Report of the meeting on operational research and strategies: Ouagadougou, 3-5 April 1996

WORLD HEALTH ORGANIZATION ORGANISATIONMONDIALE DE LA SANTE ONCHOCERCIASIS CONTROL PROGRAMME IN WEST AFRICA PROGRAMME DE LUTTE CONTRE L'ONCHOCERCOSE EN AFRIQUE DE L'OUEST I EXPERTS ADVISORY COMMITTEE Seventeenth session Ouagadougou, l0-14 June laa6 OCP/EACT7.2 ORIGINAL: FRENCH REPORT OF THE MEETING ON OPERATIONAL RESEARCH AND STRATEGIES (Ouagadougou, 3-5 April 1996) CONTENTS INTRODUCTION ... EPIDEMIOLOGICAL MODELLING MERMECTIN AND MACROFIIIRrcIDES oNcHocERctAsIs DIAGNOSIS TECHNIQUES . SPECI.AL STTJDIES DECISION ON CESSATION OF LARVICIDING PLAN OF ACTION AND BUDGET OTHER MATTERS RECOMMENDATIONS DATE AND VENUEOF NEXT MEETING CLOSURE OF THE MEETING LIST OF PARTICIPANTS . . . ANNEX - The new Onchocerciasis Control Programme in Africa: progress report on the launching activities PaSes l. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. I 2 5 . l1 l4 .25 .31 .32 .34 .35 .35 .36 a 07 .06.96 I INTRODUCTION The "Operational Research and Strategies" meeting was held from 3 to 5 April 1996 in Ouagadougou, Burkina Faso, at the headquarters of the Onchocerciasis Control Programme in West Africa (OCP). The meting was attended by the Programme Dir@tor, the Coordinator of the Office of the Director, the Chiefs of the technical units, the Chief of the Administrative unit (pro pane), the Chiefs of technical services from Ouagadougou, Bamako, Bouake and Kara, and Dr.O.W. Christensen of the OCP Office in Geneva, Switzerland. Also in attendance, and for fire first time in such great number, were guests from outside the Programme with recognized competence and experience in onchocerciasis-related fields. They were Drs K. Awadzi (OCRC, Hohoe), B. Philippon (ORSTOM, Paris), A. Plaisier @RASMUS University, Rotterdam), H. Remme (IDE/TDR, Geneva) and D.E. Etay'ale, APOC Coordinator, WHO, Geneva (see list of participants in annex appended hereto). The session was opened by the OCP Director, Dr Yankum Dadzie. After welcoming the participants, in particular the guests from outside the Programme, Dr. Dadzie stressed the importalrce of the meeting and pointed out how useful their discussions would be in directing their strategies for controlling the disease as well as their activities in applied research. The Director then went on to remind participants about the important conclusions of the Brainstorming session held in Cotonou from 16-20, October 1996 and of the JPC l6th session in Washington D.C. (USA). The Cotonou brainstorming session had allowed for a critical analysis of current methods of operation and the smategies aprplied, the identification of the problems encountered and the proposal of concrete solutions. The Programme was to: continue the control operations in order o possibly achieve complete control of the disease through v@tor control activities @y maintaining current methods and strategies), and through a community-based distribution of ivermectin; continue, at country level, current efforts for integrating ivermectin distribution and epidemiological monitoring activities with a view to rapidly detecting any possible recrudescence. With regard to JPC16, a restnrcturing of the Programme was viewed as a requirement so as to lower costs while maintaining activities at their current level. The meeting was chaired by the Chief of the Vector Control Unit, Dr J.-M. Hougard After electing the rapporteurs, the recommendations from the 1995 meeting were reviewed by the participants and were found to have been overall well implemented. 1 , 22. EPIDEIVflOI]OGICAL MODELLING 2.1. Overview of the latest results 2. l.l. Ivermectin effi cacy An important issue relating to ivermectin use is finding out whether beyond its capacity to kill microfilariae, the drug had any action on the release of microfilariae from the adult worm. Equally imporunt is finding out whether this action is temporary or permanent. This question was examined, by analysing data from annual ivermectin treatments in Asubende, Ghana with the help of the ONCHOSIM model. After testing several hypotheses, the conclusion was reached that after each treatment with ivermectin, the female worms recover during a period of l0 months after which microfilarial production stabilizes at a level 35Vo (Conf .Interval 25Vo-40Vo) lower than before treatment. 2.L.2. Combined action of vector control and ivermectin distribution This strategy of a oombined vector conhol and ivermetin distribution is currently used by OCP in almost all of the river basins under larviciding. In the study carried out with the ONCHOSIM model, various Parameters were taken into account (length of vector control operations, number of ivermectin treatments per year, level of coverage). All these data allowed for an evaluation of the risk of recrudescence after the cessation of larviciding and treatment with ivermectin, taking into account the various levels of endemicity. The results of the simulations have shown that a 12 yan period of combined (vector control and ivermectin treatment) would be sufficient to prevent any recrudescence of the infection. This is on condition, that ivermectin coverage is kept at 65Vo during the entire period, and that no significant reinfection by parasites occurs either through migrants or blackflies during that period. 2.2. Simulations for specific cases On the basis of the above results, the model was used to predict the epidemiological situation and the optimal strategies to be adopted in the following basins : Kulpawn/Mole, Ghana; Gambia, Senegal and basins in the north of Sierra l-eone. The simulations showed that ivermectin can stop the transmission in the basins where the force of infections expressed in CMFL before the intervention by ivermectin is less than 30 microfilariae per snip (mf/s) as is the case in Kulpawn/Mole and the Gambia. The ONCHOSM was used to simulate the epidemiological impact of several years of temporary intemrption of an ongoing ivermectin distribution as is the case of Sierra l-eone. The simulations showed that four years or more of suspension could result to high risk of recrudescence if the total period of treatment is less than 20 years. If it is supposed that tarviciding resumes from 1998 and continue to 2002 in the north of Sierra [rone, the ----\ 3simulations showed that at least 15 years of consecutive ivermectin distribution can bring the risk of recrudescence to less than 1%. 2.3. Study on the recnrdescence observed on the Bougouriba The Bougouriba (a tributary of the Black Volta) has been under larviciding from February 1975 to September 1990, a perid of or 15 and a half years. In December 1989, one year before the cessation of larviciding, a 6Vo prevalence of infection was observed in Zoulo, one of the villages of that area. Such a rate was higher than what would have been expected after 15 years of vector control activity, which suggests that larviciding had not been l00Vo effective during the treatment period. Subsequent epidemiological evaluations in N,Iarch 191, February 194, and November 1995 showed prevdences of SVo, ll%o and 25Vo respectively. These results seem to confirm the presence of recrudescence of infection on the Bougouriba.. To explain the occurrence of such a rapid occurrence of recrudescence, different hlpothesis or questions were considered and tested against the epidemiological data observed in the village TnuJo using the ONCHOSIM model. 1) Was vector control really inefficient?; if yes, to what extent? 2) Were the 1989 and l99l prevalence rates "artificially" low due to ivermectin distribution in the region? 3) Were there any infected migrants in the region? 4) Were there other unknown sources of the infection? For example, an important breeding site which might not have been detected through entomological surveillance? 5) Might any important aspects of the parasite's dynamics not have been taken into account in the epidemiological simulation model? For example, a loss of immunity which might have been caused by a lowering of the parasitic load. Preliminary simulation results showed that, even with perfect vector control, a sharp increase in prevalence can be observed by assuming that infected migrants entered the area during the years 1989 to 1991 (fig.1). However, both the number of simulated migrants (45 in a toal population of 400) and their assumed infection level (up to lOOMf/s) seem not to be realistic for this area. However, a migration study carried out in the area concluded that more than 5Vo of positives are not from the T,rllulo village, and less than lOVo have lived outside the village for at least 6 months. It was concluded that this problem deserved detailed studies, both by meticulous inspection of the available historical epidemiological and entomological records, and by performing simulations of a variety of scenarios. Discrepancies between model predictions and observations should further lead to a review of the assumptions presently made in the model. +ttttrr{,Ur+t 1r \,.t \\ \\ \ \ \ \ \ \ / / \\ / .'{ 4 90 80 70 60 50 40 30 U' = C;c .C, --3 be Figure I 10 o1970 1975 1980 Figure 2 90 80 Zoulo - Bougouriba / Black Volta 1OO% v.c. - immigrants in 1989,90,91 M(?reg _F CMFL x O0s. ftew l-,r."n, CMFL x Obs Ptev 20 1985 1990 1995 2000 2005 2010 Calendar year Zoulo - Bougouriba / Black Volta lOO% v.c. - immigrants in 1989. 