and it was recommended that this be left to other workers. Evidence of other changes in health, such as weight gain following ivermectin treatment, which has a broad spectrum effect on worm parasites, could be collected anecdotally or extracted from the EPI data. 3 DIAGNOSTIC TOOLS AND TRANSMISSION STUDIES 3.I Identificatlon of O.volvulus stralns ln order to redefine the limits of the OCP which is concerned with the control of the blinding form of onchocerciasis, a means of identifying the pathogenecity of parasite strains is required. 3.1.1. Ophthalmological patlerns An analytical method, relating indices of ocular onchocerciasis to the CMFL, has been developed by the OCP to describe the epidemiological pattern of ocular onchocerciasis in different bioclimatic zones. In the savanna zone of the original OCP area the ocular microfilarial load expressed as CMFL/AC and CMFL/C, as well as the standardised prevalence of onchocercal eye lesions and blindness, increase with increasing CMFL. In forest foci where S. yahense or .S. sarrclipauli are the main vectors, onchocerciasis is rarely blinding and neither the prevalence of onchocercal eye lesions nor the prevalence of blindness show an increase with increasing CMFL. The differences in the ophthalmological patterns are consistent with the hypothesis that complexes of vector species and parasite strains are responsible for the different pathogenicity of onchocerciasis which is blinding in the savanna and non-blinding in the yahense and sanctipauli forest foci. In savanna villages, onchocercal blindness usually starts to occur where the CMFL exceeds l0 mfls (15 in the highest sex or l0 in both sexes). Describing endemicity by CMFL evokes a quantitative, linear relationship between disease and infection levels and is therefore more precise than descriptions based solely on prevalence. Nevertheless, the present classification of high risk villages as those with a CMFL > l0 mf/s, is broadly comparable to the classification of hyperendemicity based on prevalence. 73.1.2. DNA probes The differentiation of the blinding from the non-blinding strains of O. volvulus is essential. The ophthalmological examination of carefully selected villages in specific geographical areas remains the surest way of differentiating blinding from non-blinding forms of onchocerciasis. However, this technique has two limitations; it is expensive and is reliable only in villages with high CMFLs(40 or more) and these are not always to be found in all areas requiring assessment. The OCP has embarked on a detailed study of the usefulness of DNA probes in differentiating blinding and non-blinding strains. Nodules are being collected from I5 foci where ophthalmological surveys have been undertaken and for which there remains no ambiguity concerning the type of ocular disease. From each focus, ten subjects will be selected from whom three nodules will be removed. Each nodule will be coded and one nodule per person sent to the University of Alabama for identification. It is hoped that the results achieved yrill confirm the expectations based on preliminary findings reported at O-NOIY! in September 1989. The remaining nodules will be preserved for possible future testing with other probes. Once a probe has been shown to be satisfactory using adult worm material, it is important that a technique be developed which will enable its employment in the identification of L3 larvae. 3.2 Differentiation of O.volvulus and animal OnchocercaL3s Since human and animal Onchocerca L3s are notoriously similar, ATPs cannot be accurately estimated and thus the success of vector control cannot be correctly determined in areas where there is significant zoophily. Inevitably target species cannot be properly defined. Two techniques are or should soon be useful to the OCP: length measurement and DNA probes.. Recent studies in the OCP area have indicated that the careful measurement of populations of infective larvae can yield valuable indications of the proportion of O. volvulus. Rarely, as with Type D which may form up to 70% of head L3s on the Baoulé in lVestern Mali, larvae can be separated morphologically. Length measurements can provide probabilities of animal Onchocerca presence as in the Milo ivermectin trial (see above) and on the Gambia where the mean lengths were 130 microns S,reater than that observed for O. volvulus. Sierra Leonean L3s collected fiom S. soubrense B, fitted the distribution for O. volvulus closely but some bimodality in the distribution suggested that the presence of animal parasites cannot be ruled out. There is a need for further measurements of L3s from populations where other filarial species are very rare or absent in the vector. Ideally, the DNA probes developed to separate Onchocerca at the genus, species and strain level could be applied to L3s. Unfortunately, the extraction olDNA from the L3s still remains an obstacle. Until laboratories receive large samples of L3s for experimentation, no further progress can be expected. Therefore, the colleJtion of L3s shou]ld be intensified in order to stimulate laboratories to work on methods for extracting DNA so thatblinding o. volvulus fly infection can be separated from non-blinding and animal infection. 3.3 Diagnosis of new infections The future diagnostic value of the skin snip method will be limited because of large scale ivermectindistribution in the extension areas and the need for a more sensitive method fàr the diagnosis of new infections after cessation of vector control in the central ocp area. Further computer simulations of recrudescence have been undertaken in order to study the associated incidence of parasite infection and the incidence of patent infection as evidencèd by skin snips. Isolated incident cases of onchocerciasis infection are likely to occur after the cessation of vector control but these do not necessary reflect recrudescence which implies transmission andincidence of (super)infection at a sufficiently high level to result in the piogressiue increase of the parasite reservoir. The main difficulty in epidemiological surveillance wiil be the timely and 8correct epidemiological diagnosis of a recrudescence situation. The availability of a diagnostic test for pre-patent infections is not as crucial as was previously thought because of the relatively short duration of the pre-patent period. Much more valuable would be a diagnostic test for infection with adult live worms, whether involved in reproduction or not, because this would allow the detection of an increasing worm population many years before this would be possible with tests for patent infection. Nevertheless, whatever the test available, the epidemiological interpretation of test resulrs is going to be very difficult. Significant progress has been made recently in the field of immunodiagnosis of onchocerciasis and several research groups have reported the identification and production oî Onchocerca-specific antiSens. A meeting of research groups from six countries was held in November 1989 in Heidelberg, and OCP and TDR were also represented at this meeting. A diagnostic tool for onchocerciasis infection must be nearly 100% specific to be of practical value during the post-larviciding period, when the parasite reservoir has been virtually eliminated. Nearly all research groups reported a specificity of more that 95%, but no test was proven to be sufficiently specific for use in the field. The Heidelberg meeting proposed as a solurion to the specificity problem the development of a cocktail of those antigens which already have a high sensitivity and specificity. Seven of the research groups agreed to join a multicentre study on Onchocerca recombinant antigens. The first phase of this study will involve the blind testing of the currently available antigens for sensitivity and cross-reactivity using selected sera from rhe WHO serum bank in Basel. This first phase should be completed by mid-1990 when a cocktail will be made of the most promising antigens. The cocktail will be tested in the field during the second phase of the study. The outcome of the second phase will determine if a start can be made with bulk production of antigens and development of a practical field test kit. OCP will have to play a leading role in field testing and in further epidemiological testing because the laboratory based research groups have little interest in this part of the study. The field testing will be difficult as it requires longitudinal serum samples of newly infected individuals who are not yet in the patent stage. With the extension of vector control operations it will be increasingly difficult to find such persons in the OCP. Nevertheless, the Programme has already capitalized on the special circumstances in the Dienkoa focus where baseline sera have been collected from l3l skin snip negative persons who will not be treated with ivermectin unless they become skin snip positive. Follow-up sera will be collected at annual intervals. It is also intended to take bloodsamples from skin snip negatives from the Asubende focus. Furthermore, the cocktail will need to be tested with sera from a previously hyperendemic area where the infection has died out, such as the Koulpeolgo basin. 