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Effect of dose and route of application on the action of decamethrin against cattle grubs
Veterinary Parasitology, 14 (1984) 65--74 Elsevier Science Publishers B.V., A m s t e r d a m -- Printed in The Netherlands
65
EFFECT OF DOSE AND ROUTE OF APPLICATION ON THE ACTION OF DECAMETHRIN AGAINST CATTLE GRUBS
CHANTAL BOULARD
Institut National de la Recherche Agronomique, Centre de Tours--Nouzilly, Pathologie Aviaire et Parasitologie, 37380 Monnaie (France) J.L. T R O C C O N
INRA, Production Laiti~re, Station du Rheu, 35000 Rennes (France) ( A c c e p t e d for publication 18 J u l y 1983)
ABSTRACT Boulard, C. and T r o c c o n , J.L., 1984. Effect of dose and r o u t e of application on the action of d e c a m e t h r i n against cattle grubs. Vet. Parasitol., 14: 65--74. The efficacy of pour-on or orally administered d e c a m e t h r i n against bovine hypodermosis was investigated on naturally infested yearlings. T r e a t m e n t at dose rates of 1, 2 or 10 m g per kg b o d y weight were ineffective, but the highest dose had a longt e r m lethal effect on warbles. The severe side effects which followed the high dose suggest that this drug is unsatisfactory for systemic grub control. Investigations on the dynamics of circulating anti-Hypoderma antibodies in the p o s t - t r e a t m e n t period showed that there is s o m e subqethal activity of d e c a m e t h r i n o n the larval physiology even at the lowest doses.
INTRODUCTION
Since the introduction in 1978 of three national schemes to control bovine hypodermosis, in Eire, France and Gt. Britain, organophosphorus (O.P.) compounds have been widely used in systemic autumn treatments (Tarry, 1981; Boulard et al., 1983) against the endoparasitic stage of Hypoderma about 4--6 months before the larvae reach the dorsal subcutaneous tissue of cattle and moult into the ectoparasitic stages called warbles. Organophosphorus compounds are highly effective against the endoparasitic larvae of Hypoderma, but occasionally induce side effects (Rich, 1964; Nelson et al., 1967; Khan, 1971), and this limits the autumn treatment. Moreover, these post-treatment reactions in cattle increase with the abundance and size of the Hypoderma larvae (Scharff et al., 1962; Boulard, 1975). The need for new compounds to supplement the current products led us to study the efficacy of the new synthetic pyrethroids. Their high toxicity to ectoparasites (Bailie and Wood, 1979) and low mammalian fox0304-4017/84/$03.00
© 1 9 8 4 Elsevier Science Publishers B . V .
66 icity (Elliott et al., 1978) suggest t h a t t h e i r activity should be investigated against t h e e n d o p a r a s i t i c stages o f Hypoderma. I n v e s t i g a t i o n s were t h e r e f o r e c o n d u c t e d o n t h e s p e e d o f a c t i o n and e f f i c a c y o f d e c a m e t h r i n on first instar larvae o f Hypoderma in r e l a t i o n to t h e r o u t e o f a d m i n i s t r a t i o n to c a t t l e a n d t h e e f f e c t i v e dose level. MATERIALS AND METHODS
Animals T h e e x p e r i m e n t s w e r e c o n d u c t e d in a u t u m n 1 9 7 8 and 1 9 7 9 o n an exp e r i m e n t a l f a r m at t h e N a t i o n a l I n s t i t u t e o f A g r o n o m i c R e s e a r c h ( I . N . R . A . ) in T h e i x ( F r a n c e ) . T h e animals, Friesian heifers, w e r e 1 2 - - 1 4 m o n t h s - o l d w h e n t r e a t e d . T h e y h a d all b e e n n a t u r a l l y i n f e s t e d w i t h Hypoderma during t h e p r e v i o u s s u m m e r . I n E x p e r i m e n t 1, t h e animals w e r e h o u s e d f r o m N o v e m b e r 1 9 7 8 t o M a y 1 9 7 9 , in six loose b o x e s w i t h six a n i m a l s p e r b o x . E a c h u n i t b o x was sepa r a t e d b y a m e t a l gate. T h e t r e a t m e n t w i t h d e c a m e t h r i n was a p p l i e d as a f o o d a d d i t i v e o n 6 a n i m a l s ( G r o u p A), or b y p o u r o n m e t h o d at 1 o r 2 m g active i n g r e d i e n t kg -~ live w e i g h t o n 8 animals, r e s p e c t i v e l y ( G r o u p s B a n d C). S e v e n a n i m a l s r e m a i n e d u n t r e a t e d ( G r o u p D) a n d 7 o t h e r s received a t r i c h l o r f o n t r e a t m e n t ( G r o u p E). T h e design o f t r e a t m e n t s p e r b o x f o r E x p e r i m e n t 1 is p r e s e n t e d in T a b l e I. In E x p e r i m e n t 2, c o n d u c t e d in N o v e m b e r 1 9 7 9 , t h e animals w e r e h o u s e d until M a y 1 9 8 0 in 5 u n i t b o x e s o f six t o eight animals. N o o t h e r antiparasitic treatments were administered during the experiments. TABLEI Experimental design (Experiment 1) first year Treatment
Decamethrin
Group
Methods of application
Experimental unit box no.
