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.     

Comparison of the activity of some fasciolicides against immature liver fluke in calves

The anthelmintic activities of nitroxynil, closantel and rafoxanide were tested in cattle against six- and eight-week-old infections of Fasciola hepatica. Administered by subcutaneous injection, nitroxynil and rafoxanide at dose rates of 10 and 3 mg/kg bodyweight respectively were 88.5 and 36.1 per cent effective in eliminating a six-week-old infection of F hepatica and 85.8 and 60.4 per cent effective against an eight-week-old infection. Closantel administered by intramuscular injection at a dose rate of 2.5 mg/kg bodyweight was 60.0 per cent effective against an eight-week-old F hepatica infection.     

Comparative efficacy of closantel and triclabendazole against Fasciola hepatica in experimentally infected sheep

The effect of closantel (10 mg/kg orally) and triclabendazole (10 mg/kg orally) on the reappearance of a patent infection of Fasciola hepatica was studied in experimentally infected sheep. The treatments resulted in the interruption of faecal egg output for 11 weeks with triclabendazole and 13 weeks with closantel. Necropsy of untreated control animals revealed a mean burden of 360 flukes with a mean (+/- se) surface area of 171 +/- 64.3 mm2, whereas the fluke burdens in the closantel and triclabendazole-treated animals 14 weeks after treatment were 61 (83 per cent reduction) and 21 (94 per cent reduction), respectively. The surface areas of the flukes in the triclabendazole-group were comparable with the untreated controls (141 +/- 51.8 mm2), but the flukes in the closantel group were markedly smaller (43.1 +/- 26.9 mm2). It is concluded that closantel has, in epidemiological terms, a potency comparable with that of triclabendazole, despite its slightly lower efficacy against the very immature stages.     

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.     

An evaluation of the efficacy of netobimin against Dicrocoelium dendriticum in sheep

A trial was carried out to assess the efficacy of a nitrophenylguanidine compound, netobimin against Dicrocoelium dendriticum in naturally infected sheep. At a dose rate of 20 mg/kg bodyweight administered orally the drug was highly effective, producing a mean reduction of 98.9 per cent in the fluke burdens of treated animals compared with untreated controls. No side effects were observed in the treated sheep.     

The activity of triclabendazole against immature and adult Fasciola hepatica infections in sheep

SUMMARY The efficiency of a new benzimidazole anthelmintic, triclabendazole, was tested against cumulative infections with Fasciola hepatica aged 1 to 12 weeks in sheep and compared with that of rafoxanide. At 10 mg/kg, triclabendazole was 99% effective in eliminating both immature and adult flukes. At a lower dose rate of 5 mg/kg, triclabendazole was highly effective against adults and significantly reduced the number of early immature flukes with an 87% overall reduction of fluke burden. Rafoxanide at 7.5 mg/kg showed high efficiency against adult fluke, but its effect on immatures was not significant, and overall efficiency was 64%.     

THE EFFICIENCY OF CLIOXANIDE AND RAFOXANIDE AGAINST FASCIOLA HEPATICA IN SHEEP BY DIFFERENT ROUTES OF ADMINISTRATION

Groups of sheep were infected with 100 viable metacercariae of Fasciola hepatica. The efficiencies of clioxanide and rafoxanide were evaluated against infections aged 6 and 12 weeks, by using 3 dose rates of each compound by each of 3 routes of administration. Clioxanide, at 40 mg/kg, administered orally and intra-ruminally against 6-week-old liver fluke was 85 and 90% efficient respectively. At 80 mg/kg intra-abomasally its efficiency was 43%. Clioxanide at 20 mg/kg was 96% efficient against 12-week-old liver fluke when given orally or intra-ruminally and 82% efficient when given intra-abomasally. Because of its lower efficiency intra-abomasally, clioxanide may be unsatisfactory in a proportion of sheep, for use against immature liver fluke at a dose rate of 40 mg/kg. It may be expected to give a moderate to high efficiency against mature infections at 20 mg/kg.     

The efficacy of triclabendazole (Fasinex) against immature and adult Fasciola hepatica in experimentally infected cattle

Eighteen Chinese cattle were experimentally infected with metacercariae of Fasciola hepatica and randomly assigned to 6 groups. Five groups of cattle were treated with a single oral dose of triclabendazole at a dose rate of 12 mg kg-1. At necropsy, the reduction in fluke burden compared with the untreated group was 85, 99.6, 99.8, 100 and 100% for cattle treated 2, 6, 8, 12 and 16 weeks after infection, respectively. Data are also presented on body weight changes during the experimental period and on serum gamma-GT activity in cattle from selected groups. Triclabendazole is considered to be safer and more efficacious than currently available fasciolicides in China.     