3.4 Vector feedlng and Transmlssion Experiments Previous studies in Ghana, Mali and Guinea had each shown that the retionship between the number of potentially infective larvae per fly and the skin mf load of the human host was similar. Since this relationship is a key parameter in the simulation model, additional experiments were undertaken at Asubende with people recently treated with ivermectin and at Mano on the R. Taia in southern Sierra Leone where S. soubrense B is the main vector. Two months after ivermectin distribution at Asubende, 1040 flies were engorged on 20 treated patients with high pre-treatment mf loads and low post-treatment loads between 0 and l8 mf per skin snip. Of the 803 mf ingested, only 2l became potentially infective confirming, as in previous studies, that individuals with low mf loads contribute very little to transmission. -9- The peritrophic membrane of S. soubrense B was found to form much more slowly than in savanna vector species allowing 45%-55% of the mf ingested to escape from the gut. The relationship between human mf load and the number of potentially infective larvae per fly was less than clear in this study. [n fact many flies allowed over a hundred mf to escape through the peritrophic membrane and, since the maximum recorded in 456 wild-caught infective flies did not exceed 27 infective larvae per fly, considerable mortality may occur in highly infected flies. Further studies of the fate of these mf and fly survival are planned. A series of cross-transmission studies showed that, compared to savanna flies, §. soubrense B may allow 60 times more of the mf ingested to become potentially infective whether the mf are from strains of Malian, south-east or south-west Sierra Leonean O. volvulus. Some differences in the capacity for savanna flies to become potentially infective with the three strains was observed and merits further study. 3.5 Diagnostlc tools for the vector complex The identification of the members of the S. damnosun complex is fundamental to all vector control activities. Three methods are used in the OCP: larval cytotaxonomy, adult morphology and morphometry, and electrophoresis. Fig.4 gives a family tree of the cytotaxonomically identifiable taxa currently used by the OCP. Formal descriptions are in preparation for several species and forms in the S. sanctipauli sub-complex (only the old names are given in this report). Larval cytotaxonomy still remains the only definite means of separating members of the vector complex. All identifications have now been entered into a computer database and can be retrieved, sorted and mapped. In routine identification, only diagnostic inversions are scored but full karyotyping is useful when trying to identify and track sub-populations which mây vary in Ievels of insecticide resistance or vectorial role. The cytotaxonomy of adults is still not feasible. Using the computer 'cytodatabase', simple maps of each vector species' distribution can now be prepared on demand. A suitable system for transferring the data onto a detailed map of the Programme Area is under investigation. Adult morphological or morphometric identification is less exact. Populations of savanna species can be separated from forest vectors in most areas but, in many areas where S. squamosum is present, overlap may occur both with savanna vectors and with species of the S. sanctipauli sub-complex. TDR funded research is exploring the use of multivariate analysis to resolve this problem. Electrophoresis does, however, provide a tool for separating S. squamosum and S. yahense from other vector species, a portable unit was developed with OCp funàing and two teams (one for each operational area) have been trained in its use. The use of DNA probeifor ttre identification of adult vectors is being studied outside the OCP but may eventually be helpful within the area. The Programme plans to invite a consultant cytotaxonomist to visit cytotaxonomy technicians on a regular basis to maintain quality and ensure that new developments are not missed. Studies on variations between populations of savanna vector species should remain a cytotaxonomicpriority in the light of reported differences in the levels of temephos susceptibility, anthropophily and long distance migration. It was recommended that because of the operational importance of larval and adult taxonomy, Guinean and Sierra Leonean technicians be selected for training by OCp research staff in cytotaxonomy, morphometry and electrophoresis. 10 Fig.3: S.damnosum complex - taxa used by OCP for cytotaxonomic identification S. DAMNOSUM COMPLEX D.Boa§e 1989 & Boakye et al (in prep). ,/ S. damnosum s.sLr S. dieguerense S. sirbanum FOREST GROUP S. squamosum S. yahense SANCTIPAULI SUB_COMPLEX S. sanctipauli s.s tr (S. konkourense s.n.) ,'""forme i, konkoure ",(menankaya) form standard S. soubrense B (S. leonense s.n.) form' djodji S. soubrense s.str. --' I -- standard (chutes milo) beffa form N.B. Species and forms in brackets have not yet been published. Their names should be restricted to internal OCP use only SAVANNA GROUP DAMNOSUNI SUB_COTIPLEX SQUAMOSUM SUB-COMPLEX -11 - 4 EPIDEMIOLOGICALMODELLING Modelling has become a fully integrated tool for evaluation and planning in the OCP, and most model applications are therefore discussed in other chapters in this report. The computer programme ONCHOIN! has been developed by collaborators of the University of Rotterdam. This programme allows interactive quantification of model parameters and inspection of graphical presentations of corresponding distributions (see Fig.4 for an example of the user interface). It will be made available to all OCP centres with computer facilities to allow the staff of all units to scrutinize and provide feedback on the current model quantification. The simulation programme ONCHOSIM has been modified to allow the continuous display of statistics summarizing the changing epidemiological and entomological situation during the execution of a simulation. These various enhancements greatly facilitate discussions and demonstrations of the use of modelling in the OCP. Fig.4: Ex le of the computer displa duri a session with the ramme ONCHOIN! A meeting, in which the OCP ophthalmologist participated, was held in Rotterdam in September 1989 to discuss ways of improving the simulation of ocular disease. A model extension was designed which allows the separate simulation of lesions of the anterior and posterior segment of the eye and which, therefore, enables more realistic simulations of morbidity control by ivermectin treatment. This model extension is currently being implemented. The collaborating institution has undertaken two sensitivity analyses upon request of OCP. The first concerned a detailed sensitivity analysis of the parameters which determine the distribution of the reproductive lifespan oî O. volvulus. The uncertainty in associated model variables was taken into account in this analysis. The main conclusion was that the mean reproductive lifespan of O.volvulus lies between 9 and ll years and that 95% of the adult worms reach the end of their reproductive period before the worm-age of l3 to l4 years. The second sensitivity analysis concerned the risk of recrudescence in relation to duration of vector control. The results confirm previous conclusions that the risk of recrudescence is still too great after l3 years of control, and that at least l4 years interruption of transmission are required. In all simulations with the model quantification, which is currently considered to be the most plausible, there was no recrudescence after l4 years of successful control. However, in certain (ÆcTm+ LART,,II Miot{ sIHtt-ATIOT (Pr t{IL >U ti lËul.t ion .nd tnitl.l FoI h.z.rd bvt ænttr) { IrltEl2(]50 1802.fi)mûrr:t m 3t.rttlhc (J-r) stopt llr ( J.n) llonthly Bit ing Eatcs {txx, 35()() 3()0(] 25(x) 2fiX) 15()(, lü)o 5q, o lo4 1a H8A ,rdrth FLI ES: - totel - inrlgrat ing St:rt- Stoo-tlne, Initial FoI (UIIL1-{} t=-r, -12- simulations with combinations of less plausible parameter quantifications there was still some risk after l4 years. The final results of this analysis have not yet been received in the OCp, but they will be taken into account in decisions on where and when to stop larviciding (see also sectioni 5.2 and 5.3). Plans and priorities for further modelling include the continued use and refinement of the modelin data analysis and operational planning, the quantification and testing of the ocular disease module, and the simulation of regional variations in transmission dynamics. The main focus of modelling will be surveillance and recrudescence control under devolution. For this reason rhe model needs to be extended to allow simulation of the application of immunodiagnosis, treatment with a macrofilaricide, and lvorm-âge dependant effectiveness of ivermectin. Sensitivity analyses of the importance of immigration of infected persons and the delay between the beginning of recrudescence and the start of its control will be conducted. 