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Current status of pyrethroid resistance in anophelines
ParasitologyToday,vol. 4, no. 7, 1988
S13
Current Status of Pyrethroid Resistance in Anophelines C.A. Malcolm Similarities between DD T and pyrethroid insecticides have led to widespread concern that cross-resistance between them might limit the usefulness of the latter. Both types of insecticide have similarities .in chemical structure, both have a negative temperature coe~cient (ie. they are more active at lower temperatures), both act as neurotoxins on sodium channels, and both produce the twin effects of knockdown and kill. As discussed by Tom Miller (see pages $8-S 12) there is firm evidence for pyrethroid resistance in some species of medical and veterinary importance - especially in the hornfly, Haemotobia irritans. But in the case ofanopheline mosquitoes, the evidence for pyrethroid resistance is much lessstrong. As Colin Malcolm explains here, a critical analysis of available data indicates that true physiological resistance of anophelines to pyrethroids is much less widespread than previous commentaries suggest. Moreover, the risk of cross-resistance between pyrethraids and DDT may have been over-emphasized, since different resistance mechanisms appear to be involved. In discussing pyrethroid resistance, it is important to distinguish between cases of 'physiological resistance' involving physiological mechanisms that stem from specific genetic mutations, and cases of 'vigour tolerance' or reduced susceptibility, which arise out of the natural genetic variation of a population (see Box I). The magnitude of the latter is generally low, but significant, whereas homozygous physiological resistance can range from very low ( ~ 1 0 x ) to very high (~1000x). To tell the difference when resistance levels are low requires studies of much greater detail than just bioassays on 'discriminating' doses of insecticide. This is particularly so with pyrethroids, where knockdown recovery and a negative correlation between temperature and toxicity add to the many problems associated with obtaining reproducibility in the standard W H O test kit. The knowledge that a particular type of physiological resistance has been identified within a species enables generalized predictions about the likelihood of resistance and cross-resistance in particular populations and should aid resistance management. However, the importance of the resistance from an operational point of view is another matter, and better discussed in specific rather than general terms. The major physiological resistance mechanism causing most concern for the future of the pyrethroids, is controlled by the gene kdr, first identified in Musca domestica. This involves an alteration in the neural target site which confers resistance both to pyrethroids and to DDT t. In Aedes aegypti 2 and Culex quinquefasciatus 3 there are sufficient detailed laboratory studies to confirm DDT/pyrethroid resistance conferred ~) 1988,ElsevierPublications,Cambridge0169-4758/88/$02.00
by a single gene and to leave little doubt that the mechanism is of the kdr type. Results of this type prompted Georghiou4, referring specifically to anophelines, to state: "The prospect for success of pyrethroid insecticides, which now represent the end of the line, is made uncertain by high prevailing levels of DDT resistance." Following reports of pyrethroid resistance in strains of nine speciesof anophelines5'6 (Table I) it should, by now, be possible to make more certain predictions about potential pyrethroid resistance in anophelines especially since this list of species includes Anopheles albimanus, An. stephensi, An. culicifacies and An. sacharovi, the four major vectors of malaria which Georghiou4 described as critical. Unfortunately this does not appear to be the case because the available information makes it impossible to confirm physiological resistance in many of the species in Table I. There is an apparent lack of detailed laboratory studies on pyrethroid resistance in anophetines and it has been difficult even to establish the original source of some 0fthe reports of pyrethroid resistance (Table I ). Brown s quotes his eight examples of pyrethroid resistance as cases from the field. Rather surprisingly a search of the current W H O data base (G.R. Shidrawi, pers. commun.) produced only two species with cases of resistance in the field. One was An. albimanus, in which resistance to deltamethrin has been detected in six localities in Guatamala, first reported in 1980, and also in Mexico where it was first reported in 1982. The other was from an isolated report of permethrin resistance in An. sacharovi in Syria made in 1985. Herath, in a visit to Turkey in 1977, obtained survivors on
0.2% permethrin with adult An. sacharovi from three localities7. However, the significance of these results is difficult to evaluate because the tests were performed at temperatures over 31°C when, because of the negative temperature coefficient of pyrethroids, lower toxicity might be expected, and no additional data for known susceptibles was available. Nevertheless, 'clear' pyrethroid resistance apparently developed in An. sacharovi following two rounds of winter fogging with Neopybuthrin (a mixture of permethrin, bioallethrin and piperonyl butoxide) in the warmer areas of Turkey 8.
