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Anthelmintics
Veterinary Parasitology, 46 ( 1993 ) 113-120 Elsevier Science Publishers B.V., Amsterdam
113
Anthelmintics Roger K. Prichard and Sivaja Ranjan Institute of Parasitology, Macdonald Campus, McGill University, 21111, Lakeshore Road, Ste-Anne-de-Bellevue, Que. H9X 3V9, Canada
ABSTRACT Pilchard, R.K. and Ranjan, S., 1993. Anthelmintics. Vet. Parasitol., 46:113-120. Anthelmintics remain the principal means for the prevention and control of subclinical and clinical ostertagiasis. The selection of an appropriate anthelmintic depends on whether one is controlling or preventing Type I ostertagiasis (caused by the establishment of adult worms derived from recently acquired infective larvae), preventing Type II (treating pre-Type II or inhibited larvae) or controlling Type II ostertagiasis (caused by the development of inhibited larvae to adults), or using the anthelmintic as part of an epidemiologically based plan to reduce pasture contamination with infective Ostertagia ostertagi larvae. In the latter case, the choice of an anthelmintic may depend on whether the targets for treatment are only adult worms and developing larvae or whether the targets include hypobiotic larvae. Thus for Ostertagia control, anthelmintics must be divided into those that normally control all stages, such as the avermectin group (ivermectin, abamectin and moxidectin ) and some of the benzimidazoles (albendazole, oxfendazole and fenbendazole at appropriate does rates ), and those that only control adult worms and developing larvae (levamisole, morantel, coumaphos, phenothiazine and thiabendazole).
INTRODUCTION
Presently, anthelmintics remain the principal means for the prevention and control of clinical and subclinical ostertagiasis in cattle. The choice of anthelmintic and timing of treatment are essential considerations for optimal results. The selection of an appropriate anthelmintic depends on the ostertagiasis disease type (Type I, Type II or pre-Type II) one is dealing with and whether the anthelmintic is being used for therapeutic or prophylactic purposes. Clinical ostertagiasis occurs in two forms, Type I which occurs as a result of recently ingested larvae developing to adults and Type II, which occurs as a result of maturation of larvae ingested during the previous grazing season (maturation of inhibited early fourth stage larvae (EL4)). Thus the choice of anthelmintic for the prevention and control of these disease types Correspondence to: R.K. Prichard, Institute of Parasitology, Macdonald Campus, McGill University, 21111, Lakeshore Road, Ste-Anne-de-Bellevue, Que. H9X 3V9, Canada.
© 1993 Elsevier Science Publishers B.V. All rights reserved 0304-4017 / 93 / $06.00
114
R.K. PRICHARD AND S. RAN JAN
will depend on whether the targets for treatment are adult worms and developing larvae only or whether the targets include hypobiotic larvae (e.g. treating pre-Type II ). For the purpose of ostertagiasis control, anthelmintics currently on the market can be divided into those that normally control all stages (including EL4 ), such as the avermectin group (ivermectin (IVM), abamectin and moxidectin), the modern benzimidazoles [albendazole (ABZ), fenbendazole (FBZ) and oxfendazole (OFZ) in appropriate doses ], some probenzimidazoles (netobimin at higher dose rates) and those that control adult worms and developing larvae only (levamisole, morantel, thiabendazole, phenothiazine and coumaphos). AVAILABLEANTHELMINTICS The anthelmintics available in North America for the treatment of ostertagiasis in cattle are listed in Table 1. Until recently, IVM and FBZ were the only anthelmintics available in North America with activity against EL4, and were thus the only means of preventing and controlling Type II ostertagiasis and preventing production losses due to the maturation of EL4 to adult worms. However, in recent years, other broad spectrum benzimidazole anthelmintics, with high efficacies against EL4, have been approved by the Food and Drug Administration for use in cattle (Table 2 ). Other avermectins, namely abamectin (Williams et al., 1992 ) and moxidectin (Ranjan et al., 1992 ), with broad spectrum activity similar to ivermectin, have been developed and marketed in other parts of the world. However, they are not yet available in North America. Netobimin, a probenzimidazole, is also effective against inhibited EL4 at a higher dose rate. However, this drug is not available in North America. Apart from the above-mentioned anthelmintics, other available anthelmintics show activity only against adult and developing Ostertagia ostertagi. Therefore, these anthelmintics could be used only during periods when developing and adult worms are the prime targets and when epidemiological factors make the presence of large numbers of EL4 unlikely in the host.
