Efficacy and safety of clorsulon used concurrently with ivermectin for control of Fasciola hepatica in Florida beef cattle

The safety and anthelmintic efficacy of clorsulon (7 mg/kg of body weight, orally) given concurrently with ivermectin (0.2 mg/kg, subcutaneously) for control of Fasciola hepatica were evaluated in 75 crossbred beef cattle. Twenty-three control animals were given only ivermectin. Fluke egg counts were significantly lower (P less than 0.0001) in clorsulon-treated animals by day 14 after treatment than before treatment (base line) and were significantly lower (P less than 0.005) after treatment in clorsulon-treated animals than in controls. There was no significant change in fluke egg counts of controls after treatment. The efficacy of clorsulon in reducing F hepatica egg counts was 99%. Clorsulon showed poor efficacy against paramphistomes. Adverse reactions were not observed.     

Comparative efficacy of clorsulon and albendazole against Fasciola hepatica in cattle

In a dosage-confirmation trial, anthelmintic activities of clorsulon and albendazole against Fasciola hepatica were evaluated and compared. Twenty-eight cattle (8 to 12 months old) with natural F hepatica infections were randomly allotted to 4 groups of 7 cattle each: group 1, no treatment (controls); group 2, clorsulon suspension given orally at 3.5 mg/kg of body weight; group 3, clorsulon suspension given orally at 7 mg/kg; and group 4, albendazole paste given orally at 10 mg/kg. At necropsies, performed 7 and 8 days after treatment, control cattle harbored a geometric mean of 133.2 F hepatica, 16.0 of which were immature. Clorsulon administered at 3.5 mg/kg or 7 mg/kg resulted in greater than 99% removal of F hepatica, including immatures. Albendazole treatment resulted in a 76% overall reduction in F hepatica, including a 91% reduction of immatures. Fascioloides magna also were found in the cattle, but neither clorsulon nor albendazole caused significant reductions of the parasite. Adverse reactions to the 2 drugs were not observed.     

Efficacy of clorsulon for the treatment of experimentally induced infections of Fasciola hepatica in goats

A dose titration study was undertaken to determine the efficacy of clorsulon against the adult stage of Fasciola hepatica in goats. Thirty-nine goats were experimentally infected with metacercariae of F hepatica. At 14 weeks after infection, each goat was assigned randomly to 1 of 5 groups. Goats in groups 1 to 4 received a single oral administration of clorsulon at dosages of 3.5, 7, 11, and 15 mg/kg of body weight, respectively. The fifth group of goats (control group) was infected with F hepatica, but were not treated with clorsulon. Postmortem examination of goats at 3 weeks after treatment revealed mean reductions in numbers of flukes of 83, 98, 99, and 100% for groups 1 to 4, respectively. Mean percentage of reduction in eggs following treatment of groups was 82, 98, 100, and 100%, respectively. The clinical effects of clorsulon in 24 goats that were not infected with F hepatica were studied. Goats in groups 1 to 3 received a single oral administration of clorsulon at dosages of 7, 21, and 35 mg/kg, respectively, every other day for a total of 3 doses/goat. Group-4 goats (control group) received a vehicle placebo. Goats in group 3 were subject to postmortem examination at 14 days after dosing. Abnormal signs or lesions that could be attributed to clorsulon were not found in any goat.     

Evaluation of clorsulon against immature Fascioloides magna in cattle and sheep

Efficacy of clorsulon was evaluated against infection with immature Fascioloides magna in 24 cattle and 12 sheep. Infections were induced by oral administration of 600 metacercariae/host. In cattle, clorsulon at dosages of 7 and 21 mg/kg of body weight was 65 and 100% effective against 8-week-old flukes, and 20 and 74% effective against 16-week-old flukes, respectively. In sheep, clorsulon at a dosage of 21 mg/kg was 92% effective against 8-week-old flukes. Significantly (P less than 0.05) more F magna were recovered from untreated sheep than from untreated cattle.     

