Variations in sheep serum conglutinating and haemolytic activity for sheep erythrocytes sensitized by rabbit antibody

Based on conglutinating and haemolytic reactions with sheep erythrocytes (E) sensitized by rabbit antibody (A), three types of sheep sera were encountered. Type 1 sera do not conglutinate or haemolyse sheep E-rabbit A. Type 2 sera failed to conglutinate, but are haemolytically active. Type 3 sera have both activities. Serum from one type 1 sheep still failed to conglutinate 5 days after venepuncture but was now haemolytically active (i.e., type 2). Some sheep that initially had type 2 sera had, five days after an intraperitoneal injection of yeast cells, sera with conglutinating activity (type 3 sera). Type 1, 2 and 3 sera all had haemolytic activity with human E-sheep A indicator cells.Pooled type 3 sera have the highest conglutinating titres with sheep E-rabbit A after 10 min incubation at 39 °C. At this stage, the haemolytic titres were very low. From 10 min, the conglutinating titres decreased whereas the haemolytic titres gradually increased until 80 min. Optimal conglutinating activity required less rabbit A to sensitize sheep E than did haemolytic activity.     

羊源肠球菌溶血素特性分析及其对兔红细胞作用的观察

对致羔羊脑炎肠球菌E129-3菌株溶血素进行检测分析，并利用光学显微镜和电子显微镜观察其对兔红细胞的作用，探讨了肠球菌溶血素的特性及溶血类型。结果表明，小白鼠、兔、犬红细胞对该溶血素最敏感，牛红细胞不敏感。该溶血素可以被DTT、Ca^2＋活化，被蛋白酶K、EDTA、Zn^2＋、Cu^2＋抑制。在培养后2h，细胞浆内着色不一致或密度降低，5h时红细胞数量明显减少，细胞膜较完整。提示，肠球菌溶血素为成孔蛋白类溶血素。     

Pharmacokinetics of levamisole in sheep after intravenous administration

The pharmacokinetics of levamisole at doses of 5, 7.5 and 10 mg/kg were determined after its intravenous administration to eighteen healthy Merino sheep. Using compartmental analysis, the disposition of the drug best fitted a two-compartmental open model. The mean values for the compartmental volume of distribution at steady state (Vss) were 2.034 +/- 0.23 I, 2.347 +/- 0.720 and 2.001 +/- 0.367 I/kg for each dose, respectively, and values obtained using the statistical moment theory were 2.141 +/- 0.269,2.390 +/- 0.536 and 2.140 +/- 0.345 l/kg for each dose, respectively. There were no dose-related differences (one-way ANOVA) in the constants describing distribution and elimination phases (alpha and beta) or Vss, but significant differences were detected in the total body clearance (Cl) and the area under the plasma concentration-time curve (AUC). After non-compartmental analysis, no significant differences were found when the parameters lambda (the linear terminal slope) and Vss were compared, but significant differences were detected in Cl and AUC. There were no significant differences between the values obtained using the compartmental and non-compartmental analysis when lambda -beta, Cl, Vss, and AUC were compared.     

The efficacy of mixtures of albendazole sulphoxide and levamisole against sheep nematodes resistant to benzimidazole and levamisole

Faecal egg count reduction tests and an anthelmintic efficiency assay were used to assess the efficacy of combinations of albendazole sulphoxide and levamisole against populations of Ostertagia and Trichostrongylus sp. which contained different proportions of worms resistant to both benzimidazole and levamisole anthelmintics. Compared to the effects of either drug alone, significantly greater efficacy was obtained using combinations which included dose rates similar to those recommended for the separate components. At these dose rates, the mixtures reduced mean faecal egg counts by 95% or more, and caused a reduction of 68% in adult Ostertagia sp. and more than 95% for 4th stage Ostertagia and T colubriformis. The increased efficacy of the mixtures could be accounted for by actions of the drugs acting independently.     