A
Feed additive 1 mg kg -~ Pour-on 1 mg kg -~ Pour-on 2 mg kg -~
1
6
2 5 3 5
6 +2 6 +2
B C
Number of animals
Control
D
None
4 5
6 +1
Trichlorfon
E
Pour-on 17 mg kg -~
6 5
6 +1
Treatments All t r e a t m e n t s
and
b l o o d samplings w e r e d o n e in t w o c a t t l e crushes
67 TABLE II Experimental design (Experiment 2) second year Treatment
Group
Methods of application
Experimental unit box no.
Number of animals
Decamethrin (Decis) Decamethrin (Wellcome) Decamethrin (Hoechst) Control Trichlorfon
F
Pour-on 10 mg kg-1 Pour-on 10 mg kg-~ Pour-on 10 mg kg-I None Pour-on 17 mg kg-1
1
8
2
8
3
8
4 5
6 6
G H I J
by two teams of technicians, treated cattle being handled away from their experimental unit. The serial numbers, nature, dose and route of treatments administered on N o v e m b e r 21, 1978 ( E x p e r i m e n t 1) and N ovem ber 20, 1979 (Experiment 2) are presented in Tables I and II. Volumes of drugs were given on a b o d y weight basis.
Insecticides The d ecameth r i n formulations were registered products of Roussel Uclaf. The pour-on formulation of RU 22974 and RU 22475 were solutions which co n tain ed 50 g of decamethrin 1-1, and were applied at 1, 2 or 10 mg active ingredient kg-1 live weight. The feed additive f or m ul a t i on was decamethrin RU 22974 powder, inc o rp o r ated in one day, into commercial supplement feeds at 1 mg kg rate in relation to t he total weight o f heifers in G roup A. The p o u r - o n f o r m u l a t i o n of Varlute (N.D. M~rieux, L y o n , France) was a solution containing 45 g 1-1 of trichlorfon, administered at a dose rate of 17 mg kg -1 live weight.
Observations The following observations were recorded in the treated, as well as the control animals: (a) p o s t - t r e a t m e n t clinical reactions; (b) numbers o f grubs checked at intervals t h r o u g h o u t the following spring for each e x p e r i m e n t ; (c) p o s t - t r e a t m e n t a n t i b o d y p r o d u c t i o n within various time intervals following E x p e r i m e n t 1. The immunological assay was c o n d u c t e d by the tanned red blood cell haemagglutination technique, using larval proteins of Hypoderma lineatum as antigen (Boulard et al., 1970).
68 RESULTS
Post-treatment reactions
During the post-treatment period, no adverse reactions were observed following an oral or pour-on dosage of 1 mg kg-1 or 2 mg kg-1 pour-on administration of decamethrin. After a 10 mg kg- ~ dosage with decamethrin, heifers were closely watched for 3 days after treatment because of the excitation which followed treatment. Group F (8 animals) showed lachrymation within 10 h, with profuse sweating in one animal. Intense hyperactivity continued for the next 2 days. Group G (8 animals} showed immediate irritation at the treatment site, and within 6 h all the calves were hyperactive, continuing so for the next 12 h. 24 hours after treatment, there was still local irritation at the site of treatment b u t this decreased within 2 days. All (8) Group H animals showed hyperactivity and profuse sweating 4 h after treatment, continuing for the next 28 h. In control group I (6 animals), there was a transitory hyperactivity in one heifer and another began to lachrymate 6 h after treatment. The lachrymation lasted 24 h. Two animals treated with trichlorfon in Group G showed a transitory hyperactivity 4 h after treatment. Complete recovery started on the 3rd day in all groups. T A B L E III G r u b i n f e s t a t i o n s in E x p e r i m e n t 1 Group
A
B
C
D E
Treatment
Decamethrin p e r os 1 m g kg -~ Decamethrin pour-on 1 m g kg -1 Decamethrin pour-on 2 m g kg -~ Control Trichlorfon pour-on 17 m g kg -1
No. animals
M e a n g r u b s p e r animal* 4 April
17 April
30 May
27 J u n e
6
11.6 (9--37)
24.8 (1--52)
17.16 (2--30)
10 (2--20)
8
10.8 (7--19)
21.1 (13--30)
19.8 (5--38)
8.75 (2--12)
8
20.6 (8--31)
23.3 (13--36)
22.8 (3--35)
7 (0--13)
18.7 (2--25)
22.2 (10--47)
21 (5--47)
4.4 (0--15)
7
6
0
0
0
0
* V a l u e s in p a r e n t h e s e s are ranges o f grub c o u n t s o b s e r v e d in t h e g r o u p for each date.