88, 91 Once/year Iv. during l0 years @ 40 30 20 10 .t c;C -c , s o 1990 200,0 2010 Calendar year rttlal \ \ \\ \\ \ \ \ \ \ \ t \ \ I rrl 1 970 1980 2020 2030 \* \r'f,*--"**"* 5Using this fitting and assuming one treatment of ivermectin per year for a period of 10 years, frg. 2 shows a risk of resumption of infection in the area. It is therfore concluded that the optimal strategy for ivermectin distribution to stop the transmission in the area will be twice a year for at least l0 years. The various explanations given in an attempt to justify this rapid recrudescence of the infection were not very convincing. The view that emerged from the discussions was that the case of Tnulo on the Bougouriba called for an in-depth detailed study of the situation. The suggestion was made to set up a 'Task Force" to study the case and provide an explanation for this recrudescen@ detected less than five years after the termination of larviciding. This would require an integrative analysis of all existing data, old and new, in the fields of entomology, hydrology, transmission intensity measurement, v@tor control and chemotherapeutic treatment, epidemiology, and a study of human settlement and behaviour (seasonal and permanent migrations, farming practices, etc.). If necessary, fltne-tuned enomological, epidemiological and socio-anthropological studies should be undertaken in the whole basin and a community-based distribution of ivermectin every six months for a period of fifteen years instituted. 3. TVERMECTIN Ah[D MACROFILARICIDES 3.1. Field trials with Amocarzine Amocarzine (CGP6 140) is a pink-red chemical powder. Its development for human onchocerciasis began in 1985. Since then, 2 030 infected patients have been treated with this drug in 40 different regimens in Africa (Ghana and Mali) and South America (Guatemala and Ecuador). The rials carried out in Latin America indicated that amocarzine had a macrofilaricidal effect if administered at the dose of l8 mg/kg over a three-day period (table 1) and a microfilaricidal effect at the dose of 10 mg/kg over two days. Side-effects have proved to be tolerable. Unlike Latin America, studies in Africa up till 1988 had not yielded a promising dose regime. Trials at the Onchocerciasis Chemotherapy Research Centre (OCRC) in Ghana, determined that doses above 20mglkg produced severe though reversible central nervous system effects, whiles a total dose of l2mglkg had no effect. Furthermore suppression of skin microfilaria lasted for less than 3 months. In view, however, of the persistent reports of macrofilaricidal effects of amocarzine from Latin America using doses considered to be within safe limits, and the fact that the dose of 3m/kg, three times a day for three days had not been tested in Africa, trials of amocarzine have been resumed wittr a view to is development for use in the community. The study design and treatment allocation are as shown in table 2. All patients were to be entered in the trial by mid-May 1996, and results from nodule examinations are expected by the end of 1996. 63.2. Macrofilaricidal effect of ivermectin Ivermectin is an excellent microfilaricide. At the dose of 150 prglkg it does not kill the adult worms. However, it can qruse a blockage of the uterus in the adult worm thus preventing the release of the microfilariae, allowing these to degenerate "in utero". Previous attempts to investigate the macrofilaricidal potential of ivermectin have administered dose of 10G150u9/kg repeatedly. tn 1994 the OCRC in Hohoe canied out trials using increasing doses of ivermectin both to assess tolerability at such doses, as well as the effect on the adult worm These trials carried out at OCRC Hohoe demonstrated: 1. that high-dose ivermectin use (800 pglkg in a single dose or I 600 pglk9 spread over two weeks) presents no danger; 2. that highdose ivermectin use (1 600 pglkg produces the same effect on the reproductive capacity of the adult worm as the 150 pglkg dose; (table 3.) 3. that multiple doses seem to be more effective than single doses. 4. that "in vitro' tochniques to determine the effect of ivermectin on the adult worn call for more in-depth studies. Table l: Amocaruine in Latin America Pivotal studies + *"*n.i*t#ffi.1i,,X,','ff * "r..".iRapi<lly reversible $ As a % of initial count Dose=3nrgftg bi<l x 3 Retreatrrreut {rt one year with Snrg/kg daily x 2 at one year is recolturtemlod (Grlerian). Feature Snrly site Gtratemala Ecuador Study poprlation 200 adult males 66 arlult malesr 34 a<lult femnbs{ Total l0O Systemic adverse effectsi Dizziness mild 5l % Prurinrs arxl rash ranild20% Dizziness rrnild74%, moderate 19% Pruritus mild 56%, moderate 57 % Rash mild 54%, twJerate34% Positive Romberg 12% Incordination 4% None due to drus effectOcrrlar adverse effects None Adverse [ab effects None None Adult female wornu 8l% of 612 dead or moriburxl 88% of 1059 desd or moriburrl Intrarrterine staces Degonerate embryos arxl mf Degenerate embryos arxl mf Adult male wofins 69% of 130 dead or moriburxl 82% of 396 de{d or moribund Geomean initial count (SD) 46.3 (71.1) 7.7 (24.0) Geomean I year count (SD) 9.9 67.3t 12t%t 8.1 (33.0) 1105.2%t i 7Table 2: Current OCRC studies with amocarzine Safety, efrcacy and the influence of ivermectin *Administerql ono hour before brealdast. I ndministe.e.l one hour after breakfast arxl srrpper 12 hours apart. { tOO p"tiunt. to be entored. Table 3. High dose ivermectin in onchocerciasis Effect on reproductive activiry Feahrre Treatment qroun; and ivermectin dosace l50rrs/ks 400-550rre/ke 600-750rsftg 80O-9501efts l600rreftE Live adult female worms Total 80 't9 62 68 36 with nearly empty rferi 5(6..2%r 14(17.7%r 8il2.9%l 9(r3.2%l 2(5.6%) With oocvtes onlv 30(67.5%r t6(20.3%l 22(35.5%l 15(22.t%l 't(t9.4%) With young embryos 23Q8.8%r t9(24.0%l 9(r4.5%l 15(22.t%\ 2(5.6%) Wilh coiled mf 2',t03.8%l 2602.9%l 7(r1.3%l t'l(25.0%\ 4(r.t%) Wilh strerchecl mf 4t(51.2%l 47(59.5%l 27(43.5%l 39(57.4%l 26(',12.2%\ Of thesc, no. with deqenerated mfe l7(4l.1Vol 3l(66.09o1 23(85.2?ol 32(t2.0?o) 25(96.27o1 No irrdgement rrossible 5(6.2%) 0 2(.3.2%\ 3(4.4%l t(2.8%) Study area: Ongoing transmiss ion; no ivermectin d istribution Skin mf prevalence 6O-%)%; nodule prevalence 3040% Baseline adult worm viabiliry 85-90% Study pop: Adult males 18-55 years, wt > 40kg, nodule carrier Skin mf density : 20/ms Study design Feature Treatment qrouos Phase I (double-blin!) day I lvermectin l50pgftgr Ivermectin l5Opgftg* Placebot Phase 2 (open) day 8 throueh l0 Amocarzine 3mgftg bidf Placebo bid{ Arrrocrrzine 3rns/kg bi(ll Minimum No of patients i 33 33 33 * Percentages expressal are those with stretched microfilariae Higher prolrcrtion of degenerate mf in all groups as cotrrpare<l to control. 83.3. Xenodiagnostic study of ivermectin impact on transmission An experimental study on transmission was carried out at Asubende from 15 December 1995 to 18 January 1996. The study involved 19 patients who had been treated seven times with ivermectin and whose microfilarial loads were from 0 to l1 microf,rlariae per skin snip biopsy (each patient having had an average of four biopsies). All the patients had microfilarial load of more than 80 mf/s before treatment started in 1987. 230 blacKlies were bloodfed from each patient. One part of the blackflies ( 30 ) was dissected immediately after the bloodfeeding in order to search for microfilariae. The rest of the blackflies was bred in the laboratory in order to allow for O. volvulus larvae to develop up to the infective staBe. The results could reveal some aspects of ivermectin impact on transmission from the evaluation of the parameters used for the study of the development cycle of O. volvulw in female S. darnruswn sl. The parameters usually used are: the proportion of females having ingested microfilariae and their resulting parasitic loads. These two parameters relate to the parasitic load of the females at "Day 7nro", i.e. the load consecutive to the blood ingestion; the proportion of microfilariae which entered the hemocelium (exoperitrophic microfilariae), the proportion of females hosting such microFrlariae and the parasitic load of those females. These three parameters indicate parasitic development in the females following the appearance of the peritrophic membrane (6 to 8 hours after the blood ingestion); the proportion of infected blackflies at the end of the cycle and their respective parasitic loads. These two parameters reflect the growth potential of exoperitrophic microfilariae toward the infective stage. Table 4 summarise the results obtained Table 4: Ability of S.damnosum s.l. to acquire infectiors from 19 patients from Asubende, Ghana after 7 treatments with ivermectin. No.flies dissected No.flies with parasites (%) No.microf,rlaria Parasitic load (mf) Day o (Do) Bood meal 570 l l0 (19.3) 514 4.7 Day I (6-8H) Limitation 110 l8 (16.4) 19 l.t Day 8-10 End of survival 1753 39 (2.2) 53 1.4 Final development stage 1753 5 (0.3) 5 I I 9The frrst study carried out in Asubende, Ghana in 1988 on onchocerciasis affected patiens shortly before ttreir first treatment with ivermectin. The patients had been divided into six groups accordhg to their respective skin loads with the least infected group comprising the 12 least infected individuals (0.5 to 4 mf/snip). Observations had been limited to the dissection of the female blackflies (50 female flies/patienQ, 4 to 8 hours after the blood ingestion (the time span necessary for the consolidation of the peritrophic membrane). Figures 3 and 4 compare the parasitic evolution in the engorged blackflies after the formation of the peritrophic membrane for the experiments done in 1988 and 1995/96. The