Naphthalophos combinations with benzimidazoles or levamisole as effective anthelmintics for sheep

Objective: To investigate the relative efficacy and safety of the anthelmintic naphthalophos in sheep, either given alone or in combination with benzimidazole (fenbendazole and albendazole) or levamisole anthelmintics.
Design: A parasitological study using faecal egg count reduction tests, a validating slaughter trial and field safety trials.
Procedure: Faecal egg count reduction tests were carried out on 13 farms. Naphthalophos and combinations of naphthalophos with levamisole and fenbendazole were included in the drench tests. On one property a controlled efficacy study was carried out to validate faecal egg count reduction test findings. In this trial, sheep were slaughtered 10 days after treatment and the remaining parasites recovered from the gastro-intestinal tract. Safety trials were carried out on eight farms where approximately 50 000 sheep were treated with naphthalophos and albendazole that were tank mixed in the backpack.
Results: The efficacy of naphthalophos alone in faecal egg count reduction tests ranged from 59 to 98% with one test showing 95% reduction. The efficacy of naphthalophos and levamisole ranged from 74 to 100%, with 5 farms showing 95% reduction. The efficacy of naphthalophos and fenbendazole ranged between 88 and 100% with 95% reduction achieved on 10 farms. The controlled efficacy study showed a good correlation between the faecal egg count reduction tests and numbers of parasites recovered, except for Nematodirus where the faecal egg count reduction tests overestimated efficacy. The mortality rate in the safety trials was 0.05%, with most fatalities occurring on one farm.
Conclusion: The combination of naphthalophos and fenbendazole was more effective than a combination of naphthalophos and levamisole, and will provide a sufficiently safe drench rotation option.     

Bioavailability of levamisole after intramuscular and oral administration in sheep

AIMS: To determine the bioavailability of levamisole in sheep. METHODS: Levamisole was administered to three groups of six Merino sheep orally and intramuscularly at three dose levels of 5, 7.5 and 10 mg/kg. There was a washout period of 1 week between treatments. Blood samples were collected by jugular venepuncture and plasma was separated immediately by centrifugation and stored at 20 degrees C until analysed. The levamisole concentration in plasma was determined by high performance liquid chromatography with a U.V. detection method. Individual plasma levamisole concentration-time data were analysed using the compartmental method. RESULTS: The values obtained for k(a), C(max), t(max) and F show a moderate rate and extent of absorption after oral administration of levamisole while, after intramuscular administration, these values demonstrate a high rate and extent of absorption of levamisole. The intramuscular bioavailability was higher than the oral bioavailability (rate of absorption three-fold faster, extent of absorption 25-33% higher and C(max) two-fold higher). The Friedman test involving dose and route of administration showed that the route of administration affects k(a), C(max), t(max) and F; significant differences were found in these parameters. CLINICAL RELEVANCE: On the basis of these data, the recommended routes for the administration of levamisole in sheep are oral for gastro-intestinal nematodiasis and intramuscular for extragastric nematodiasis.     

Effectiveness of morantel tartrate and naphthalophos against levamisole resistantOstertagia in sheep

Adult worms from a levamisole resistant population ofOstertagia consisting ofO. circumcincta andO. trifurcata showed no dose response to morantel tartrate. The lowest dose rate of 2.2 mg/kg removed 30.8% of worms while the highest dose rate of 17.6 mg/kg removed 39.2%. A dose response was obtained against naphthalophos and the LD₅₀ and LD₉₅ were determined as 12.54 mg/kg and 23.25 mg/kg respectively. It was concluded that the strain was cross resistant to morantel tartrate but not to naphthalophos.     

Effect of levamisole on immunity to Corynebacterium pseudotuberculosis in mice and sheep

The stimulating effect of levamisole on immunity to Corynebacterium pseudotuberculosis in mice was marginal, while no enhancement of immunity could be detected in sheep. The conclusion was reached that, as levamisole has no potentiating effect on immunity to C. pseudotuberculosis in normal sheep, it is of no practical value as an immunostimulant in this instance.     

