Consultation on insecticides in the Onchocerciasis control Programme in the Volta River Basin Area: Lomé, Togo 27-28 May

ONCHOCERCIASIS CONTROL PROGRAMME IN THE VOLTA RryER BASIN AREA PROGR^MME DE LUTTE CONTRE L'ONCH@ERCOSE DANS LA REGION DU BASSIN DE LA VOLTA EXPERT ADVISORY COMMITIEE Fifth session Geneva 1 9-22 June 1 984 CONST]LTATION ON INSECTICIDES IN THE ONCHOCERCIASIS CONTROL PROGRAI'IME IN THE VOLTA RIVER BASIN AREA Lom6, Togo 27-28 l{,ay 1. Adoption of timetable and election of Chairman and Rapporteur Vector control situation in the Progr:me between April 1983 and May 1984 Development of new insecticides ........ 3.1 Acutely toxic chemical insecticides Laboratory screening of new formulations River trials Operational trials 3.2 Preparations of Bacillus thuriqglens:ls H-14 . 3.2.1 Screening of new formulations and spot tests in the river 3.2.2 Operational trials of B.t. H-14 3.3 Insect grorrth regulators (IGR) Evaluation methods WORLD HEALTH ORGANIZATION AFRICAN REGION ORGANISATION MONDIALE DE LA SANTE REGION DE L'AFRIQUE OCP/EAC5 .8 Rev. 1 ORIGINAL: FRENCH 2 3 Page 3 3 4 4 4 5 6 7 7 7 8 3 3 3 3.3.1 3.3.2 3.3.3 1 2 3 Test results . .. 8 9 10Prospects for evaluation of IGRs 3.4 Larvicide evaluation methods 3.4.1 The various screening devices 3.4.2 Standardization of the water used for 11 screen].ng 11 11 4 5 6 7 3.5 Larvicide development system ..... Adulticiding . .. Improvement of insecticiding techniques Insecticide resistance Operational restrictions due to resistance .. 7.1 Operational plan for 1984 7.2 Replacement insecticides 11 12 12 13 14 14 15 158. Relations with industry for Lhe development of new larvicides OCP/EACs.8 RCV. l page 2 Annex 1 . ....... Annex 2 ........ Annex 3 ........ Annex 4 ........ 17 18 21 22 OCP/EAC5.8 Rev. l Page '1 1. Adoption of timetable and election of Chairman and Rapporteur The group elected Dr N. Gratz, Director of VBC,I as Chairman, and Dr J. Houchet as Rapporteur. The Chairman recalled the joint efforts of VBC and the Programme since 1980 to develop new formulations and new insecticides applicable to blackfly control. Two informal meetings of the same parEicipants had already taken place in 1982 and 1983 to sum up the progress made, to determine priorities for work in hand or to be undertaken, and to examine the needs of the Prograrmne and the difficulties encountered in vecEor control. Bacillus thuringienrsis H-14 (Teknar) wit@ lower Bandama suspected of temephos resistance had 2. Vector control situation in che Proqramne between Apr il 1983 and May 1984 The entomological situaEion had been excellent throughout the Programe since the end of the dry season in 1983, admittedly having been favoured by the appreciable shortage of waterin 1983. The Chairman was anxious that Ehe meeting of the group should advance from its infornal staEus and that its conclusions should be more widely disseminated and should in particularbe brought to the attention of EAC2 and JPC.3 Th" irog..r*" Direclor was of the same op inion. During Ehe rainy season in 1983 the whole of the eastern part of the prograrrne area had been treaEed with temephos (Abate). The western part had been treated with temephos in the savanna basins where only S. damnosum and S. sirbanum were present. Farther south (theAtrantic basins in the r"oiyTo,flt)-, ,here.ffilfr?frry pop;larions were remephos-resistanr, rivers with a discharge of 50 mj/sec or lesfTEES6frealea wittr will continue so to be. A large helicopter with a 1200 kg payload had been stationed in theIvory Coast for thaE purpose. As the dry season progressed and discharges declined, airborne treatment with temephos was considerably reduced to the point of complete elimination at the time of the lowest vrat.er. Chlorphoxim vras gradually replaced by Teknar and was no longer used from February onward. Discharges increased again from May 1984. The whole of the Sassandra basin, thl Marahou6 and the como6 were treated with Teknar, while the Black Volta, t.he Bafing, and thebasins of the oti and the M6 were treated with Abate. 1984 promises to be a normal or even an excessively wet year, in which respect it will contrasE with the two preceding years.Even now, reinvasion consequent upon the early rains has been seriously roanifested in the west of the Prograrune. From June onward, increases in the discharges tt tn. rivers maypossibry rule out further treatment of some of Ehem with reknar. The use of Teknar always raises serious problems and there are many setbacks inEreatment with it. Furthermore it is extremely costly. The current phase rv treaEment (the souE.h and middle of rhe Ivory Coast) cost US$ 1 800 ObO , and rivers with a discharge of more than 50 ,3/"ecbasin, where an S. damnosum/S. sirbanum population been detected, hffiiih'Teknar and 1 vsc: vector Biology and control - Division of wHo, Geneva, specialized in vectorbiology and control. ,) - EAC: Expert Advisory commitEee, a consultative body of the progranune. 3 'lpc: Joint Prograrmne cormnitEee - the highest authority of the progranme, consistingof the member states, the funding states and 0rganizations "r,i th".fo.r"ori.rg Agencies. ) > OCP/EAC5.8 Rev. 1 page 4 It should be recalled that the estimated insecticide consumption for a nonnal year is: 350 000 litres of Teknar; I20 000 litres of Abate; 60 000 litres of chlorphoxim. For 1984 \re musE add, to this figure 15 000 litres of Abate for experimental treatmenE of the Sankaranr rn Guinea recomnended by the last JPC. J. Development of new insecticides 3.1 Acutely toxic chemical insecticides 3.1.1 Laboratory screeni of new formulations Screeniug was carried out in troughs and minitroughs. (a) Pyrethroids (gee Table 1 of Annex 2 fot E,he results) Peruethrin - two 2O7, ECrl Coop"*, a registered product from Wel1cooe, and Talcord, a regietered product frm Shell, and a beteeen 0.013 and 0.038 ng/1/10 min). 502 Ec from Wellcome performed idenEically (lc fOO The tvo 2O7" EC were selected for river trials. Mavrik (Fluvalinate), a registered product produced by Zoecon, ehich is a concentrated(tforiE'i.)