frtting curye in the figure 3 for resuls obtained in 195/96 shows that the lowering of the microfilariat load after ivermectin treatment results in the decrease of the transmission potential of the blackflies. On the other hand, the effect of the drug seems to be marginal on the proportion of microfilariae not trapped in the peritrophic membrane as well as on their intramuscular development potentid. It was recommended that these findings be taken into consideration in the epidemiological prediction model after detailed statistical analysis of the data. 3.4. Planning for the irstitutionalization of community-based treatment by l99E Following the results and recommendations of the Cotonou brainstorming session (Retreat) which bncught together from 16 to 20 October 1995 senior staff from OCP and National Coordinators of the Oncho Programme, workshops for the preparation of Plans of Action and Budget for the decentralisation of epidemiological surveillance and the establishment of community-based ivermectin distribution were organized by health ministries in collaboration with OCP in Burkina Faso, Togo, Senegal, Sierra l-eone and Guinea. Besides Medical Officers and/or nurses serving in onchocerciasis affected areas, the workshops were also attended by national health directors, programme officers or division chiefs from Ministries of Health. The status of ivermectin distribution in the various countries was examined, and plan of action and budget prepared for the implementation of community-based ivermectin distribution in the basins currently treated by the mobile teams between 1996-1998. With regard to the morJe of the distribution, the participants expressed preference for a community-based disribution to be gradually replaced by community self-treatment. For the two t)?es of treatment, health workers will be actively involved with the communities in the planning, implementation and management of the distribution. The sources of funding for these activities were also identified by the participants. The funds would be solicited from the national budgets of the respective countries as well as from other development partners (such as NGOs). The Programme's intervention was requested by the participants, especially the funding of training activities for the implemenution of the community-based distribution. From the plans designed in the frve countries mentioned above, the implementation of lrigurc 3 l(J Experimental transmission studY Asubende - 95/96 orig in al i q) o- c? N r) 0)(0 L(0 -: 0) -o o + c(g o) 0 70 0.60 0.00 Figure 4 0.50 0.40 0.30 0.20 0.1 0 \ -.- \ \. T i : i I I I a I I o + I I I 0 B642 fitted curve c (1988) a 10 12 I % lolcclcd fcmohr tr 96 cro- ml. El,Pororilic lood Mean no. Mf Per skin-sniP 50 45 40 35 30 25 20 l5 10 o A {1988) __l 47.40 r r.so% 4.200/o 5.90yo 1.4 3.40% 3.ora/o 4 '1.3 B (95-96) A. 1988 = Il 95-9(r --(-. lass,. IJclirrc trr'atrnent, fronr patients rvith vcry lorv nricrofilarial load (disscctcd fcnralcs 600) llcsrrlts irorn pati!'r'rts with vcry lorv nrfload after sevcn ivcrnrcctin trcltnrcnts (disscctecl fenrales5T0) ljcl()rc trcilti)rcn1. fronr l)itti(-nts rvith high nrf load (clisscctcd fcnrait:s 5CX)) TVERMECTIN MPACT ON TRANSMISSION ASUBENDE : XENODIAGNOSTIC STUDIES 1988 AND 1995/96 Parasitism in females after the constitution of peritrophic membrane 11 community-based distribution will be carried out over a three-year period (1996-1998) Similar workshops will be organized in the other Participating Countries of OCP. By 1998, the implementation of community-based distribution should be in place in all basins currently under large-scale treatment by the OCP-financed mobile teams. To support decision-making regarding the definitive cessation of larviciding in some of the remaining river basins, namely those of the Southern Extension-Cdte d'Ivoire, it was recommended that a mechanism be found that will allow for temporary intemrption of community-based treatment in the areas in question. This is to help obtain more reliable epidemiological data uninfluenced by the presence of ivermectin. 3.5. Management of ivermectin distribution data The staff at health centres in areas where community-based distribution is carried out will be involved in the management of the ivermectin and the collection of data from the rural communities. The data will be related to the number of patients identified and treated as well as the number of ivermectin tablets distributed. 4. ONCHOCERCIASISDIAGNOSISTECHMQUES 4.1. Report on the Geneva workshop A workshop on diagnostic methods for epidemiological surveillance of onchocerciasis in the OCP was held on 12 and 13 February 1996 in Geneva.The objective of the workshop was to critically review results from diagnostic currently under development and to recommend i) a tesUs to be used for epidemiological surveillance in the OCP ii) any additional studies to validate or improve such test/s. The desired method had to be simple, cheap, and field applicable, and to allow for the detection of infection at low levels. Epidemiological modelling based on skin snip data required that such a test be capable of detecting a 1.5% annual incidence infection in the human population. The current diagnostic method used in the OCP is the parasitological test based on the shn snip. Although this method is highly specific it lacks enough sensitivity at low levels of infection. Furthermore populations are becoming more and more reticent toward the method due to its inconvenience and the pain it causes. The workshop reviewed the profile and requirements of an ideal test which might replace the skin snip. These requirements are the following: 1. the test must be of high a specificity; 2. it must be sensitive enough to detect a rate of 1.5 % of new infection in a year; 3. it must be cheap, easy to use and to evaluate in the field; 4. the method used for the collection of test material must be acceptable to the t2 population and must be safe from any risk of transmission of disease such as HIV; 5. the reagents for carrying out the test must be easily available; 6. the test must be easily integrated in the activities of health services in the respective countries. Tabte 5 shows the performance and characteristics of different tests currently being evaluated for the diagnosis of onchocerciasis. They can be classified into three categories: a) Immunodiagnostic tests - the tri-cocktail antigens (Ov 7, Ov 11, Ov 16) - the tri-cocktails (Ov 10, Ov 11, Ov 29) - the C 27 antigen - Ov 3.6 (Ov 7), Ov 9.4 (C27) b) DNA tests using 0 - 150 PCR - skin scratching - skin snip material c) The diethylcarbamazine (DEC) patch test. Table 5. Performance/Characteristics of the Diagnostic Tests Test species slrec Epid stru, % Sens % Method Cost Reag Serology Tricock I Tricock 2 c27 Ov 3.6 Ov 9.4 Excellent Good Excellent !)6-100 98% 98% Not done 26-89 4t-100 t0-88 98 Blood spots Blood spts sera Blood spots Sera 15-25 US Cents Not yet rearlily available DNA 0-150 PCR Scratch test Excellent too% Excellent t@% ? 100% 87% Skin snip Scrntch 66 cents (3.3) cents Available DEC Patch tqst To be daennined 97% 80% vnriatrle in different geogrnphical areas Non lnv8slve Cost less thnn a few cents Available 13 After reviewing the test results from these different diagnostic methods, the group recommended to OCP the use of the DEC (patch tesQ because it satisf,red most of the criteria set above. This test will however need to be evaluated in different zones of the OCP area in order to clarify the following points: study the skin reaction (allergy) to the cream used for the test determine whether individuals become sensitized to the assay if tested repeatedly measure the species specificity in individuals infected by Marconella perstans determine the sensitivity of this test compared to the other available tests (skin snip, DNA test and the tri-cocktail antigen test). The group recommended that OCP continue to evaluate the "WHO tri-cocktail antigen" as a "fall back" test and carry out trials using other human body secretions such as tears, saliva and urine. 4.2. Detecting infective larvae in crushed mass of blackflies The method of detecting blackfly infection by O. volvulus through DNA probes being available, its operational use was tested during a special study undertaken in 1995 on the Bougouriba at Zambo. The study objective was not only to verify the level of transmission of O. volvuhts in that area using the classical method (catches/dissection) but also to compare the results obtained with this method to those provided by DNA probes. Out of a total of 18 135 blackflies caught during the special study on the Bougouriba, 6 401 were dissected and provided the following results: - Number of parous females = 3 401 - Number of infective females : 20 - Number of L3T : 24 - Infectivity rate = 5.88Voo Among the undissected females, 11 488 heads were put in alcohol and sent to the DNA laboratory in Bouake. 