69 Grub c o u n t s
Data for grub counts are summarized in Tables III and IV. Maximum averages grubs per head in u n t r e a t e d or decamethrin treated groups were of 24.8 in E x p e r i m e n t 1 (Group A April) and 22.5 in E x p e r i m e n t 2 (Group G April). Grub counts ranged from 0 to 47 in E x p e r i m e n t 1 and from 0 to 50 in E x p e r i m e n t 2. TABLE IV Grub infestations in Experiment 2 Group
F G
H
Treatment
No. animals
Decamethrin (Decis) pour-on 8 10 mg kg-~ Decamethrin (Wellcome) 8 pour-on 10 mg kg-' Decamethrin (Hoechst) 8
Mean grubs per animal* 24 March
23 April
21.2 (12--37)
21.3 (7--34)
18 (0--40)
22.5 (0--50)
19.8 (7--40)
19.6 (6--44)
14.8 (0--30)
12.5 (0--29)
pour-on
I J
10 mg kg-~ Control Trichlorfon pour-on 17 mg kg-'
6 6
0
0.33 (0--2)
*Values in parentheses are ranges of grub counts observed in the group for each date. A n t i - H y p o d e r m a a n t i b o d i e s -- d y n a m i c s
The a n t i b o d y titre dynamics following E x p e r i m e n t 1 t r e a t m e n t are shown in Fig. 1. T he following data should be emphasized. Within the first 2 p o s t - t r e a t m e n t days serological variations of a n t i - H y p o d e r m a antibodies were observed in one animal in each of the following groups: control G r o u p D, trichlorfon G r oup E and the decamethrin Group A, in three cattle in decamethrin G r oup B and in five cattle in decamethrin Group C. Within one week, no modification was observed in control G roup D. Three heifers in each of Groups A and E showed variations, five heifers displayed variations in G r oup B and seven in G roup C. Three weeks later, the animals in cont rol G roup D showed an increase in antibody, with a marked peak between February and April, as observed previously (Boulard, 1975; R o b e r t s o n , 1980) during natural infestations.
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Fig. 1. Development of haemagglutinating antibodies (HA) against Hypoderrna lineatum following pyrethroid applications (Groups A, B, C), trichlorfon treatment (Group E), or control group (Group D) in heifers naturally infested with Hypoderma spp. Each line represents an individual heifer.
Groups A, B and C began a similar pattern. In Group E, only 3 heifers out of 7 displayed such a pattern between January and March. DISCUSSION
Systemic treatment given in the autumn for hypodermosis with oral or pour-on decamethrin at 1, 2 or 10 mg kg -1 was ineffective, although the higher dose rate delayed warble evolution. Strangely, this effect also occurred in the control group kept close to the treated groups (Table IV). However, our results show that such high dosage also induces severe post-treatment reactions, so that decamethrin cannot be recommended. These side effects are quite different from those associated with O.P. treatment. There was no diarrhoea, dyspnoea, unsteady gait, paralysis or prostration, but there was intense hyperactivity, perspiration and lachrymation.
72 The hyperactivity is in accordance with the previously described s y m p t o m s of poisoning by pyrethroids (Aldridge et al., 1978; James, 1979). One may assume that the rapid metabolism of pyrethroids by esterases and oxidases, which limits their toxicity in mammals (Casida and Ruzo, 1980), also reduces their effectiveness towards endoparasitic insects. Further data on the efficacy and speed of action of decamethrin have been obtained from the analysis of circulating antibodies against Hypoderma larval antigens, within few hours following treatment with the drugs. Immediate antibody variations after O.P. treatment due to the release of Hypoderma larval proteins into the tissue and blood stream of the host have been described previously (Boulard, 1975). It should be emphasized that first instar larvae of Hypoderma induce antibody production directed against their metabolic products (Boulard and Weintraub, 1973). These antigens are mostly stored in the larval mid gut (Boulard, 1968). Any insecticide provoking an effect on the larval nervous system stimulates a regurgitation of the antigenic gut content into the host, which complexes with circulating antibodies. Therefore serum antibody analysis during the 72 h following treatment could offer a technique for monitoring immediate drug activity on endoparasitic insects. The survey of the antibody response in the following months could also provide an estimation of the possible lethal efficacy of the drug. The number of cattle showing antibody variations in each group in our study depended on the dose or route of decamethrin administration. At 1 mg kg -1, oral treatment induces less variation than pour-on, indicating that the insecticide may reach fewer larvae by the oral route. This could also indicate accelerated degradation of the decamethrin after oral administration. A comparison of the pour-on dosages of decamethrin, 1 mg kg -1 (Group B) and 2 mg kg -~ (Group C), indicated faster and greater activity against the larvae in cattle at the higher dose. During the same post-treatment period, only one heifer in control Group D showed any antibody variation. This was also the only control heifer grouped with treated cattle in experimental unit 5, suggesting diffusion of decamethrin vapour in this stall or active b o d y contact between animals. The other animals of control group D were in unit 4, positioned between two treated animal units and showed no variation. Licking was possibly involved in unit 5 as other results support such conclusions. The final treated Group (E) in this experiment received trichlorfon. Trichlorfon induces well-characterized antibody variations within 2--4 h after treatment. In this experiment the first reaction occurred 48 h later. The delay seen in this experiment m a y have been due to an interaction of pyrethroids with the organophosphorus insecticide. Decamethrin vapour is apparently not involved because as most pyrethroids, it has a very low vapour pressure (Elliott et al., 1978). However, Group E was treated in the metal pen where decamethrin treatments had just been carried o u t and there were traces of pesticide on the gate. Possibly these low doses of pyrethroids
73
which were unintentionally administered could have depressed the activity of acetylcholine (Aldridge et al., 1978), and could temporarily antagonize the O.P. activity without affecting its efficacy on the following days. Such a delay of trichlorfon activity on Hypoderma larvae has also been observed in combined treatment with oxfendazole (Foraz, 1981). This experiment revealed some activity of decamethrin against endoparasitic Hypoderma larvae. Nevertheless, doses up to 10 mg kg -1 did not improve efficacy, but only induced adverse effects. It appears that under these experimental conditions, decamethrin does not provide an alternative to organophosphorus compounds in hypodermosis control. ACKNOWLEDGEMENTS
The authors acknowledge the technical assistance of Mrs. M. Plat and Mrs. C. Villejoubert. The Roussel Uclaf Company supported in part this research and the authors thank Dr. Scheid who supplied them with the drugs.
