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%.     

Intraruminal controlled release of cyromazine for the prevention of Lucilia cuprina myiasis in sheep

The efficacy of cyromazine, continuously released from intraruminal capsules at dose rates from 0.5 to 2 mg kg-1 d-1, was evaluated against implants of eggs and first instar larvae of Lucilia cuprina on Merino sheep. Estimates from the non-linear relationship between the success of implants and plasma concentrations showed that 95 per cent protection of sheep could be achieved at a mean release rate of 1.39 mg kg-1 d-1 cyromazine which gave rise to a mean plasma concentration of 0.26 mg litre-1. Present formulations allowed protection for about 90 days in a 40 kg sheep. The 'square wave' type of release profile provided negligible suboptimal dosing thus limiting the potential for selection of resistance. Systemic application of cyromazine provides control of covert and overt strike among sheep and could be used in ecologically based strategies for the control of L. cuprina populations.     

Intravascular plasma disposition and salivary secretion of closantel and rafoxanide in sheep

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(alpha)) of <30 min), long elimination half-life (t1/2(beta)) of 17.0 +/- 4.0 days for closantel and 7.2 +/- 0.6 days for rafoxanide), small apparent volume of distribution (V(SS) of <0.15 l/kg) and a slow rate of total body clearance (Cl of <0.01 ml/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(beta) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(alpha)), whereas the parameters of elimination (k10, t1/2(beta) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04 +/- 0.05 microg/mL) and rafoxanide (mean of 0.07 +/- 0.04 microg/mL) was observed during the 24-h examination period after dosing.     

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.     

Flukicidal action of closantel against immature and mature Fasciola hepatica in experimentally infected rats and sheep

The relative importance of peak level- and residual level-related flukicidal activity of closantel against immature and mature Fasciola hepatica was evaluated in a comparative efficacy trial using two animal species with a different plasma elimination pattern, that is, the rat and the sheep with an elimination half-life of less than one week and of two to three weeks, respectively. The rats were dosed orally with closantel at 20 mg kg-1 at two, four, six, eight and 10 weeks; the sheep at 10 mg kg-1 at eight, 10 and 12 weeks after artificial infection. Necropsy was performed either one week after treatment or 12 weeks after infection. Efficacy rates and the length of the recovered flukes were evaluated. It was demonstrated that the flukicidal effect of closantel is directly related to its peak plasma levels and less to its residual plasma concentrations. In the rat, a high efficacy (P less than 0.001) could be demonstrated against immature stages of four weeks or older. The two-week immature stages were less markedly affected. No significant differences in efficacy and size of the flukes were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection. In the sheep, the efficacy against six-week and eight-week-old immature stages varied between 70.3 and 76.8 per cent and between 92.8 and 96.5 per cent, respectively. As in the rats, no marked differences in efficacy were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Disposition of oxfendazole in goats and efficacy compared with sheep

The disposition of intraruminally administered oxfendazole (OFZ) in goats was studied at 5, 10 and 20 mg kg-1. The area under the plasma concentration with time curve (AUC) increased with increasing dose but at a declining rate. AUC was lower after intra-abomasal compared with intraruminal administration. OFZ was less effective against drug resistant Trichostrongylus colubriformis in goats than in sheep but was of similar efficacy against drug resistant Haemonchus contortus in both host species. In the same experiment peak plasma levels of OFZ in goats were about half those in sheep given the same dose. Of 70 goats tested in the field, total rumen bypass occurred in 12 per cent and partial bypass in 67 per cent. Lower systemic availability due to bypass would be expected to reduce further anthelmintic efficacy in goats. From the results of these experiments a dose rate of 10 mg kg-1 is recommended for goats. When given at this rate as a divided dose at 12 hourly intervals over 24 hours, OFZ was significantly more effective than a single dose in reducing egg counts.     

Relative bioavailability of rafoxanide following intraruminal and intra-abomasal administration in sheep

The bioavailability of rafoxanide was compared after intraruminal and intra-abomasal administration in healthy adult sheep (n = 6) in a single dose, 2 parallel group study at 7.5 mg/kg. Rafoxanide concentrations in plasma were measured by means of HPLC analysis. Primary pharmacokinetic parameters for bioavailability and disposition of rafoxanide in plasma for both routes of administration were determined by non-compartmental and non-linear, 1-compartmental pharmacokinetic analysis, respectively. Significantly (P < or = 0.05) higher peak plasma concentrations (c(max)) of rafoxanide and a more rapid rate of absorption (c. 3.5 times) was observed in sheep after intra-abomasal (i-a) administration compared to intraruminal (i.r.) administration. A significantly (P < or = 0.05) longer lag period (t(lag)) before absorption (6.8 +/- 2.9 h) occurred after i.r. than after i-a treatment (1.9 +/- 0.6 h). There was no significant difference (P > 0.05) in AUC, MRT and in the rates of elimination (k10-HL and t(1/2beta)) between the i.r. and i-a routes of administration. The results of the study demonstrated the important influence of the rumino-reticulum on absorption of rafoxanide in sheep.     