-euepension, yielded an LC 1002 of A.2 lr.rel LlL0 min. This product should be included in tfiIOPESJ for evaluation of the act.ivity of Ehe active principal against morquitoe and for toxicity asseaanenE. The LC 100 is relatively high, but it should be remembered that flowable formulations are, in general, of lotrperfornance. Several fornulations of ry, manufacEured by ttitsui Toatsu, were screened. Tt.e 207. and 302 EC formulations all had an LC 100 >0.f rg/1/10 min in the trough. One of them was selected for river trials although its activity is only moderate for a Pyrethroid, because the active principal, eimilar t.o fenvalerate, is different from the other compounds of this group and could Prove of interest should resistance develop. Cypernethrin ie highl y active Ln a 4OX EC with an LC 100 of 0.0064 rrelll 10 roin. In 1983 two 1982, uere re-Ees The 1Z EC synergi 0.0003 ng/1/10 ni operational doaes concenErat ions. formulations of deltanethrin produced by Roussel-UCLAF, already screened in ted. The IZ EC, known as rts imulid A" produced 1002 mortality at 0.00067. sed by L2.57 piperonyl butoxide , known as t'simulid B", is active at n. t'Simulid Bt' and cyPernethrin were tested in the river to determine the and evaluate their toxicity againet the non-target fauna at these The pyrethroids produce a knockdonn effect on the larvae wtrich Preserves sooe of them; they are dltachea, but survive and eubeequently recover. The doee often has to be doubled to advance frm 1002 detachoent to 1002 actual mortality. In a t,riel with permethrin, the nine larvae out of 1000 that Ehus survived treatment. at O.OZ agll/Io min were treated once again at the same concentration and two of them survived. fi;.s Iot poesible Eo say whether a behavioural reection or a phenomenon of resistance is involved. I uc, emuLeifiable concenErate. 2 f,C tOO: the concentration that produces 1002 larval mortaliEy under experimental condiEions. 3 w*orrs: tlllo Pesticide Evaluation Scheme. a aI OCP/EAC5 .8 Rev. 1 page 5 (b) Carbamates (see Table 2 in Annex 2 for the results) Methiocarb, a promising product as a water-dispersible powder, is unfortunately unusable by the Prograrrne operationally and cannot be formulaE.ed as an EC. Bayer, the product, has prepared a 5O7" suspension which causes 100% mortality at 0.5 mg/l/10 min and Ehis will be tested in the river. The two Propoxur formulaEions produce 1002 mortality only at or above doses of 1.5 mg/1/10 min. The effectiveness of Padan (Cartap) is of the sarne order. As soon as a formulation of ethiofencarb is available, it will be reevaluated. (c) organophosphoru s compounds (see Table 2 of Annex 2 for E.he results) The two azamet.hiphos formulations supplied by Ciba-Geigy in 1983 were noE superior to those previously screened. The four formulations so far Eested are to be retested in a trough to select the one with the best performance with a view to river trials. (d) Organochlorine compounds (see Table 2 of Annex 2 for the results) Tvo 257d EC of DDT, one experimental, the other indust.rial, produced 100% mortality in the trough at doses above 0.4 ng/ 1/10 min. (e) Sulfonate (see Table 2 of Annex 2 for the results) Bensultap, a synEheEic nereitoxin, produced by Takeda as a waEer-dispersible powder, caused 1002 mortality at 0.75 mg /1/10 min. Given thaE t.his product belongs to a class that is completely different from conven!ional larvicides, cont.acE has been maintained with the manufacturer in order to look for better formulations. A request is also to be made for 1 g of the active principal in order to carry out suscepEibility tests on populaEions of temephos-resi stanE blackf lies. (f) ProducEs available for screening At the present time there are five pyrethroids, two carbamates available for screening. They have already either been sent Eo the order. and one thiadiazol testing cenE.res or are on 3.L.2 River trials (see Table 3 of Annex 2 for E.he results) River trials were limited in 1983-84, owing to the weak discharge of the rivers', not all of these trials were carried out under hydrological conditions best suited to assessment of the carry of the formulations. (a) Azamethiphos The trials were carried out under poor hydrological conditions. Only at 0.3 rrrC/l/10 min was complete larval mortality achieved over a distance of 1.6 km when river discharge was 0.7 nJ/sec. The trials should be repeaEed in rivers with a discharge of at least l0 m3lsec. (b) Permethrin Talcord and Coopex, in a 2011 EC, rrere both equally effective, yielding 1002 mortality 0.02 ngl 1/10 min, with a carry varying between 0.6 and 4 km in rapid-release airborne application. An application raEe of 0.01 rrrg/l/10 min, on the ground also produced 100% nortality over 2.5 kn in a river with a discharge of 4 mr/sec. at There are significant differences in carry from one trial to another t.hat do not appear to be solely correlated with discharge. I OCP/EAC5.E Rev.1 page 6 What in fact is evaluated in these river tests is the percent.age detachment of blackfly larvae, which may be different from the percentage mortality (cf 3.1.1). It is noE known whether larvae that become detached without being ki1led are subsequently able to survive in Ehe natural envirorunent in which they are subjected to many more hazards than in laboratory equipr,rent. Effects on the non-t.arget fauna were studied in some of these trials. Although the maEerial collected is sti1l being analysed, it can already be stated that there was no mortality of fishes or of macrocrustaceans. (c ) De Itamethrin The "simulid B" formulation, synergised with piperonyl butoxide, resulted in complete Iarval mortality (or rather their detachment) over a diqtance of 4 km when used at a rate of 0.002 ng/L110 min in a river with a discharge of L2.1 m3/sec. The "Siruulid Arr formulation performed poorly at the same concentration. The I'Simulid B" formulation will be retested to evaluate its impact on the non-target fauna aE the operational dose. Order of prigrity 9! Mrf lrfe1e The group proposes the following order of priority for river trials: 1. Azamethiphos 2. Deltamethrin 3. Cypermethrin 4. Methiocarb 5. OMS 3002. Deltamethrin and cypermethrin have considerable side-effects on Ehose who apply them. It is therefore essential to obtain information on t.he precautions taken in agricultural pest control where these two producEs are used extensively at the present time especially as the pilots working for the Prograrune spend far more time in their planes than is spent by those who carry out agriculEural treatmenE.. 