REFERENCES Aldridge, W.N., Clothier, B., Forshaw, P., Johnson, M.K., Parker, V.H., Price, R.J., Skilleter, D.N., Verschoyle, R.D. and Stevens, C., 1978. The effect of DDT and the pyrethroids cismethrin and decamethrin on the acetylcholine and cyclic nucleotide content of rat brain. Biochem. Pharmacol., 27: 1703--1706. Bailie, H.D. and Wood, J.C., 1979. Pyrethroids, their use in the control of animal ectoparasites. In: A.S.J.P.A.M. Van Miert, J. Frens and F. Van der Kreek (Editors), Trends in Veterinary Pharmacology and Toxicology. Elsevier, Amsterdam, pp. 256--260. Boulard, C., 1968. Anatomie et histologie du tube digestif de la larve d'Hypoderma bovis. Ann. Soc. Entomol. Fr., 5: 371--387. Boulard, C., 1975. Evolution des anticorps circulants chez les bovins trait~s contre l'hypodermose. Ann. Rech. Vet., 6 : 143--154. Boulard, C. and Weintraub, J., 1973. Immunological responses of rabbits artificially infested with the cattle grubs Hypoderma bovis and Hypoderma lineatum. Int. J. Parasitol., 3: 379--386. Boulard, C., Soria, J. and Soria, C., 1970. Possibilitd d'emploi de la r~action d'hdmagglutination passive pour le diagnostic de l'hypodermose, en utilisant comme antigbne une collag~nase brute extraite des larves de ler stade Hypoderma lineatum. C.R. Acad. Sci., Ser. D, 270: 1965--1968. Boulard, C., Billardon, G., Biron, G., Hillion, E. and Vigouroux, B., 1983. Essais de contrSle ponctuel de l'hypodermose bovine au niveau d'exploitations dispers~es ou groupies. Ann. Rech. V~t., 14: 183--188. Casida, J.E. and Ruzo, L.O., 1980. Metabolic chemistry of pyrethroid insecticides. Pestic. Sci., 11: 257--269. Elliott, M., Janes, N.F. and Potter, C., 1978. The future of pyrethroids in insect control. Annu. Rev. Entomol., 23: 443--469. Foraz, J.L., 1981. Simultaneous treatment of helminthoses and hypodermosis. Results of experiments carried out in autumn on young cattle. Bull. Mens. Soc. Vet. Prat. Fr., 65: 507--527.
74 James, J.A., 1979. The toxicity of synthetic pyrethroids to mammals. In: A.S.J.P.A.M. Van Miert, J. Frens and F. Van der Kreek (Editors), Trends in Veterinary Pharmacology and Toxicology. Elsevier, Amsterdam, pp. 249--255. Khan, M.A., 1971. Some factors involved in systemic insecticide toxicosis: esophageal lesions in heifers treated with coumaphos, crufomate and trichlorfon. Can. J. Anim. S c i . , 5 1 : 4 1 1 417. Nelson, D.L., Allen, A.D., Mozier, J.O. and White, R.G., 1967. Adverse reactions in cattle treated for grubs. Vet. Med., 62: 683--684. Rich, G.B., 1964. Post-treatment reactions in cattle during extensive field tests of systemic organophosphate insecticides. Can. J. Comp. Med. Vet. Sci., 29: 30--37. Robertson, R.H., 1980. Antibody production in cattle infected with Hypoderma spp. Can. J. Zool., 58: 245--251. Scharff, D.K., Sharman, G.A.M. and Ludwig, P., 1962. Illness and death in calves induced by treatments with systemic insecticides for the control of cattle grubs. J. Am. Vet. Med. Assoc., 141: 582--586. Tarry, D.W., 1981. Distribution of cattle warble flies in Britain: a larval survey. Vet. Rec., 108: 69--72.