The anthelmintic efficacy of netobimin against experimental infections of Fasciola hepatica in sheep

Netobimin (coded SCH 32481, Schering Corporation), a new broad-spectrum anthelmintic having both fasciolicidal and nematocidal properties was evaluated for efficacy against mature Fasciola hepatica infections in sheep. The trial was conducted with 30 cross-bred spring lambs, each experimentally infected with 250 F. hepatica metacercariae. A single treatment of netobimin was administered at 17 weeks post-infection (PI) by oral drench at 7.5 or 20 mg kg-1 body weight while 10 animals remained as untreated controls. At necropsy (either 1 or 2 weeks post-treatment), the mean number of adult flukes recovered from the control, 7.5 and 20 mg kg-1 groups were 94.7, 35.9 and 8.8, respectively. The resulting efficacies were 62% (P less than or equal to 0.05) and 90.7% (P less than or equal to 0.01), respectively. No clinical signs of fascioliasis were noted in any sheep during the trial. No signs of toxicosis nor any adverse reactions to the drug were observed.     

Efficacy of oral clorsulon in the treatment of Fasciola hepatica infections in calves

Twenty calves at each of 2 Arkansas locations were inoculated with infective Fasciola hepatica metacercariae. After 56 days, the calves at each site were randomly assigned by weight to 2 treatment groups of 10 calves/group; vehicle control or clorsulon at the rate of 7 mg/kg of body weight. All treatments were given orally as a suspension. Calves were killed 6 weeks after treatment and F hepatica counts were performed for all animals. At the 2 sites, mean levels of efficacy were 96% and 91%. Adverse reactions to clorsulon or the vehicle were not observed in the calves.     

Influence of ivermectin and clorsulon treatment on productivity of a cow-calf herd on the southern Oregon coast.

The reproductive performance of beef cows and the weight gain of their calves was evaluated after oral administration of clorsulon or clorsulon in combination with the subcutaneous administration of ivermectin. One hundred and fifty pregnant cows harboring infections of Fasciola hepatica were assigned to one of three treatment groups: Group 1 comprising 50 unmedicated controls; Group 2, 50 cows treated with clorsulon orally at 7 mg kg-1; Group 3, 50 cows treated with clorsulon orally at 7 mg kg-1 and ivermectin subcutaneously at 200 micrograms kg-1. Weights and body condition scores of the cows were measured and fecal and blood samples were taken at trial initiation and days 158 and 270. Pregnancy status was also determined at day 270. Weights and body condition scores were measured for the calves at days 158 and 270. Adjusted 205 day weaning weight of the calves was calculated and analyzed for differences between treatment groups. Four sets of tracer calves were used periodically throughout the trial to monitor the helminth challenge to the herd. Both gastro-intestinal nematodes and liver flukes were transmitted to the tracer calves during the entire trial. Even in the face of continual helminth challenge, beef cows treated with combined clorsulon/ivermectin conceived approximately 2 weeks earlier than their untreated counterparts and their calves had better body condition scores and weights than untreated calves.     

Prophylactic efficacy of clorsulon against Fasciola hepatica in calves and sheep

A daily oral 5 mg kg-1 dose of clorsulon for 28 days in calves given Fasciola hepatica cysts at 3, 5, and 7 days after initiation of treatment was highly effective in reducing worm burdens (98%) and preventing liver pathology. In similarly infected and treated sheep, clorsulon showed little effect as a prophylactic for delaying the onset of liver pathology. The size of flukes recovered from treated sheep was reduced. Although clorsulon prevented development of fascioliasis in treated calves, the host antibody response was qualitatively similar to that of untreated infected calves, but the magnitude of the response was reduced. Blood clorsulon levels in calves rose to 2.90 micrograms ml-1 within the first week of treatment then fluctuated between 2.65 and 2.90 micrograms ml-1 for the next two weeks. Clorsulon levels in sheep were 0.50-0.60 micrograms ml-1 lower than those in calf blood. The difference in bioavailability of clorsulon between sheep and calves may have contributed to differences in efficacy of the drug.     