3.1.3 Operational crials Perme thr in Trials of Talcord at 0.015 rlrgllllO min carried out on the Bagb6 (an untreated Ivory Coast river with a discharge of Z0 m3/sec) resulted in a 90 to 992 reduction in larvae. There was hardly any mortality of blackfly larvae when the same product was applied at the same rate to the Sassandra (discharge 6 mJ/sec). In the attempt to explain this ineffectiveness, the industrial product was trough EesEed and found to be identical to the experimental product screened at Lqu6, which had been assessed as highly active. Furthermore, the blackfly larvae of the Sassandra were more susceptible to permethrin than were Ehose of the Togo. The physicochemical characteristics of the highly alkaline water of the Sassandra were investigaEed. At the presenE time it is impossible to give any explanation for chis ineffectiveness, and other trials will be carried out on the Como6 and other river sysEems of the Ivory Coast. This setback is a perfect illustration of the difficulties of developing larvicides for use against blackflies, since it is an operation that retains an enpirical aspect, partly because of gaps in our knowledge on the behaviour of the formulations in the water and on E.heir mode of action on the insect. IoCP/EAC5 .8 Rev. l page 7 3.2 Preparations of Bacillus t.hur ineiensis H-14 3.2.L Screening of new formulations and spot tests in the river Four firms: Solvay, Sandoz, AbbotE, and Tate and Lyle sent formulations that have all been tested at IRTOr in Bouak6, Ivory Coast. Mini-trough trials were followed by point trials of promising formulations in Ehe river in so far as was possible with the amount of the product senE by the firm. Formulations supplied by Solvay (Bactimos) Two of the seven indusE,rially producible formulations proved to be very good under experimental conditions and one of them was Eested under operational conditions. Eleven other batches were recently sent by Solvay, but had noE reached IRTO by the time of the meeting. The firm is awaiting the results of trials on these most recent batches before reformulating them. Formulations sup plied bv Sandoz (Teknar) Nine new formulations were screened and two were kept under consideration: - frt 85 27. This forrnulation is of equivalenE effectiveness to Teknar, but disperses spontaneously without the addition of water. The results in the river were saEisfactory and 1002 mortality was obE.ained at 1.6 ngl1-/ 10 min. OCP has ordered 1000 litres of this formulation for large-scale trials. - SC 93. This formulation is obtained from an asporogenous st.rain. SevenEy litres rdere sent for river trials; Ehe results obtained were encouraging and there was 1002 mortaliEy at 0.8 mg/1/10 min. However, the viscosity of the formulation was such as to require prior dilution with an equal amount of water. The firm has prepared 1000 litres of spontaneously dispersible SC 93. Mini-trough trials of the effectiveness of a sample from this batch yielded 1002 mortality at 0.8 mgll/ 10 min, as expected. Large-scale trials will be corrnenced as soon as 1000 litres. the Prograrmne has received the Another Ehree new formulaEions have recently been tested and one of them, SC 99, is highly promising, yielding 100% mortality at 0.8 mg/1/10 min, and self-dispersing. Field trials have been reconunended in so far as the firm is able to produce this formulation industrially. Formulations supplied by AbboEt (Veccobac) Of four new formulat.ions sent for screening, three yield 100% mortality at 1.6 mg/1/10 min. Two others have been recomnended for field trials. One, ABG 6145, will be available conrnercially in the United States. For good dispersion 10% water has to be added. Tate and Lyle aa None of Ehe three formulations sent yielded good results (LC 100 3 ng/1/10 nin). 2 Operational !riats of g.t. H-14 The Teknar formulations currently in use do not disperse well sponEaneously. They have to have 202 of water added to them and must be applied by spraying aE a fixed point, which is possible only with helicopters. I tRto: InstiEut de Recherches sur la Trypanosomiase et lrOnchocercose (Institute for Trypanosomiasis and Onchocerciasis Research) . JCP/EAC5.8 Rev. 1 page 8 Given the large amounts of the product to be released at each spraying poinE, helicopters with a large carrying capacity must be used for rivers with a discharge of more '-han 50 mJ/sec. Furthermore, although the carry of Teknar has not. been well evaluat.ed, it would not appear Eo exceed 5 km under the best conditions and consequently the number of spraying points must be increased in the rainy season. Formulation 831692.4 from Solvay proved to be excellent in the river both from the poinl of view of the dispersion capacity and the facilities for applicationr and from the poinE of view of carry. The Prograrune ordered 15 000 litres that uere tried under operational conditions on the Bagb6. The results uere extremely disappoincing and the performance of the industrial product was greatly inferior to that of the experimental batch. Of the three bat.ches in the consignment, only one had a performance almost equal to that of Teknar, and the other two were greatly inferior. The firn has not yet been able to supply an explanation for the difference between the experiment.al bat.ch and the industrial product. 3.3 Insect owth re lators (IGR) 3.3.1 Evaluation uethods In accordance with the reconmendation of the informal Deeting held in Geneva in August 1983, IRTO and the OCP Insecticides Unit have devoted themselves to the development of screening methods for IGRs in the laboratory and to river trials. The results are given as percenEage reductions in the emergence of viable adult insects. 3.3.1.1 Laboratory tests The facilities at IRTO are: - a minitrough in which oetal plates colonised by blackfly Iarvae are placed 24 hours before treatment; - a circulating-water trough sysEem in which the plates are placed for the conEact time required for the trial; - a system of troughs supplied with river water by gravity feed in which the plates are placed during the observation period. Each is isolated in an emergence cage inside the apparatus; in the controls the proportion of viable adults obtained at the end of the experiment is 70 to 95i( of the initial number of larvae present on the plate. This aPParaEus is currently used in the screening of IGR formulalions. The apparatus (troughs) in the OCP laboratory at Lon6 is Ehe same as that used for the screening of acutely toxic larvicides with emergence cages placed over the plaEes for the observation period. 3.3.1.2 River trials Supports rich in larvae are located in the reach selected for the trial. A gravity-fed trough is set up downstream. Treatment is carried out with a push-pu1l apparatus for 10 to 20 minutes. Some three hours afEer treatment the supports are gathered up and placed in the trough located downstream of the treated reach, where they are kept for 24 hours to reveal any possible insecticide retardation effect (adhesion of the particles to the botEom or on Ehe vegetation, followed by continued release at a very low concentration). Larvae from the trough are subsequently used to colonise plates which are placed in the observation equipment used for screening unEil the adults emerge; this equipment is installed uPstream from the treaEment point. 