220 batches of 50 heads each were made up and DNA extracted from the crushed mass of each batch was magnified for identification of Onchocerca sp. Seventeen batches were found positive with the magnifying of the PCR. This magnifying allows for specific detection of the Onclwcerca species thanks to the lures use. The results tested with the binomial equation developed by Dr. Katoli (University of Alabama, Birmingham) for determining the estimated probability of finding females infected by Onchocerca sp. gave a value of 0.2% with an interval of confidence varying from 0.1 to 0.3. I-ooking at the upper limit of the interval of confidence, the probability of f,rnding infective females among the tl 000 used in the study may be estimated to be 0.3%.lf only the parous females estimated at 5 841 (53.1% of I I 000) were considered, the probability would be close to 6 Voo or a value comparable to the observed 5.88Voo infectivity rate. The conclusion may then be drawn that the method of determining infectivity level using crushed mass of blackfly yields satisfactory results. The positive batches were submitted to the identification of O. volvulw and seven of l4 them showed a positive reaction. Using the binomial equation, the probability of finding females infected with O. volvulus is 0.064% (0.1%) with an interval of confidence varying from 0.026 % to 0.133%. The percentage calculated after identification of 24 infective larvae extracted from the 3 401 heads of parous blackflies is 0.1% or a value within the interval of confidence of the estimated probabilities. The protocol for the conduct of such studies will be finalized in the very near future and a validation testing undertaken on the Irraba or on other watercourses. 5. SPECIAL STTJDIES 5.1. Entomological situation in nofthern Sierra Leone - trTask Force[ studies 5.1.1. Impact of larviciding in loo3-lao4 In 193-1994, larviciding in the river basins of northern Sierra l-eone had the following results: a significant reduction (98Vo) of female savanna blackflies on the Seli/Bagbe a marginal change in the percentage of savanna blackflies on the Mongo/Kaba a zoro involvement of savanna flies in transmission on the Seli/Bagbe very little involvement (only 0.2Vo of savanna flies) on the Mongo/Kaba. 5.1.2. l-tynamics of the savanna fly population after the suspension of larviciding Larviciding on the Mongo/Kaba was suspended in March 1995 as a result of security problems. A decrease was observed in the proportion of savanna flies in the blackfly population and no infective savanna blackfly was reported. On the Seli/Bagbe where larviciding was suspended since 1992 for the same reasons as above, a relative upward trend of savanna flies was observed in 1995. The daily biting rate by savanna flies in April-May 1995 was 9.88, but none was infective. During the first quarter of 1996, the daily biting rate was 14.3 hence an increase of about 57o. One infective female savanna blackfly was reported at Sankalaia on the Bagbe in mid-March 1996. 5. 1.3. Ongoing activities CarcheVdissection activities were resumed since the 4h week (end of January) 1996 in all catching poins of northern Sierra leone. As of March 1996, the catches/dissection and the collection of blackfly larvae for cytotaxonomic identification were intensified. Meanwhile, a refresher course on sample preservation and morphological identiFrcation of vectors was given to involved technicians. Furthermore, a "Task Force"-type operation is to be undertaken from mid-April to mid-May 1996 (the peak period of reproduction of savanna flies and of south-west to north- east migration of blackfly populations). This "Task Force" operation which is to be carried out by the National Team of Sierra Leone will consist in an intensification of catches and dissection in all the catching points of the entomological evaluation network of northern Sierra Leone. Collected blackfly larvae will be preserved in carnoy and alcohol for cytotaxonomic r5 identification by technicians at the Bouake and Bamako laboratories. All captured blackflies will be dissected in the field after morphological identification by the technicians of the National Teams. Infective larvae of the parasite wilt be systematically submitted to DNA identification; infective savanna blackflies will be sent in priority to the DNA laboratory for identification by the heteroduplex method. The obtained data will be analyzed and the conclusions presented at the next meeting of the Expert Committee in June 1996 with a view to supporting decision-making regarding resumption of larviciding in that area. Seasonal treatment on the Kolente, Kaba, Mongo, Seli and even Bagbe basins from January to June could be considered if the trend of reinvasion by savanna flies is confirmed. Such larviciding could allow for the control of transmission in Guinea by ensuring that reinvasion by S. sirbarum from northern Sierra l-eone is not amplified to the extent of reactivating extinguishing residual transmission foci in Guinea. 5.2. Entomological studies in southwestern Guinea Human migrations from the north to the south and deforestation are known to be marked phenomena in West Africa. This naturally constitutes a favorable condition, especially in the forest zone, for contact between blackfly species and O. volvulus strains from sometimes very different origins (forest v@tors-savanna parasites or savanna vectors-forest parasites). Given the techniques available for a reliable identif,rcation of the vector and parasite of onchocerciasis (cytotaxonomy, morphometry, DNA probes), the study of the transmission of the disease in the West African forest zone (determination of O. volvulas strains transmitted and the involved blacKly species) could contribute to a strengthening of the knowledge on the epidemiological impact of the above-mentioned phenomena. It is in consideration of such a contribution that studies involving the major part of the entomological evaluation work using all the identification techniques currently available at OCP are planned to be carried out in the southwestern part of Guinea, a forest zone situated outside the Programme area. Kolta and Serissou are two points selected for these studies. The first is sinrated on the Oule (a tributary of the Diani river) in the vicinity of the village bearing the same name, while the second, located further north, is situated on the main course of the Diani river. The studies are to begin at the start of the rainy season, the period during which the villagers from Kolta report the first bites of S. datnnoswn sl. 5.3. Protocol for the epidemiological evaluation of selected villages in the Kankelaba and Marahoue basins To measure the real impact of vector control in the basins where larviciding is planned to be discontinued but which are under ivermectin distribution (Kankelaba and Marahoue cases), an evaluation protocol was put at the disposal of the National Teams of Mali and Cdte d'Ivoire. Steps will be taken during the study period to temporarily interrupt ivermectin distribution in the selected villages in order to carry out the epidemiological evaluations (skin snip and/or ophthalmologicat checkup) with a view to obtaining reliable results. A global analysis of the results of the epidemiological and entomological situation will allow for a decision on the definitive cessation of vector control operations initially scheduled for June lgg7. (First results obtained after one year of suspension of ivermectin treatment in the Kankelaba are indicated under section 6.1.1) l6 5.4. Post-control studies on the Kulpawn and the Mole Aerial larviciding was definitively stopped on the Mole and Kulpawn rivers on 3l December 1994 after 19 years of vector control operations. The catching points of Bielikpong and Yagaba being inaccessible during the rainy season, catching activities took place during the dry season only. The few entomological results at our disposal are good but do not necessarily reflect the real situation in the field. In 1994, an epidemiological evaluation made in 10 villages of the area showed a prevalence range of l0 to 20Vo with some children found positive. It was therefore decided at the June 1995 EAC meeting to carry out special studies with a view to better ascertaining the entomo- epidemiological situation in these two basins. Entomological studies are planned to be undertaken over a three-year period (1995, 1996 and 1997) to verify whether or not the transmission has been at a negligible level after the cessation of larviciding. Because the Bielikpong catching point on the Kulpawn is inaccessible during the rainy season, catching activities took place at Yayanyori on the right bank from 17 luly to 5 October [995, and at Chiasa on the Mole from 3l July to 9 October 1995. The studies were undertaken by two mobile teams from the Tamale Sector. The results are shown on Table 6. At Yayanyori, a total of 13 904 flies were caught in 28 days. 8 920 were parous (647o) among which 13 infective flies with 17 ln or 1.46 infective flies per I 000 parous. The identification thrrough DNA probes showed that l0 flies were infected by O. volvuhu or l.13 infected flies per t 000 parous. At Chiasa, 6 217 flies were caught in 26 days, 6 274 were dissected among which 3 903 parous (62%) and eight infective flies with 1l I4 (2.05 infective flies per I 000 parous). After analysis through DNA probes, six flies were found to be infected by O. volvuhu or 1.54 infective flies per I 000 parous. Table 6. Entomological study on the Kulpawn and Mole - Results Following the presentation of these results, the Committee decided that these post- control studies should be continued in [996, preferably for a longer period (July to November) and village level catching made at Bielikpong. Catching points (Riverc) Period Dissectal perous fernales No of infective females(Orhucru sp) Infective females (O. volvulus'1 Infective females 1000 parous Transmission level Yayanyori (Kulpwn) from t7.07.95 to 05.10.95 8 920 l3 t0 l,l3 Acceptable Chiasa (Mole) from 31.07.95 to 09.10.95 3m3 8 6 1,54 Acceptable t7 The National Team of Ghana would have to undertake a complete epidemiological evaluation in the zone currently under treatment so as to allow for all eligible villages to be treated with ivermectin for a better therapeutic coverage. 