W e a k Evidence f o r Resistance
Shidrawi 9 includes in a list of records of insecticide resistance submitted to WHO, a case of pyrethroid resistance in An. multicolor from Egypt, but gives no further data. Accumulated bioassay data from 1981-84 on field collected mosquitoes in Sri Lanka showed for An. culicifacies 75% mortality (380 adults tested) and 100% mortality (244 adults tested) on discriminating doses of permethrin and deltamethrin respectively,
Table I Reportsof resistance to pyrethroids in anophelines Species An. albimanus
Country Guatemala
References G.R. Shidrawi (pers. commun.)
Mexico
G.R. Shidrawi (pers. commun.) 16
El Salvador
An. arabiensis An. culicifacies
Sudan Sri Lanka
An. gambiae
Nigeria Burkina
An. multicolor
Egypt
Shidrawi
An. nigerrirnus
Sri Lanka
6', Herath and
Faso
13 6~, Herath and Joshi (unpublished) 12, 13 II
fl 98s) Joshi(unpublished) An. pseudo-
puncUpennis
Guatemala
6~
USA
6a 8
An. quadri-
rnaculatus An, sachar0vi
An. stephensi
Turkey Syria India~ Pakistan United Arab
Emirates
- no original source found
G.I~ Shidrawi (pers. commun.) 6a, 17 14 H. Ladonniand H. Townson (pers. commun.)
S14 and 80% mortality of An. nlgerrimus (393 adults tested) on deltamethrin (P.R.J. Herath and G.P. Joshi, unpublished). For An. culicifacies any significant levels of pyrethroid resistance would also appear to be inconsistent with the recent findings of the Sri Lanka Anti-malaria Campaign (J. Hemingway, pers. commun.). Moreoverl a recent study has shown that the major DDT resistance mechanism in An. culicifacies in Sri Lanka is a glutathione-S-transferase and consequently does not confer cross-resistance to pyrethroids ~°. Reports of pyrethroid resistance in An. arabiensis from Sudan, and in An. gambiae from Nigeria, originate from selection studies undertaken in London, and do not represent evidence for existing resistance in the field. In fact the first report of tolerance to a pyrethroid in An. gambiae was of a strain originally from Burkina Faso, which showed 5.8fold tolerance to bioallethrin in larvae and which could be reduced by piperonyl butoxide - su~esting the involvement of oxidases". A strain of An. gambiae from Togo, which showed
ParasitologyToday,vol. 4, no. 7, 1988 about fourfold DDT resistance in adults, was raised to about 17-fold with DDT selection. This increased its crosstolerance to permethrin by just over twofold. Direct selection with permethrin raised tolerance slightly more but had little or no effect on DDT resistance. The strain from Nigeria showed slightly more DDT resistance than the Togo strain (about fivefold) and this was also raised to 17-fold by DDT selection, but an earlier generation showing 13-fold DDT resistance showed virtually no change in response to permethrin. Direct selection with permethrin for the same number of generations increased tolerance fivefold, but produced no increase in resistance to DDT 12. In a subsequent study, the permethrin-selected strain lost most of its tolerance in the absence of selection, but this was restored to similar levels with renewed selection. At the same time strains from three other anopheline species were put under selection pressure. Only the An. arobiensis strain from Sudan showed a reduction in mortality, dropping from 54% to 12% on 0.25%
permethrin in one generation and then gradually lower in later generations ~3. No further studies have been made to determine if the upper limits of resistance had been reached, nor to determine its inheritability or the possible mechanisms. Consequently, as the levels of resistance are low it is not possible to confirm true physiological resistance.
Resistance in An. stephensi Omer et ol. L4found that larvae of An. stephensi from Pakistan, initially showing low-level resistance to DDT but susceptible to pyrethroids, developed 18-fold cross-resistance to permethrin after six generations of selection with DDT had produced 144-fold DDT resistance. Up to 23-fold cross-resistance to permethrin was obtained in a sub-colony selected with DDT in conjunction with the synergist DMC. Synergist studies provided no evidence for enhanced metabolism due to dehydrochlorinase, or oxidases, of either insecticide in the resistant strains.