Ivermectin Ivermectin is now available in both injectable and pour-on formulations and because of its high efficacy, broad spectrum of activity, and long half-life, it can be used in the prevention and control of all types of ostertagiasis. However, ivermectin is not approved for use in lactating dairy cattle and female dairy cattle of breeding age.
Albendazole, fenbendazole and oxfendazole These broad spectrum benzimidazole (BZ) anthelmintics have high activity against adult, developing and inhibited larval stages (FBZ, 10 mg kg- ~for
220-4403
Suspension Medicated block Feed/H20 additive Solution Pellets Bolus/oblets Gel Pour-on Feed additive Bolus (2.5 g) Bolus ( 19.8 g)
Feed additive Medicated block Bolus ( 15 and 2 g) Suspension Paste Suspension Paste Feed additive Paste Suspension
Suspension Solution Pour-on
Phenothiazine
Thiabendazole
Oxfendazole Ivermectin
OR OR OR OR OR
10 10 5 5 5,10 mg kg- l for the removal of inhibited O. ostertagi larvae 4.5 0.2 0.5 OR SC P-on
OR
OR SC OR OR OR P-on OR
OR
OR
Route ~
66/88/1102
tOR, oral; SC, subcutaneous. 22 mg of active ingredient/kg bwt/day for 6 consecutive days. 3Therapeutic dosage. 4NLD, not for use in lactating dairy animals.
Fenbendazole
Albendazole
Morantel
8 7 8 1 bolus (200-350 kg) 8 10 10 1 bolus (170-300 kg) 1 bolus at turnout
2 X 62
Feed additive
Coumaphos
Levamisole
Dose (mg kg-t )
Formulation
Anthelmintic
Anthelmintics for treating O. ostertagi
TABLE 1
4 (USA)
3 (Can.) 0 0 (Can.)
2.5 (Can.)
2 (Can.) 2 (Can.)
0 (usa)
o (USA)
Not for calves < 3 months of age Do not use last 4 weeks of pregnancy NLD 4
Restrictions
NLD
NLD
7 NLD 49 (USA), 35 (Can.) NED 48 (USA), 49 (Can.) Not for use in female dairy animals of breeding age
8 (USA) 8 (USA, 10 (Can.)
13 (USA)
27
2 (USA), 10 (Can.) 7 All formulations--NLD (USA) 10 (Can.) 2 (USA), 10 (Can.) 6 (USA) 9 (USA), 10 (Can.) 14 (USA), 30 (Can.) 30 (Can.) NLD (USA, Can. ) 106 (USA) 102 (Can.) NLD (2 g bolus) 3 (USA)
0 (USA)
Meat
Milk
Withholding period (days)
7-
z
m
> z
116
R.K. PRICHARD AND S. RANJAN
TABLE 2 Anthelmintics for treating O. ostertagi Anthelmintic
Anthelmintic spectrum o f activity Adults
DL4
Coumaphos Phenothiazine Levamisole Morantel Thiabendazole Albendazole Fenbendazole
+ + + + + + +
+ +
Oxfendazole Ivermectin
+ +
+ +
EL 4
+ + + + ( 10 m g / k g ) + +
DL4, developing larvae. ELa, inhibited fourth stage larvae.
removing EL4) and can be used at any time for the prevention and control of both Type I and Type II ostertagiasis. In a recent study, Williams ( 1991 ) has shown both ABZ and FBZ to be highly effective against EL4. However, in the past there have been reports of variable efficacies of these BZ anthelmintics a g a i n s t E L 4 (Prichard, 1988; Williams, 1991 ). Although many reasons have been suggested for variability in efficacy, no clear explanation has been given. Larval metabolic activity is one suggested reason. In a study conducted by Miller and Olson (1990) in Louisiana, where naturally infected calves were treated with OFZ between March and September, it was found that the efficacy of OFZ varied between 42 and 94%. Efficacy was highest during induction of inhibition and emergence of inhibited larvae and was lowest during the quiescent period. These anthelmintics, like IVM, are not approved for use in lactating dairy cattle.
Thiabendazole When compared with the above-mentioned, newer BZ anthelmintics, thiabendazole (TBZ) has a reduced spectrum of activity. At the recommended dose rates, it is effective against adult and developing stages of O. ostertagi but not against EL4. Thus, TBZ cannot be used for the removal of EL4 before they develop to adult worms. TBZ is approved for use in lactating dairy cattle with a 96 h milk discard restriction after treatment.