Treatment of Fasciola hepatica infection in horses with triclabendazole

Thirteen thoroughbred foals with an adult infection and a presumed immature infection with Fasciola hepatica were treated with 12 mg triclabendazole/kg bodyweight. The absence of eggs from samples of faeces examined at intervals up to 110 days after treatment showed that all the animals were cured. In a second trial the same dose of triclabendazole cured 11 of 12 foals whereas nitroxynil at 7 mg/kg cured only six of 12 foals. No side effects were observed after treatment.     

Experiments on anthelmintic control of Fasciola hepatica in Brazil.

Two separate field trials involving naturally infected cattle were carried out on two farms known to have a history of Fasciola hepatica infection. On the first farm, 15 animals per group were allocated as follows: G1, triclabendazole (TCBZ) four times a year; G2, TCBZ twice a year (May and September); G3, untreated control. All groups grazed together and after 3.5 years the animals were slaughtered and their livers examined by federal meat inspectors who condemned 100% of livers in G3 and 8.3% in G2 owing to the presence of lesions of fasciolosis. In G1 no livers were condemned. Significant differences in weight gains were not detected and fluke counts remained at low levels in the treated groups. Also, in the control group, egg counts started to decrease when animals were 2 years old. On the second farm, groups of 20 animals were treated as follows: G1, TCBZ three times a year (May, September and December); G2, TCBZ twice a year (May and September); G3, nitroxynil twice a year (May and September); G4, rafoxanide twice a year (May and September); G5, untreated controls. All animals were weighed and faecal samples examined at approximately 28-day intervals. During the period of the study, larger weight gains were detected in the TCBZ treated groups than in the others. TCBZ treatment kept F. hepatica egg counts at a lower level for longer periods than the other drugs and significant differences in weight gains were only obtained between the group receiving TCBZ three times a year and the control group.     

Chemoprophylaxis of fascioliasis with triclabendazole

In a field experiment, moderate to heavy natural concomitant infections with immature and mature Fasciola hepatica were treated with triclabendazole 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.     

Efficacy of a novel sustained release anthelmintic device in preventing parasitic gastroenteritis in first-season calves

The efficacy of the first of a new generation of intraruminal devices for cattle, the morantel sustained release trilaminate, was assessed in two field trials. In each trial the animals were divided into a control group and a treated group. The device was administered to each calf before turn out in the spring and the reduction of gastrointestinal parasitism resulted in a substantial reduction in the level of pasture contamination with infective helminth larvae later in the season. Compared with the control calves the treated calves had a 94 per cent reduction of worm burdens acquired over the entire grazing season in the first trial, despite the controls being treated for clinical disease in September. In the second trial four anthelmintic treatments were administered to the control calves during the grazing season, but nevertheless a 64 per cent reduction of worm burdens in the treated group compared to the control group was recorded. The control of parasitic infection by the sustained-release devices resulted in mean weight gain advantages of 28.3 kg and 34.7 kg by the treated animals in the first and second trials respectively.     

Chemotherapy of paramphistornosis in sheep

Controlled trials were used to assess the efficacy of various anthelmintics against immature and adult paramphistomes in 75 experimentally or naturally infected sheep. Albendazole (20 mg/kg), praziquantel (10 mg/kg), nitroxynil (10 mg/kg) triclabendazole (10 and 100 mg/kg), profenophos (25 mg/kg) and netobimin (15 mg/kg) had little or no activity against adult or immature fluke. Niclosamide at 100 mg/kg had high efficacy (99%) against intestinal fluke but none against adult fluke. A 2- tertiary-butyl benzthiazole compound (CGA 72630) at 25 mg/kg and resorantel at 65 mg/kg had very high efficacy against both adult and immature fluke in the rumen and small intestine respectively. The efficacy of other anthelmintics which have been used against paramphistomes in sheep is reviewed.     