Efficacy of concomitant early summer treatment with fenbendazole and clorsulon against Fasciola hepatica and gastrointestinal nematodes in calves in Louisiana

The efficacy, safety, and compatibility of fenbendazole (FBZ) and clorsulon (CLN) were tested after oral administration of label recommended and of higher (5x) dosage rates to calves naturally infected with gastrointestinal nematodes and Fasciola hepatica. Results for 42 calves allotted to 4 treatment groups indicated a similar efficacy against mature F hepatica by FBZ (5 mg/kg of body weight) and CLN (7 mg/kg) in a combined oral suspension, compared with CLN (7 mg/kg) alone (100 vs 99% reduction). A lesser efficacy was observed against immature flukes (88.6 and 84.9% reduction, respectively). Calves given 25 mg of FBZ/kg and 35 mg of CLN/kg had nearly complete reduction of both mature (99.6%) and immature flukes (99.1%). Fasciola egg counts were reduced by greater than 99.5% in all treated groups. Against Ostertagia ostertagi, the percentage of efficacy of the combined FBZ (5 mg/kg) and CLN (7 mg/kg) treatment was 94.3% against adults and 81.3% against inhibited larvae. Efficacy against all other nematodes was 100%, except against Cooperia spp adults (98.3%) and immature Oesaphagostomum radiatum (88.0%). At 5 x dosage rates for FBZ and CLN, percentage of removal of adults and inhibited larvae of O ostertagi was 99.3 and 99.0%, respectively, and 99 to 100% for other nematodes. Results indicate that FBZ and CLN are compatible when mixed together and administered as an oral suspension to cattle and that the efficacy is similar to that of the drugs individually. On the basis of further results, we suggest that summer treatment may be superior in preventive value for gastrointestinal nematodes and F hepatica, compared with spring treatment, because of seasonal infection dynamics of the major cattle parasites in Louisiana.     

Efficacy of clorsulon against Fascioloides magna infection in sheep

In a study to evaluate the efficacy of clorsulon against Fascioloides magna infection in sheep, 12 ewes were inoculated orally with 100 metacercariae of F magna, and 6 were treated with clorsulon (15 mg/kg of body weight) 8 weeks after inoculation. The sheep were euthanatized 16 weeks after inoculation, flukes were recovered, and the liver and other tissues were subjectively scored for the severity of lesions (0 to 4+). The number of flukes recovered from the clorsulon-treated group (3.8 +/- 1.2 flukes) was significantly (P = 0.025) lower than the number of flukes recovered from the group of untreated controls (10.0 +/- 6.6 flukes). The severity of lesions was significantly (P = 0.004) reduced (45.9%) in the treated group (2.0 +/- 1.1), compared with that in the untreated controls (3.7 +/- 0.5). In the untreated group, 3 sheep died and 1 became moribund 14 to 16 weeks after inoculation. The data suggested that a single treatment with clorsulon at a dosage of 15 mg/kg 8 weeks after inoculation was not effective in preventing F magna infection in sheep, because the survival of only a few F magna is potentially fatal in sheep within 6 months after infection.     

Field trial on comparative efficacy of four fasciolicides against natural liver fluke infection in cattle

A controlled trial was conducted to evaluate the current efficacy of albendazole (ABZ), rafoxanide (RFX), triclabendazole (TRC) or clorsulon (CLS) against Fasciola hepatica in naturally infected cattle. This trial was conducted in Turkey during the spring, the time of year when liver fluke infection is endemic. Fifty crossbred cattle were selected for inclusion in the trial based on finding eggs of F. hepatica in the feces. The cattle were weighed and randomly allotted into five groups of 10 cattle and treatments were as follows: Group 1 served as non-treated control (CONT), Group 2 was treated orally with ABZ at 12 mg/kg, Group 3 was treated orally with RFX at 10 mg/kg, Group 4 received TRC orally at 12 mg/kg and Group 5 received CLS administered subcutaneously (s.c.) at 2 mg/kg. On day 0 (inclusion day), individual fecal samples were collected on days 0 (inclusion day), 7, 14, 28 and 56, after treatment. The drug efficacy was assessed as a percentage of the egg or fluke reduction and body weight gain relative to the untreated control. The results in the study showed a mean reduction of egg counts by 66.7%, 68.2%, 78% and 84.2% in Groups 2-5, respectively. In conclusion, our results indicate that CLS is a highly effective compound for the treatment of F. hepatica in cattle under these field conditions.     