ANTHELMINTICS
1 17
Levamisole Levamisole (LEV) is efficacious against adult and developing stages of O.
ostertagi but has low activity against EL 4 stages. Thus, this anthelmintic may be used in the prevention and treatment of Type I ostertagiasis. When used in the treatment of Type II disease, repeated administration is needed to remove adults maturing from EL4. Some workers have reported poor activity of LEV against adult stages (Williams, 1991; Williams et al., 1991 ) and LEV resistance is suggested as a possible cause for the diminished activity.
Moranteltartrate This has similar activity to LEV in being effective against adult and developing stages and ineffective against EL4. It is presently available as a feed premix and as a long-acting sustained release bolus for therapeutic purposes. The long-acting bolus (which is not presently marketed in the USA) is not approved for use in lactating dairy cattle. Other approved formulations have no milk discard restriction after treatment. Resistance to morantel tartrate (MT) has been reported for Ostertagia ostertagi (Borgsteede, 1991 ).
Phenothiazine Phenothiazine shows activity against adult O. ostertagi but not against EL4 and is not approved for use in lactating dairy cattle. When using phenothiazine, care should be taken to avoid photosensitization and the potentiation of organophosphate toxicity.
Coumaphos This organophosphate anthelmintic is used mainly as a feed additive and is efficacious against adult O. ostertagi but not against EL4. It is approved for use in lactating dairy cattle with no milk discard restriction after administration. C O N S I D E R A T I O N S IN THE USE O F A N T H E L M I N T I C S FOR THE C O N T R O L O F OSTERTAGIASIS
Choice of anthelmintic This is an important consideration because all available anthelmintics do not have the same spectrum of activity against different stages of O. ostertagi. As mentioned earlier, all of the above-listed anthelmintics can be used effectively for the prevention and treatment of Type I ostertagiasis. However, for
118
R.K. P R I C H A R D A N D S. R A N J A N
the prevention of Type II ostertagiasis and for the treatment of pre-Type II ostertagiasis where the target is the EL4 stage, anthelmintics such as the avermectins and the newer benzimidazoles, which have high efficacy against EL4 stages, must be used.
Timing of treatment Because of the seasonal nature of arrested development which occurs with
Ostertagia infection, proper timing of treatment is an essential consideration for effective control of this parasite. Transmission patterns and inhibition are influenced by the prevailing climatic conditions. In previous reports (Williams, 1986; Williams and Knox, 1988), North America has been divided into northern and southern regions, each showing a different pattern of Ostertagia inhibition: the cool temperate region which includes the northern states of the USA and Canada, where inhibition occurs during winter, and the warm temperate region, which covers the southern states of the USA, where inhibition occurs during summer. However, recent studies on inhibition patterns in the central and western states have indicated that such a distinct delineation is not possible and that there is a rather wide variable transition zone between the northern and southern regions (Fig. l ) ( Z i m m e r m a n and Worley, 1990). Thus, recognition of the transmission and inhibition patterns for each area is essential for the optimal timing of treatment. Control strategies using anthelmintics for the cool temperate and warm temperate regions of North America have been discussed in detail by Prichard (1988 ) and little has changed in the basic principles outlined for the control of ostertagiasis. Strategic, epidemiologically based anthelmintic control programmes, when implemented correctly, should be most economical, as they would maximise production benefits at minimal cost and would also reduce the risk of selection for drug resistance. In the cool temperate region of North America where distinct a u t u m n / w i n ter inhibition of O. ostertagi is recognised and where animals are housed from late autumn to spring ( O c t o b e r / N o v e m b e r - M a y / J u n e ) , a single treatment at housing with an anthelmintic effective against all stages of O. ostertagi would prevent the occurrence of both pre-Type II and Type II ostertagiasis. Ostertagia ostertagi infective larvae are known to overwinter successfully on pasture. Thus, an anthelmintic treatment is necessary soon after turnout to prevent the establishment of adult worms from overwintered larvae ingested in the spring. However, a single treatment after turnout may not be adequate to decrease pasture contamination and the late s u m m e r / a u t u m n rise in pasture larvae. A second and perhaps a third treatment may then be necessary during the early summer months. The need and timing of these treatments would depend on many factors, including the type of anthelmintic used for the initial treatment, the management of pasture and herd (stocking density, move-
119
ANTHELMINTICS
"7
°;
Fig. 1. Generalised concept of patterns of O. ostertagilarval inhibition in the USA and Canada. m, Northern pattern (autumn/winter inhibition); [], variable transition zone (variable inhibition); g~, southern pattern (spring/summer inhibition); 7 , probable northern pattern; ~ , probable variable pattern. Adapted from Zimmerman and Worley (1990).