1 OCP/EAC5.8 RCV.1 page 9 3.3.2 Test results 3.3.2.1 Diflubenzuron (a) In the IRTO laboratory A considerable number of trials have been carried out with a 257" water-dispersible powder. The results express the ratio between the number of viable adults collected in the upper part of the cage and Ehe number of larvae used for the trial. Whatever the quantity of IGR employed, between 0.1 and 4 ^glt, the reduction of emergence with 10 minutes contactnever exceeds 50 to 602. The results were not significantly improved by increasing the contact time and proportionally reducing the application raEes (to 0.0625 nglL/32O minutes). The short intestinal transit time of blackfly larvae (15 to 20 minutes in final insEar larvae) would not appear to explain the lirnited effectiveness of this product. Young larvae (instars 3 to 5) are little more susceptible Ehan late instars (6L.72 reduction of emergence at 6.4 ngl 1/10 min). Thirteen different formulations were screened at 0.1 and 0.5 ngl 1/20 min. Very significant differences in effectiveness were noEed from formulation to formulation, and the best did not yield more than 80% reduction of emergence. (b) At the OCP unit in Lom6 A series of trials was carried out at Lom6. A 1002 reduction of emergence was obtained at 0.25 rlglLl 15 min. At 0.L25 ngl 1/15 min the reduction was 447, but half the adulEs were not viable. An ovicidal effect was also noted; the hatching rate was only O to 24% at 0.5 mg/1/60 min; the subsequent fate of the larvae to emerge from these eggs is not known. (c) It is difficult at present to explain the great difference beEween the results obtained at IRTO and aE the OCP unit in Lom€. It cannot be connected with the formulation since the Ewo formulations tested in parallel by IRT0 yielded similar results. One possible explanation could be cont.amination of the observation trough by the transfer of exposure plates to the observation system without rinsing. There could then have been release of very lon concentrations of Dimilin to wtrich the larvae would have been exposed throughout Ehe observation period. Trials will be carried out to verify this hypoEhesis. (d) River trials Treatment. was carried out three times on the Bagb6 in the Ivory CoasEl - 0.1 rtglll2O min yielded a 3OZ reduction of emergince (discharge 1.2 m3/sec) - 0.2 nglL/ 10 min yielded a 607. reduction of emergence (2.3 m3/sec) - 0.5 rlglL1ZO min yielded a 4lZ reduction of emergence (1.2 m3/sec). A simultaneous trial with the same formulation in Ehe screening equipment yielded a 32.57. reduction of emergence at 0.1 mg/1/20 min and 567" at 0.5 mg/1/20 min. There is therefore a close correlation between the laboratory results and Ehe results obtained in the r iver. Complementary trials are Eo be carried out with the most effective formulatioo (52 concentrated suspension). 3.3.2.2 Methoprene Two Altosid (Zoecon) formulations rrere EesEed in the laboratory: - SR 10 (slow-release microcapsules); OCP/EAC5.6 Rev.1 i,aga- 10 - PS 10 (a powder of particles coated in a substance that dissolves in the alkaline medium of the alimentary canal of blackfly larvae); this formulation has proved to be far more effective against Nearctic simulids than SR 10. PS 10 at 0.125 rrrglJ /80 min yielded an 81.62 reduction of emergence of viable adults. Brief contact, I mg/1/10 min, yielded only a 50.81t reduction in the emergence of viable adults (many hatch but die immediately). SR 10 yielded a 78.57" reduction of emergence at L ng/Ll 10 min and a 1002 reduction at 1 mg/1/40 min. 'these Erials were conducted on sixth and seventh instar larvae which are Bost sensitive to the action of methoprene. 3.3 .2.3 Other IGRs Avermec t in This is a producE that cumulates the effects of conventional larvicides and growth inhibitors. A 1.8"A EC (Merck, Sharp & Dohroe) was tested. At 0.005 mg/1/10 min a LOOZ reduction of emergence was obtained on late instar larvae. The larvicidal effect alone counted for 992 of mortality at 0.03 urglLl 10 min; this morEality was not imediate and took 72 hours to reach its maximr.m. Although the active principal is highly toxic to marmals (10 mg/tg rat), the producE is of some inEerest because of its effectiveness at very 1ow doses and the extremely low concenEration of the formulation. Before proceeding any further with the evaluation of this product it must be introduced into the WHOPES system. Phenoxycarb (Maag RO. 12 ) This compound is a carbamate possessing the properties of a growth inhibitor. A L2.52 EC was tested. At 0.4 mgl 1/10 min a LO}Z reduction of emergence was obtained. The compound has properties similar E.o those of methoprene. AE the LC 100 high as 702 pupated, but none of the adults from these pupae was viable. The effect of the compound on early instar larvae will be evaluated in the near future. 3,3.3 Prospects for evaluation of lGRs The indusEry is highly geared at the present time tosards the production of new IGRs, some of which are highly active against mosquito larvae. A fair number of them are being evaluated in WHOPES. The meEhods currenEly available enable roany IGR formulations to be screened most rapidly. Consequently, OCP and its collaborating laboratory at IRTO will be in a position to study all products submitted. Ir is still not possible to presenE a syslem for Ehe development of IGRs similar to that which has been put forward for acutely toxic larvicides (cf. 3.5). IGRs are liable to be active at very 1ow concentrations if their conEact with the insect extends over several days and the Group advised study of the effect of very low concenErations over an extended exposure time. Advances in the technology of slorrrelease formulations would in fact make it possible to envisage the treatment of some watercourses with solid slow-release formulaEions. Given that it is very difficult for the females to obtain blood meals in the laboratory, it is impossible at present to determine whether viable adult blackflies from treated larvae are capable of feeding themselves and transmitting onchocerciasis. A11 that can be done, ocP/EACs .8 Rev. 1 page 1 1 therefore, is to refer to what has been observed in mosquitos. Viable Aedes aesypti females from larvae treated with diflubenzuron exhibited apparently normal troph behaviour and produceci fertile egg bacches. 