5 ORIGINAL OCP AREA 5.1 Report on larviciding in 1989 A brief report on larviciding throughout the area during 1989 was presented. The relative importance of the five classes of insecticide was highlighted as lvirs the relative scale of activitiesin the core area and the extensions. Yery high river discharges were recorded in the t989 rainy season and greater quantities ofpermethrin and carbosulfan were applied. However, this meant that less B.t. Hl4 was used (a more expensive larvicide to apply) and more suspensions were possible when breeding sites were flooded. The costs of larvicide and flight hours used were generally similar to those in 1988. 5.2 Criteria for stopping larvlcldlng The following criteria were proposed for stopping larviciding in any area. Firstly, the trends in the CMFL and the trends in the prevalences of cohorts in the indicator villages should be in accordance with or faster than the trends predicted assuming complete interruption of transmission. Secondly, in these villages, there should be no incidence in children born since the start of vector control or in persons snipped twice u/ith negative results on both occasions. In the other, non-indicator, villages, the prevalence and distribution of mf should be consistent with that found in the indicator villages. In addition to considering these epidemiological factors the entomological data, from the beginning of activities in each area, are also studied in depth. Where there is evidence that transmission was taking place at some stage after control began, even more intensive EPI surveys are likely to be made. In any case in such areas great caution is exercised before a decision to permanently cease larviciding is taken. If the above criteria have been met, larviciding can be stopped after 14 years but subsequent confirmation is needed from detailed entomological studies of vector infectivity levels. If they have not been met, detailed studies should be undertaken to determine the risks of cessarion of larviciding, the likely delay required before larviciding can be safely discontinued and the possibility that other solutions may be appropriate . 5.3 Latest Entomologlcal results In Phases I and II of the core area, entomological results were very satisfactory as regards levels of transmission. In the White and Red Volta valleys, especially in the latter, there were higher numbers of flies.than in any year since l98l but these were almost entirely devoid of infective larvae. [n Niger, where vector control has been discontinued, 1854 parous flies were stained and l3 examined for parasites. Only two L3 larvae were detected (less than Ll head L3s per 1000 parous flies), both from the Mekrou river where it forms the border between Niger and Benin. Pig.S: Biting Rates and Transmission Potential at Folonzo 16 000 t4 000 l2 000 l0 000 I 000 6 000 before, during and after vector control L Q)t û) 32 ÉZ è0() FC çac 4 000 2 000 0 800 700 600 500 400 300 200 100 0 l97l-1973 (Pre-control) Vector control From the Sota valley, where larviciding has been abandoned in favour of disease control using ivermectin, 6650 parous flies u/ere examined, 3359 after staining. These yielded a total oî 27 infective larvae, a rate of less than 4.1 head L3s per 1000 parous flies. These are very satisfactory results given the circumstances. In the western part of the core area, transmission levels were acceptable in almost all areas, except on the R. Dienkoa (suspended for an ivermectin trial) and the Lower Bandama (treatment problenrs due to excessive fluctuations in discharge caused by a dam). In the reinvasion zones near the borders with the \Yestern Extension, ATPs at last approached acceptability (cf section 9.2). At Folonzo on the Upper Comoé, a river where larviciding has been discontinued since February 1989, l5 days of intensive collections produced 2,022parous flies of which only 2 were infective, each with I L3 in the head (see Fig. 5). Such low levels justified the decision to stop ve6or control on this river. e) O > q) D -kdx Érrol zË.ÈrréEié .9 ., aê oia (,)odoAT -LoF.O t975- t977 I 978- l 988 I 989 vector control ceased -14- 5.4 Latest Epldemlologlcrl Results Data concerning the latest EPI results were presented from 4 countries. In Mali, the results from the Farako area, the first area in tho Programme where larviciding was discontinued, indicate the virtual elimination of onchocercal infection. Reiults from the reinvasion areas of the same country were very promising and showed a delayed but progressive decline in the CMFL and prevalences of infection. In the previously highly endemic Bougouriba Basin of Burkina Faso, the evaluation of l5 first line villages showed excellent results. Prevalences of infection were below 6% in all villages. The prevalence of 2.8% at Mouvielo lvas particularly noteworthy since, before vector control started, it was the village with the highest intensity of infection in the total OCP area (the CMFL in males was I l5 mf/s) and the prevalence of blindness u/as as high as l2%. Fig. 6 shows for Mouvielo the trend in CMFL and prevalence of infection in adults during the control period. In spite of the initial delay in the decline of the CMFL, which was previously attributed to reinvasion of the Bougouriba between 1975 and 1978, the final fall in the prevalence of infection is highly satisfactory and only slightly slower than predicted. The epidemiological situation in the Bougouriba valley is therefore better than expected. Fig.6: Epidemiological trends in Mouvielo, R.Bougouriba 110 100 90 80 70 60 50 40 30 20 l0 0 0 èR q (É :1H> OJ a f:<àà 0) rr q) l.À z4 6 I l0 L2 t4 16 Years of vector control r8 20 In Ghana, the villages surveyed on the \Yhite Volta, Sissili, and Oti Rivers'have prevalences declining in acèordance with, or slightly slower than, the predicted trends. In the village of Nakong, howovêr, the trends are delayed by a few years and indicate partial failure of the vector control effort. ' In the intermediate area of Côte d'lvoire, the results from the lower Nzi and lower Bandama Basins were geneially disappoihting. The epidemiological tiends in villages along the Comoé were better and close to the predicted trends. However, for dhe latter villages there was evidence of new infections during the control period and a more detailed âssessment of the risk of recrudescence is required before decisions can be made to stop larviciding along this river. ii, CMF . --.------- - Predicted r---t 0bserved I L mf in adults'revalence of 15 5.5 trYhere and when to stop larvlclding The latest epidemiological surveys will be completed by April. Once all the data have been analysed, a small group will study this information in conjunction with the longitudinal entomological data in order to assess the feasibility of safely interrupting vector control in additional parts of the original ocP area during the forthcoming wet season. Governments and populations should be informed immediately a decision is taken to discontinue vector control in significant areas. Weekly maps will be prepared with transmission highlighted so that control actions are more closely geared to the threat of transmission and excessive concern is not accorded to biting rates. 5.6 Entomologlcal evaluatlon durlng two years after cessation of larviciding In order to evaluate the accuracy of decisions to stop larviciding in any area, it is desirable that a very large sample of flies be examined for infective larvae (which are likely to be rare during the subsequent two or three years). Normal entomological evaluation practise does not usually produce a sufficiently large sample. A small working group chaired by Chief VCU should look into suitable methods for obtaining a large body of data concerning the proportions of infective parous flies in the two years following the suspension of vector control, in order to assess the accuracy of the judgements which led to the decision to discontinue larviciding treatments. 