65
EFFECT OF DOSE AND ROUTE OF APPLICATION ON THE ACTION OF DECAMETHRIN AGAINST CATTLE GRUBS
CHANTAL BOULARD
Institut National de la Recherche Agronomique, Centre de Tours--Nouzilly, Pathologie Aviaire et Parasitologie, 37380 Monnaie (France) J.L. T R O C C O N
INRA, Production Laiti~re, Station du Rheu, 35000 Rennes (France) ( A c c e p t e d for publication 18 J u l y 1983)
ABSTRACT Boulard, C. and T r o c c o n , J.L., 1984. Effect of dose and r o u t e of application on the action of d e c a m e t h r i n against cattle grubs. Vet. Parasitol., 14: 65--74. The efficacy of pour-on or orally administered d e c a m e t h r i n against bovine hypodermosis was investigated on naturally infested yearlings. T r e a t m e n t at dose rates of 1, 2 or 10 m g per kg b o d y weight were ineffective, but the highest dose had a longt e r m lethal effect on warbles. The severe side effects which followed the high dose suggest that this drug is unsatisfactory for systemic grub control. Investigations on the dynamics of circulating anti-Hypoderma antibodies in the p o s t - t r e a t m e n t period showed that there is s o m e subqethal activity of d e c a m e t h r i n o n the larval physiology even at the lowest doses.
INTRODUCTION
Since the introduction in 1978 of three national schemes to control bovine hypodermosis, in Eire, France and Gt. Britain, organophosphorus (O.P.) compounds have been widely used in systemic autumn treatments (Tarry, 1981; Boulard et al., 1983) against the endoparasitic stage of Hypoderma about 4--6 months before the larvae reach the dorsal subcutaneous tissue of cattle and moult into the ectoparasitic stages called warbles. Organophosphorus compounds are highly effective against the endoparasitic larvae of Hypoderma, but occasionally induce side effects (Rich, 1964; Nelson et al., 1967; Khan, 1971), and this limits the autumn treatment. Moreover, these post-treatment reactions in cattle increase with the abundance and size of the Hypoderma larvae (Scharff et al., 1962; Boulard, 1975). The need for new compounds to supplement the current products led us to study the efficacy of the new synthetic pyrethroids. Their high toxicity to ectoparasites (Bailie and Wood, 1979) and low mammalian fox0304-4017/84/$03.00
© 1 9 8 4 Elsevier Science Publishers B . V .
66 icity (Elliott et al., 1978) suggest t h a t t h e i r activity should be investigated against t h e e n d o p a r a s i t i c stages o f Hypoderma. I n v e s t i g a t i o n s were t h e r e f o r e c o n d u c t e d o n t h e s p e e d o f a c t i o n and e f f i c a c y o f d e c a m e t h r i n on first instar larvae o f Hypoderma in r e l a t i o n to t h e r o u t e o f a d m i n i s t r a t i o n to c a t t l e a n d t h e e f f e c t i v e dose level. MATERIALS AND METHODS
Animals T h e e x p e r i m e n t s w e r e c o n d u c t e d in a u t u m n 1 9 7 8 and 1 9 7 9 o n an exp e r i m e n t a l f a r m at t h e N a t i o n a l I n s t i t u t e o f A g r o n o m i c R e s e a r c h ( I . N . R . A . ) in T h e i x ( F r a n c e ) . T h e animals, Friesian heifers, w e r e 1 2 - - 1 4 m o n t h s - o l d w h e n t r e a t e d . T h e y h a d all b e e n n a t u r a l l y i n f e s t e d w i t h Hypoderma during t h e p r e v i o u s s u m m e r . I n E x p e r i m e n t 1, t h e animals w e r e h o u s e d f r o m N o v e m b e r 1 9 7 8 t o M a y 1 9 7 9 , in six loose b o x e s w i t h six a n i m a l s p e r b o x . E a c h u n i t b o x was sepa r a t e d b y a m e t a l gate. T h e t r e a t m e n t w i t h d e c a m e t h r i n was a p p l i e d as a f o o d a d d i t i v e o n 6 a n i m a l s ( G r o u p A), or b y p o u r o n m e t h o d at 1 o r 2 m g active i n g r e d i e n t kg -~ live w e i g h t o n 8 animals, r e s p e c t i v e l y ( G r o u p s B a n d C). S e v e n a n i m a l s r e m a i n e d u n t r e a t e d ( G r o u p D) a n d 7 o t h e r s received a t r i c h l o r f o n t r e a t m e n t ( G r o u p E). T h e design o f t r e a t m e n t s p e r b o x f o r E x p e r i m e n t 1 is p r e s e n t e d in T a b l e I. In E x p e r i m e n t 2, c o n d u c t e d in N o v e m b e r 1 9 7 9 , t h e animals w e r e h o u s e d until M a y 1 9 8 0 in 5 u n i t b o x e s o f six t o eight animals. N o o t h e r antiparasitic treatments were administered during the experiments. TABLEI Experimental design (Experiment 1) first year Treatment
Decamethrin
Group
Methods of application
Experimental unit box no.