5.5. Deforestation and onchocerciasis in the South-West of Ghana The gradual change into a savnna ecology of the South of Ghana, (outside the OCP area), and the possibility that this zone might become a potential source of blackfly contamination of the Bui area were discussed during the EAC meeting of June 1995. The first indication of such a potential came from the first EPI survey carried out in 1994 in the Black Volta basin where prevalence of infection at Mpeasem was found to be about 60Vo. The parasiologicat tests conducted at the beginning of 1995 in the Wenchi area also revealed the presence of many infected children. DNA identification of the microflrlariae found in the skin snips showed that they belonged to the savanna strain of the O. volvulus. Prospections carried out in the 1980's had indicated the presence of important breeding sites of S. sirbanum on the Tano and S. danruswn s.s. on the Pra rivers. Furthermore, the region was found to be characterized by intense human population migrations mainly in the North-South direction. As a result of such a situation, it was considered urgent to: determine the extent of blinding onchocerciasis in the South-West of Ghana; determine the prevalence and intensity (CMFL) of onchocerciasis among the human populations of the South-Western basins nearest to the Programme area; determine whether the South-West represented a risk to the Original Area in terms of the importation of infection by both man and vector; establish a link between the entomological and epidemiological data of the area with a view to making suggestions for appropriate control activities to be undertaken; provide the National Team of Ghana with the basic data for guiding iverrnectin distribution in the area. 5.5. 1. Fntomological evaluation The South-West of Ghana being the object of studies financed by WHO/TDR, it was recognized that OCP would benefit from working in close collaboration with the researchers and the Institute in charge of these studies. Such collaboration had already been initiated with some res@rchers from the "Noguchi Memorial Institute for Medical Research" in Accra. Current ongoing studies are related to the following subjects: a) Entomological evaluation - prospection of breeding sites of S. damnoswn sl. and collection of larvae in carnoy for cytotaxonomic identifi cation ; - catching, morphological identification and dissection of blackflies in the Tano and Pra-Ofin basins; - DNA identification of onchocerca larvae and heteroduplex identification of infected female flies; - collection of basic epidemiological data from researchers, organizations and l8 institutions working or having worked in the area; - collection of demographic, climatological, biogeographic and canopy related data on the area. b) Socio-demographic evaluation and migration studies. c) Linking of the entomo-epidemiological data on the zone with a view to making suggestions for appropriate control activities. 5 .5.2. trIidemiological evaluation In September 1995, a simple epidemiological evaluation (skin snips) was conducted in 20 villages of the Pru, Tano and Bia basins ( maps 1 and 2). In the Upper Pru basin (untreated with larvicides), standardized prevalence rates ranged from 2.0 to 7.1% with (CMFL) of 0.08 to 0.20 mf/s. In the Bia basin, the prevalence rates ranged from 5.0 to 4.2Vo with CMFL of 0.01 to 0.21 mf/s. On the other hand, in the Tano and Ofin basins, the prevalence rates observed in some villages were high and ranged from 2.2 to 58.0Vo with CMFL of 0.04 to 5.22 mf/s on the Tano river.The village of Betenase had a standardized prevalence rate of 52.4Vo with a CMFL of 4.86 mf/s. Prevalences were also high on the Ofin river ranging from 3.2 to 60.4% with CMFL of 0.1t to 7 .14 mf/s. l9N z TZ9fd9 Y'i FBfr oB =IAF!E c./) a4-z->o-o,uOr<o) ur-9- dgkg>E?E agia 5;'! s xo:oooEd =[ufio 2o-6u - tlJEd3EsoT!N 0.) 63 O .l.- I a _ *--.-' )t /'l ,.t I I I I I I I .E F) o € !Ig€o ,! o z :?. 6 I o' z It E 6 -t -g o B 13. B o o2 I o 46 a(, E o' ; o' o- o' E c o 3: o 5B. FN. E;ft !ir t ! E- Ig !i :9 io ; I I I s c uq 8 .E lo !I06J -L + 3: -i 3 E; EE .9 I Eo == .n J *6 af Iqq a6 0 E er ;: >u Vg tsi6c o-!ys a ,/e ! 9 E! "t i!8rd6 .- _84 :9qi c! 3!!T EH IH is iEjg s ig-ini!s ic l: E E iE NZO> E t 6 ! N ; cO € E d'l ,E .! -:d V O o H3E" -4rvZ usgfo -> (,;HE;Fo*a Ei23 Z)74 LL.l /-\ LJ l- r.u 5 P:35{vJ... -1 Y *zt3 33$HNco<F(fu:OJ{=F!)tt-z LJO'l!O zOotrO$z( Z<lJLU :\0aFoa --cr*z(,;\ o :d.'- -91 r! o ()F 6J(J 9o ) I I .. ,t .a'to .,@ ' --* ir>/ .>4 r '--,':^.in,"' l'' l-o* . ' : 'o ; c ,o zI ea ..--..-\----\\\.. \,, I t 2r 20 5.6. Special studies on the Haho-Yoto In compliance with recommendation 8. l3 of the meeting on Operational Research and Strategies held in Ouagadougou on 16 and 1.7 March 1995, an entomological evaluation was carried out on the Haho and Yoto rivers from July o October 1995. The Haho and its tributary the Yoto are short coastal rivers in Togo which are not under larviciding. The entomological evaluation undertaken has dlowed for decision-making regarding actions to be taken. trntomological eval uation s A mapping of the breeding sites was made, along with catching and dissection of S. darnnosurnsl. Carching was made at six points (four points on the Haho and two points on the Yoto). A total of 158 female flies were caught in 34 days giving an average of 4 to 5 females/person/day. The parturity rate was 427o and only two females were found to be infected with L. in the thorax (no female was infective). The area is treated annually with ivermectin. The low blackfly population recorded this year on the Haho and the Yoto rivers is a rcsult of poor rainfall. Discharges at Yoto-Kope were about 2 msls in July, 9 m3/s in August, and 6 m3/s in September. When rainfall is good, however, discharges may be much higher, in the 3 to 5 range, and blackfly population much more abundant. Cytotaxonomic identification showed thatgl%o of the larvae examined belong to the savanna species (5. dannoswrs.s. and S. sirbanum) with only SVo being of the forest species (5. squanosum). Morphological and morphometric identification resulted in 42 to 75% savanna flies and 56 to 25Vo forest flies depending on the catching point. The significant proportion of savanna blackflies caught would tend to indicate the existence of a potential transmission of the blinding form of onchocerciasis. As this basin is located near the Mono to the east and the Sio to the west (30 and 20 km respectively in straight line) and extending nearly to the Amou and its tributaries, the meeting decided that selective larviciding should be carried out (a few weeks per year as on the Nzo in C6te d'Ivoire) in order to prevent the savanna blackflies of this basin from reinvading the Mono, the Amou and the Sio already under larviciding. It must be noted that breeding sites on the Haho and the Yoto are active only four to five months per year during the rainy season. 5.7. Special studies on the Oueme and Okpara 5.7 .1. Objective of the study In 1995, the DNA laboratory of the University of Alabama (USA) identified some adult blacldlies with dark coloured wing-tuft, from the Oueme basin in Benin (M'Betekoukou and Kaboua ile), as savanna blackflies (5. sirbanum). In view of the high PATs recorded every year in that area, it was then urgent to determine whether the epidemiological pattern of the disease in that zone pointed to a serious case of the blinding form of onchocerciasis or the forest torm. It was decided therefore at the June 1995 EAC meeting that epidemiological (parasitological and ophthalrnological) and entomological studies should be undertaken. 2T 5.7 .2. Fntomological evaluation a) Interctfied catching The intensified carching made at 1l points on the Oueme and the Okpara from July to Ocober allowed for infective larvae to be collected a part of which was identified with DNA probes ( Table 7). It must be noted rhatS6Vo of the females caught had dark-coloured wing-tuft and morphologically identified as forest flies. Table 7. Infection identification Oueme River (1995) - Summary Out of a total of l22l-, Head identified, 32Vo (39 L Head) did not betong to the volvulus species. 