5.7 Effect of Vector Control on Animal Onchocerclasis In the discussion on O. volvulus transmission in areas where the vector(s) was significantly zoophilic,it was acknowledged that long-term vector control operations could have a considerable effect on the transmission of non-human filariae in wildlife and domestic stock. In fact, a study conductedin Togo had clearly shown that the prevalence of filarial infections in cattle had appreciably declined in an area where blackfly control operations had been conducted for several years. It was suggested that this point might be of interested to FAO. 6 DEVOLUTION This very important subject was introduced by a brief summary of the overall concept of devolution and of the components considered essential to ensure that Participating Countries are eventually able to sustain Programme achievements long after the Programme comes to an end. Accordingly, during the discussions which followed, attention was focussed largely upon the technical .rpÀ.t, of epidemiological surveillance, treatment with ivermectin, training, inter-country coordination and the exchange of information. The ultimate success of the Programme will depend on the Participating Countries being able to detect new cases of onchocerciasis after the end of OCP operations (recrudescence) and tà control recrudescence by means of ivermectin application. In the case of premature interruption of larviciding,, new parasites will develop in infected personsfairly soon afterwards although at an initially slow rate. The ATp will also show an early, bur moderate, increase, while the CMFL will remain low for several years. Blindness will only occur several years thereafter. Even if effective larviciding has virtually eliminated the human reservoir of the onchocercalparasite, individual, isolated instances of new cases will occur (e.g. as a result of migration). This, however, should not give rise to excessive control measures. The level of incidence signifying recrudescence is still to be determined. 76 The essential components of devolution are active (mobile) surveillance focussed on predetermined high risk zones and control of any instance of recrudescence that may occur by large-scale ivermectin distribution. Early detection of recrudescence is of crucial importance. It is imirortant to establish, or strengthen, a central epidemiological surveillance and control unit at the national (ministerial) level of the Participating Countries. Such units, with qualified and experienced epidemiologiss in charge, will deal with onchocerciasis surveillance as one of several activities and will plan, direct and evaluate field activities and institute control whenever called'for. Further research on the determination of the incidence level at which recrudescence control must be instituted is of priority concern to the Programme as are the effectiveness and modalities of ivermectin control. Also, field studies must be conducted to determine the optimal frequency and intensity of onchocerciasis surveillance. Cases of new onchocerciasis infection detected by health centre staff should be reported to the central epidemiological surveillance and control unit as a support for decision-making at that level. The active surveillance will concentrate on first-line villages and consists of simple evaluation without the visual acuity test. Surveillance teams will have the results of previous evaluations available during the visit to allow for immediate comparison and reporting of new (recrudescent) cases. Each first-line village will be examined at least once every three years, one village in each zone being examined once a year. The OCP will train national staff and coordinate and initially supervise surveillance and control activities. The EPI epidemiological evaluation manual will be updated as and when required, and OCP staff üill accompany national surveillance teams to ensure conformity in field operations. National teams are already heavily involved in ivermectin distribution programmes. The training of high-level epidemiological units at the national level is of particular importance, and the OCP is actively exploring the possibility that postgraduate courses at universities/academic institutions in Ghana and Mali (Bamako) can be set up with the aid of US and Canadian universities. It is expected that the knowledge and operational experience of the Programme will be given due consideration in the course curricula. The importance of OCP staff at all levels maintaining a positive and constructive attitude to devolution was stressed. It is important to ensure that nationals become involved in OCP operations at the earliest possible moment and,that activities that lend themselves to'hand-overn, partly or fully, be taken in hand by nationals as soon as possible. In addition to training, coordination and supervision, the OCP will help the Participating Countries in preparing devolution documents and with advice in fund-raising from bilateral sources. Furthermore, the Programme will ensure and encourage inter-country information exchange concerning the findings and results of surveillance, instances of recrudescence and its control. Such exchange should be instituted at an early date and extended gradually to become fully operational before the end of the Programme. For this purpose, field teams could be equipped with simple, portable computers using OCP programmes with the findings of surveillance being transmitted to the central national epidemiological unit. It was agreed that entomological surveillance would not play a role in recrudescence detection, and vector control will not normally be part of devolved activities. However, in clearly defined and restricted zones, which are not source or recipient areas of important numbers of migrating vectors, limited ground control actions may play a part in helping to maintain the level of transmission below that which results in recrudescence of disease. -17 - 7 FT.JRTHER RESEARCH FOR OPERATIONS IN THE EXTENSION AREAS 7.1 Epidemiologlcal mapplng and ophthalmological patterns The epidemiological mapping of the lrVestern Extension is nearing completion. The areas with high endemicity and high risk of blindness are situated in the upper Niger basin, Gambia basin in Senegal and upper Bakoye basin, and the Tienfala focus along the R. Niger in Mali. To avoid misunderstanding, the terms hyper-, meso and hypo-endemicity should be used only for communities and other terms be used to describe zones. The southern limit of transmission of the blinding parasite strain, and, consequently, the southern limit of the operational area, still needed to be determined in the Western Extension. Ophthalmological examinations were therefore carried out in selected villages in the Upper Niger basin in Guinea and in Sierra Leone in order to determine the ocular disease pattern in these areas. The data collected were analysed by applying the analytical method to describe communiry patterns of ocular onchocerciasis in different bioclimatic zones (see section 3.1). Fig.7: Ocul l0 ar onchocerciasis patterns in the lTestern Extensic(Dottcd line ir rc3ression line for original OCP area) ! male population a femalepopulation 0 20 40 60 r00 o C)a 6 o 6 oL G) o o o o I o â è0 o x o o t,() ! D q) o q) 6 ok 0. 9 I 7 6 5 1 3 2 I 0 lo 9 I 7 6 5 4 3 ) I 0 0 a) Guinee ôa Ia b) Sierra Lcone a I I ô ô 20 40 ClvlFL 60 80 100 80 f D I hc community patterns of ocular onchocerciasis in these areas of Guinea and Sierra Leone were corlrpared with the patterns found in the savanna zone of the Original OCP area. For sinrilar lcvels of CMFL, the corneal microfilarial load in the community and the prevalence of advance«l sclerosing keratitis were much lower in Guinea and Sierra Leone than in the original OCP area. llowever, in both Guinea and Sierra Leone, there was a clear relationship between the prevalence of other sever eye lesions and onchocercal blindness and the CMFL. The relationship in Guinea was similar to that observed in the savanna of the Original OCP area (see Fig. 7a). In Sierra Leone there was also a linear relationship and, although the blindness levels were generatly lower than irr the original OCP area, onchocercal blindness reached significant levels of 4%-6ÿo for high values of the CMFL (Fig.7b). This inrplies that the parasite strain in each area in question is of 3 sc\/ere blinding form, qualifying both areas for vector control. ln the southernmost part of the Upper Niger Basin in Guinea, CMFLs are too low to determine w'hether the disease strain is blinding or non-blinding. The patterns of infection observed in two villages studied in northern Sierra Leone suggest rhat a non-blinding strain, different to that found in the south-west of the country, occurs in this zone. Further ophthalmological investigations will be conducted in Sierra Leone to delimit the distribution of blinding onchocerciasis. Further studies should also be undertaken on ophthalmological patterns in foci with sufficiently high GMFL where s. squantosunl is overwhelmingly the pre-dominant vector. 7 .2 Distribution of vector species Work has concentrated on obtaining the fullest information on species distributions in southern Sierra Leone. Nine species or forms have now been identified from the country. S. soubrense B is confined to the large rivers of lowland western Sierra Leone being absent from rivers and streams over 100 m of altitude. In highland Eastern Sierra Leone it is replaced by the Menankaya form of S. soubrense, S. squamosum aod S. yahense. Compared to 1988, in the 1989 dry season the savanna species were much rarer in the southern part of the country being virtually confined to the R. Moa, where biting densities were also considerably lower. In September, when larval collections were very difficult because of the high discharges, morphological and electrophoretic adult identification methods confirmed that savanna flies were common only in the extreme north(though up to 0.3% were still found on the R. Moa) and that S. soubrense was dominant everywhere else, except in the mountainous north-east where S. yahense was the commonest species. Species distribution maps prepared from larval cytotaxonomic identifications suggest that vector control is having a radical effect on the species composition of many rivers. The standard and Chutes Milo forms of S. soubrense and the Djodji form of S. sanctipauli have not been recorded for some time and have probably been eradicated. The man-biting Menankaya Form of S. soubrense on the Bafing in Guinea appears to have been replaced by the zoophilic Forme Konkouré. 