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.     

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 a substituted methyl benzimidazole carbamate against developing and adult helminth parasites

The efficacy of a substituted methyl benzimidazole carbamate, methyl 5(6)-[4-N-(2-pyridyl)] piperazino carbamoyl benzimidazole-2-carbamate, was assessed against larval and adult forms of Ancylostoma ceylanicum (hookworm), Nippostrongylus brasiliensis (trichostrongylid), Hymenolepis nana (tapeworm) and Brugia malayi (filariid) in experimentally-infected animals. The compound was found to have high efficacy against the developing stages (L3, L4, L5) of A. ceylanicum in hamsters at a single dose of 12.5 mg kg-1, against larvae of N. brasiliensis at 17.5 mg kg-1 and against cysticercoids of Hymenolepis nana at 100 mg kg-1 daily for 3 days given per os (p.o.) or intraperitoneally (i.p.). All the stages of B. malayi in Mastomys were killed when the compound was given i.p. at a dose of 6.25 mg kg-1 for 5 consecutive days. A dose of 6.25 mg kg-1 eliminated all adult A. ceylanicum from infected hamsters, 100 mg kg-1 resulted in complete removal of Syphacia obvelata adults from 63.6% of infected mice, 25 mg kg-1 X 5 dose eliminated 100% of adult B. malayi from infected Mastomys and a single 50 mg kg-1 dose expelled all H. nana adults from infected rats.     

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.     

Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.     

Anthelmintic efficacy of febantel paste in naturally infected calves

The purpose of the present study was to verify results of the lowest dose (5 mg kg-1) of febantel evaluated in an earlier trial in which there were no differences in efficacies of three dose rates (5, 7.5 and 10 mg kg-1 body weight) against natural gastrointestinal nematode infections of cattle. Fourteen Angus calves (mean weight and age of 155 kg and 525 days, respectively), from the same farm, with relatively heavy (mean of 448 eggs g-1 feces (epg] parasite burdens were selected. After an adjustment period of 8 days in drylot, beginning on 25 July, seven calves were treated with a 45.5% paste formulation of febantel. On Day 7 post-treatment, calves were necropsied for determination of residual worms. Rectal fecal samples were obtained prior to adjustment, at treatment, 5 days post-treatment and at necropsy. On both Day 5 post-treatment and at necropsy a mean of less than 1 epg was recovered from treated calves compared with 765 and 1566 epg, respectively, in control calves. Worms counts at necropsy revealed an efficacy of 98.5% against all adult abomasal worms (Haemonchus placei, 100%, P less than 0.02; Trichostrongylus axei, 99.4%, P less than 0.0001; Ostertagia ostertagi, 90.5%, P less than 0.0002). Treatment was 100% efficacious against adult small and large intestinal worms. However, numbers of Bunostomum phlebotomum, O. radiatum and Trichuris spp. recovered in the control calves were too low to enable a reliable test of drug efficacy. Treatment was not effective against either mucosal or luminal fourth stage larvae of abomasal O. ostertagi.(ABSTRACT TRUNCATED AT 250 WORDS)     

国产三氯苯咪唑驱除山羊肝片形吸虫效果试验

以国产三氯苯咪唑对自然感染肝片形吸虫的山羊进行了驱虫试验，并以硝氯酚为药物对照。结果表明，三氯本咪唑5mg/kg体重的剂量对肝片形吸虫成虫和童虫的驱虫率分别为99.3%和92.9%，驱净率为75％；三氯苯咪唑10mg/kg体重的剂量对肝片形吸虫成虫和童虫的驱虫率均为100％，驱净率为100％；硝氯酚5mg/kg体重剂量对肝片形吸虫成虫驱虫率为100％，但对童虫的仅为74.3%，而驱净率仅为60％。在整个试验期间试验羊均无不良反应。     

Efficacy, toxicity and metabolism of imidocarb dipropionate in the treatment of Babesia ovis infection in sheep