Efficacy against Fasciola hepatica and the pharmacokinetics of triclabendazole administered by oral and topical routes

Objective   To determine the efficacy of triclabendazole (TCBZ) against 28-day-old, early immature liver fluke in cattle and its pharmacokinetics following administration by the oral or topical (pour-on) route.
Procedures   Cattle (n = 18) were infected with 500 TCBZ-susceptible liver fluke metacercariae and randomly allocated to three groups. At 28 days after infection, the groups were: (1) untreated controls; (2) treated with oral TCBZ at 12 mg/kg in combination with oxfendazole and selenium (TOS); (3) treated with pour-on TCBZ at 30 mg/kg in combination with abamectin (TA). Blood samples were taken immediately prior to treatment and serially after treatment to assess the plasma profile of TCBZ metabolites. Ten weeks after treatment all animals were slaughtered and total liver fluke counts, fluke egg counts and liver pathology were assessed.
Results   Both the TOS and TA treatments resulted in significant reductions of 28-day-old liver fluke, as assessed by fluke counts and fluke egg counts at slaughter, and the reductions following TOS treatment were significantly greater than those following TA treatment. The blood profile of TCBZ metabolites in TOS-treated animals showed a significantly greater area under the plasma concentration time curve and a higher maximum observed concentration than those treated with TA. There was significantly less liver pathology in TOS-treated animals than in the TA-treated animals.
Conclusion   TCBZ administered orally at 12 mg/kg resulted in greater efficacy against 28-day-old, early immature liver fluke than was achieved by topical administration at 30 mg/kg. Plasma metabolites of TCBZ were higher and liver pathology was less in TOS-treated animals than in TA-treated animals.     

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.     

Efficacy of mebendazole against Dictyocaulus arnfieldi in the donkey.

In a controlled trial in naturally infected donkeys the efficacy of mebendazole against Dictyocaulus arnfieldi infection was evaluated. A powder formulation of mebendazole given orally at a dosage rate of 4.3 to 5.7 mg per kg per day for five days had no apparent effect on existing lungworm burdens. However a paste formulation of mebendazole given orally at a higher dosage rate of 15.2 to 20.0 mg per kg per day for five days was 75 to 100 per cent effective in the removal of lungworms from individual animals.     

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.     

Failure of oral zinc therapy to alleviate Bacteroides nodosus infections in cattle and sheep

Cattle and sheep with Bacteroides nodosus infection were treated orally with both high (65 mg Zn/kg and 82 mg Zn/kg) and low (1 mg Zn/kg and 8.6 mg Zn/kg) doses of zinc sulphate respectively. The lower dose rates administered weekly for one month, in the case of cattle, or daily for 2 weeks, in the case of sheep, had no effect either on serum zinc levels or the prevalence or severity of infection in treated animals. High dose rates of zinc (approximately 2.5 g Zn per head per day) were required to elevate serum levels above those normally present in both cattle and sheep. Even these dose rates continued daily for about 2 weeks had no beneficial effect on B. nodosus infection in either species.     

Comparison of the efficacy of dermal formulations of ivermectin and levamisole for the treatment and prevention of Dictyocaulus viviparus infection in cattle

Four groups of six parasite-naive calves were infected at seven day intervals with three doses of infective larvae of Dictyocaulus viviparus. Twenty-one days after the first dose three of the groups were treated either with an injectable formulation of ivermectin at a dose rate of 200 micrograms/kg bodyweight, or with pour-on preparations of levamisole at 10 mg/kg or ivermectin at 500 micrograms/kg. On day 28 two calves from each group were slaughtered and their burdens of lungworms counted. On day 35 the remaining calves were reinfected with D viviparus infective larvae at a rate of 80 L3/kg. The levamisole preparation was 94.6 per cent effective and both ivermectin preparations were 100 per cent effective against the initial infections. The ivermectin-treated calves were protected from the reinfection which subsequently became patent in the levamisole-treated and control calves.     

Enhancement of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica by co-treatment with ketoconazole

An in vivo study in the laboratory rat model was carried out to monitor morphological changes in adult Fasciola hepatica over a 4-day period resulting from combination treatment of triclabendazole (TCBZ) and the metabolic inhibitor, ketoconazole (KTZ). Rats were infected with the TCBZ-resistant Oberon isolate of F. hepatica and divided into 3 groups at 12 weeks post-infection. The first group was dosed orally with TCBZ at a dosage of 10mg/kg and KTZ at a dosage of 10mg/kg. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.). A second group of rats was treated with TCBZ alone (10mg/kg) and sacrificed at 96 h p.t. The third group acted as untreated controls. Surface changes were monitored by scanning electron microscopy (SEM). In flukes from the TCBZ+KTZ-treated group, the results showed a progressive and time-dependent increase in the level of disruption to the tegumental syncytium. Swelling, furrowing, blebbing and sloughing of the syncytium increased with time p.t. Another feature seen was a thick layer of tegumental shedding in some fluke samples at different times p.t. By comparison, flukes treated with TCBZ alone remained unaffected. The results demonstrated that the Oberon isolate is only sensitive to drug action in the presence of ketoconazole, indicating that combining triclabendazole with a metabolic inhibitor could be used to preserve the effectiveness of the drug against TCBZ-resistant populations of F. hepatica.