7.3 Role of different vector species Until the infective larvae recovered from man-biting vectors can be separated into blinding and non-blinding strains, determining which vectors should be targets for control will continue to depend on cross-transmission studies (cf section 3.4) and knowledge of man biting rates, anthropophily, survival rates, natural infection levels and associations with blinding foci. The savanna vectors and ,S. soubrense B are clearly control targets though their vectorial role may be reduced at certain seasons and in certain zones allowing the controller to larvicide on a seasonal and selective basis. S. sirbanum has been found to be highly zoophilic in north-western Mali and very lightly infected in December in Eastern Guinea and in the late dry season in Sierra Leone. S. soubrense B appeared to have a very low survival rate in southern Sierra Leone in September. l8 -79 - Less than 6% of flies caught on the lower R. Sewa were parous and none were infective. This was partly due to mermithid parasitism (with over 48% of nulliparous flies infected). Comparisons of onchocerciasis blinding rates and the vector species composition in larval, biting and infective biting populations suggest that the Menankaya Form of S. soubrense may be the principal vector responsible for blinding foci along short sections of the Upper Milo and Niandan Basins in Eastern Guinea. Pure §. squamosum and §. yahense associated foci have never been lound to have disease of public health importance but the vectorial role of the forest species will continue to be evaluated in liaison with the EPI unit. 8 OPERATIONS IN THE EXTENSION AREAS 8.1 Results and plans for the Western Extension In 1989, another successful anti-reinvasion campaign was conducted in the Upper Sassandra Basin in south-eastern Guinea. Since 1985, when this basin was first brought under vector control, May-July MTPs in the reinvasion zones of Northern Côte d'Ivoire and south-western Burkina Faso have been maintained at l%-5% of pre-control levels. ATPs are now very low and human infection indices are falling rapidly. Some localised savanna vector breeding sites have been detected to the south-west of this zone in southern Sierra Leone and Liberia, but it would appear that they do not provide an impediment to successful control in the OCP area. The plan to extend larviciding to southern Sierra Leone in 1990 will further reduce this potential threat. Savanna vector breeding sites in Northern Sierra Leone were treated for the first time in May-July 1989 in an attempt to stop their reinvasion of eastern Guinea and southern Mali. Biting and transmission rates at most capture points in Sierra Leone were reduced by over 95%. In the Upper Niger Basin in eastern Guinea, biting and transmission was reduced by over 8090 compared topre-control levels (see FIg.8). In the reinvasion zone of south-eastern Mali, ATPs were for the first time satisfactory, with biting rates reduced by 70% compared to the period before anti-reinvasion larviciding in theÏVestern Extension. The continuing presence of invading flies was believed to have been duepartly to difficulties in treating the complex rapids in Northern Sierra Leone for the first time with B.t Hl4 and partly to tributaries of the Great and Little Scarcies which, at critical times, were dry near their confluence with the main river but flowing productively upstream in the mountains. Treatments of the Upper Niger Basin was suspended at the highest discharges and, as in previous years, vector populations took a long time to recover. This selective, seasonal approach will be continued. Now that the serious blinding nature and public health importance of the disease has been confirmed by detailed ophthalmological investigations, from 1990, vector control will be extended to rivers in southern Sierra Leone. S. soubrense B will be the principal target of vector controlin this area. In the northern part of the \ryestern Extension, only the R. Gambie Basin was treated in 19g9. Larviciding was conducted at exceptionally high discharges. Despite successful treatment, capturepoints were clearly reinvaded from river basins to the south-west and ATps, although including a large proportion of animal Onchocerca. were still very high. In the light of all available factors, it is intended that, in addition to the Gambie and Bakoye Basins, vector control be extended to the headwaters of the Senegal Basin, some of the Atlantic coastal rivers and the left bank tributaries of the Niger River in Mali. -20 - q) 6 à0 4J ço h ! {00 350 300 250 200 150 100 50 0 450 {00 310 300 250 200 150 100 50 0 Fig.B: Vector biting rates after larviciding in l9B9in comparison to previous years Arfanya, R. Seli, Sierra Leone (pale wing tufts onl,v) Sansanbaya, R. Niandan, Guinea 13 15 t7 19 2L 23 25 27 29 31 33 lleeks The entomological evaluation network of national teams in the five countries of the \Yestern Extension is now practically complete. The last operational base (Bo in southern Sierra Leone) was opened on the l4th January 1990. The network currently consists of 8 sectors with 25 operational bases housing 52 teams of 322 people. 8.2 Results and plans for the South-eastern Extension Entomological results in the South-eastern Extension were satisfactory except in two areas. These were the lower Ouémé Basin, where the Okpara River forms the frontier between Benin and Nigeria. There larviciding has helped reduce the transmission rate, but this remains unacceptably high. Also, in the Lower Ouemé River itself, transmission, though reduced by over 75%, still continues at high rates. In contrast, in the lower Mono where, before control, Beffa was an important vector, larviciding has been very successful. In the virtual absence of Beffa, repopulation by the vector (5. damnoszrr s.str.) has been slow and it has been possible to practise intermittent larviciding with the perennial Mono treated for only three cycles in every six. The other zone yielding unsatisfactory results is the Togo/Ghana border where the Asukawkaw and Dayi Basins have small forested headwater streams with ^S. squamosum populations. --+-- 1989 ---+-- 1988 Larviciding stuts /\in 1989 -4 / + a \ \ \ + ---D-- 1989 ---+-- t986 ""'-'o "-- 1987 ÿ Larvrcrd_ rng starts909tnl 21 Fig. 9 shows the ABRs attributed to "dark wing tufted" flies (classes 04/05) and "other" flies (classes 0l/02/03) caught at Djodji since 1984. At that site all'other" flies are S. squamosum and nearly all of the ndark" flies caught before control began were the Djodji form. None of the 'dark" flies collected since control began, and which have been examined morphometrically, have proved to be the Djodji form. Furthermore, Djodji appears to be absent from Ghana, west of Lake Volta, where only the typical form of S. sanctipauli is found. It now seems likely, therefore, that the Djodji form of the §. sanctipauli sub-complex has been eradicated, with a consequent decrease in transmission as S. squamosum is unable to replace it in target rivers. However, in 1989, S. yahense began to spread from its untreated sites and has become the dominant vector in the Dayi Basin. The significance of the transmission there remains to be determined. Fig.9: Annual Biting Rates for different members of the S. damnosum complex at Djodji (Togo) 260 000 240 000 220 000 200 000 r80 000 160 000 l.to 000 r20 000 too 000 80 000 60 000 40 000 20 000 0 84 85 86 87 88 89 ! Oart llng-tufted flies 77 OtrrLer Î\es For the second year, treatment in the South-eastern Extension has resulted in greatly reduced transmission in the border region of the Original OCp area. Larviciding in 1990 will closely resemble that carried out in 1989 given similar hydrological conditions. 