1C and sexual to the Group (Annex 3) was considered Eo meet the It fits into WHO!s general system for the development of , Ehe various stages of selection are to be carried out on under the conditions of t.he Progrartrtre area, which are very different counEries, especially as regards the physico-chemical charact.eristics 3.4 Larvicide evaluaEion methods J.4.1 The various screenl devices A comparison of trough and mini-trough tests on acutely toxic chemical insecticides has shown that, when the concentration is the same, mortality is twice to three times greater in the firsE device. The difference between the results obtained in the two devices is particularly marked for pyrethroids. The lesser activity of the formulations in mini-troughs could be due to the shortness of the period between the formulation coming into contact with the water and passing the larvae. The inEeractions between the water and the formulation (adsorption, diffusion of the active principle, etc.), which may ofEen condition the activity of the formulation, do not have t.ime Eo take place. By contrast, the mixing of the water and the formulation that occurs in troughs before and during exposure is conducive to these interactions between the water and Ehe formulation. The Group reconrnended that acutely toxic chemical insecticides should be screened in troughs. Those carrying out Ehe tests may, however, carry out complementary studies wit.h oEher devices if they consider it necessary and if rhey have t,he tirae. IRTO has developed a compromise between these two methods in order to increase iEs working capacity. Larvae arranged on metal plates 24 hours before the test are kept, in a minitrough. The treatment is carried out in troughs. The plate is then returned to the minitrough for the observation period. This compromise increases working capaciEy roughly tenfold and makes it possible to take advanEage of che favourable conditions of high larval production which are often of short duration; furthermore, there are only a few hours wtren electricity is needed. The use of ninitroughs to screen B.t. H-14 formulations is still recormnended. in the development of IGRThe Group noted with sacisfaction Ehe very rapid progress screening equipment. 3.4.2 Standardization of the water used for screening Troughs are a laboratory evaluation system in which most parameters can be controlled and therefore standardized. Even so, the turbidity and the suspended matter content of the river water used in the troughs vary in the course of the year and from river to river. It has therefore been proposed that the aE.Eempt should be made to standardize the water by filtering it and by adding suspended matter. The addition of 50 mg of kaolin per litre does noE affect the trophic behaviour of the larvae and does make it possible Eo obtain better results with Abate than are obE,ained by the use of river waE.er a1one. 3.5 Larvicide developmenE system The sequence for the development of acutely toxic chemical larvicides against Simulium damnosum s. I. proposed requlrements o e Prograrmne. insecticides (WHOPES) . t Except for phase I Simuliurn damnosum s.1. from Ehose of temperate of the river waters. From the preliminary stage onwards it must be established on S. damnosum s.1. populations resistanE to organophosphorus insecticides and possibly to other products that the candidate larvicide does not exhibit cross-resistance with them. OCP/EAC5. 8 Rev. 1 page 1 2 Large safety margins have been built into the discriminating doses in each sEage of selecEion so as not to risk the elimination of promising products. We are st.ill unable to suggest a similar system for IGRs, since the experience gained with these products in blackfly conErol remains very inadequate. 4. Adulticiding Further to the 1982 recormendations of the JPC, aE Bamako, VCUI carried out trial adulticiding in 1983 on the Faya, near Bamako in Mali. The object was to evaluate its impact on invading blackflies. The operation consisted of ground spraying witt:. 25X EC permethrin on the gallery forest. In seven spraying operationsr 4 km of gallery forest (2 km on each bank) were treated in one week. Ground spraying in the rainy season proved to be very difficult. It. wae impossible to make a proper assessment of the operaEion because of the very slight reinvasion that occurred in 1983. Although significant contamination of the river was noted, it did not result in any fish mortality. In line with the recomendations of the 1983 JPC, in Paris, the Prograrme decided to carry out important trials during the 1984 rainy season. The selected site was a well-known reinvasion zone 4 km in diameter on the M0 river and its tributaries, in Togo. Treatment will be carried out by helicopter. The aircraft has been fitted with a standard spraying device using a bank of nozzles; iE has been provided with outside tanks to a toEal capacity of 600 litres. The producE applied will be 2O7, EC permethrin at a rate of. 250 g/ha. Preparation of the work began in April with the delinitation of the treatnent zone, the specification of blackfly cat.ching points inside and outside the zone, and of aquatic monitoring sites. An evaluation will also be made of the inpact of adulticiding on the terrestrial fauna. Collection of the basic data has already begun with the assistance of a Dutch consultant. At the presenE time the nozzles are being calibrated and a physical study is being made of spraying (droplet size) with the assistance of a consulEant from Cranfield. The spraying operations should begin on 18 June. Permethrin is reputed to have a residual effect. A decision on wtreEher to repeat the Ereatment will be made after observation for two weeks. It is the intention of the experimenters to use adulticiding only over very limited areas to deal with the effecgs of reinvasion or possibly breakdown in treatment, and it is recognized that the purpose is noE Eo apply adulticiding over large areas as a replacement for larviciding. 5. Improvement of insecticiding techniques The consEraints irnposed by the application of different larvicide formulations have led VCU to develop various pieces of spraying equipment over and above those used for the application of temephos. Spraying at fixed points by helicopter could be envisaged for the application of formulations Ehat disperee 1ittle when expended in massive doses by rapid delivery systems that are derived from the rapid-release EyPe. The equipment used for adulticiding could be envisaged for some Pyrethroids such as deltamethrin, cypetmethrin, pernethrin and possibly other products. The shock effect on the aquatic fauna tirat ttre abrupt release of large amounts of insecticides might have by producing locaI very high concentrations of toxic products would be minimized. Furthermore, the treatment could be applied imediately upstream from the breeding place, thus avoiding dissipation of the insecticide in passing through stagnant wat,er above breeding places. 1 vector Control Unit of the Programe. 