The efficacy of levamisole, and a mixture of oxfendazole and levamisole, against the arrested stages of benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in sheep

Sheep were allowed to graze pasture that had been seeded with benzimidazole-resistant Haemonchus contortus and Ostertagia circumcincta in order to acquire a burden of arrested larvae. Following housing, sheep were dosed orally with either oxfendazole at a dose rate of 4.7 mg/kg (to confirm the benzimidazole-resistant status of the species of nematode), levamisole at a dose rate of 7.5 mg/kg, or an oxfendazole/levamisole mixture at a dose rate of 4.6 mg/kg oxfendazole and 8.1 mg/kg levamisole. The efficacies of the treatments were assessed by estimation of the arrested larval burden in the abomasum of each sheep, either at 10 or 11 days (oxfendazole and oxfendazole/levamisole mixture), or 12 or 13 days (levamisole), after treatment. Compared to the untreated controls, the protection afforded by a single dose of either levamisole or the oxfendazole/levamisole mixture was >99% against the arrested stages of both Haemonchus contortus and Ostertagia circumcincta. Treatment with oxfendazole confirmed the benzimidazole-resistance status of the two species.     

Vaccination of mice and sheep with Fh12 FABP from Fasciola hepatica using the new adjuvant/immunomodulator system ADAD

We evaluate the ability of a Fasciola hepatica FABP native antigen (Fh12) with a new vaccination system called ADAD to protect mice and sheep against an experimental F. hepatica infection. The vaccination protocol consists of a set of two injections. The first injection contains a micelle in which two components are included, saponin from Quillaja saponaria (Qs) and/or Anapsos (A) a Polypodium leucotomos hydroalcoholic extract, both emulsified in a non-mineral oil (Montanide) in a water/oil emulsion (30/70). This is subcutaneously injected to achieve the "adaptation" of the immune system to subsequent stimuli. The second injection contains in addition the Fh12 antigen. Two different experiments were carried out using two mouse strains (BALB/c and CD-1). Mice vaccinated with Qs+A+Fh12 presented a survival rate of 40%, when compared with control groups. Furthermore, we evaluated the efficiency of the vaccination in sheep against an experimental F. hepatica challenge. The vaccinated sheep presented lower fluke recovery (24.5%), number of eggs in bile fluid (58.1%) and faeces (40.3%) than control groups. The recovered flukes were shorter (32.7%), immature (34.0%) and with lower body mass (31.6%) than non-complete vaccinated sheep. Thus, the new ADAD system could be a good alternative for future vaccination experiments against fasciolosis.     

The anthelmintic efficacy of thiabendazole and levamisole against inhibited Haemonchus contortus larvae in sheep

Fifty-five dogs, 6 to 18 months old, from 11 areas of New Zealand were examined for gastro-intestinal helminths. Thirty-eight (69.1%) were infected. Twenty-one (38.2%) had Toxocara canis, 20 (36.4%) Trichuris vulpis, 20 (36.4%) Uncinaria stenocephala, 3 (5.5%) Toxuscaris leonina, 3 (5.5%) Dipylidium caninum and 1 (1.8%) Taenia sp. Helminth infections were less frequent and populations were smaller in females than in males.     

Certain features of erythrocytes of normal and glutathione-deficient sheep.

Studies were made of certain characters of erythrocytes of normal and glutathione (GSH)-deficient sheep. The results indicate that erythrocytes of GSH-deficient sheep are no more sensitive to oxidative damage than those of normal sheep.     

Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep

Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.     

The relation between the rabbit potency test and the response of sheep to sheep clostridial vaccines.

Six commercially available clostridial vaccines comprising one oil-emulsion, two alum-precipitated and three aluminum hydroxide adjuvanted preparations, each containing between two and seven antigenic components, were administered to groups of 10 rabbits and eight sheep in accordance with manufacturers' recommendations. Serum antitoxic values to Cl welchii beta, Cl welchii epsilon, Cl septicum, Cl oedematins and Cl tetani toxins were determined 14 days after completion of each vaccination course. The overall pattern of mean antitoxic values was found to be similar in sheep and rabbits, a vaccine eliciting a comparatively high antibody titre to any given antigen component in sheep also inducing a comparatively high titre in the corresponding group of rabbits. Similarly, comparatively poor responses in sheep were associated with poor responses in rabbits. The degree of variation in response within groups of animals was greater in sheep than in rabbits for all five antigenic components assayed. Sheep consistently developed higher titres than rabbits to Cl oedematins component but consistently lower titres to both Cl welchii beta and epsilon components irrespective of the type of vaccine used. The response of both species to Cl tetani antigen was similar in terms of serum antitoxic values. It was concluded that rabbits provide a suitable model for the assessment of potency of sheep clostridial vaccines.