ment o f herd to aftermath/'safe' pasture etc. ) and precipitation. If an anthelmintic with a long half-life (e.g. IVM ) is used for treatment after turnout, the second and if necessary the third treatment, can be administered 5 and 10 weeks after the initial treatment. If, however, a long-acting bolus with 6 0 - 9 0 day continued release o f anthelmintic (e.g. Paratec Flex diffuser) is administered at turnout, then a second and third treatment would be unnecessary. In the warm temperate region, grazing seasons are long and cattle may graze all year round. Therefore, transmission o f O. ostertagi can occur throughout the year. As inhibited development occurs during s p r i n g / s u m m e r months in
120
R.K. PRICHARD AND S. RAN JAN
this region, a t r e a t m e n t m a y be necessary d u r i n g this t i m e with an a n t h e l m i n tic effective against EL4 stages. A t r e a t m e n t o f all susceptible a n i m a l s in aut u m n / w i n t e r with an a n t h e l m i n t i c effective against adult stages w o u l d be n e c e s s a r y to p r e v e n t subclinical a n d clinical T y p e I ostertagiasis. T h e s e strategic t r e a t m e n t s c o m b i n e d w i t h g o o d m a n a g e m e n t practices s h o u l d m i n i m i s e p r o d u c t i o n losses d u e to O. ostertagi in this region. In the t r a n s i t i o n z o n e w h e r e w e a t h e r , r a t h e r t h a n region or the state, is considered the m a j o r c o n t r i b u t i n g factor, i n h i b i t i o n p a t t e r n s m a y v a r y f r o m y e a r to y e a r a n d f r o m the n o r t h e r n a n d s o u t h e r n p a t t e r n to n o i n h i b i t i o n at all ( Z i m m e r m a n a n d Worley, 1990). In these areas, t i m i n g o f a n t h e l m i n t i c t r e a t m e n t , ideally, s h o u l d b e b a s e d o n k n o w n t r a n s m i s s i o n p a t t e r n s o f O. ostertagi. In m a n y areas, especially in the arid w e s t e r n states, a single t r e a t m e n t each y e a r m a y be a d e q u a t e with g o o d m a n a g e m e n t practices. In the m o r e central states, two or three strategic a n t h e l m i n t i c t r e a t m e n t s m o d i f i e d for each cattle m a n a g e m e n t o p e r a t i o n w o u l d s h o w p r o d u c t i o n benefits in b o t h adult a n d y o u n g cattle. REFERENCES Borgsteede, F.H.M., 1991. Further studies with a strain of Ostertagia ostertagi resistant to morantel tartrate. Int. J. Parasitol., 21: 867-870. Miller, J.E. and Olson, T., 1990. Critical evaluation of oxfendazole against inhibited larvae of Ostertagia ostertagi. Proceedings of the American Association of Veterinary Parasitology, 21-24 July, San Antonio, TX p. 41. Prichard, R.K., 1988. Anthelmintics and control. Vet. Parasitol., 27:97-109. Ranjan, S., Trudeau, C., Prichard, R.K., von Kutzleben, R. and Carrier, D., 1992. Efficacy of moxidectin against naturally acquired nematode infections in cattle. Vet. Parasitol., 41: 227231. Williams, J.C., 1986. Epidemiologic patterns of nematodiasis in cattle. In: H.C. Gibbs, R.P. Herd and K.D. Murrel (Guest Editors), The Veterinary Clinics of North America--Food Animal Practice. W.B. Saunders, Philadelphia, PA, Vol. 2 (2), pp. 235-246. Williams, J.C., 1991. Efficacy of albendazole, levamisole and fenbendazole against nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae. Vet. Parasitol., 40:59-71. Williams, J.C. and Knox, J.W., 1988. Epidemiology of Ostertagia ostertagi in warm temperate regions of the United States. Vet. Parasitol., 27: 23-38. Williams, J.C., Knox, J.W., Marbury, K.S., Swalley, R.A. and Eddi, C.S., 1991. Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January). Vet. Parasitol., 40: 7385. Williams, J.C., Loyacano, A.F., Nault, C., Ramsey, R.T. and Plue, R.E., 1992. Efficacy of abamectin against natural infections of gastrointestinal nematodes and lung worms of cattle with special emphasis on inhibited, early fourth stage larvae of Ostertagia ostertagi. Vet. Parasitol., 41: 77-84. Zimmerman, G.L. and Worley, D.E., 1990. Epidemiology of bovine nematode parasites in the northern United States. In: J. Guerrero and W.H.D. Leaning (Editors), Epidemiology of Bovine Nematode Parasites in the Americas. Proceedings of the MSD AGVET Symposium, 13-17 August, Salvador, Bahia, Brazil, Veterinary Learning Systems, Trenton, N J, pp. 8387.