PREGNANCY IN SLAUGHTERED COWS IN NORTH-EASTERN AUSTRALIA

A total of 7495 postpuberal beef cows from herds in north Queensland and the Northern Territory were examined at abattoirs to define the extent of wastage due to the slaughter of pregnant cows. On the basis of examination of teeth most cows (57%) were considered mature (approximately 3.5 to 7 years) at slaughter; 14% were young (9 months to 3.5 years) and 29% were old (over 7 years). In herds where pregnancy diagnosis by rectal examination had not been used at time of culling, 71.6% of slaughtered cows were pregnant and 42% of these cows were in the second trimester. This high pregnancy rate was considered an important source of herd wastage. Pregnancy rate varied little with season, but the highest percentages of cows pregnant in the first and third trimesters were recorded in autumn and spring, respectively. Most cows found non-pregnant had active ovaries at time of slaughter. Anoestrus was observed to be most common in winter and in old cows. Lactational status was not recorded. Mean cold carcase weight of 4229 cows was 161 +/- 40 kg. Maximum carcase weight was observed in cows slaughtered at 4 to 6 years of age; old cows had the lowest carcase weight (147 +/- 31 kg) of the age groups considered. Highest (170 +/- 43 kg) and lowest (135 +/- 41 kg) carcase weights in relation to pregnancy or ovarian status were observed in non-pregnant/ovary-active and non-pregnant/anoestrus cows respectively. Carcase weight of cows in the third trimester (165 +/- 35 kg) was greater than in the second (161 +/- 35 kg) or first (157 +/- 36 kg) trimesters; difference between the first and third trimesters was significant (P less than 0.01).     

Evaluation of the comparative efficacy of a moxidectin plus triclabendazole pour-on solution against adult and immature liver fluke, Fasciola hepatica, in cattle

The objective of this study was to evaluate the efficacy of a pour-on solution containing moxidectin plus triclabendazole (MOX plus TCBZ) against immature and adult stages of the liver fluke in cattle and compare the efficacy with other commercially available preparations. To this end, 104 male Holstein-Friesian calves aged between 3 and 4 months, were randomly allocated to 13 groups of eight animals each, and infected with approximately 500 Fasciola hepatica metacercariae. One group remained untreated, four groups were treated with MOX plus TCBZ at a dose rate of 0.1mL/kg, four other groups were treated with ivermectin (IVM) plus clorsulon injectable at a dose rate of 0.02mL/kg, and the remaining four groups were treated with IVM plus closantel pour-on at a dose rate of 0.1mL/kg. Each treatment was applied to one of the groups at 4 weeks, 6 weeks, 8 weeks and 12 weeks after the experimental infection. At necropsy (99-102 days after infection), all untreated animals were infected with a minimum of 30 flukes. The MOX plus TCBZ treated animals had significantly (P<0.0001) lower fluke counts compared to the untreated control animals at all time points after treatment. Efficacy against 8-week old and adult flukes was >99.5%. For 6-week old immature fluke, the efficacy was 98.0% and for 4-week old immature fluke the efficacy was 90.9%. The IVM plus closantel pour-on treated animals had significantly lower fluke counts compared to the untreated control animals for adult and 8-week old flukes (P<0.0001), and for 6-week old flukes (P=0.002). The efficacy was 26.8%, 68.2%, 90.6% and 99.3% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. The IVM plus clorsulon treated animals had significantly lower fluke counts compared to the untreated control animals for adult (P<0.0001) and 8-week old (P<0.05) flukes. The efficacy was 29.7%, 43.4%, 53.2% and 99.2% against 4-week, 6-week and 8-week old immature flukes, and adult flukes respectively. For treatments at 4, 6 and 8 weeks after infection, the fluke counts were significantly (P<0.0001) lower for the MOX plus TCBZ treatment than for IVM plus closantel or IVM plus clorsulon. The results confirm the high efficacy (>90%) of the MOX plus TCBZ pour-on combination against 4-week old to adult liver fluke in cattle. The IVM plus closantel pour-on combination was effective (>90%) against 8-week old and adult flukes, but had low efficacy against 4- and 6-week old fluke. The IVM plus clorsulon injectable combination was effective (>90%) against adult fluke only.     