Parasitology Today, vol. 4, no. 7, 1988 Neurophysiological studies however, showed that the resistant strains required approximately 20 times more permethrin than the susceptible strain to induce an increase in the frequency of miniature endplate potentials. This suggested that the resistance mechanism was of the kdr type. The levels of resistance to permethrin were particularly low for larval resistance and hardly compare with the 4000-fold resistance found in Cx. quinquefasciatus, which may indicate that the kdr mechanism in An. stephensi confers only moderate to low resistance. In adults the resistance levels in the selected strains were lower, with a maximum of I I-fold. Unfortunately no follow-up studies on the genetics of this resistance have been published, which might have indicated whether or not the population had been selec:ed for complete homozygosity, and confirmed if a single gene was responsible for both DDT and pyrethroid resistance. Certainly the relatively straight log-dose probit lines and constant slopes obtained at each generation of selection were not consistent with monofactorial inheritance. A difference in response to permethrin can be selected in larvae of An. stephensi ts of a similar magnitude to that found by Omer et aL~4, which is also not reduced by oxidase- or dehyd~ochlorinase-inhibiting synergists. However, this was shown 1:o be subject to multigenic inheritance and not associated with the major source of DDT resistance which was controlled by a single gene located on chromosome 3 t~. A new study on pyrethroid resistance in An. stephensi has, for the first time for any anopheline, demonstrated high levels of resistance to permethrin - at least 300-fold in larvae. Ir contrast to previous studies, this resistance can be blocked almost to the susceptible levels by the synergist piperonyl butoxide indicating an oxidase-based resistance mechanism. Crossing studies indicated clear monofactorial inheritance (H. Ladonni and H. Townson pers. commun.). To conclude from the information reviewed, which admittedly is incomplete, there is only one species (An. stephensi) in which true physiological resistance has been confirrned by laboratory studies, and two species (An. albimanus and An. sacharovi) where the field evidence is strong. Georghiou 4 noted that concern for the future of pyrethroids was greatest in countries where their introduction would follow DDT. In fact t h e field pyrethroid
S 15 resistance has appeared in species subjected to a wide range of insecticides, and has included evidence of selection by insecticides used for agriculture. The question of whether or not DDT resistance in these species confers crossresistance to pyrethroids will have to be answered by laboratory studies. In other anophelines there are several studies that indicate high levels of DDT resistance without cross-resistance to pyrethroids - as with An. stephensi ~4'Js and An. culicifacies ~°. The selection data on An. gambiae also indicate little or no correlation between DDT resistance and tolerance to permethrin ~2, which agrees with studies that have implicated a glutathione-S-transferase as the major D D T resistance mechanism in this species. An. stephensi is so far the only anopheline for which there is evidence of a kdr-type resistance mechanism H and the data presented suggest that it may be of much less importance than the oxidase-based mechanism found by Ladonni and Townson. It is difficult to discuss the full implications of these results until the details of the latter study are published, butthe indications are that concern that the kdr type of resistance will prove to be the major pyrethroid resistance mechanism among anophelines, is misdirected.
Acknowledgements: I thank G.R. Shidrawi for help in tracing relevant reports for this commentary, and H. Townson for accessto unpublished data. References
I Farnham,A.W. (I 977)Pestic.Sci.8, 6312o36 2 Malcolm,C.A.(1983)Genetica60, 221-229 3 Priester, T.M. and Georghiou, G.P. (1980) J. Econ.Entomol.73, 165-167 4 Georghiou,G.P.(1986) in PesticideResistance. 5 6 7 8 9 10 II 12 13 14 15 16 17
Strategies and Tactics for Management, National Academy Press Brown, A.W.A. (I 986)J. Am. Mosq. Control Assoc. 2, 123-140 WHO (1986) WHO Tech. Rep. Set. 737 Herath, P. (1977) Unpublished report to WHO, Geneva Clarke, J.L. (I 985) WHO Document VBCIECVI EC/85.8 Shidrawi, G.R. (1985) WHO Document VBCJ ECV/EC/85.7 Herath P.R.J.et al. (1988) Bull. E.ntomol. Res. (in press) Rongsriyam, Y. and Busvine, J.R. (1975) Bull. EntomoL Res.65,459-47 I Prasittisuk, C. and Curtis, C.F. (1982) Bull. EntomoL Res. 72, 335-344 Hemingway, J. ( 1981 ) PhD Thesis, University of London Omer, S.M., Georghiou, G.P. and Irving, S.N. (1980) Mosq. News 40,200-209 Malcolm, C.A. (1988) Meal Vet. Entomol. 2, 37-46 Priester, T.M. et aL (1981) Mosq. News 41, 143-150 Verma, K.V.S. and Rahman, S.J.(1986) Curr. Sci. 55,914-916
Colin Malcolm is with the Department of Medical Microbiology, The London Hospital (Whitechapel), Whitechapel Road, London E I, 2AD,UK.