29Vo (35 I. Head) were identified as forest O. volvulus and 39% @8) identif,red as savanna O. volvultu. Tables 7,8,and 9 compare the identification of the vectors using heteroduplex and wing- tuft methods, as well as transmission by these vectors respectively. Larval stage Catching point Identi[ication TOTALOther Darasites O. volvulus Forest O. volvulus Savanna Infective larvae (L3H) Angaradebou Konfokpa Beterou Vossa Kaboua Atchakpa M'Betekoukou Atcherigbe Aguigadji Okeo Djabata Total I3H 2 0 I 4 8 0 3 I 2 9 9 39 0 0 0 I 9 I 5 2 5 2 l0 35 0 I I 2 t2 0 6 0 7 10 9 4E 2 I 2 7 29 I l4 3 l4 2r 28 t22 22 Table E. Cornparison of vector identification (wing-tuft and heteroduplex) Table 9. Parasite transmission by vectors identified by heteroduplex Table 10. Parasite transmission by vector identified by morphology Wing- tuft Vector identification by HDA Total S. dannoswn s.s. S. sirbanwn S. squatnoswn S. yahense 01 05 8 31 4 t6 0 3 0 2 t2 52 Total 39 20 3 2 il Vector Identification HDA Parasites (I3tI) identification Total Non Onclncerca volvuhts O. volvulus forest O. volvulus savanna S. datnrusum s.s. S. sirbanwn S. squatnoswn S. yahense 7 5 I 2 t7 4 1 0 15 lt I 0 39 20 3 2 Total 15 22 27 G Wing- tuft Parasite (I3H) identilication TotalNon Onchocerca volvuhts O. volvulus forest O. volvulus savanna 01 05 3 t2 3 r9 6 2t t2 52 Total r5 22 27 64 23 It should be noted that the heteroduplex method uses the DNA of the mitochondria, i.e. the DNA of the cells' cytoplasm whereas cytotaxonomy uses the chromosomes in the cells nuclei. To date, there is no heteroduplex technique using the nuclear DNA of blackfly cells. Discordances between the cytotCI(onomic and the heteroduplex methods in the identification of blackflies with dark-coloured wing-tuft are probably due to these different elements. b) Laboratory rearing of blacfflies Laboratory rearing of bloodfed blackflies with dark wing-tuft from the Kaboua and M'Betekoukou areas gave l|J0_Vo forest blackfly larvae identified by cytotaxonomy as S. soubrerce (Beff{. On the other hand, rearing of blackflies with light-coloured tuft from the same areas resulted in S. dorunstrn s.s.larvae along with hybrids from S. darnnosam s.s. and S. soubrerae (Beffa). Pending the DNA identification results, it is interesting to note the full agreement between the morphological and the cytotaxonomic data. These preliminary results confirm previous data and show that the flies with dark-coloured wing-tuft caught at Kaboua and M'Betekoukou belonged mostly to the forest species. 5 .7 .3 . Parasi tological and ophthal mological studies Parasitological and ophthalmological studies were carried out in five villages of the Oueme basin. The results are presented in the table 11 below. Table 11. Ophtalmological evaluations in the Oueme basin in Benin (November-December 1995) - Results % Comprre to those: present (l); examined (2); recorded (3) In all the villages evaluated, the ophthalmological results show a relatively low ocular parasitemia ,with an onchocercal blindness rate of below lVo. ln some of the villages, a relatively high rate of onchocercal ocular lesions was observed in contrast with a low blindness rate (esions were most frequently located in the posterior segmenQ. Some of the individuals affected by these lesions were migrants from other endemic zones, which could in part explain Village No. persons examinql Preval. Skin Parasit. (t) Preval. ocular Parasit. % Q) Preval. Serious oncho lesions % Q' Preval. severe sight impair % Q) Prevalence of blin<lness % (3) Global Dtre to oncho Wokp t35 12,02 0,74 4,44 0 0 0 Mendengbe Gabassa 339 12,42 4,26 15,29 5,26 l,l6 0,57 Okpa 229 29.04 6,1I 22,25 3,49 1.57 0,87 Sarxleorr 79 12,19 5.06 20.25 5.06 0,98 0,98 Moka 2to 5,32 0 15,23 3,33 0,34 0,34 24 the phenomenon During the meeting, the relationship between the intensity of infection (CMFL), ocular lesions and onchocercal blindness in West Africa in general, and in Sierra l-eone in particular was reviewed. It was noted that several studies concerning such relationships have been undertaken in West Africa and the following had been observed: i) In the northern part of West African (savanna zone), there is a direct and positive linear relationship between intensity of infection and ocular pathology. Thus as intensity of infection increase so does ocular pathology and blindness. ii) In the Southern (forest) zone of West Africa with the exception of Sierra kone, the linear relationship between intensity of infection, ocular lesions and blindness is less steep. Thus in the forest zone, for a given intensity of infection , the blindness rate and ocular lesions are lower than observed in the savanna zone. iii) In Sierra l-eone the pattern is different from what is observed in the forest and savanna areas of West Africa. Communities with very high intensities of infection are common and high prevalence levels of blindness are common in the degraded forest areas in the south. However, the comparative analysis of indices of ocular onchcoerciasis of southern Sierra I-eone and the savanna areas of OCP, shows onchocerciasis in southern Sierra I-eone to be significantly less blinding than in the OCP savanna. 25 6. DECISION ON CESSATION OF LARVICIDING 6.1. The Latest epidemiological results 6.1.1. Kankelaba basin in Mali The resuls obained in January 1996 were satisfactory in six villages. No new infection was observed among the autochthonous population. Eleven cases with positive skin snip were detected: six at Kankelaba, one at Fininko, and four at Warakana. All 1[ cases were either former patients or migrants having sojourned in southern C6te d'Ivoire. They were all over 20 years old with the exception of one woman aged 19 at Warakana who had been found positive in previous evaluations, and an eight years old girl born in C6te d'Ivoire and brought to the village about a year earlier. Microfilarial loads were overall low. The participation rate among the population ranged from 69.5Vo to 8L.6Vo. 6.1.2. F*tension -ones under larviciding and iyermectin treatment In the extension zones under larviciding and ivermectin distribution, epidemiological evaluation (skin snip) were carried out with a view to studying incidence levels in selected cohorts to be monitored over three to four years and who will not receive iverntectin treatment. In Sierra l-eone, after the suspension of larviciding and ivermectin distribution in the IQba/Mongo and Seli/Bagbe basins for over one year, evaluations are under way to deterrnine the epidemiological situation prevailing among the population. In C6te d'Ivoire, evaluations were carried out in the Comoe basin in connection with the ongoing studies on incidence of infection. The evaluation carried out in eight villages in September 1995 showed prevalence rates of 5.8 to 50.6Vo and CMFL of 0.12 to 3.05 mf/s. Participation rates ranged from 42.7 to75.2Vo. Infection was observed in all age groups at Abradinou, Alosso, Niandan, Ahininkro. [n four other villages, no infection was detected in the 0 to 4 years old groups. In the village of Alosso, 12 positive children under 5 years old and 21 positive children aged 5 to 9 were detected. ln Benin, ophthalmological diagnosis along with skin snip evaluation were carried out in five villages of the Oueme and Okpara basins. Standardized prevalence rates ranged from 5.32% to 29.04Vo with onchocercal blindness rates in the range of 0 to 0.98%. Further evaluations were conducted in five villages of the Kouffo and 7au basins in connection with the studies on onchocercal incidence with a view to allowing the selection of a cohort with negative skin snip who will not be treirted with ivermectin and who will be monitored over a few years period. No infection was detected among the 0 to 4 years old group in the five villages evaluated. Three villages in the Pru basin (Ghana) and one village in the Sene basin in an area not covered by ivermectin treatment were evaluated in December 1995. Prevalence rates in the three villages in the Pru basin ranged from 39.5 to 50.7Vo with CMFL of 0.99 to 3.00 mf/s. No infection was detected in the Sene basin. 26 Finally, in Togo, the epidemiological evaluation carried out in October 1995 by the National Team involved seven villages in the Todje basin (not treated with larvicides). The evaluation was conducted in order to determine the epidemiological situation prevailing in this basin with a view to extending ivermectin distribution if necessary. The prevalence rates observed in the seven villages were in the range of 2.5 to 48.7Vo with CMFL of 0.07 to 2.75% mf/s. 6.1.3. Fvaluation of ivermectin distrihution after five years treatment in the Rio Geha (Guinea Rissau) and the Koulountou Koliba (Guinea) basins In these two basins treated only with ivermectin, the epidemiological results after five years of ivermectin distribution were satisfactory in all the villages evaluate in 1995 (six villages in the Koulountou Koliba basin , and five villages in the Rio Geba basin. No new infection was detected, particularly among children under five. Populations' participation rates ranged from 65 to 85%. 6.2. Current entomological situation The results of entomological evaluations for 1995 were overall satisfactory Map 3 shows the Annual Transmission Potential (ATP) results regarding species of the S. darnrnsuz complex infected by Onchocerca sp. (animal and human origin combined). 13 points showed a ATP above 100 (Koutoukro and Betie on the Comoe, Pont Dylamba on the Dylamba, Faya on the Faya, Tienfala on the Niger in the western zone, Asubende on the Pru, Kouniouhou and Djodji on the Ghan Houo, Bagan on the Mo, Titira and Tapounde on the Keran, Kaboua and Djabata on the Okpara in the eastern zone). Considering that human onchocerciasis (Onchocerca volvulus) is transmitted by the ^S. dntnnosutn species complex (Map 4), it may be noted that five out of the 13 points mentioned above have a ATP below 100. They are Pont Dylamba, Faya, Tienfala, Kouniouhou and Djabata. Furthermore, it may be observed that transmission at Kaboua and Tapounde is reduced by almost one half, thus indicating a significant presence of animal onchocerca at these seven catching points. If only the transmission of the savanna strain of O. volvulus by the S. damnosum species complex (Map 5) is considered, ATP at Kouniouhou, Bagan, and Titira falls below 100, thus indicating that transmission is due primarily to the forest strain of O. volvulu.s. Tasfly, if onlythetransmission of O. volvulus by the S. damnosurn savanna species is considered, five points have a ATP above 100. They are Betie, Asubende, Bagan, Titira and Tapounde. (Map 6) .l t -i\. 