Efficacy of albendazole for prevention of fascioliasis in sheep

Daily doses of albendazole administered as a premix in the feed for 35 days were effective in preventing Fasciola hepatica infections in 17 sheep in three groups: 5 mg/kg/day (6 sheep) was 100% effective; 3 mg/kg/day (5 sheep) was 98% effective; and 1 mg/kg/day (6 sheep) was 42% effective. Infective cysts were given daily for 5 days during the first week of treatment, treatment was continued an additional 28 days, and sheep were necropsied 14 weeks after final cyst inoculation. There were no visible lesions in any livers of sheep given albendazole at the rate of 5 mg/kg/day or in three of five livers of sheep dosed at the rate of 3 mg/kg/day. Sheep treated with albendazole had a mean weight gain of 2.7 kg, 4.0 kg, and 4.0 kg greater than the controls for the dosages of 1, 3, and 5 mg/kg/day, respectively. Determination of bile duct damage by measurement of serum gamma-glutamyl transpeptidase activity at 9 weeks after final cyst inoculation revealed increases of 3.0X, 1.0X, and 1.1X for the dosages of 1, 3, and 5 mg/kg/day, respectively, and 2.3X for the control, as compared with 7 weeks after final cyst inoculation.     

The efficacy of triclabendazole and other anthelmintics against Fasciola hepatica in controlled studies in cattle

In eight controlled tests 274 cattle were used to assess the efficacies of triclabendazole, albendazole, clorsulon, nitroxynil, oxyclozanide and rafoxanide against Fasciola hepatica. Against one-, two- and four-week-old early immature fluke the mean efficacies of triclabendazole given orally at 12 mg/kg were 88.1, 95.3 and 90.7 per cent, respectively. Clorsulon, nitroxynil and rafoxanide administered at recommended dose rates showed negligible activity against these stages of the parasite. Against six- and eight-week-old infections the mean efficacies of triclabendazole at 12 mg/kg were 87.5 per cent and 95.7 per cent, respectively. Against F hepatica aged six weeks, albendazole and oxyclozanide showed no activity and clorsulon, nitroxynil and rafoxanide had only slight to moderate activity. The efficacies of triclabendazole, clorsulon, nitroxynil and rafoxanide against 10- or 12-week-old parasites were 100, 99.0, 99.1 and 90.1 per cent, respectively. Albendazole and oxyclozanide showed poor efficacy against 12-week-old infections.     

Clorsulon pharmacokinetics in sheep and goats following oral and intravenous administration

Clorsulon was measured in plasma and urine of sheep and goats after administration of a single intravenous (i.v.) and after a single oral dose of 7 mg/kg. A three-compartment model with elimination occurring from the central compartment was determined to best describe the i.v. data, whereas a one-compartment model with a single exponential absorption phase best described the oral plasma data. The bioavailability of orally administered clorsulon was approximately 55% in goats and 60% in sheep. Peak plasma concentrations occurred at 14 h and 15 h after oral administration in goats and sheep, respectively. Absorption from the gastro-intestinal tract effectively prolonged the elimination of clorsulon by increasing the elimination half-life from 17 to 28 h in sheep and from 12 to 23 h in goats for the i.v. and oral routes, respectively. In both goats and sheep, approximately 50% of the i.v. dose was recovered in urine as parent drug at 48 h after administration, whereas 41% and 30% of the dose was recovered after oral administration for goats and sheep, respectively. The elimination rate constant (kel) in goats was nearly twice as large as the value determined in sheep, and the urea under the i.v. plasma curve in goats was only 63% of the value in sheep indicating that goats are more effective in their capacity to eliminate clorsulon than are sheep. These differences in drug disposition between sheep and goats may account for the reduced efficacy of clorsulon reported in goats.     

Efficacy of clorsulon and albendazole against Fascioloides magna in naturally infected white-tailed deer

The efficacy of clorsulon and of albendazole against Fascioloides magna were evaluated in 36 naturally infected white-tailed deer (Odocoileus virginianus) in southern Texas. A single oral dose of clorsulon suspension (12 to 30 mg/kg of body weight; mean = 24 mg/kg) was given to each deer and killed 153 (92%) of 167 mature flukes and 4 (80%) of 5 immature flukes recovered at necropsy. A single oral dose of albendazole paste (17 to 46 mg/kg; mean = 26 mg/kg) was given to each deer and killed 148 (89%) of 167 mature flukes and 4 (67%) of 6 immature flukes recovered at necropsy. In 82 nontreated control deer, 271 live flukes were recovered; dead flukes were not recovered.     