A
Feed additive 1 mg kg -~ Pour-on 1 mg kg -~ Pour-on 2 mg kg -~
1
6
2 5 3 5
6 +2 6 +2
B C
Number of animals
Control
D
None
4 5
6 +1
Trichlorfon
E
Pour-on 17 mg kg -~
6 5
6 +1
Treatments All t r e a t m e n t s
and
b l o o d samplings w e r e d o n e in t w o c a t t l e crushes
67 TABLE II Experimental design (Experiment 2) second year Treatment
Group
Methods of application
Experimental unit box no.
Number of animals
Decamethrin (Decis) Decamethrin (Wellcome) Decamethrin (Hoechst) Control Trichlorfon
F
Pour-on 10 mg kg-1 Pour-on 10 mg kg-~ Pour-on 10 mg kg-I None Pour-on 17 mg kg-1
1
8
2
8
3
8
4 5
6 6
G H I J
by two teams of technicians, treated cattle being handled away from their experimental unit. The serial numbers, nature, dose and route of treatments administered on N o v e m b e r 21, 1978 ( E x p e r i m e n t 1) and N ovem ber 20, 1979 (Experiment 2) are presented in Tables I and II. Volumes of drugs were given on a b o d y weight basis.
Insecticides The d ecameth r i n formulations were registered products of Roussel Uclaf. The pour-on formulation of RU 22974 and RU 22475 were solutions which co n tain ed 50 g of decamethrin 1-1, and were applied at 1, 2 or 10 mg active ingredient kg-1 live weight. The feed additive f or m ul a t i on was decamethrin RU 22974 powder, inc o rp o r ated in one day, into commercial supplement feeds at 1 mg kg rate in relation to t he total weight o f heifers in G roup A. The p o u r - o n f o r m u l a t i o n of Varlute (N.D. M~rieux, L y o n , France) was a solution containing 45 g 1-1 of trichlorfon, administered at a dose rate of 17 mg kg -1 live weight.
Observations The following observations were recorded in the treated, as well as the control animals: (a) p o s t - t r e a t m e n t clinical reactions; (b) numbers o f grubs checked at intervals t h r o u g h o u t the following spring for each e x p e r i m e n t ; (c) p o s t - t r e a t m e n t a n t i b o d y p r o d u c t i o n within various time intervals following E x p e r i m e n t 1. The immunological assay was c o n d u c t e d by the tanned red blood cell haemagglutination technique, using larval proteins of Hypoderma lineatum as antigen (Boulard et al., 1970).
68 RESULTS
Post-treatment reactions
During the post-treatment period, no adverse reactions were observed following an oral or pour-on dosage of 1 mg kg-1 or 2 mg kg-1 pour-on administration of decamethrin. After a 10 mg kg- ~ dosage with decamethrin, heifers were closely watched for 3 days after treatment because of the excitation which followed treatment. Group F (8 animals) showed lachrymation within 10 h, with profuse sweating in one animal. Intense hyperactivity continued for the next 2 days. Group G (8 animals} showed immediate irritation at the treatment site, and within 6 h all the calves were hyperactive, continuing so for the next 12 h. 24 hours after treatment, there was still local irritation at the site of treatment b u t this decreased within 2 days. All (8) Group H animals showed hyperactivity and profuse sweating 4 h after treatment, continuing for the next 28 h. In control group I (6 animals), there was a transitory hyperactivity in one heifer and another began to lachrymate 6 h after treatment. The lachrymation lasted 24 h. Two animals treated with trichlorfon in Group G showed a transitory hyperactivity 4 h after treatment. Complete recovery started on the 3rd day in all groups. T A B L E III G r u b i n f e s t a t i o n s in E x p e r i m e n t 1 Group
A
B
C
D E
Treatment
Decamethrin p e r os 1 m g kg -~ Decamethrin pour-on 1 m g kg -1 Decamethrin pour-on 2 m g kg -~ Control Trichlorfon pour-on 17 m g kg -1
No. animals
M e a n g r u b s p e r animal* 4 April
17 April
30 May
27 J u n e
6
11.6 (9--37)
24.8 (1--52)
17.16 (2--30)
10 (2--20)
8
10.8 (7--19)
21.1 (13--30)
19.8 (5--38)
8.75 (2--12)
8
20.6 (8--31)
23.3 (13--36)
22.8 (3--35)
7 (0--13)
18.7 (2--25)
22.2 (10--47)
21 (5--47)
4.4 (0--15)
7
6
0
0
0
0
* V a l u e s in p a r e n t h e s e s are ranges o f grub c o u n t s o b s e r v e d in t h e g r o u p for each date.