Pyrethroids in the W H O Pesticide Evaluation
Scheme (WHOPES) G. Quelennec A W H O scheme for the evaluation and testing of new pesticides for public health use has been in operation since 1960 I. By 1982, when the scheme was reconsidered, nearly 2000 chemical compounds had been tested in this scheme. The main objectives of the new W H O Pesticide Evaluation scheme (WHOPES) were: (I) to speed up the evaluation of and reporting on new compounds in order to maintain the interest of industry in the development of pesticides for public health use; (2) to broaden the scope of the evaluation scheme to include vectors of human disease as well as the main nuisance pests for man; (3) to concentrate efforts on those compounds that have already shown insecticidal activity when screened by manufacturers; (4)to organize phase 3 of
the scheme, which involves the cooperation of governments of countries where trials are carried out, industry and WHO; (5) to reinforce the quality control of pesticides in developing countries; and (6) to provide the users with products that are safe and efficient when transported, stored and used according to the instructions 2. New compounds submitted by the pesticide industry are screened for their effectiveness as insecticides, acaricides, molluscicides or rodenticides. Technical information including chemical structure, physical characteristics and toxicity are provided to W H O on a confidential basis, and new compounds are identified by a W H O code number. Thus compounds entered in the former scheme (1960--1982) were numbered from ~) 1988,ElsevierPublications,Cambridge0169-4758/88~02.00
S13
Current Status of Pyrethroid Resistance in Anophelines C.A. Malcolm Similarities between DD T and pyrethroid insecticides have led to widespread concern that cross-resistance between them might limit the usefulness of the latter. Both types of insecticide have similarities .in chemical structure, both have a negative temperature coe~cient (ie. they are more active at lower temperatures), both act as neurotoxins on sodium channels, and both produce the twin effects of knockdown and kill. As discussed by Tom Miller (see pages $8-S 12) there is firm evidence for pyrethroid resistance in some species of medical and veterinary importance - especially in the hornfly, Haemotobia irritans. But in the case ofanopheline mosquitoes, the evidence for pyrethroid resistance is much lessstrong. As Colin Malcolm explains here, a critical analysis of available data indicates that true physiological resistance of anophelines to pyrethroids is much less widespread than previous commentaries suggest. Moreover, the risk of cross-resistance between pyrethraids and DDT may have been over-emphasized, since different resistance mechanisms appear to be involved. In discussing pyrethroid resistance, it is important to distinguish between cases of 'physiological resistance' involving physiological mechanisms that stem from specific genetic mutations, and cases of 'vigour tolerance' or reduced susceptibility, which arise out of the natural genetic variation of a population (see Box I). The magnitude of the latter is generally low, but significant, whereas homozygous physiological resistance can range from very low ( ~ 1 0 x ) to very high (~1000x). To tell the difference when resistance levels are low requires studies of much greater detail than just bioassays on 'discriminating' doses of insecticide. This is particularly so with pyrethroids, where knockdown recovery and a negative correlation between temperature and toxicity add to the many problems associated with obtaining reproducibility in the standard W H O test kit. The knowledge that a particular type of physiological resistance has been identified within a species enables generalized predictions about the likelihood of resistance and cross-resistance in particular populations and should aid resistance management. However, the importance of the resistance from an operational point of view is another matter, and better discussed in specific rather than general terms. The major physiological resistance mechanism causing most concern for the future of the pyrethroids, is controlled by the gene kdr, first identified in Musca domestica. This involves an alteration in the neural target site which confers resistance both to pyrethroids and to DDT t. In Aedes aegypti 2 and Culex quinquefasciatus 3 there are sufficient detailed laboratory studies to confirm DDT/pyrethroid resistance conferred ~) 1988,ElsevierPublications,Cambridge0169-4758/88/$02.00