113
Anthelmintics Roger K. Prichard and Sivaja Ranjan Institute of Parasitology, Macdonald Campus, McGill University, 21111, Lakeshore Road, Ste-Anne-de-Bellevue, Que. H9X 3V9, Canada
ABSTRACT Pilchard, R.K. and Ranjan, S., 1993. Anthelmintics. Vet. Parasitol., 46:113-120. Anthelmintics remain the principal means for the prevention and control of subclinical and clinical ostertagiasis. The selection of an appropriate anthelmintic depends on whether one is controlling or preventing Type I ostertagiasis (caused by the establishment of adult worms derived from recently acquired infective larvae), preventing Type II (treating pre-Type II or inhibited larvae) or controlling Type II ostertagiasis (caused by the development of inhibited larvae to adults), or using the anthelmintic as part of an epidemiologically based plan to reduce pasture contamination with infective Ostertagia ostertagi larvae. In the latter case, the choice of an anthelmintic may depend on whether the targets for treatment are only adult worms and developing larvae or whether the targets include hypobiotic larvae. Thus for Ostertagia control, anthelmintics must be divided into those that normally control all stages, such as the avermectin group (ivermectin, abamectin and moxidectin ) and some of the benzimidazoles (albendazole, oxfendazole and fenbendazole at appropriate does rates ), and those that only control adult worms and developing larvae (levamisole, morantel, coumaphos, phenothiazine and thiabendazole).
INTRODUCTION
Presently, anthelmintics remain the principal means for the prevention and control of clinical and subclinical ostertagiasis in cattle. The choice of anthelmintic and timing of treatment are essential considerations for optimal results. The selection of an appropriate anthelmintic depends on the ostertagiasis disease type (Type I, Type II or pre-Type II) one is dealing with and whether the anthelmintic is being used for therapeutic or prophylactic purposes. Clinical ostertagiasis occurs in two forms, Type I which occurs as a result of recently ingested larvae developing to adults and Type II, which occurs as a result of maturation of larvae ingested during the previous grazing season (maturation of inhibited early fourth stage larvae (EL4)). Thus the choice of anthelmintic for the prevention and control of these disease types Correspondence to: R.K. Prichard, Institute of Parasitology, Macdonald Campus, McGill University, 21111, Lakeshore Road, Ste-Anne-de-Bellevue, Que. H9X 3V9, Canada.
© 1993 Elsevier Science Publishers B.V. All rights reserved 0304-4017 / 93 / $06.00
114
R.K. PRICHARD AND S. RAN JAN
will depend on whether the targets for treatment are adult worms and developing larvae only or whether the targets include hypobiotic larvae (e.g. treating pre-Type II ). For the purpose of ostertagiasis control, anthelmintics currently on the market can be divided into those that normally control all stages (including EL4 ), such as the avermectin group (ivermectin (IVM), abamectin and moxidectin), the modern benzimidazoles [albendazole (ABZ), fenbendazole (FBZ) and oxfendazole (OFZ) in appropriate doses ], some probenzimidazoles (netobimin at higher dose rates) and those that control adult worms and developing larvae only (levamisole, morantel, thiabendazole, phenothiazine and coumaphos). AVAILABLEANTHELMINTICS The anthelmintics available in North America for the treatment of ostertagiasis in cattle are listed in Table 1. Until recently, IVM and FBZ were the only anthelmintics available in North America with activity against EL4, and were thus the only means of preventing and controlling Type II ostertagiasis and preventing production losses due to the maturation of EL4 to adult worms. However, in recent years, other broad spectrum benzimidazole anthelmintics, with high efficacies against EL4, have been approved by the Food and Drug Administration for use in cattle (Table 2 ). Other avermectins, namely abamectin (Williams et al., 1992 ) and moxidectin (Ranjan et al., 1992 ), with broad spectrum activity similar to ivermectin, have been developed and marketed in other parts of the world. However, they are not yet available in North America. Netobimin, a probenzimidazole, is also effective against inhibited EL4 at a higher dose rate. However, this drug is not available in North America. Apart from the above-mentioned anthelmintics, other available anthelmintics show activity only against adult and developing Ostertagia ostertagi. Therefore, these anthelmintics could be used only during periods when developing and adult worms are the prime targets and when epidemiological factors make the presence of large numbers of EL4 unlikely in the host.
Ivermectin Ivermectin is now available in both injectable and pour-on formulations and because of its high efficacy, broad spectrum of activity, and long half-life, it can be used in the prevention and control of all types of ostertagiasis. However, ivermectin is not approved for use in lactating dairy cattle and female dairy cattle of breeding age.