8.3 Evaluation of the impect of vector control The concomitant larviciding and ivermectin treatment in the extensions areas will make it verydifficult to assess the impact of vector control on transmission using the currently available toolsfor epidemiological evaluation. However, it is planned to limit large scate ivermectin treatment to the first 6-7 years of control which would be sufficient to control onchocerciasis as a public health problem. After this period, vector control alone will continue for the purpose of transmission control. The classical epidemiological evaluation techniques, therefore, would again apply during the last 4-5 years of the vector control period. Other possibilities of using the skin snip téchniquàduring the first years of control may be considered, such as the longitudihal follow-up and exclusion from treatment of skin snip negative groups. However since thesé would largely comprise children who are not sensitive indicators, the benefit would be limited and the test might even create false optimism. o É èt) ca (! Pre -control Vector contr 22 jl''' ()nly satisf'actory sol'-;rion to the problcei remains the application of a specific and sensitive r;irr;runodiagnostic field trst which would lre able to identify new infections (see secrion 3.3). i',-t I'lan for large scalr irerrncctin distriLuiion l ir'' plan for large scalc i'*'ernrectin distri[:ution has trvo objectives: firstly to carry out disease , rrrtrol for the preventioil of onchocercal e1'e lesions and blindness and secondly to investigate , ,l lr, r i-ll0thocls of delivery' ior tirc clrug as par t oI national outreach services (for example ivermectinir ';rr,-nt in conjunction r,,.ith r,lccination cl;npaigns). l,r i',,'t:xtensions, areas a'e stlected for cl!:,.'rse control by ivermectin treatment only after rhe r.,r'llsof thegeneralandri.rlrilctlepidenriolrrgical nrappinghavebecomeavailable.Epidemiological ':'.', I'iirg in the IVesteni Il:<tcnsicn has nelrly been completed but, in the Southern Extension,i',il'tli: n'ork has still to l',-'done. Ivermectin treatment in the extensions is planned to lsst 6-7 .\\ i:. In the Original OCI'arr'a treatment rvili be restricted to some foci of relapsed transmission.rrj itigations into conductinq ivermectin trcetment with outreach services will be unclertaken in r;"')r'.i-Bissau, Scncgal ('l'urnbacoundr anci iiedougou), Mali (Faya) and Guinea (Koulountou). i ; ;i.i EFING ON INI-JIÀ.UI{IT RESE..IRCH ACTIYITIES '1 .: lnsccticide researclr ' , .ompounds are subrnittcd by the industrv to VYHO, and, after registration by lVllOPES, thel, ,, nt to the OCP for t-'r'eluation. In tl,l'first stage, the activity of these netÀ'compouncls is1 ''i crn .S. dantno.sunt s.l. larvae by thc Irsecticide Research Unit (lRU). If the activity is ;r,1ir'11'111sfl, selectivitl,is e'v'aluated by perl,rrrr.ring impact tests on the non-target fauna. In 1989 rr i: ",1. pyrethroid , OI\4S 3051 (Bayer) , ar,rl a new organophosphate, OMS 3052 (Bayer), were e.';;irrlted. OMS 305 I was found to be vcry'ective and will be tested further. Sevcral contacts ','t'r,'rttade with the industry in 1989 by tl:e Director and the Liaison Office in Geneva, and in Jrrnc 1990 a meeting has been planned betrveen WHO and chemical manufacturers. It is hoped tlrlt the industries'intercst in the needs of the OCP will be revived through these activities. []t'cltrse the efficacy of each compound dcpcnds on its formulation, research continues on ne\\, l,,r,rr:lations of currently used and closell,related insecticides. In 1989, five new formulations ol'crrbosulfan (FMC Int.) were evaluated. Two of the micro-emulsion formulations were rerained for further testing in 1990. The objective of this project is to improve the carry and selectivity ol operational carbosulfan. A new formulation of bioresmethrin (Roussel UCLAF) will be rested in sntall rivers; research on this compound continues because it is the best prospect for the replacement of permethrin should resistance arise. A new formulation of phoxim (Bayer) will alsc be tested in 1990, to evaluate its potential as an eventllF]l,replacement for chlorphoxim. With respect to B.t.Hl4 formulations, experimental formulations provided by Solvay were tested and found to be very active. It is hoped that larger samples of these formulations can be secured. A ncw quality control procedure for testing B.t.Hl4 operational lots has been initiated in 1989. 'Iltis procedure will help verify the efficacl, and stability of operational B.t.Hl4, and it will also provide sufficient background data for new experimental samples to be evaluated. The availability of niore efficient B.t.Hl4 formulations renrains a high priority for the OCP, because of the con:.iclcrable volume used annually and because of the costs of aerial application. Pvraclofos (Takeda Ind.) has reached tlrc operational stage of evaluation in 1989. This or'liunophosphate had already shown adequate efficacy and selectivity and this was confirmed b)' [u]l-scale operational tests on the Bandama Rlanc River (Sept.-Oct. 1989). Additional river tests rlriilcnstrated that the carrl,of pyraclofos is cquivalent to that of temephos (up to 20 km at 100 nr.l,is of river discharge). Although pyraclolos is an organophosphate, with the methods available, no cross-resistance could be detected between this insecticide and temephos or chlorphoxim. Even 23 the highly resistant S. sanctipaulf populations of the Lower Comoé River showed normal levels of susceptibility. 9.2 Insecticlde susceptibility testlng The resistance to operational insecticides is assessed continuously across the OCP operational area. Results of the last 3 years (1987-89) have been analyzed by a new method and included in a data bank. After compilation of the data, thresholds of resistance were re-assessed for S. damnosum s.l. populations. Cross- referencing with the cytotaxonomic data bank will help to redefine the range of susceptibility of the various members of the s, damnosun complex. 9.3 Optimlzatlon of larvlcldlng operetions It has now been proved that the carry of insecticides in rivers can be predicted for all conditions found in the OCP operational area. Prediction models of carry have been calculated for OCP operational insecticides through experimental river treatments, use of fluorescent tracer(Rhodamine WT), and bioassays. For some operational insecticides, such as temephos and carbosulfan, there is an obvious need for additional tests in 1990, in order to confirm model predictions. An optimization scheme based on these models and on the "Graph and Network' mathematical theory led to the production in l9E9 of an optimization computer programme. This programme calculates treatment plans that minimize both insecticide and application costs by taking into account simultaneously all relevant insecticide, river and aircraft parameters. The practicality of the programme wzls ensured through extensive consultation with VCU staff. The principle of optimization, although mathematically complex, is straightforward. A first programme, PERLES (produced by ORSTOM hydrologists), predicts discharges for the nexr seven days based on best and most recently available hydrological data. A data bank of the potential breeding sites on each river is then activated and a list of active breeding sites with their associated discharge can then be produced. The river bief to be treated, the insecticides, and the treatmenr scheme can then be chosen by Aerops staff. Different treatment schemes are available: fixed dose, optimized dose, etc. The programme then calculates optimal treatment points, doses and routes for the aircraft, taking into account the location of depots and night stops. Several levels of optimization are offered: one river, one aircraft for one day, or a whole area for several aircraft and several days. This last option is in development and should be completed in 1990, but the rest of the programme is now operational. The initial step for the OCP, the actual recording and coding of breeding sites at the different water levels, was initiated in 1989 and will be completed in 1990. Seven hundred and fifty'biefs'in the Western Operational Area have now been digitized and the hydrological model has been established for the Comoe, Bandama, Sassandra and Bani river basins, in addition to the Milo and Dion rivers. In 1990, the models will be extended to the rest of the \Yestern Extension area. Once tested and validated this optimization system shoutd extend to the Eastern Operational area. 9.4 Ecologlcal monltorlng Two principal activities are undertaken by the Programme's aquatic environment surveillance unit testing the impact of new larvicides and new formulations and evaluating the long term impact of vector control operations on the non-target fauna. A great deal of data on both the short and the long term impact of the.programme's larvicides now exists. Although the analyses have not revealed any significant long term;ffect on the fauna, several questions remain to be answered. Does each insecticide group have an individual and distinctive effect on the fauna? Are the members of each insect family affected in the same wayby a given larvicide? Can these effects be characterised in the long term? \yill it eventually bô 24 i. iblc to predict long t:'r.i:t clfccts from sliort term results? These studies are in progress and 'rlr,irlcl soon enable the Progranrme to predict the long term effect of new insecticides with great .,;'. -',i and precision u'hilst reducing the volunre of routine work. :'i.",1ilres have been takt'rt, in collaboration rvith BIS, to improve the processing, analysis and Ir.' rt'ntation of hydrobi<;logical data. luit rcsults on all tliesc lctivities will be rrrsrgnlgd at the Ecological Group Meeting at the end oj' i-r'bruAry 1990. rr " .Socio-cconornic sturlics ;'" S-,cio-economic Dcveloprnent Progra!nnre is in progress under the supervision of the CSA. ir ,.'rniists of two complerlcntary regionol studies aimed at identifying areas with prorlising t],".'i,tptneltt potential and reviewing land c,rtienrent experience in the entire oncho zone in order t(, ,1r3.