27 Carte3/Map3 I I I li i i 'I I O <too Q roo.rr Q rooor Q roo.zr a >too Ila&e de labc hilial dc 0OCP. Bouatloy of thc origitralOCP tca- Jen.t995 - D6c.1995 Limite nord a nd ar &sba oud da tailcns$ hnictt cs / Noriha'a aad totdtar lbdil ol lantffiE ia ntalaa datsilttt ' I)miuduprogtanma hogromne limX POTENTIELS ANNUELS DE TRANSMISSION AN NUAL TRANSMISSION POTENTIALS Esp&cs du coaplcxc Simulium damnosum infccttcs par @!9949 sp Simulium damnosum cmrpto< spccics infcctcd with Onchoccrca sp -/-C : I ) e o <100 100.1t9 200J99 {00.799 >100 Carte 4 l'MaP 4 Jan.1995 - Dec.l995 l)nic dc l'qitc initiab dc I'OCP Boundaq'o/ thc originol OCP orcq Limite nord ct sud.n cicnsion ouesl dcs timit o/ tan'iciding in vestern crtcntion' l.inilc ttu programme. fuogromnrc limit. POTENTIELS ANNUELS DE TRANSMISSION ANNUAL TRANSMISSION POTENTIALS Espcccs du complcxc S imuIunr damnosum tn fcctccst par qnchggglgg re!1ru!$ Onchoccrca volvulusSinrulium m spcclcs $,rth I i 1 I I I I I I Cartc5/Map5 Liane dc laiac hiriale dc IOCP. BanalotT ol thc origiacl OCP ut Jan.l995 - OCc.'!995 Limitc aod a ud ca cacation ouea dct . e:eilr;ln.atr bricUct I Northctn and rcurtaa Amb ollanicidiag h Naa cncasion. - Limiudaprogroamc hogramme limL POTENTIELS ANNUELS DE TRANSMISSION ANNUAL TRANSMISSION POTENTIALS Espcccs du complo<c Simulium damnosum infcctdcs par ftq!9g334qlg{95 savanc Simulium damnosum complcr spccics infcacd with savanna Onchoccrca volwlus - 3 .) e o <100 r00.ttt t00Jtt aoo-rtt >100 Carte 6 lMap 6 3 r) e o <100 t00.ttt 200Jtt {00-rtt >100 l)mc dc l'attc iaitink dt l'OCP Bounda4' o/ thc otigiacl OCP arct l-imitc nord cl sud cn eutcnsion oucsl dcr tdiramcnls lanicidcs / Noahcrn qn.l tourt<rd limil of hn'iciding in wcstcrn .-f,.nlion Limitc du progrommc. f)ogramrnc linit. Jan.1995 - D6c.1995 [;sDc.-cs savanre olcs du contplcxc StrydtCrn !*]!-Sl1111l infcctccs par Onchoccrco Yolvulus l, rnrrr I t_ttnt rl alln-<ts u-nt ccrrr:p I cs savart nr spccics rn fcctcd rvi th Qlc\crcc1gq 191\1l-!s POTENTIELS ANNUELS DE TRANSMISSION ANNUAL TRANSMISSION POTENTIALS 29 6.3. Status of current larviciding coverage and cessation plans. 6.3. 1. Original Area (Map 7) After 22 years of unintem.rpted vector control on the lower Black Volta and its tributaries in Ghana, larviciding is planned to cease definitively on I January 1997. Some villages in the area, however, show relatively high prevalence of infection requiring intensified ivermectin distribution in the area. The most recent epidemiological findings on the Kankelaba in February 1996 were very encouraging and definitive cessation of larviciding is planned for the end of June 1997 provided these results are confirmed by a final epidemiological evaluation. As of July 1997, therefore, only the Dienkoa (treated from the ground by the National Team of Burkina Faso with technical assistance from the PET unit) and the tributarics of the Oti, Keran, Kara and Mo will remain under larviciding in the Original Area. The Dienkoa basin will probably continue to be treated up to the end of 1997 or even the end of 1998 depending on the results of the epidemiological evaluations. The tributaries of the Oti having constantly been reinvaded by infective blackflies up to February 1998, when lan,icicling was initiated in the south-eastern Extension, will most likely continue to be treatecl beyond 1998. 6.3.2. Southern Fvtension_C6te d'Ivoire (Map g) The most recent epidemiological findings on the Marahoue in 1995 were very encouraging and definitive cessation of Iarviciding is planned for the end of 1997 , providecl these results are confirmed by a final epidemiological evaluation. The other basins oi the Southern Extension in Cdte d'Ivoire Qower Comoe, lower Nzi, lower Bandama and Sassandra) will continue to be treated in 1997 but larviciding will probably cease at the end of 1998. 6.3.3. South-F^stern and Western F-tensions Larviciding coverage on the basins of the South-Eastern Extension will renrairr unchanged in 1997. In the Western Extension, ground larviciding on the Niger and its tributaries around Bamako will continue to be ensured by the National Team of Mali rvitlr the technical assistance of the Vector control unit. larviciding will probably conre to an end bv the end of 1998. In Guinea, larviciding coverage will remain unchanged in conrparison tc) 1996. In Sierra I-eone, the problem of insecurity had repercussions on the aerial operations. However, the situation at present should allow the resumption of larviciding son're tirnc in 1996 provided the results of the epidemiological and entomological evaluations carriecl out rlrrrins the first six months of 1996 are satisfactory. j() ClarteT/Map7 VCU PLAN OF OPERATIONS FOR 1997 I PLAN D'OPERATIONS DE VCU POUR 1997 Ground larviciding Lutte a lle au sol t, Ptcscnt Ptogramme fmit Umitc lclua{e du Ptogrammc Original Programmc atea Alr. inhial. du Programme \,- Rivcr ttcatcd / RMArc t aitde --{' Trcatmenl suspcnded / Traitement susp€ndu ( t97 i Carte8/MaP8 VCU PLAN OF OPERATIONS FOR 1998 / PI-AN D'OPERATIONS DE VCU POUR 1998 larviciding antivectorielle au sol 1/9E Pr6ent Plogrammc lmit Llmitc actuclle du Programme Orlgln!l Proorammc arca Air6 laldalc du Progr!mme \*/- Rivo( trectcd / RMere lrs(Ce (j\L a-o : Treatmenl suspencec / JI!iiemonl suspcndu ,' )\ ..! ,-' ) I 31 7. PLAN OF ACTION AND BI,JDGET 7.1.. Plan of Action and Budget for 1996 and 1997 7.1.1. 1qq6 The approved budget for 1996 is US $ 24 278 000. At the date of 31.03.96, expenditures were standing at US $ 2 997 125. Considering the quantity of insecticides already ordered, the number of helicopter flight hours and other personnel related expenditures, it appears certain that this budget provision will be sufficient to cover the whole year. With regard to projected activities for 1996, the following actions will be taken: closing of the OCP offices in Bamako on 30 June 1996 and transfer of some of the personnel and equipment to Odienne; closing of the Tamale and Parakou sectors on 31 December 1996. The vehicles and equipment will be redeployed in the Programme; setting up of training programmes for the gradual transfer of some of OCP's activities to the National Teams. 7.1.2. 1q-q7 The Plan of Action and Budget for 1997 is being prepared. The draft docurnent will be presented to the CSA meeting in April and also to the EAC meeting in June. The final document will be submitted to the JPC for approval in December 1996 in Cotonou. With regard to personnel, given that the OCP Programme is nearing its termination phase, all new recruitments will be made on the basis of short term SSA type (Special Services Agreernents) contracts. Salaries will be in line with private sector wage practices in the Participating Countries. The resulting savings will amount to about 12% compared to the salaries paid to the General Services. For such recruitments, priority will be given to former OCP staff members whose positions were terminated. As for the fleet of vehicles, the strategy adopted is to reduce their number in proportion with remaining technical activities. From a number of 309 vehicles in 1996, only 200 will remain in use by 2002. All vehicles older than 10 years will soon be replaced so as to allow the use of the new vehicles to be extended up to the end of the Programme. 32 a 8. OTHER MATTERS E.1. Strengthening the Bouake DNA l,aboratory capacity for analyses 8. l. 1. Current capacity of the laboratory Three techniques are curently used in the laboratory: the southern blot technique, the heteroduplex technique and the ELISA test. The southern blot technique is used for i) the identification of parasites found in the blackflies during dissection as well as microfilariae and macrofilariae taken from patients; ii) early detection of O. volvufta infective larvae in the crushed mass of blacKly batches; and iii) the diagnostic test by detection of O. volvuhu DNA in skin fragmens collected through mere scratching. The heteroduple' techniqu. is used for the identification of members of the S. datnnosarn complex. Finally, the ELISA test is used in the immunodiagnostic detection of onchocerciasis. With regard to the personnel, three technicians currently work in ttre laboratory; one entomologist, one research assistant, and one laboraory technician. At their disposal are an extraction r@m, a room for immunodiagnosis and PCR preparation, a main room for experiments, and an office. From 1992 to 1995, only ttre southem blot technique which requires a whole week of experimentation for each test was used. As a result of this and because of the great number of samples to be identified (entomological surveillance, epidemiological evaluation, special studies) overlapping of experimentation times is practiced al most systematically. 8.1.2. The new techniques In the near future, three major changes will be introduced in the identification of onchocercal parasites. The first is an improvement of the southern blot technique in order to allow for the identification of a greater number of samples in.a shorter time. The second change consists in a shift from the southern blot technique to that of the ELISA test with the subsequent advantages as previously mentioned, plus a reduced cost. It is worth noting however, that compared to the southern blot, the ELISA test applied to the identification of blackflies uses only two probes, one specific to O. volvuhts, the other specific to the forest strain of O. volvuhts. The third change is related to the shift from the southern blot to the heteroduplex technique for a more refined identification of onchocercal species, particularly the savanna O. wlvthu t)?e. For blackfly identification, the heteroduplex t€chnique could be improved to reduce experimentation time and increase the number of samples to be treated. Vector identification through the heteroduplex method and the early detection of parasites in crushed mass of blackfly are now routine techniques which will be used in particular for the identification of parasites and vectors in the transition zones from forest to savanna. 