69 Grub c o u n t s
Data for grub counts are summarized in Tables III and IV. Maximum averages grubs per head in u n t r e a t e d or decamethrin treated groups were of 24.8 in E x p e r i m e n t 1 (Group A April) and 22.5 in E x p e r i m e n t 2 (Group G April). Grub counts ranged from 0 to 47 in E x p e r i m e n t 1 and from 0 to 50 in E x p e r i m e n t 2. TABLE IV Grub infestations in Experiment 2 Group
F G
H
Treatment
No. animals
Decamethrin (Decis) pour-on 8 10 mg kg-~ Decamethrin (Wellcome) 8 pour-on 10 mg kg-' Decamethrin (Hoechst) 8
Mean grubs per animal* 24 March
23 April
21.2 (12--37)
21.3 (7--34)
18 (0--40)
22.5 (0--50)
19.8 (7--40)
19.6 (6--44)
14.8 (0--30)
12.5 (0--29)
pour-on
I J
10 mg kg-~ Control Trichlorfon pour-on 17 mg kg-'
6 6
0
0.33 (0--2)
*Values in parentheses are ranges of grub counts observed in the group for each date. A n t i - H y p o d e r m a a n t i b o d i e s -- d y n a m i c s
The a n t i b o d y titre dynamics following E x p e r i m e n t 1 t r e a t m e n t are shown in Fig. 1. T he following data should be emphasized. Within the first 2 p o s t - t r e a t m e n t days serological variations of a n t i - H y p o d e r m a antibodies were observed in one animal in each of the following groups: control G r o u p D, trichlorfon G r oup E and the decamethrin Group A, in three cattle in decamethrin G r oup B and in five cattle in decamethrin Group C. Within one week, no modification was observed in control G roup D. Three heifers in each of Groups A and E showed variations, five heifers displayed variations in G r oup B and seven in G roup C. Three weeks later, the animals in cont rol G roup D showed an increase in antibody, with a marked peak between February and April, as observed previously (Boulard, 1975; R o b e r t s o n , 1980) during natural infestations.
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Fig. 1. Development of haemagglutinating antibodies (HA) against Hypoderrna lineatum following pyrethroid applications (Groups A, B, C), trichlorfon treatment (Group E), or control group (Group D) in heifers naturally infested with Hypoderma spp. Each line represents an individual heifer.
Groups A, B and C began a similar pattern. In Group E, only 3 heifers out of 7 displayed such a pattern between January and March. DISCUSSION
Systemic treatment given in the autumn for hypodermosis with oral or pour-on decamethrin at 1, 2 or 10 mg kg -1 was ineffective, although the higher dose rate delayed warble evolution. Strangely, this effect also occurred in the control group kept close to the treated groups (Table IV). However, our results show that such high dosage also induces severe post-treatment reactions, so that decamethrin cannot be recommended. These side effects are quite different from those associated with O.P. treatment. There was no diarrhoea, dyspnoea, unsteady gait, paralysis or prostration, but there was intense hyperactivity, perspiration and lachrymation.
72 The hyperactivity is in accordance with the previously described s y m p t o m s of poisoning by pyrethroids (Aldridge et al., 1978; James, 1979). One may assume that the rapid metabolism of pyrethroids by esterases and oxidases, which limits their toxicity in mammals (Casida and Ruzo, 1980), also reduces their effectiveness towards endoparasitic insects. Further data on the efficacy and speed of action of decamethrin have been obtained from the analysis of circulating antibodies against Hypoderma larval antigens, within few hours following treatment with the drugs. Immediate antibody variations after O.P. treatment due to the release of Hypoderma larval proteins into the tissue and blood stream of the host have been described previously (Boulard, 1975). It should be emphasized that first instar larvae of Hypoderma induce antibody production directed against their metabolic products (Boulard and Weintraub, 1973). These antigens are mostly stored in the larval mid gut (Boulard, 1968). Any insecticide provoking an effect on the larval nervous system stimulates a regurgitation of the antigenic gut content into the host, which complexes with circulating antibodies. Therefore serum antibody analysis during the 72 h following treatment could offer a technique for monitoring immediate drug activity on endoparasitic insects. The survey of the antibody response in the following months could also provide an estimation of the possible lethal efficacy of the drug. The number of cattle showing antibody variations in each group in our study depended on the dose or route of decamethrin administration. At 1 mg kg -1, oral treatment induces less variation than pour-on, indicating that the insecticide may reach fewer larvae by the oral route. This could also indicate accelerated degradation of the decamethrin after oral administration. A comparison of the pour-on dosages of decamethrin, 1 mg kg -1 (Group B) and 2 mg kg -~ (Group C), indicated faster and greater activity against the larvae in cattle at the higher dose. During the same post-treatment period, only one heifer in control Group D showed any antibody variation. This was also the only control heifer grouped with treated cattle in experimental unit 5, suggesting diffusion of decamethrin vapour in this stall or active b o d y contact between animals. The other animals of control group D were in unit 4, positioned between two treated animal units and showed no variation. Licking was possibly involved in unit 5 as other results support such conclusions. The final treated Group (E) in this experiment received trichlorfon. Trichlorfon induces well-characterized antibody variations within 2--4 h after treatment. In this experiment the first reaction occurred 48 h later. The delay seen in this experiment m a y have been due to an interaction of pyrethroids with the organophosphorus insecticide. Decamethrin vapour is apparently not involved because as most pyrethroids, it has a very low vapour pressure (Elliott et al., 1978). However, Group E was treated in the metal pen where decamethrin treatments had just been carried o u t and there were traces of pesticide on the gate. Possibly these low doses of pyrethroids
73
which were unintentionally administered could have depressed the activity of acetylcholine (Aldridge et al., 1978), and could temporarily antagonize the O.P. activity without affecting its efficacy on the following days. Such a delay of trichlorfon activity on Hypoderma larvae has also been observed in combined treatment with oxfendazole (Foraz, 1981). This experiment revealed some activity of decamethrin against endoparasitic Hypoderma larvae. Nevertheless, doses up to 10 mg kg -1 did not improve efficacy, but only induced adverse effects. It appears that under these experimental conditions, decamethrin does not provide an alternative to organophosphorus compounds in hypodermosis control. ACKNOWLEDGEMENTS
The authors acknowledge the technical assistance of Mrs. M. Plat and Mrs. C. Villejoubert. The Roussel Uclaf Company supported in part this research and the authors thank Dr. Scheid who supplied them with the drugs.