65 6 OCP/EAC5.8 Rev. I page 1 3 This technique caIls for very serious evaluation since airborne spraying trials of temephos have been disappointing. Insec t.ic ide resistance 1 Resistance to organophosphorus compounds 1.1 Temephos resistance Temephos resistance in S. soubrenge/S. j4nctrpafili has remained very stable since 1981. rlvers o f Ghana and a reduction in suscept.ibility has also been noted on the border between Togo and Ghana. This diffusion is effected by the migration of resistant individuals. It correlates with the spread of a particular chromosome inversion in S. soubrense populations. The reduction of temephos susceptibility noted early in 1983 in an S. damnosum s.s./S. sirbantrm population from the lower Bandama has been at least stabilized by intensive Teknar treaEment of this parE of the river made all the easier by Ehe shortage of waEer in recent years. A few isolat.ed females of these savanna species have been found from time to time near these sites, but it has been impossible to determine whether or not they belong to a resistant population since susceptibility trials are currently carried out only on larvae. Since this alert, temephos-resistant savanna-dwel1ing-forms have not been found. of rhe S. damnosurn c omp 1 ex No resistance was found in tests carried out in Guinea on the Sankarani, which will be the next to be treated with temephos . The S. damnosum population of this river consisEs principally of savanna species, but S. soubrens S. sancEipauli had previously been reported. 6.L.2 Chlorphoxim resistance In previous years a reduction of chlorphoxim resistance was not.ed following the interruption of treatment during the dry season on the Sassandra and the Marahou6. Consequently, this compound was once again used for several weeks around the high-water period until resisEance increased again', the switch was then made to Teknar. This year the regression did not show up on Ehe Sassandra itself, but only on its tributaries. The situation as regards the Marahoud is not yet known. It should be recalled that there has never been any regression in chlorphoxim resisEance in certain rivers such as the Como6. 6.2 Susceptibility to DDT Although no clear resistance Eo DDT has been noted in recent years, there are large variations in Ehe LC 50 and LC 95 from place to place and time to time. It is difficulc to diagnose resistance, but also Eo assert that susceptibiliEy is everywhere normal. It should be recalled that the insecticidal pressure of DDT comes from agricultural treatment, especially the treatment of cotton. It so happens that cotton-growing is very unevenly distributed throughout the Prograrune area and that treatment is concentraEed inEo a small period of the year. It is impossible to reconcile the situation with the heterogeneity of the response of blackfly larvae Eo DDT. In itself, resistance to DDT would not be of importance for the Progranrne, but in other vectors iE is someEimes crossed with resistance Eo pyrethroids which could be used subsequently in the Prograrmue. Accordingly, the Group reconmended Ehe production of a map of susceptibility to DDT in the Prograrune area and the extension zones. It has spread into the untreated S. soubrense populations of the lvory CoasE than the S. damr.'rosum s.1. populations of Togo. TEffi;iliT'e explicable either by resistance or by a negative correlation between resistance ocP/EAC5 .8 }-l.ev. I ^ " :o 1 /. 6 .3 Susceptibili ty to permethrin It was noEed that permeEhrin formulations were far more effective against the resistant Eo temephos and permethrin activity. It had been noted in the Ivory Coast that an S. soubrense population susceptible to temephos had an LC 95 of 0.008 mg/l for permethrin. However, the LC 95 of a resistanE strain was only 0.001. The Eemephos-resistant population therefore appeared to be eight times more susceptible to permethrin than the temePhos-susceptible population. In Togo, LC co 0 .015 mg/ 1 . 95 of S. damnosum s.s. populations for permethrin ranged from 0.005 Consequently there was very great variability in the permethrin susceptibility of various blackfly populations of the S. damnosum complex. It should be recalled that pyrethroids and, in particular, deltamethrin are used very freely against cotEon pests in the Ivory Coast and Togo (and possibly elsewtrere). The OCP team in LomE is in the course of determining the susceptibility of the S. damnosum s.1. populations to tenephos, DDT and permethrin in rivers in which larvicides are to be tested in order to avoid obtaining results of d isputable reliability. So far all the populations appear to be suscePtible. 7. Operational restricEions due t.o resistance 7.L ational lan for 1984 It has been proved Ehat temephos-resi6tant PoPu lations of S. soubrense in the Ivory Coast could not be controlled by increasing the amounts of tenephos used. Faced with resistance of this order it is therefore necessary to use another insecticide, for wtich cross resistance with temephos does not exist. This is the principle governing the tactics adopted by OCP. Having regard to the shortage of water and the regression of chlorphoxim resistance during the 1983 rainy season in the Ivory Coast, the situation Ehroughout the Progrenme area had to be handled by adopting the measures described in section 2. The situation in 1984 looks different with rainfall anticipated as normal if not above normal. From June onwards some water courses, especially those i S. soubrense populations, could have a discharge in excess of 50 nh ur3 abited by resistant /sec and they could therefore be difficult to treat with Teknar. On the other hand, the regression of resistance to chlorphoxim has been slight or unaPParent. Under Ehese conditions the Prograrmne envisaged the following measures: (a) Savanna water courses in which S. damnosum/S. sirbanum susceptible t.o temephos are lhe dominant,ifnoEtheon1yspecies,wffiephosasinpreviousyears. (b) In regions where savanna and forest species coexist, i.e., in the wet savanna and the foresE-transitional and forest zones of the Ivory Coast, the water courses will be treated with Teknar, switching to chlorphoxim when discharge exceeds 50 nr/sec. Only the lower reaches of the Bandama wilI continue to be treated with Teknar what,ever Ehe river discharge, for Ehe reasons set out above (see sections 2 and 6). Should a perceptible increase in blackfly populations be noted, enEomological moniEoring will be intensified in order to identify savanna species and, should they be present, to test their susceptibility to insecEicides. Should resisEance to organophosphorus compounds appear in the savanna