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.     

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.     

Activity of closantel against experimentally induced Fascioloides magna infection in sheep

The efficacy of closantel against experimentally induced Fascioloides magna infection in sheep was studied. In each of 3 experiments, closantel was administered 8 weeks after the sheep were given (oral inoculation) 100 metacercariae of F magna. In the 1st experiment, closantel was given orally to 5 groups of 6 sheep each at dosages of 0 (nontreated control), 5, 7.5, 10, and 15 mg/kg of body weight. In the 2nd and 3rd experiments, groups of 10 or 12 sheep were treated to confirm the efficacy of the previously determined optimal dosage of 15 mg/kg. An additional group of sheep (n = 10) was used in the 3rd experiment to evaluate the efficacy of closantel given IM at a dosage of 7.5 mg/kg. Closantel given orally at a dosage level of 15 mg/kg was highly effective (94.6% to 97.7%) in reducing F magna burdens. Also, pathologic scores associated with the F magna infection were reduced by 81.3% to 92.6% in sheep given this dosage of closantel. Efficacy of the IM administered dosage of 7.5 mg of drug/kg was equivalent to that of the 15 mg/kg oral dosage. Other than mild, transient lameness of the limbs which were injected with the drug (group 10), side effects were not observed.     

Efficacy of triclabendazole against experimentally induced Fascioloides magna infections in sheep

Efficacy of oral administration of 20 mg of triclabendazole/kg of body weight was evaluated against 12-week Fascioloides magna infections in 12 sheep, each inoculated orally with 250 viable metacercariae. From 6 sheep treated with triclabendazole, 1 immature F magna was recovered, whereas 116 F magna with a mean length of 19 +/- 6.5 mm were recovered from 6 untreated control sheep. Efficacy of triclabendazole was 99.14%. Signs of toxicosis or illness were not observed in the sheep.     

Pathogenicity of immature Fascioloides magna in white-tailed deer.

The pathogenesis of early prepatent Fascioloides magna infection was investigated in seven fawns (Odocoileus virginianus) given 500 metacercariae and examined at one, two, three, five, eight, 12 and 13 weeks postinoculation. Blood samples were taken from eight inoculated deer every two weeks up to 16 weeks postinoculation. Eosinophilia with a mild transitory anemia were the main clincopathological features. Postmortem examination at two weeks postinoculation revealed extensive migration of immature flukes. Subcapsular tracks in the liver, nodules on the blind sacs of the rumen, as well as retroperitoneal granulomas on flanks and necrotic tracks on the diaphragm were found. Evidence of penetration of flukes into the lung was found at two weeks postinoculation and there was early granuloma formation at three weeks postinoculation. Flukes migrating into tissues other than the liver were destroyed in large granulomas, although remnants of degenerating parasites were not found. At eight weeks postinoculation, widespread granuloma formation characterized the infection with this lesion present in nodes along the gastrointestinal tract, in the mesentery, flanks, psoas muscles, diaphragm, between the ribs and in the lungs. By 12 weeks postinoculation subcapsular tracks were observed in the liver.     

Prevalence of Fascioloides magna in cattle and deer in Michigan

A survey among 1.12 million cattle slaughtered in 357 packing plants in Michigan during 1977 to 1981 was conducted to determine the prevalence of liver fluke infection. The condemnation rate of liver fluke-infected livers was 0.41, 3.7, and 13.9% in the southern, northern-lower, and upper regions of Michigan, respectively. The same trend in infection rates was observed in white-tailed deer that had been examined in diagnostic laboratories in the state. A serologic survey among 50 randomly selected dairy farms detected Fascioloides antibody-carrying cattle in 3 farms. The data on prevalence in slaughter cattle were slightly biased, because many slaughter cattle originated from other states in which F magna may be less common.     

Pathophysiologic effects of experimentally induced Fascioloides magna infection in sheep

The pathophysiologic responses of 13 sheep inoculated orally with 100 metacercariae of Fascioloides magna were monitored for 4 months after inoculation. There were no differences in weight gains between these and a number of noninoculated control sheep throughout the experiment. Complete blood cell counts showed an increase only in the absolute number of eosinophils. Serum preparations (2 times a week) from 7 inoculated and 7 noninoculated sheep did not identify any significant changes in alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase activities. There were no changes in total bilirubin, BUN, creatinine, inorganic phosphorus, calcium, albumin, chloride, potassium, and sodium values. Four months after they were inoculated, all sheep were necropsied, and flukes were recovered. Gross lesions attributed to fluke migration were found in the liver and portal lymph nodes, diaphragm, lungs, kidneys, and spleen. Microscopically, liver lesions in inoculated sheep occurred in the portal areas, veins, and Glisson's capsule and were characterized by both active and chronic forms of inflammation. Abundant infiltrates of eosinophils and plasma cells often marked the portal areas. Endophlebitis, with or without thrombosis, was the predominate vascular lesion. The flukes recovered varied greatly in size (6.5 to 48.0-mm long) and demonstrated some sexual development, but none was sexually mature.     

A controlled evaluation of albendazole against natural infections with Fasciola hepatica and Fascioloides magna in cattle

Albendazole administered to cattle at doses of 45, 35, 25, and 15 mg/kg of body weight reduced the number of viable Fasciola hepatica adults by 99.8%, 97.6%, 97.6%, and 95.7%, F hepatica immatures by 100%, 98.6%, 98.6% and 91.9% and Fascioloides magna by 96.5%, 99.1%, 94.0%, and 94.0%, respectively. Statistical evaluation by one-way analysis of variance, showed significant (P less than 0.05) differences in burdens of each fluke species between treated and untreated cattle, but differences in efficacy between any two of the four drug doses were not significant. Signs of toxicosis were not observed between the time of drug administration and slaughter 7 to 10 days later.     