Albendazole, fenbendazole and oxfendazole These broad spectrum benzimidazole (BZ) anthelmintics have high activity against adult, developing and inhibited larval stages (FBZ, 10 mg kg- ~for
220-4403
Suspension Medicated block Feed/H20 additive Solution Pellets Bolus/oblets Gel Pour-on Feed additive Bolus (2.5 g) Bolus ( 19.8 g)
Feed additive Medicated block Bolus ( 15 and 2 g) Suspension Paste Suspension Paste Feed additive Paste Suspension
Suspension Solution Pour-on
Phenothiazine
Thiabendazole
Oxfendazole Ivermectin
OR OR OR OR OR
10 10 5 5 5,10 mg kg- l for the removal of inhibited O. ostertagi larvae 4.5 0.2 0.5 OR SC P-on
OR
OR SC OR OR OR P-on OR
OR
OR
Route ~
66/88/1102
tOR, oral; SC, subcutaneous. 22 mg of active ingredient/kg bwt/day for 6 consecutive days. 3Therapeutic dosage. 4NLD, not for use in lactating dairy animals.
Fenbendazole
Albendazole
Morantel
8 7 8 1 bolus (200-350 kg) 8 10 10 1 bolus (170-300 kg) 1 bolus at turnout
2 X 62
Feed additive
Coumaphos
Levamisole
Dose (mg kg-t )
Formulation
Anthelmintic
Anthelmintics for treating O. ostertagi
TABLE 1
4 (USA)
3 (Can.) 0 0 (Can.)
2.5 (Can.)
2 (Can.) 2 (Can.)
0 (usa)
o (USA)
Not for calves < 3 months of age Do not use last 4 weeks of pregnancy NLD 4
Restrictions
NLD
NLD
7 NLD 49 (USA), 35 (Can.) NED 48 (USA), 49 (Can.) Not for use in female dairy animals of breeding age
8 (USA) 8 (USA, 10 (Can.)
13 (USA)
27
2 (USA), 10 (Can.) 7 All formulations--NLD (USA) 10 (Can.) 2 (USA), 10 (Can.) 6 (USA) 9 (USA), 10 (Can.) 14 (USA), 30 (Can.) 30 (Can.) NLD (USA, Can. ) 106 (USA) 102 (Can.) NLD (2 g bolus) 3 (USA)
0 (USA)
Meat
Milk
Withholding period (days)
7-
z
m
> z
116
R.K. PRICHARD AND S. RANJAN
TABLE 2 Anthelmintics for treating O. ostertagi Anthelmintic
Anthelmintic spectrum o f activity Adults
DL4
Coumaphos Phenothiazine Levamisole Morantel Thiabendazole Albendazole Fenbendazole
+ + + + + + +
+ +
Oxfendazole Ivermectin
+ +
+ +
EL 4
+ + + + ( 10 m g / k g ) + +
DL4, developing larvae. ELa, inhibited fourth stage larvae.
removing EL4) and can be used at any time for the prevention and control of both Type I and Type II ostertagiasis. In a recent study, Williams ( 1991 ) has shown both ABZ and FBZ to be highly effective against EL4. However, in the past there have been reports of variable efficacies of these BZ anthelmintics a g a i n s t E L 4 (Prichard, 1988; Williams, 1991 ). Although many reasons have been suggested for variability in efficacy, no clear explanation has been given. Larval metabolic activity is one suggested reason. In a study conducted by Miller and Olson (1990) in Louisiana, where naturally infected calves were treated with OFZ between March and September, it was found that the efficacy of OFZ varied between 42 and 94%. Efficacy was highest during induction of inhibition and emergence of inhibited larvae and was lowest during the quiescent period. These anthelmintics, like IVM, are not approved for use in lactating dairy cattle.
Thiabendazole When compared with the above-mentioned, newer BZ anthelmintics, thiabendazole (TBZ) has a reduced spectrum of activity. At the recommended dose rates, it is effective against adult and developing stages of O. ostertagi but not against EL4. Thus, TBZ cannot be used for the removal of EL4 before they develop to adult worms. TBZ is approved for use in lactating dairy cattle with a 96 h milk discard restriction after treatment.
ANTHELMINTICS
1 17
Levamisole Levamisole (LEV) is efficacious against adult and developing stages of O.
ostertagi but has low activity against EL 4 stages. Thus, this anthelmintic may be used in the prevention and treatment of Type I ostertagiasis. When used in the treatment of Type II disease, repeated administration is needed to remove adults maturing from EL4. Some workers have reported poor activity of LEV against adult stages (Williams, 1991; Williams et al., 1991 ) and LEV resistance is suggested as a possible cause for the diminished activity.