species S. damnosum/S. sirbanum, which is a possibility that cannot be ruled out, Ehe Group ffii1ab1emeansshou1dirunediate1ybebroughtintoplaytocirrrmscribe ocP/EACs.8 Rev. I page 1 5 and if possible eradicate the focus of resistance. Teknar is obviously the irunediately available weapon in reserve in applicaEion of the ConEingency Plan proposed to the Ecological Group (Annex 4). However, as there may be operational difficulties over its use in large rivers at Ehe highwater period, it would be essential to be able, if required, to use lhe available replacemenE insecEicides, e.g. permethrin, at this period, i.e., for less than two months and on siE.es of limited area in emergency situations. Permethrin has not yet undergone the whole sequence of development for new insecEicides. Nevertheless, spot tests in a river with a weak discharge have shown that in operational doses it does not kill either tishes or the macrocrustaceans and it may be foreseen that any toxicity for the aquatic ecosysEem would be less at the highwaE,er period when it could be required t,o be used. The Group considered that iE should make its analysis available to the Ecological Group. The Group also considered that some latitude should be left to the Prograrme Director and Ehe Chief of VCU to take the necessary measures to deal with problems that may arise in the field. Aware of the possible implications of decisions made, the Group vouched all necessary support. 7.2 Replacement insecticides In 1983 the Ecological Group wanted treatment of the extension zones not to begin before the Prograrune had two reserve insecticides available in addition t.o temephos. This statement gave rise Eo some commenE on the part of the Group and it should firstly be defined what are or could be replacement insecticides. (l) Products related to temephos that do not exhibit obvious cross resistance to it but that are likely to develop such resistance afEer some length of time following E.he selective pressure Eo which the blackfly populations would be subjected. This is the case of chlorphoxim and possibly of other organophosphorus compounds such as azamethiphos. (2) Products of different, classes frorn temephos that do not exhibit any known cross resisEance with organophosphorus compounds. This is the case of the pyrethroids; however, it should be borne in mind that some insect species other than blackflies have developed resisEance to pyrechroids, in part.icular cross resistance with DDT. These products may be considered in the Programme strategy with the proviso that the susceptibility of vector populations should be kept under surveillance. (3) Products Ehat. have never exhibited resistance. This is the case of Bacillus thuringiensis H-14. It may be a solid basis for the strategy of the lrogEffiilid its extensions in so far as operational formulations are available. Should effective IGRs or Products of new classes become operational, they would obviously be in Ehis category. The rapid progress in the developmenE of new larvicides gives hope that the Prograrune will have available to it in the near future, apart from Ehe organophosphorus compounds: temephos, chlorphoxim and azamethiphos, one or more pyrethroids and an operaEional formulation of B.E. H-14. Under Ehese conditions it is reasonable to undertake research and prepare an 6TErational plan for some exEension zones. 8. Relations with indust ry for the development of new larvicides Ninety-five per cent. of world consumption of insecticides is used in agriculture. Thepublic health market is, consequently, a very limited one and would not in itself justify theinvestment required for the developmenE of new products, wtrich is of the order of 20 million US dollars for each such product. In addition, the various trials that theproducts undergo and the formalities involved in obtaining marketing permission take five to six years. For these reasons WHO has sought new compounds for vector control among products inEended for agriculture. Special mention should be made here of B.t. H-14, which has beendestined only for public health, and the efforts made by t.he manufa--cturer to develop thisproduct must be applauded. More than 20 years ago, VBC set up a scheme for the developmenE. of new producEs. This scheme, which was reorganized in 1982, is described in section 5.5 and in Annex 3 as regardsIarvicides intended for blackfly control. ocP/EAC5.8 Rev. 1 page 1 6 In order to strengthen relations with the producers of insecticides, WHO entered inEo direcE contact from 1981 onwards with manufact.urers in Europe, North America and Japan to inform them of the needs of the Programne for new compounds and to seek their collaboration. In 1983 the Organization invited them to an informal meeting in Geneva. The response of the industrialists has been very encouraging. Not only have t.hey supplied products that \rere already available, but several of them have agreed Eo prepare formulations better adapted to blackfly control than the products on saIe. In order to respond to this effort by the indusE.ry and to maintain its inEeresE, as full an account as possible of the experiments carried out on their products in the Programme or at IRTO must be provided in return whether the results be positive or negative. VBC is obviously in a privileged position in relation to the industry, to which ir expresses the needs of the Prograrmre and E,ransmits the results, keeping the Prograrmne and the collaborating laboratories continuously informed. Obviously this does not rule out direct contacts between Ehose testing the products and industrial producers, but VBC should be advised of them. This circulation of information is essent.ial to the good harmonisation of relations with the industry and t.o satisfactory progress of t.he prograrme for the development of insecticides for the control of Simulium damnosum s.1. OCP/EAC5.8 Rev.1 page 1 7 ANNEX 1 LIST OF PARTICIPAMS Dr D. Baldry, Entomologist, VecEor Control Unit, Onchocerciasis Control Progranrne, B.P. 549, 9.rag@., Upper Volta Dr N.G. Gratz, Director, Division of VecEor Biology and Control, I^IHO/HQ (Chairman) Dr P. Guillet, lnstitut de Recherches sur la Trypanosomiases et 1 Onchocercose, @!i, Ivory Coast Dr J.