8.1.3. Toward a strengthened analysis capacity Because of saturation in the analysis capacity of the laboratory due to the increasing number of parasite samples to be identified, and considering the increasing needs for analysis in connection with ttre special studies underaken, as well as the operationalization of the new techniques, a strengthening of capacity, in terms of both equipment and personnel, is now a necessity. Such a smengthening should allow the Programme to maintain its achievements and to rapidly frnd adequate solutions to current or future problems (trouble spots) by the end of the Programme. To accomplish this, a research assistant and a laboratory technician are required. They would be in charge of vector identification by means of the heteroduplex a 33 method, and of the early detection of parasites in blackfly barches. In addition, the research assistant could help the entomologist in the training of trainees, thus allowing the entomologists to spend more time on data analysis and the preparation of publications. t.2. Status of the AFOC and operational researrch A document on the status of the APOC Programme start-up activities was specially drafted for this meeting and is annexed hereto (APOC/DOC/OOl/Diskl). E.3. Other research on onchocerciasis of interest to APOC Dr. Philippon presented a summary of the results of research carried out from 1987 to 1995 by a team of parasitologisb from ORSTOM based at the Centre Pasteur in Cameroon @r.J. Prod'hon, J-P. Chippeaux and Dr. M. Boussinesq in succession). The studies related to the phase 4 trial of ivermectin in the Vina Valley in northern Cameroon, the severe reaction to ivermectin treatment in patients infected by [.oa-[na, and the evaluation of the macrofilaricidal potential properties of ivermectin on O. volvuhts. Further studies are under way. They relate to i) the evaluation of an immunologic test appropriate for the diagnosis of onchocerciasis; ii) the impact of repeated ivermectin treatment on the transmission of loase; iii) individual factors influencing the participation of populations in ivermectin distribution programmes; iv) the conelation benveen geographic and epidemiological factors in the pattern of onchocerciasis prevalence; v) the severity of onchodermatitis; and lastly, vi) the correlation benreen clinical and parasitogical indicators in various foci of onchocerciasis with a view to rapidly determining which populations should receive priority treatment with ivermectin. a a aa 9.1 9.2 34 9. RECOMMENDATIONS The meeting was informed about the latest results of the epidemiological modelling and it recommended that the simulations should continue within the particular context of the Phasing-out of the Programme. The model should particularly take into ac@unt the data from mouble spots such as the Bougouriba basin. (PET/BIS). The meeting examined the latest results of the studies carried out in the Bougouriba basin which started from the village of Zoulo where a recrudescence of the infection was detected by the National Team of Burkina Faso. In line with the JPCI6 recommendations and with technical and financial support from OCP, it proposed: a) the institution of a Task Force to seek explanations for the detected recrudescence less than five years after larviciding was ceased; b) the continuation and intensification of survey activities, the integrative analysis of all existing data, old and morc r@ent in the fields of en0omology, epidemiology, hydrology, transmission intensity measurement, v@tor control and chemotherapeutic treatments, human settlement and behaviour (seasonal or durable migrations, farming practices, etc.); c) the conduct, should it be needed, of fine-tuned entomological, epidemiological and socioanthropological field studies throughout the basin; d) the development of an exhaustive epidemiological mapping of the basin using the GPS (Global Positioning System); e) the institution of a community-based distribution of ivermectin in the basin every six months for a period of fifteen years. With regard to the first treatment of the villages where recrudescence was detected for the first time, it appeared highly desirable that the epidemiological data collected be jointly analyzrt by OCP and the National Team of Burkina Faso prior to any ivermectin distribution. @ET-VCU-National Team). 9.3. The meeting examined the plans for the implementation of community-based distribution of ivermectin. In order to enable VCU to make decisions on the termination of larviciding on some of the river basins, namely those of the Southern Extension-Cdte d'Ivoire, the meeting recommended that particular attention be paid to this mode of distribution so as to allow for is temporary suspension in the indicator villages concerned in order to carry out a more reliable epidemiological evaluation. (vcu-PET). On the basis of the preliminary findings from the epidemiological evaluations carried out in the Kankelaba basin, the meeting recommended that the temporary suspension of ivermectin distribution in the indicator villages be maintained for two years in order to allow for more reliable epidemiological evaluations in support of decision-making regarding the cessation of larviciding as of 1997. For the same reasons, the meeting recommended that the temporary suspension of ivermectin a 9.4. 35 9.5. 9.6. 9.7. 9.8 distribution in the indicator villages of the Marahoue be maintained for 18 months. (PET-VCU). After reviewing the entomological resuls obtained on the Kulpawn and the Mole, the meeting recommended that the training of the villagers of Bielikpong (recommendation 4.1 of the Fastern zone meeting) be implemented as soon as possible and that an exhaustive epidemiological evaluation be carried out around the area currently being heated so as to put all eligible villages under ivermectin treatment for a better therapeutic coverage. (PET). The meeting was informed about the deliberations of the workshop held in Geneva in February 1996 and it suggested that the DEC parch be used as the diagnostic test for onchocerciasis. It further rccommended that a protocol be prepared, taking into account all the specificity and sensitivity aspects of the test, and that this protocol be field tested with a view to making it operational by the end of 1997. (PET). Following a review of the results of the detection of infective larvae in crushed mass of blackfly, the meeting recommended the Bouake DNA probes laboratory to rapidly finalize the technique allowing the isolation of blackfly heads from among batches brought from the freld. The meeting further recommended the entomological service of the PET unit: i) to define the possibilities of utilisation of this tool in the field; ii) to prepare a detailed protocol for the collection and preparation of samples in the field for later use by the National Teams. (VCU-PET). I As a result of the saturation of the analysis capacity of the DNA probes laboratory due to ttre increasing number of parasite samples to be identified, and considering the increasing need for analyses in connection with special studies (Bougouriba, Oueme, Sierra l-eone...) and the use of new techniques (Elisa test, heteroduplex method, blackfly crushed mass...), the meeting recommended the strengthening of the analysis capacity of the laboratory in terms of equipment as well as personnel in order to allow the Programme to maintain its achievements and to rapidly find appropriate solutions to current or future problems ("trouble spots") before its termination. (VCU) IO. DATE OF NEXT MEETING The next meeting on Operational Research and Strategies will be held at OCP headquarters in Ouagadougou from Tuesday I April to Friday 4 April 1997 unless otherwise notified. 11. CLOSI.JRE OF THE MEETING The Programme Director and the Chairman of the meeting thanked all participants for their positive contributions. Special courtesies were expressed to the guests from outside the Programme. a a 36 I a t 12. LIST OF PARTICIPANTS OCP Participants Other Pafticipants 13. Dr. 14. Dr. 15. Dr. 16. Dr. 17. Dr. Observers 21. Dr. 22. Dr. 23. Dr. 24. Dr. 25. Dr. 26. Dr. K. Yankum Dadzie, DIR/OCP H. Agoua, CAT/VCU, Kara (Rapporteur) L.K.B. Akpoboua, CAT/VCU, Bamako B.A. Boatin, CPET, Ouaga Y. Bissan, VCU, Bamako O.W. Christensen, OCP, Geneva N. Demb€16, PET, Ouaga (co-rapporteur) J.-M. Hougard, CVCU, Ouaga (Chairman) A. Sdket6li, COORD, Ouaga E.W. Soumbey-Alley, CBIS/PET, Ouaga L. To€, VCU, Bouake L. Yam6ogo, CEEH/VCU, Ouaga 1. Dr. 2. Dr. 3. Dr. 4. Dr. 5. Dr. 6. Dr. 7. Dr. 8. Dr.9. Dr. 10. Dr. It. Dr. 12. Dr. K. Awadzi, OCRC, Hohoe D.E. Etya'ale, COORD APOC, WHO Geneva B. Philippon, ORSTOM, Paris A. Plaisier, University ERASMUS, Rotterdam H. Remme, TDE/TDR, Geneva O Kale, University College of lbadan, Nigeria U. Amazigo, University of Nsukka, Nigeria K.E. Siam6vi, [om6, Togo B. Kollo, Yaound6, Cameroun J. Catraye, PASE Project, Ouagadougou S.A. Tohon, Community Health, Porto Novo, Bdnin , ,t