by a single gene and to leave little doubt that the mechanism is of the kdr type. Results of this type prompted Georghiou4, referring specifically to anophelines, to state: "The prospect for success of pyrethroid insecticides, which now represent the end of the line, is made uncertain by high prevailing levels of DDT resistance." Following reports of pyrethroid resistance in strains of nine speciesof anophelines5'6 (Table I) it should, by now, be possible to make more certain predictions about potential pyrethroid resistance in anophelines especially since this list of species includes Anopheles albimanus, An. stephensi, An. culicifacies and An. sacharovi, the four major vectors of malaria which Georghiou4 described as critical. Unfortunately this does not appear to be the case because the available information makes it impossible to confirm physiological resistance in many of the species in Table I. There is an apparent lack of detailed laboratory studies on pyrethroid resistance in anophetines and it has been difficult even to establish the original source of some 0fthe reports of pyrethroid resistance (Table I ). Brown s quotes his eight examples of pyrethroid resistance as cases from the field. Rather surprisingly a search of the current W H O data base (G.R. Shidrawi, pers. commun.) produced only two species with cases of resistance in the field. One was An. albimanus, in which resistance to deltamethrin has been detected in six localities in Guatamala, first reported in 1980, and also in Mexico where it was first reported in 1982. The other was from an isolated report of permethrin resistance in An. sacharovi in Syria made in 1985. Herath, in a visit to Turkey in 1977, obtained survivors on
0.2% permethrin with adult An. sacharovi from three localities7. However, the significance of these results is difficult to evaluate because the tests were performed at temperatures over 31°C when, because of the negative temperature coefficient of pyrethroids, lower toxicity might be expected, and no additional data for known susceptibles was available. Nevertheless, 'clear' pyrethroid resistance apparently developed in An. sacharovi following two rounds of winter fogging with Neopybuthrin (a mixture of permethrin, bioallethrin and piperonyl butoxide) in the warmer areas of Turkey 8.
W e a k Evidence f o r Resistance
Shidrawi 9 includes in a list of records of insecticide resistance submitted to WHO, a case of pyrethroid resistance in An. multicolor from Egypt, but gives no further data. Accumulated bioassay data from 1981-84 on field collected mosquitoes in Sri Lanka showed for An. culicifacies 75% mortality (380 adults tested) and 100% mortality (244 adults tested) on discriminating doses of permethrin and deltamethrin respectively,
Table I Reportsof resistance to pyrethroids in anophelines Species An. albimanus
Country Guatemala
References G.R. Shidrawi (pers. commun.)
Mexico
G.R. Shidrawi (pers. commun.) 16
El Salvador
An. arabiensis An. culicifacies
Sudan Sri Lanka
An. gambiae
Nigeria Burkina
An. multicolor
Egypt
Shidrawi
An. nigerrirnus
Sri Lanka
6', Herath and
Faso
13 6~, Herath and Joshi (unpublished) 12, 13 II
fl 98s) Joshi(unpublished) An. pseudo-
puncUpennis
Guatemala
6~
USA
6a 8
An. quadri-
rnaculatus An, sachar0vi
An. stephensi
Turkey Syria India~ Pakistan United Arab
Emirates
- no original source found
G.I~ Shidrawi (pers. commun.) 6a, 17 14 H. Ladonniand H. Townson (pers. commun.)