-M. Haugard, Institut de Recherches sur la Trypanosomiases et 1'Onchocercose, Bouak6 Dr D. Kurtak, Vector Control Unit, Onchocerciasis Control Programme, Ouagadougou Mr J.D.l'1.Ilarr, OCP Liaison Of f icer, WHO/HQ Mr J. I"louchet, Consultant, OCP (Rapporteur) !1r M. Ocran, Entomologist, Vector Control UniE, Onchocerciasis Control Programme, Lom6, Togo Dr D. Paugy, Hydrobiologist, Vector Control Unit, Onchocerciasis Control Programme, Ouagadougou Dr B. Philippon, Chief, Vector Control Unit, Onchocerciasis Control Programme, Ouagadougou Dr G. Qu6lennec, Pesticides Development and Safe Use, Division of Vector Biology and control, wHo/HQ Dr J. Raybould, Consultant, OCP Dr P. Renaud, Vector Control Unit, Onchocerciasis Control Programme, @1 Dr E.M. Sarnba, Director, Onchocerciasis Control Programme, 9-11ggde-gg. Dr R. Subra, VecEor Control Unit, 0nchocerciasis ConErol Programme Ouagadougou Mr L. Yam{ogo, Vector ConErol Untz, Onchocerciasis Control Programme, Ouagadougou OCP/EAC5.8 REV. 1 page l B ANNEX 2 TABLE I Group Insec r ic ide and barch LC 100 (late instar larvae) in troughs in mini Eroughs Acceptability for tests in r iver Pyrethroid s PermeEhrin Coopex EC 20% We 1 1c ome 0.025 - 0.038 7 EesEs 0.03 3 EesEs + PermeE.hrin Talcord EC 20"1 Shell 0.0r3 - 0.038 6 test.s 0 .03 3 tests + Perme thr in EC 50% We I lcome 0.038 0.03 + 4 Eescs l"lavrik 2 F(Fluvalinare) Flowable 24% 0.1 - 0-2 4 tesEs 0.2 2 tesEs Refer back to I./HOPES O!1S 3002 Mitsui Toatsu EC 20iL batch 5702 0.1 3 EesLs oMs 3002 EC 20% baEch 5703 3 tests 0.4 2 t,eSE S 0.1 + oMS 3002 EC 20% l,atch 5803 0.I o.4 2 Lests4 tests oMS 3002 EC 30% batch 5802 0.I 0.4 0.8 2 tests4 t.esEs Pyrerhroid s oMS 3002 wDP* 207" batch 5802 0.2 NoE usable in the Programme oMS 3002 Ec 2% batch 5804 0,2 6 t.esEs 0.4 Cypermethrin EC 40% Shell 0.0064 0.03 + Delcamethrin EC 1% Simulids A Roussel UCLAF 0.00067 2 tesls 015 esEs 0.0 2E Deltamethrin EC ,17. + PB 121( Simulids B o WDP, Water dispersible powder 0 .0003 0.00i5 + OCP/EAC5.8 Rev. 1 page 19 Annex 2 TABLE 2 Group lnsec t ic ide and batch 100 (late instar larvae) in troughs in mini Eroughs Accept abi 1i ty for tests in river Methiocarb 50% flowable Bayer 0.5 + Propoxur EC 207" Bayer 1.3 2 tests 2.0 C arbamaEe s Propoxur 250 YL Bayer 1.5 not usable Padan 1.5 Ethiofencarb(Croneton) EC 505 Bayer to be screened 0.2 Macbal EC 207. Hodogay o.2 0rganoch lorine DDT EC 257" Lab Sennre June 0.2 - December 4 tests o.4 0.4 0.32 DDT EC 252 Industrial December 1 test 0.4 Organophosphorus AzameEhiphos EC 102 Ciba Geigy 48 Bl 83 0.25 - 0.3 0.5 + Azamethiphos EC L07" A 5809 B 83 0.25 - 0.3 + Bensu I E ap ( synthecic Nereitoxin) 50% wDP Takeda early 1 ate instars ].nstars 2 Su1 fonate 0.5 0.75 ocP/EACs.8 Rev.1 Page 20 Annex 2 TABLE 3. RIVER TRIAL OF PER},IETHRIN AND AZAMETTIIPHOS Formulation Dose How applied River { mg/I./10 mn n3 i scharge , / sec Mortality and carry 0 .01 Treatment on ground 4.4 Total mortality for 2.5 km P erme thr i n Coopex EC 20'l 0 .01 Airborne "dumpi ng" 0.6 Partial morEalit.y for 0.6 km 0 .015 Airborne ttdumpingt' 0.6 Conplete mortalit.yfor 0.4 km 0.02 Airborne rapid re Iease 2.7 Complete mortality for 4 krn Pernethrin Talcord EC 2OZ 0.01 Treatment on ground 4.0 Cornplete nortality for 2.5 km 0.01 Airborne ttdumpingt' 0.7 Partial mortalityfor 0.8 km 0 .015 Airborne "dumpi ng" 2.5 Complete nrortality for I.6 km, partial for 2.5 km 0.02 Airborne rapid re lease 6.2 Complete mortality for 0.6 km Azame thiphos EC 102 batch 580 83 o.2 Ai rborne "dumpi ngt' 0.t 0 0.2 Treatment on ground 0.01 0 o.2 Treatment on ground 1.55 ToEal srortality of early insEars for I kn, partial mortality of late inst ar s 0.3 Treatment on ground 0.73 Total mortality of early insEars for 1.6 krn and of late instars for 0.6 kn Azamethiphoe EC toz bat.ch 48 B o.2 Airborne "dmping" 0.1 0 0.3 Treatment on ground L2 ToEal mortality for O.5 km De ltamethrint'Simulide A" EC tz 0.002 Treatment on ground L2 0 De lEaneEhrinI'Simulida B" EC L7. + 127, PR Treatment Complete rnort.ality for 4 kn 0.002 on ground t2 OCP/EACs.8 REV. l page 2 1 ANN]]X 3 Sequence of development of acute-acting chemical larvicides for Simulium damnosum control in tlest Africa Phase I of WHOPES Toxicity as regard non-Earget fauna Phase 2 of WHOPES less than 502 morcality should mortality be less than I00Z at 0.5 mg/ 1/ l0 nin Phase 3 of WHoPES Verification of impact on non-targeE fauna (in nultiple troughs) aE Ehe operational dose and at twice that dose, taking tenephos (and chlorphoxim) as controls Ecological monrtoring of Ehe river (Surber, drift ners, ordinary trough) Corrosive effect of fomulation mortalrty 502 above 1002 mortali ty at 0.5 mg/l, or ac least 951 ac 0.2 ng/L s Deci,sion from operational trtals Mamalian toxicity 1 River water Signrficant acEivity of active prrncipl-e against mosquito larvae rn WHOPES Absence of cross resist.ance with temephos(susceptibrlrty tests with resrstant and susceptible S, damnosw s.1. larvae Trough screening ( 1,2 ) 500 Larvae (earIy and late insEars) at 0.5 mg/l/10 min Duplicated at 0.5 mg/ I/ I0 nin Report. 0ther fomulatrons vilI possibly be tested. Trrplicated in troughs aE 3 concentratrons (I00 larvae for each concentration selected to obtarn 1002 aod 90-952 mortality. If time and the numbers of larvae are unlimited, an intermediate scale of concentrations will be tesEed to determine LC50 and LC95. This evaluation should, if possible, be carried out in clear and turbid weter. Report - RevieH of other fornulacions River tests aE the lowest concenEration yielding I00Z mortality in a trough. Increase concentration if necessary to obtain 1002 nortrlity in rrver. Suggested operational dose Rrver Eests at assumed operational dose 2. Trough and minitrough observations (cf. 5.4) Ease of handling O.li']li,:\Cj 8 Rer,.1 1'r''rr- 21. p-\llEx 4 Contingency p1an, March 19841 (It is possible that. temephos resistance may occur and that chlorphoxim could be used. However, the worsr possible case is assumed here) Resiscance to temephos and chlorphoxrm in savanna specles o'l/Ye'r in the dry season 0.5 In the high-water period p 0.5 Restric ted2 area 0.9 tJide3 a rea P 0.I Restricted area 0.2 0.8 area P very large Treatment with Bl. H-14 TreaEmenE sith B,r. H-14 River discharge 250 rrJlsec or less River di scharge over 250 n3/sec succes s P = 0.99 fai Iure P = 0.01 success P = 0.75 fai Iure P = 0.25 Treat.ment uith B.t. H- 14J success P = 0.99 Treatment with pernethrin or with azamethiphos fai lure P = 0.01 Treatment wrth azamethrphos or other available alternative - permerhrin4 p = probability of event. I Actions which could be taken without necessity of increasing the aircraft fleet except 5. 2 oaa or more rivers. ? - Exceeding the present resistance zone. 4 1f operational, adulticide spraying uith syntheric pyrethroids could support Iarvicide,:reaEments. 5 Use of B.t. H-I4 would require bringing in more aircraft (one month delay). N.B. Azamethiphos is not yet operational. l^lere resistance Eo occur quickly, it sould be impossible to increase stocks rapidly, and only permethrin is available.