\\'conclusions for fur(her in depth rir,rl),ses of oncho-freed zone development progranlmes :ti ltrr' national level l'h.'t'irst of these studies u'as completed in 1988. Its recommendation led to the identification Itittl formulation of natiorral oncho freed zone programmes or projects in most Participating Countries in the core area. In spite of the interest expressed by several donors, financial support rcnrrins the limiting factor. -l'hc' report of the second study which is targeted on land settlement experience and migration is due by April 1990. A1;lrt from these activities, ECO has been conducting socio-economic surveys in the Western I-.itt'nsion. These surveys include assessments of migration patterns and are therefore of direct rclr-r'ance to OCP activitics. IO DATA ANALYSIS AND COMPUTEIT SUPPORT Conrputerized data processing and analysis is now well established in the OCP. The entomological tlata anall'sis systenr developed by BIS, notably the programme MONTIILY, is used intensively in tlrt'opcrational centres of Bamako, Bouake, Odienne and Kara. It was noted that not all VCU strl'f'ntenrbers concerned are aware of the {'ull potential of the system and BIS was requested to kt'cp up its training efforts in this respect. I--lL;tronic databases have greatly improved tlie utilization of evaluation data and their accessibiliti, rrJrl,5S units. However, the entomdlogical data are currently much more accessible than the r'lri,lt'ntiological data. It was explained that the c,pidemiological database was extremely large and ,--rrnrplicated because of individual record linking which makes it impossible to copy the data base it';':ll'to drt'ferent computers. A start has been made with developing a EPI data base with ùrr)i'i-scctional summary statistics for each village survey, but the utility of such a data base llould be limited as the proper interpretation of the epidemiological data requires a longitudinal anal5,sis. Nevertheless, the meeting recommcnded that an EPI summary data base be made, and tl)at efforts continue to make data from all units as accessible as possible. 'l'hc computerization of aerial operations and logistics has been less successful and the current clata base programmes are considered inadequate. These programmes were first developed in 1984 and have undergone various non-documented modifications by subsequent consultants. It was agrced that a more powerful and flexible AOPS data base system would need to be developed and it was recommended that this would be done by an experienced programmer on a contractual basis under the joint supervision of BIS and VCU. -25 - With the rapidly increasing use of microcomputers in the OCP, software standardization becomes more important than ever. The main standards for OCP are SYMPHONY for integrated software, SYMPHONY and 123 for spreadsheets, FREELANCE for graphics, and SAMNA for wordprocessing. The meeting was informed that WHO/ISS is expected to recommend IVORDPERFECT 5.x as the WHO standard for wordprocessing. As soon as this happens, OCP will drop the unpopular SAMNA and change to WORDPERFECT for all wordprocessing even though this will require considerable retraining. There is a great need in both EPI and VCU for improved facilities to summarize computerized information on maps. The meeting was informed about the Geographic Information System (GIS) which is a computerized mapping system which combines different sources of spatial and descriptive data to produce maps for easy analysis. Though promising, the system is quite expensive and requires additional equipment. It was recommended that the OCP further explore the potential of new equipment and software in order to improve the presentation of Programme data on maps. The computer literacy of Programme staff, which has recently shown great improvement, should further be encouraged and facilitated by providing reference manuals in French for the major software packages used in the OCP and facilities should be made available for self-training in all major bases. 11 MISCELIÂNEOUS The question of internal research coordination and collaboration was considered. The meeting itself which was stimulating and good humoured indicated a good spirit within the Programme staff. Nevertheless, the geographical scatter of senior technical staff meant that a real effort had to be made to maintain the rapport within and between units. The appointment of a research coordinator within VCU was welcomed. From the viewpoint of external collaboration, the fact that a member of the OCP now sat on the Filariasis Steering Committee (SC/FIL) was discussed. It was suggested that technical colleagues should consider what suggestions they might usefully make to the Committee member, who in turn promised to keep fellow staff members informed of events in this important TDR Committee. In September the important O-NOW! Conference was held in Leiden. OCP staff, led by the Director, were much in evidence. The meeting was an unqualified success, participants far outnumbering the organizers' expectations. Despite a very crowded programme, the meeting was a \rery friendly occasion. Contacts made there have already resulted in important collaborative ventures with outside researchers (see section 3.1.2. and 3.3). tn addition a large body of research workers had gained a valuable insight into the operations of the OCP, and its scientific needs. The published proceedings will doubtlessly prove a valuable resource during the coming decade. The OCP was also well represented, by past and present staff members and associated workers, at the prestigious Royal Society of London meeting on Migratory pest. The year l9E9 proved an excellent one from the viewpoint of publications, thanks partly to rhe stimulus given by the above mentioned meetings. A list of papers which have appeared, or are in press, is appended. The Director called for continued efforts in this respect and requested more senior staff members to help their less experienced colleagues to prepare papers for publication. It was agreed that there remained a number of recent OCP studies fully justifying publication in the scientific press. The question of an OCP glossary was addressed. It was agreed that this glossary should be conf ined to a relatively short list of terms, specific to the OCP, or for which the OCP had developed a specialized usage. A preliminary list of terms thought to require definition was compiled. Words would initially be defined either in English or in French, and thereafrer a similar definition in the alternate language developed. 26 12 ITI'COMMENDAI'IONS I Further parasitological studies should L,c undertaken to clarify the impact of iverntectin Irt3tn]ent in situatir-)ns rvith relapsing on;l,ocerciasis inlection. .' (iiven the mljor clinical improventt nt :.fter ivermectin treatment, as demonstratr'cl [.r .trirthalntological [ollou -up after two trcr','.ir)cnt rounds, and the severe deterioration in sonrt' :l',;l-treated patients, it rvas rêcoflrrr)cnrltrl llr:t MSD be urged to revierv the current e.rclusioit r'i it.'ria lor ivcrntcctin treatrnent. -i \lrrr!' that the serious blinding nature anci ;rublic health importance of onchocerciasis in soulh,-,;;r .'-'rra Leone has been confirmed by tlctuilcd ophthalmological investigations, froût l(),/,). ',,.ctor control will be extended to rivers i;r this area. 'i. .'\s vector control operations are likely to continue for about l4 years in parts of the Progranrnre Itrca it is strongly recommended that elltrrts be intensified to secure new insecticides fro;l the chentical industry and that the Prograrnrne's capacity for the screening and evaluetion rrl' n,:rv larvicides and improved formulations be maintained. 5. New AEROPS computer programmes should be developed by an experienced programmer on a contractual basis under the joint supervision of BIS and VCU. 6. 'l'he nodule collection programme for testing DNA probes should be accelerated. Such probes rvould be invaluable in enhancing the n)ethod of determination of the distribution of blincling and non-blinding parasite strains. 1. Human migration studies should be conducted in key foci in the core area of the Prograrnnre to help predict the risk of infection being imported from outside the Programme. 8. The specificity and sensitivity of immunodiagnostic tests have at last reached an advancc.cJ stage and the Programme should make preparations for the extensive epidemiological evaluation of this technique. 