S14 and 80% mortality of An. nlgerrimus (393 adults tested) on deltamethrin (P.R.J. Herath and G.P. Joshi, unpublished). For An. culicifacies any significant levels of pyrethroid resistance would also appear to be inconsistent with the recent findings of the Sri Lanka Anti-malaria Campaign (J. Hemingway, pers. commun.). Moreoverl a recent study has shown that the major DDT resistance mechanism in An. culicifacies in Sri Lanka is a glutathione-S-transferase and consequently does not confer cross-resistance to pyrethroids ~°. Reports of pyrethroid resistance in An. arabiensis from Sudan, and in An. gambiae from Nigeria, originate from selection studies undertaken in London, and do not represent evidence for existing resistance in the field. In fact the first report of tolerance to a pyrethroid in An. gambiae was of a strain originally from Burkina Faso, which showed 5.8fold tolerance to bioallethrin in larvae and which could be reduced by piperonyl butoxide - su~esting the involvement of oxidases". A strain of An. gambiae from Togo, which showed
ParasitologyToday,vol. 4, no. 7, 1988 about fourfold DDT resistance in adults, was raised to about 17-fold with DDT selection. This increased its crosstolerance to permethrin by just over twofold. Direct selection with permethrin raised tolerance slightly more but had little or no effect on DDT resistance. The strain from Nigeria showed slightly more DDT resistance than the Togo strain (about fivefold) and this was also raised to 17-fold by DDT selection, but an earlier generation showing 13-fold DDT resistance showed virtually no change in response to permethrin. Direct selection with permethrin for the same number of generations increased tolerance fivefold, but produced no increase in resistance to DDT 12. In a subsequent study, the permethrin-selected strain lost most of its tolerance in the absence of selection, but this was restored to similar levels with renewed selection. At the same time strains from three other anopheline species were put under selection pressure. Only the An. arobiensis strain from Sudan showed a reduction in mortality, dropping from 54% to 12% on 0.25%
permethrin in one generation and then gradually lower in later generations ~3. No further studies have been made to determine if the upper limits of resistance had been reached, nor to determine its inheritability or the possible mechanisms. Consequently, as the levels of resistance are low it is not possible to confirm true physiological resistance.
Resistance in An. stephensi Omer et ol. L4found that larvae of An. stephensi from Pakistan, initially showing low-level resistance to DDT but susceptible to pyrethroids, developed 18-fold cross-resistance to permethrin after six generations of selection with DDT had produced 144-fold DDT resistance. Up to 23-fold cross-resistance to permethrin was obtained in a sub-colony selected with DDT in conjunction with the synergist DMC. Synergist studies provided no evidence for enhanced metabolism due to dehydrochlorinase, or oxidases, of either insecticide in the resistant strains.
Parasitology Today, vol. 4, no. 7, 1988 Neurophysiological studies however, showed that the resistant strains required approximately 20 times more permethrin than the susceptible strain to induce an increase in the frequency of miniature endplate potentials. This suggested that the resistance mechanism was of the kdr type. The levels of resistance to permethrin were particularly low for larval resistance and hardly compare with the 4000-fold resistance found in Cx. quinquefasciatus, which may indicate that the kdr mechanism in An. stephensi confers only moderate to low resistance. In adults the resistance levels in the selected strains were lower, with a maximum of I I-fold. Unfortunately no follow-up studies on the genetics of this resistance have been published, which might have indicated whether or not the population had been selec:ed for complete homozygosity, and confirmed if a single gene was responsible for both DDT and pyrethroid resistance. Certainly the relatively straight log-dose probit lines and constant slopes obtained at each generation of selection were not consistent with monofactorial inheritance. A difference in response to permethrin can be selected in larvae of An. stephensi ts of a similar magnitude to that found by Omer et aL~4, which is also not reduced by oxidase- or dehyd~ochlorinase-inhibiting synergists. However, this was shown 1:o be subject to multigenic inheritance and not associated with the major source of DDT resistance which was controlled by a single gene located on chromosome 3 t~. A new study on pyrethroid resistance in An. stephensi has, for the first time for any anopheline, demonstrated high levels of resistance to permethrin - at least 300-fold in larvae. Ir contrast to previous studies, this resistance can be blocked almost to the susceptible levels by the synergist piperonyl butoxide indicating an oxidase-based resistance mechanism. Crossing studies indicated clear monofactorial inheritance (H. Ladonni and H. Townson pers. commun.). To conclude from the information reviewed, which admittedly is incomplete, there is only one species (An. stephensi) in which true physiological resistance has been confirrned by laboratory studies, and two species (An. albimanus and An. sacharovi) where the field evidence is strong. Georghiou 4 noted that concern for the future of pyrethroids was greatest in countries where their introduction would follow DDT. In fact t h e field pyrethroid
S 15 resistance has appeared in species subjected to a wide range of insecticides, and has included evidence of selection by insecticides used for agriculture. The question of whether or not DDT resistance in these species confers crossresistance to pyrethroids will have to be answered by laboratory studies. In other anophelines there are several studies that indicate high levels of DDT resistance without cross-resistance to pyrethroids - as with An. stephensi ~4'Js and An. culicifacies ~°. The selection data on An. gambiae also indicate little or no correlation between DDT resistance and tolerance to permethrin ~2, which agrees with studies that have implicated a glutathione-S-transferase as the major D D T resistance mechanism in this species. An. stephensi is so far the only anopheline for which there is evidence of a kdr-type resistance mechanism H and the data presented suggest that it may be of much less importance than the oxidase-based mechanism found by Ladonni and Townson. It is difficult to discuss the full implications of these results until the details of the latter study are published, butthe indications are that concern that the kdr type of resistance will prove to be the major pyrethroid resistance mechanism among anophelines, is misdirected.