Moranteltartrate This has similar activity to LEV in being effective against adult and developing stages and ineffective against EL4. It is presently available as a feed premix and as a long-acting sustained release bolus for therapeutic purposes. The long-acting bolus (which is not presently marketed in the USA) is not approved for use in lactating dairy cattle. Other approved formulations have no milk discard restriction after treatment. Resistance to morantel tartrate (MT) has been reported for Ostertagia ostertagi (Borgsteede, 1991 ).
Phenothiazine Phenothiazine shows activity against adult O. ostertagi but not against EL4 and is not approved for use in lactating dairy cattle. When using phenothiazine, care should be taken to avoid photosensitization and the potentiation of organophosphate toxicity.
Coumaphos This organophosphate anthelmintic is used mainly as a feed additive and is efficacious against adult O. ostertagi but not against EL4. It is approved for use in lactating dairy cattle with no milk discard restriction after administration. C O N S I D E R A T I O N S IN THE USE O F A N T H E L M I N T I C S FOR THE C O N T R O L O F OSTERTAGIASIS
Choice of anthelmintic This is an important consideration because all available anthelmintics do not have the same spectrum of activity against different stages of O. ostertagi. As mentioned earlier, all of the above-listed anthelmintics can be used effectively for the prevention and treatment of Type I ostertagiasis. However, for
118
R.K. P R I C H A R D A N D S. R A N J A N
the prevention of Type II ostertagiasis and for the treatment of pre-Type II ostertagiasis where the target is the EL4 stage, anthelmintics such as the avermectins and the newer benzimidazoles, which have high efficacy against EL4 stages, must be used.
Timing of treatment Because of the seasonal nature of arrested development which occurs with
Ostertagia infection, proper timing of treatment is an essential consideration for effective control of this parasite. Transmission patterns and inhibition are influenced by the prevailing climatic conditions. In previous reports (Williams, 1986; Williams and Knox, 1988), North America has been divided into northern and southern regions, each showing a different pattern of Ostertagia inhibition: the cool temperate region which includes the northern states of the USA and Canada, where inhibition occurs during winter, and the warm temperate region, which covers the southern states of the USA, where inhibition occurs during summer. However, recent studies on inhibition patterns in the central and western states have indicated that such a distinct delineation is not possible and that there is a rather wide variable transition zone between the northern and southern regions (Fig. l ) ( Z i m m e r m a n and Worley, 1990). Thus, recognition of the transmission and inhibition patterns for each area is essential for the optimal timing of treatment. Control strategies using anthelmintics for the cool temperate and warm temperate regions of North America have been discussed in detail by Prichard (1988 ) and little has changed in the basic principles outlined for the control of ostertagiasis. Strategic, epidemiologically based anthelmintic control programmes, when implemented correctly, should be most economical, as they would maximise production benefits at minimal cost and would also reduce the risk of selection for drug resistance. In the cool temperate region of North America where distinct a u t u m n / w i n ter inhibition of O. ostertagi is recognised and where animals are housed from late autumn to spring ( O c t o b e r / N o v e m b e r - M a y / J u n e ) , a single treatment at housing with an anthelmintic effective against all stages of O. ostertagi would prevent the occurrence of both pre-Type II and Type II ostertagiasis. Ostertagia ostertagi infective larvae are known to overwinter successfully on pasture. Thus, an anthelmintic treatment is necessary soon after turnout to prevent the establishment of adult worms from overwintered larvae ingested in the spring. However, a single treatment after turnout may not be adequate to decrease pasture contamination and the late s u m m e r / a u t u m n rise in pasture larvae. A second and perhaps a third treatment may then be necessary during the early summer months. The need and timing of these treatments would depend on many factors, including the type of anthelmintic used for the initial treatment, the management of pasture and herd (stocking density, move-
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"7
°;
Fig. 1. Generalised concept of patterns of O. ostertagilarval inhibition in the USA and Canada. m, Northern pattern (autumn/winter inhibition); [], variable transition zone (variable inhibition); g~, southern pattern (spring/summer inhibition); 7 , probable northern pattern; ~ , probable variable pattern. Adapted from Zimmerman and Worley (1990).