Effects of naloxone on ad libitum intake and plasma insulin, glucose, and free fatty acids in maintenance-fed sheep

The dose-dependent effects of naloxone on feed intake, and plasma chemicals (insulin, glucose, FFA) purportedly involved in feed intake regulation, were determined in 16-hr fasted sheep that were lean and chronically fed maintenance. Dorset ewes (n = 5) were treated with 0 (saline), 0.3, 1 or 3 mg/kg of naloxone in a generalized randomized block experiment with at least 7 d between successive doses. Feed intakes and plasma insulin, glucose and FFA were determined frequently during 24 hr of ad libitum intake after each naloxone treatment. The 0.3, 1 and 3 mg/kg doses of naloxone reduced (P less than 0.01) the 4-hr feed intake by 30, 40, and 60% respectively, whereas the initial feed intake (10 min) was decreased (P less than 0.05) 45% only by 3 mg/kg naloxone. However, total 24-hr intakes were similar across all doses because intakes between 4 and 24 hr of feeding in sheep treated with 0.3 (839 g), 1.0 (802 g) and 3.0 (1330 g) mg/kg naloxone exceeded (P less than 0.01) that in saline-treated sheep (391 g). Feeding-induced changes in plasma insulin, glucose and FFA concentrations were independent of naloxone treatment, suggesting that endorphinergic control of feed intake may not involve coincidental changes in plasma insulin, glucose and FFA levels which are thought to play a role in systemic regulation of appetite in animals. The endorphinergic regulation of appetite in sheep may involve the central nervous system, rather than peripheral opiate mechanisms that utilize blood-borne signals. Further, the ability of naloxone to suppress appetite in sheep appears inversely related to the duration of fasting or severity of negative energy balance.     

Bovine corpus luteum regression and estrous response following treatment with alfaprostol

Two trials evaluated bovine corpus luteum (CL) regression and estrous response following treatment with alfaprostol (AP), a prostaglandin F2 alpha analogue. Expression of at least one estrous cycle (16 to 26 d) and a palpable mid-cycle CL were required prior to random assignment of females to receive 0, .38, .75, 1.50 or 2.25 mg AP/100 kg body weight. Alfaprostol was evaluated in Brahman cows and heifers that were treated on d 11 to 13 (trial 1) and in Simmental X Brahman-Hereford (crossbred) heifers that were treated on d 8 to 10 or d 11 to 13 of the estrous cycle (trial 2). In trial 1, Brahman heifers appeared to require a higher AP dose (greater than .38 mg/100 kg body weight) to elicit luteolysis and expression of estrus than Brahman cows. Alfaprostol treatment (greater than or equal to .75 mg/100 kg body weight) induced (P less than .0001) luteolysis followed by estrus in Brahman cows and heifers. In trial 2, crossbred heifers that received AP on d 8 to 10 appeared to require a higher dose of AP (greater than .38 mg/100 kg body weight) to elicit luteolysis and estrus than heifers that received AP on d 11 to 13 of the estrous cycle. Alfaprostol treatment greater than or equal to .75 mg/100 kg body weight on d 8 to 10 and d 11 to 13 of the estrous cycle induced (P less than .0001) luteolysis followed by estrus in crossbred heifers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chemoprophylaxis of fascioliasis with triclabendazole

In a field experiment, moderate to heavy natural concomitant infections with immature and mature Fasciola hepatica were treated with triclahendazole at a dose rate of 10 mg/kg and an efficiency of 99.8% was achieved. Subsequent treatments of all susceptible farm animals at the same dose rate at intervals of eight to eleven weeks were carried out for 14 months; no patent infections could be detected in sheep and cattle during the whole period. Evidence is presented that pasture contamination with liver fluke was reduced to a negligible level for a further 12 months after the final treatment. It is suggested that, if regular treatments with triclabendazole are given within the pre-patent period of Fasciola hepatica infection for the whole season, the infection can be eradicated or reduced to such a low level that control of the disease could be maintained with less frequent strategic drenching for a considerable period.