9. Research on the technical aspects of devolution should be intensified with enrphasis on rhe early detection of recrudescence by imnrunodiagnosis, the modelling of recrudescence conrrol rnd the study of the likely impact of ivermectin. 10. Nationals must be involved in all activities concerned with devolution at the earliest possible rnoment. I l. Epidemiological units at the miiristerial level should be strengthened. 12. Inter-country information exchange concerning surveillance, recrudescence and its control will be of essence in the context of successful devolution. The OCP, in collaboration with the Participating Countries, should therefore set up a system of exchange for such information. This system should be gradually extended to become fully operational by the time the Programme comes to an end. 2'l Appcndix A LIST OF PARTICIPANTS l. 2. 3. 4. 5. 6. 7. L 9. 10. I l. 12. r3. 14. 15. 16. 17. l8 r9. 20. 2t. 22 23. 24. 25. Dr. H. Dr. O. Dr. C. Dr. R. Agoua Ba Back (Rapporteur) H.A. Baker (Rapporteur) Dr. D.A.T. Baldry Dr. Y. Bissan Mr. D. Boakye Dr. D.A. Carvalho Dr. O.W. Christensen Dr. H. Cresveaux Dr. K.Y. Dadzie (Rapporteur) Dr. G. De Sole Dr. P. Guillet Mr. P.A. Kaboré Dr. F.M. Keita Dr. D. Quillévéré Dr. J.H.F. Remme (Vice-chairman) Dr. A. Sékétéli Mr. E.J. Senghor Mr. E. Soumbey Alley Mr. S.A. Sowah Dr. J.F. Walsh (Chairman) Mr. L. Yameogo Mr. D.G. Zerbo Mr. J.B. Zongo \i,'''rl'!rr Il ]S [,IST OF RECEN'I'OCP PUBLICATIONS \ri'l'-i.'-i, K., K.Y.Dadzie, I I.Schutz-Key, tl.NI.Gillcs: The chemotherapy of onchocerciasis XIll I'tr r111g1 studies with ivernrectin in onchocerciasis patients in Northern Ghanr i r.ru.N,lecl.Parasir. 40 ( 1989) 361 -366. '\ \ :r'.i.ri, K., K.Y.Dadzie, G.Dc Sole, J l'.cilme. Reactions to ivermectin treetnrcnt irr ,,r,.1)(lcerciasis patient.s. r\cta t_eidensia ( 1990) in press. ii,rl.r'r, I{.1'l .A., P.Guillet, ,,\.Séketeli, P.Pourliougo, D.Boakye, M.Wilson, Y.Bissan: [,rogress in ct.rntrolling the reinvasion of *'ind-borue vcctors into the western area of the Onchocercilsis(--uirtrol I'rogramme in \\'est Africa. phil.l-rens.Royal society B (1990) in press. llrrrir ir. K.R., B.O.L.Duke. C.D.Ginger, W.E.Gutteridge, R.Le Berre, D.Overbosch, J.Rernnre. i-.\l.Samba, Il.J.van der Kary and J.F.\\,alsh. S;,nrposium on onchocerciasis: conclusions an(l rcconlntendations. Actl Leidensia (1990) in press r- ht-'ke, R.A., M.A.Howe, M.J.Lehane, A.L.Millest, T.Kone, R.H.A.Baker: The ages of Sinruliunt srrhanum reinfesting the WI{O Onchocerciasis Control Programme in Mali; estimates b}, anall'ses of pteridine concentrations. Phil.Trans.Royal Society B (1990) in press. Cheke, R.A., M.Dutton, H.S.K.Avissey, M.J.Lehane: Increase with age and fly size of pteridine concentrations in different members of the Sintulium damnosunt species complex. Acta Leidensia (1990) in press. I)rdzie, K.Y., K.Awadzi, A.C.Bird. H.Schulz-Key: Ophthalmological results from a placebo controlled comparative 3-dose ivermectin study in the treatment of onchocerciasis. 'I'rop.Med.Parasit. 40 ( 1989) 355-360. I )rrtlzic, K.Y., J.Remme, A.Rolland, B.Thyle[ors: Ocular Onchocerciasis and intensity of infection irt tlre community. II. West African rainforest foci of Sintuliunt yahense. Trop.Med.Parasit. ,r0 (r 989) 348-354. i).rtlz-ic, K.Y., J.Remme, E.S.Alley, G.De Sole: Changes in ocular onchocerciasis four and twelve rilonths after community-based treatment with ivermectin in an holo-endemic onchocerciasis focus. Trans.roy.Soc.trop.Med.tIyg (1990) in press. [)rttlz-ie, K.Y., J.Remme, G.De Sole: Epidemiological impact of vector control : II. Changes in oculAr onchocerciasis. Acta Leidensia 59 (1990) in press. l)c Solc', G., K.Awadzi, J.Remme, K.Y.Dadzie, o.Ba, J.ciese, M.Karam, F.M.Keita, N.o.opoku: r\ community trial of ivermectin in the onchocerciasis focus of Asubende, Ghana. II. Adverse reactions. Trop.Med.Parasit. 40 (1989) 375-382. l)e Sole, G., J.Remme, K.Awadzi, S.Accorsi, E.S.Alley, O.Ba, K.Y.Dadzie, J.Giese, M.Karam, F.M.Keita: Adverse reactions after large scale treatment of onchocerciasis with ivermectin: Combined results from eight community trials. Bull.\Yld.Hlth.Org.l989,67, No.6, (1989) in p ress. 29 Appcndix B De Sole, G., J.Remme, K.Y.Dadzie: The epidemiological impact of vector control in the Onchocerciasis Control Programme in West-Africa. I. lncidence and changes in prevalence and intensity of Onchocerca volvulus infection. Acta Leidensia (1990) in press. De Sole, G.: Migration studies in the onchocerciasis controlled areas Trop.Med.Parasit. 40 (1990) in press of \Yest Africa Garms, R., R.A.Cheke, G.K.Fiasorgbor, J.F.Walsh: Seasonal extension of the breeding range of Simulium sanctipauli from forest into savanna in eastern Ghana and Togo. Z.ang,Zool. (1989) in press. Habbema, J.D.F., A.P.Plaisier, G.J.van Oortmarssen, J.Remme: Prospective evaluation of onchocerciasis control strategies. Acta Leidensia (1990) in press. Hemingway, J., A.Callaghan, D.C.Kurtak. Temephos resistance in Simuliunt damnosum Theobald(Diptera: Simuliidae): a comparative study between larvae and adults of the forest and savanna strains of this species complex. Bull.ent.Res. 79 (1989) 659-670 Le Berre, R., J.F.Walsh, et al.: The World Health Organization, Onchocerciasis Control Programme: retrospect and prospects. Phil.Trans.Royal Society B. (1990) in press. Lévêque, C.: The Onchocerciasis Control Programme monitoring activities. Paper presented for a scoPE volume on "Ecological effects in different climates" (in press) Paugy, D.: Le peuplement ichtyologique du Baoulé (Ht Sénégal, Mali) avant son trâitement aux insecticides antisimulidiens. Rev.Hydrob.Trop. (t989) in press Paugy, D., V.Benech: La faune ichtyologique des bassins côtiers du Togo. Rev.Hydrob.Trop.(1989) in press Paugy, D., C.Lévêque, R.Bigorne. La faune ichtyologique des bassins côtiers de Sierra Leone et du Libéria. Rev.Hydrob.Trop. (1989) in press Paugy, D. and J.F. Guézuan. Note a propos de trois especes d'Hydrocynus (Pisces, Characidae) du basin de Niger suivie de la rehabilitation de I'espèce Hydrocynus viuatus (Castelnau, I86l ) Rev.Hydrobiol.Trop. 22(t): I -86 (1989) Philippon, 8., J.Remme, J.F.\Yalsh, P.Guillet, D.G.Zerbo: Entomological results of vector control in the Onchocerciasis Control Programme in West Africa. Acta Leidensia (1990) in press. Plaisier, A.P., G.J.van Oortmarssen, J.D.F.Habbema, J.Remme, E.S.Alley: ONCHOSIM: A computer program for modelling the transmission and control of onchocerciasis. Computer Methods and Programs in Biomedicine (1989) in press. Remme, J., G.De Sole, G.J.van Oortmarssen: The predicted and observed decline in the prevalence and intensity of onchocerciasis infection during l4 years of successful vector control with reference to the reproductive lifespan of Onchocerca volvulus. Bull.Wld.Hlth.Org. (1990) in press. \pircn111* 1; -11 lii'n)nre, J., G.De Sole, K.Y.Dadzie, E.S.AIIei,, R.H.A.Baker, J.D.F.I{abbenra, A.p. plaisier, ( i J I an Oortmarssen, E.M.Samba: Large-scalc. ivermectin distribution and its epidenriological .'()nscqucnces. r\cta Leidensia,59 (1990) in press. i I ,';r I rrtc. J., K . \'. Dadzic, A.l?.olland, I).Thi,lel-o rs: Ocular onchocerc iasis a nd in tensiti, oI inl'ect io n ri' tlrr'corrrrtrunit;'. [. \\/est African se\']niin.'l'rop.nted.Parasit.40 (1989) 310-3.17. irn'-', J., R.rl.A Rrkcr, c.l)e Solc, l(.\'.Dadzie, J.F.\\'alsh, M.A.Aclanrs, E.s..\llcr il.S K.Avissey: r\ cotttnrunitl trial cll- ive rnrt-'ctin in the onchocercirsis l'ocus of Asubcnrlr. t ilrrttra. I. Effect on th('nricrol'ilarial rr'scrrtrir anci the transntission oI Ottchoccrca y'oltrr !:t' i roir.Mccl.Parasit. 40 (1989) lb7-37.1 r:'.'jrurre,J.artcl J.B.Zongo: Dentographicaspcctsol'theepidemiologyandcontroloIonchocr.rcrssi\ in \\'est r\[rica. Irt: Scrvice, M., ed. Denro5irlphy,and vector-borne diseases. Boce Rlrtln.( liC Press, (1989) 361-386. .:urnba, E.M.: oCP Intercounrry collaboration. Acta Leidensia,59 (1990) in press Slrnbe, E.M.: Onchocerciasis control in regartl to PHC/BHS. Acta Leidensia,5g (1990) in press Scrlghor J.E. and E.M. Sanrba. Onchocerciasis Control: The Human Perspective. Parasitologi 'l'oday. 4 (1988) 332-333. l'ltonrson, M.C., J.B.Davies and M.D.Wilson. A portable allozyme electrophoresis kit used to iclerrtify members of the Sintuliunt damnosunt Theobald complex (Diptera: Simuliidae) in tlre field. Bull.ent.Res. 79 (1989) 685-692 \Valsh, J.F.: Review of vector control prior to the OCP. Acta Leidensia,5g (1990) in press Yanreogo, L., C.Levêque, K.Traoré and C.P.Fairhurst. Dix ans de surveillance de la faune rquatique des rivières d'Afrique de I'Ouest traitées contre les simulies (Diptera:Simuliiclle) agcnts vecteurs de I'onchocercose humaine. Rev.Ecol.Syst. I l5 (1988) 281-298. YoLrngcr, S.D. and J.B. Zongo: West Africa: l'he Onchocerciasis Control Progranrme. In: Success[ul tlt-'relopment in Africa; case studies of projects, programs and policies. EDI development Jrr-rlicy case series. Analytical case studies; no.l. World Bank, Washington. (1989) 27-56.