ment o f herd to aftermath/'safe' pasture etc. ) and precipitation. If an anthelmintic with a long half-life (e.g. IVM ) is used for treatment after turnout, the second and if necessary the third treatment, can be administered 5 and 10 weeks after the initial treatment. If, however, a long-acting bolus with 6 0 - 9 0 day continued release o f anthelmintic (e.g. Paratec Flex diffuser) is administered at turnout, then a second and third treatment would be unnecessary. In the warm temperate region, grazing seasons are long and cattle may graze all year round. Therefore, transmission o f O. ostertagi can occur throughout the year. As inhibited development occurs during s p r i n g / s u m m e r months in
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this region, a t r e a t m e n t m a y be necessary d u r i n g this t i m e with an a n t h e l m i n tic effective against EL4 stages. A t r e a t m e n t o f all susceptible a n i m a l s in aut u m n / w i n t e r with an a n t h e l m i n t i c effective against adult stages w o u l d be n e c e s s a r y to p r e v e n t subclinical a n d clinical T y p e I ostertagiasis. T h e s e strategic t r e a t m e n t s c o m b i n e d w i t h g o o d m a n a g e m e n t practices s h o u l d m i n i m i s e p r o d u c t i o n losses d u e to O. ostertagi in this region. In the t r a n s i t i o n z o n e w h e r e w e a t h e r , r a t h e r t h a n region or the state, is considered the m a j o r c o n t r i b u t i n g factor, i n h i b i t i o n p a t t e r n s m a y v a r y f r o m y e a r to y e a r a n d f r o m the n o r t h e r n a n d s o u t h e r n p a t t e r n to n o i n h i b i t i o n at all ( Z i m m e r m a n a n d Worley, 1990). In these areas, t i m i n g o f a n t h e l m i n t i c t r e a t m e n t , ideally, s h o u l d b e b a s e d o n k n o w n t r a n s m i s s i o n p a t t e r n s o f O. ostertagi. In m a n y areas, especially in the arid w e s t e r n states, a single t r e a t m e n t each y e a r m a y be a d e q u a t e with g o o d m a n a g e m e n t practices. In the m o r e central states, two or three strategic a n t h e l m i n t i c t r e a t m e n t s m o d i f i e d for each cattle m a n a g e m e n t o p e r a t i o n w o u l d s h o w p r o d u c t i o n benefits in b o t h adult a n d y o u n g cattle. REFERENCES Borgsteede, F.H.M., 1991. Further studies with a strain of Ostertagia ostertagi resistant to morantel tartrate. Int. J. Parasitol., 21: 867-870. Miller, J.E. and Olson, T., 1990. Critical evaluation of oxfendazole against inhibited larvae of Ostertagia ostertagi. Proceedings of the American Association of Veterinary Parasitology, 21-24 July, San Antonio, TX p. 41. Prichard, R.K., 1988. Anthelmintics and control. Vet. Parasitol., 27:97-109. Ranjan, S., Trudeau, C., Prichard, R.K., von Kutzleben, R. and Carrier, D., 1992. Efficacy of moxidectin against naturally acquired nematode infections in cattle. Vet. Parasitol., 41: 227231. Williams, J.C., 1986. Epidemiologic patterns of nematodiasis in cattle. In: H.C. Gibbs, R.P. Herd and K.D. Murrel (Guest Editors), The Veterinary Clinics of North America--Food Animal Practice. W.B. Saunders, Philadelphia, PA, Vol. 2 (2), pp. 235-246. Williams, J.C., 1991. Efficacy of albendazole, levamisole and fenbendazole against nematodes of cattle, with emphasis on inhibited early fourth stage Ostertagia ostertagi larvae. Vet. Parasitol., 40:59-71. Williams, J.C. and Knox, J.W., 1988. Epidemiology of Ostertagia ostertagi in warm temperate regions of the United States. Vet. Parasitol., 27: 23-38. Williams, J.C., Knox, J.W., Marbury, K.S., Swalley, R.A. and Eddi, C.S., 1991. Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January). Vet. Parasitol., 40: 7385. Williams, J.C., Loyacano, A.F., Nault, C., Ramsey, R.T. and Plue, R.E., 1992. Efficacy of abamectin against natural infections of gastrointestinal nematodes and lung worms of cattle with special emphasis on inhibited, early fourth stage larvae of Ostertagia ostertagi. Vet. Parasitol., 41: 77-84. Zimmerman, G.L. and Worley, D.E., 1990. Epidemiology of bovine nematode parasites in the northern United States. In: J. Guerrero and W.H.D. Leaning (Editors), Epidemiology of Bovine Nematode Parasites in the Americas. Proceedings of the MSD AGVET Symposium, 13-17 August, Salvador, Bahia, Brazil, Veterinary Learning Systems, Trenton, N J, pp. 8387.