Acknowledgements: I thank G.R. Shidrawi for help in tracing relevant reports for this commentary, and H. Townson for accessto unpublished data. References
I Farnham,A.W. (I 977)Pestic.Sci.8, 6312o36 2 Malcolm,C.A.(1983)Genetica60, 221-229 3 Priester, T.M. and Georghiou, G.P. (1980) J. Econ.Entomol.73, 165-167 4 Georghiou,G.P.(1986) in PesticideResistance. 5 6 7 8 9 10 II 12 13 14 15 16 17
Strategies and Tactics for Management, National Academy Press Brown, A.W.A. (I 986)J. Am. Mosq. Control Assoc. 2, 123-140 WHO (1986) WHO Tech. Rep. Set. 737 Herath, P. (1977) Unpublished report to WHO, Geneva Clarke, J.L. (I 985) WHO Document VBCIECVI EC/85.8 Shidrawi, G.R. (1985) WHO Document VBCJ ECV/EC/85.7 Herath P.R.J.et al. (1988) Bull. E.ntomol. Res. (in press) Rongsriyam, Y. and Busvine, J.R. (1975) Bull. EntomoL Res.65,459-47 I Prasittisuk, C. and Curtis, C.F. (1982) Bull. EntomoL Res. 72, 335-344 Hemingway, J. ( 1981 ) PhD Thesis, University of London Omer, S.M., Georghiou, G.P. and Irving, S.N. (1980) Mosq. News 40,200-209 Malcolm, C.A. (1988) Meal Vet. Entomol. 2, 37-46 Priester, T.M. et aL (1981) Mosq. News 41, 143-150 Verma, K.V.S. and Rahman, S.J.(1986) Curr. Sci. 55,914-916
Colin Malcolm is with the Department of Medical Microbiology, The London Hospital (Whitechapel), Whitechapel Road, London E I, 2AD,UK.
Pyrethroids in the W H O Pesticide Evaluation
Scheme (WHOPES) G. Quelennec A W H O scheme for the evaluation and testing of new pesticides for public health use has been in operation since 1960 I. By 1982, when the scheme was reconsidered, nearly 2000 chemical compounds had been tested in this scheme. The main objectives of the new W H O Pesticide Evaluation scheme (WHOPES) were: (I) to speed up the evaluation of and reporting on new compounds in order to maintain the interest of industry in the development of pesticides for public health use; (2) to broaden the scope of the evaluation scheme to include vectors of human disease as well as the main nuisance pests for man; (3) to concentrate efforts on those compounds that have already shown insecticidal activity when screened by manufacturers; (4)to organize phase 3 of
the scheme, which involves the cooperation of governments of countries where trials are carried out, industry and WHO; (5) to reinforce the quality control of pesticides in developing countries; and (6) to provide the users with products that are safe and efficient when transported, stored and used according to the instructions 2. New compounds submitted by the pesticide industry are screened for their effectiveness as insecticides, acaricides, molluscicides or rodenticides. Technical information including chemical structure, physical characteristics and toxicity are provided to W H O on a confidential basis, and new compounds are identified by a W H O code number. Thus compounds entered in the former scheme (1960--1982) were numbered from ~) 1988,ElsevierPublications,Cambridge0169-4758/88~02.00