An intramuscular dose of 1.2 mg kg-1 of imidocarb dipropionate (IMDP) was effective in controlling fatal infections with Babesia ovis in sheep. The sheep were infected by the intravenous injection of sheep blood containing B ovis. A severe recrudescence of infection occurred in most sheep 10 to 14 days after therapy but this could be controlled by a second dose of 1.2 mg kg-1 IMDP. Studies on the toxicology, residues and metabolism of IMDP showed this to be a safe dosage regimen. Transient or mild signs of toxicity were seen at 2.4 and 4.8 mg kg-1 IMDP. Severe toxicity was observed in sheep treated with 9.6 mg kg-1.     

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.     

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.     

THE ANTHELMINTIC EFFICACY OF NON-BENZIMIDAZOLE ANTHELMINTICS AGAINST BENZIMIDAZOLE RESISTANT STRAINS OF HAEMONCHUS CONTORTUS AND TRICHOSTRONGYLUS COLUBRIFORMIS IN SHEEP

The anthelmintic efficacy of 6 non-benzimidazole compounds and thiabendazole against standardised, benzimidazole resistant strains of H. contortus and T. colubriformis in sheep was determined using a controlled test. All compounds were administered intraruminally at their recommended therapeutic dose rates and 4 of the compounds were also assessed at half their recommended therapeutic dose rates. Levimisole at a dose of 6.4 mg/kg body weight, morantel at 4.4 mg/kg and 8.8 mg/kg, naphthalophos at 6.25 mg/kg and 12.5 mg/kg, rafoxanide at 7.5 mg/kg and phenothiazine at 530 mg/kg were 98% or more effective in removing adult infections of benzimidazole resistant H. contortus. Rafoxanide at 3.75 mg/kg, phenothiazine at 265 mg/kg and carbon tetrachloride at 0.05ml/kg were less effective, removing 80%, 73% and 72% respectively of the benzimidazole resistant H. contortus worm burdens. Against the benzimidazole resistant T. colubriformis levamisole at 6.4 mg/kg, and morantel at 4.4 mg/kg and 8.8 mg/kg removed 99%, 68% and 86% respectively of the adult infections. All other anthelmintics had little or no efficacy at the dose rates tested. Thiabendazole at 44 mg/kg had no significant effect against these strains of H. contortus and T. colubriformis. Several non-benzimidazole anthelmintics have shown high efficacy in this experiment and should be suitable for treating infections with benzimidazole resistant H. contortus. Of the anthelmintics tested, only levamisole and morantel show high efficacy against benzimidazole resistant T. colubriformis.     

EFFECTS OF A PREVENTIVE AND SUPPRESSIVE CONTROL SCHEME ON THE DEVELOPMENT OF THIABENDAZOLE-RESISTANCE IN OSTERTAGIA SPP

SUMMARY Three years after the start of an experiment to assess the merits of thiabendazole (TBZ) treatment of trichostrongylid parasites in weaner sheep, field isolates of Ostertagia spp and Trichostrongylus spp were made from weaner sheep treated under one of three treatment schemes. Treatment frequencies were “nil”, “planned” (5 or 6/year) and “regular” (every 3 weeks). In addition an isolate was taken from a group of “tracer” sheep drenched with TBZ every 10 days. Resistance to TBZ was assessed using an in vitro egg hatch assay, pre- and post-treatment faecal egg counts and a controlled anthelmintic efficiency test. Pre- and post-treatment egg counts revealed the presence of TBZ-resistance in field isolates of mixed species. Egg hatch assays indicated a level of resistance for Ostertagia spp which was proportional to the frequency of TBZ treatment. The “planned”, “regular” and “tracer” strains of Ostertagia spp had resistance ratios for eggs of 4, 13 and 15 respectively when compared to the “nil” strain. In the anthelmintic efficiency assay treatment with 44 mg kg-1 and 88 mg kg-1 of TBZ removed 82 and 96% respectively of the total Ostertagia burden (adults and larvae) from the “nil” strain and 30 and 75% respectively from the “planned” strain. The same dose rates against the “regular” and “tracer” strains and additional rates of 132 or 176 mg kg-1 against the “tracer” strain failed to reduce the Ostertagia burden significantly. Intestinal Trichostrongylus spp from all isolates were fully susceptible to TBZ at 44 mg kg-1. Levamisole at 7.0 mg kg-1 was highly effective (99% reduction) against the “tracer” strain of Ostertagia.