REFERENCES Aldridge, W.N., Clothier, B., Forshaw, P., Johnson, M.K., Parker, V.H., Price, R.J., Skilleter, D.N., Verschoyle, R.D. and Stevens, C., 1978. The effect of DDT and the pyrethroids cismethrin and decamethrin on the acetylcholine and cyclic nucleotide content of rat brain. Biochem. Pharmacol., 27: 1703--1706. Bailie, H.D. and Wood, J.C., 1979. Pyrethroids, their use in the control of animal ectoparasites. In: A.S.J.P.A.M. Van Miert, J. Frens and F. Van der Kreek (Editors), Trends in Veterinary Pharmacology and Toxicology. Elsevier, Amsterdam, pp. 256--260. Boulard, C., 1968. Anatomie et histologie du tube digestif de la larve d'Hypoderma bovis. Ann. Soc. Entomol. Fr., 5: 371--387. Boulard, C., 1975. Evolution des anticorps circulants chez les bovins trait~s contre l'hypodermose. Ann. Rech. Vet., 6 : 143--154. Boulard, C. and Weintraub, J., 1973. Immunological responses of rabbits artificially infested with the cattle grubs Hypoderma bovis and Hypoderma lineatum. Int. J. Parasitol., 3: 379--386. Boulard, C., Soria, J. and Soria, C., 1970. Possibilitd d'emploi de la r~action d'hdmagglutination passive pour le diagnostic de l'hypodermose, en utilisant comme antigbne une collag~nase brute extraite des larves de ler stade Hypoderma lineatum. C.R. Acad. Sci., Ser. D, 270: 1965--1968. Boulard, C., Billardon, G., Biron, G., Hillion, E. and Vigouroux, B., 1983. Essais de contrSle ponctuel de l'hypodermose bovine au niveau d'exploitations dispers~es ou groupies. Ann. Rech. V~t., 14: 183--188. Casida, J.E. and Ruzo, L.O., 1980. Metabolic chemistry of pyrethroid insecticides. Pestic. Sci., 11: 257--269. Elliott, M., Janes, N.F. and Potter, C., 1978. The future of pyrethroids in insect control. Annu. Rev. Entomol., 23: 443--469. Foraz, J.L., 1981. Simultaneous treatment of helminthoses and hypodermosis. Results of experiments carried out in autumn on young cattle. Bull. Mens. Soc. Vet. Prat. Fr., 65: 507--527.
74 James, J.A., 1979. The toxicity of synthetic pyrethroids to mammals. In: A.S.J.P.A.M. Van Miert, J. Frens and F. Van der Kreek (Editors), Trends in Veterinary Pharmacology and Toxicology. Elsevier, Amsterdam, pp. 249--255. Khan, M.A., 1971. Some factors involved in systemic insecticide toxicosis: esophageal lesions in heifers treated with coumaphos, crufomate and trichlorfon. Can. J. Anim. S c i . , 5 1 : 4 1 1 417. Nelson, D.L., Allen, A.D., Mozier, J.O. and White, R.G., 1967. Adverse reactions in cattle treated for grubs. Vet. Med., 62: 683--684. Rich, G.B., 1964. Post-treatment reactions in cattle during extensive field tests of systemic organophosphate insecticides. Can. J. Comp. Med. Vet. Sci., 29: 30--37. Robertson, R.H., 1980. Antibody production in cattle infected with Hypoderma spp. Can. J. Zool., 58: 245--251. Scharff, D.K., Sharman, G.A.M. and Ludwig, P., 1962. Illness and death in calves induced by treatments with systemic insecticides for the control of cattle grubs. J. Am. Vet. Med. Assoc., 141: 582--586. Tarry, D.W., 1981. Distribution of cattle warble flies in Britain: a larval survey. Vet. Rec., 108: 69--72.