Efficacy of clorsulon against mature, naturally acquired Fasciola hepatica infections in cattle and sheep

Clorsulon (3.5 or 7 mg/kg of body weight) was given orally to mature cows (dairy or beef) and to mature mixed-breed sheep harboring patent infections of Fasciola hepatica. Eighteen animals of each species were assigned to a control group (drug vehicle) or to 1 of 2 treatment (3.5 or 7.0 mg/kg) groups of 6 animals each. On posttreatment days 8 (cows) or 14 (sheep), the animals were slaughtered for recovery of flukes. In cows, the efficacy (P values for treatment groups vs control) of clorsulon against infections of mature F hepatica was 99.21% (P less than or equal to 0.0065) at 3.5 mg/kg and was 100% (P less than or equal to 0.0039) at 7 mg/kg. In sheep, the efficacy was 93.33% (P less than or equal to 0.0104) at 3.5 mg/kg and was 100% (P less than or equal to 0.0039) at 7 mg/kg. These results indicate that clorsulon is a highly effective compound for the treatment of mature F hepatica in cows and sheep.     

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.     

Hematology and clinical pathology of experimental Fascioloides magna infection in cattle and guinea pigs.

The hematologic and clinico-pathologic response to Fascioloides magna infection in cattle and guinea pigs was investigated. Twelve calves (six infected and six controls) were monitored for 26 weeks after inoculation with 1000 metacercariae. All calves remained healthy and there were no significant differences in weight gains between infected and control groups. Flukes (mean = 9.2, range 1–32) were recovered from the liver and abdominal cavity of all infected calves. The only significant response observed in the complete blood counts was an eosinophilia present in the infected calves extending from Weeks 2 to 26 post-infection. There were no significant differences in serum levels of aspartate aminotransferase and only minor increases in the levels of gamma-glutamyl transferase and sorbitol dehydrogenase.

A total of 48 infected and 48 control guinea pigs from three separate experiments were monitored for 16 weeks after inoculation with 20 metacercariae of Fascioloides magna. Infected guinea pigs died between 7 and 114 days after infection, and flukes (ean = 2.5, range 0–13) were recovered from the liver, abdominal cavity, lungs, thoracic cavity, skeletal muscle and subcutaneous tissue. There were no differences in weight gains between infected and control guinea pigs. Complete blood counts showed increases in white blood cell, monocyte and neutrophil counts from between the third and fourteenth weeks post-infection; however, the differences were not consistently significant. Infected guinea pigs developed a significant eosinophilia and basophilia from 2 to 16 weeks post-infection. There were no significant changes in the serum levels of alanine aminotransferase or gamma-glutamyl transferase. There was an increase in the serum levels of aspartate aminotransferase beginning at 5 weeks post-infection. The response observed in the guinea pigs was similar to that reported in sheep, suggesting the suitability of the guinea pig as a model for Fascioloides magna infection in the sheep.     

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.     

Survey of Fascioloides magna in farmed wapiti in Alberta

The formalin-ethyl acetate sedimentation procedure was used to detect ova of the giant liver fluke, Fascioloides magna, in feces of farmed wapiti in Alberta. Twenty (3.2%) of the 629 fecal samples examined contained ova of F. magna. Thirteen (33.3%) of the 39 farms surveyed had wapiti positive for F. magna. The presence of F. magna in farmed wapiti north of the North Saskatchewan River is confirmed, and 3 areas where the infection has become endemic are identified.     

Fascioloides magna: Occurrence in Saskatchewan and Distribution in Canada

Infection with Fascioloides magna, the large American liver fluke, was diagnosed in two moose (Alces alces) and six wapiti (Cervus elaphus) from central Saskatchewan. This is believed to be the first record of the parasite in the province. Fecal samples collected from wild wapiti at five sites in the commercial forest zone in Saskatchewan contained eggs believed to be those of F. magna. Trematode eggs were not found in feces from five captive herds of wapiti in the province, nor in samples from wild wapiti in Moose Mountain Provincial Park. Operculate eggs were found in feces of wild wapiti from Cypress Hills, but these were believed to be from trematodes other than F. magna. The distribution and significance of F. magna in Canada, based partially on responses to a mail questionnaire, are reviewed.     

国产克洛素隆在绵羊体内的药代动力学和生物利用度研究

应用 YWG-C1 8色谱柱 ( 2 5 0 mm× 4.6mm,5 μm) ,Waters TM486型可调波长紫外检测器 ,检测波长 2 65 nm;0 .0 1 M磷酸钾 ( p H=7.0 )∶乙腈 ( 3∶ 1 )为流动相 ;含量测定采用标准曲线法 ,建立了反相 HPLC法检测绵羊血浆中克洛素隆含量的方法。同时对绵羊以 7mg/ kg单剂量经静脉注射、口服 2种途径给药的药代动力学及生物利用度进行了研究。血药浓度在 0 .0 0 5～ 2 .0 μg/ ml及 2 .0～ 5 0 .0 μg/ ml范围呈良好线形关系 ( R=0 .9941、0 .9970 ) ,平均回收率 93 .2 %,血药最低检测限 0 .0 0 5 μg/ ml,日内日间变异系数分别小于 1 0 %、1 1 %。2种途径给药后血药浓度结果经 MCPKP药代动力学统计软件处理 ,体内药物运转分别符合三室开放模型和一室开放模型。结果表明 ,绵羊静注克洛素隆后体内药物分布广泛 ,口服后吸收较好 ,但消除较静注缓慢。