Assessment of the potential toxicity of a poison for rabbits, pindone (2-pivalyl 1, 3 indandione), to domestic animals

The toxicity of pindone, a rabbit poison, to horses, cattle, goats, chickens, dogs and cats was investigated, using extension of prothrombin time (PT) as an index of poisoning. The daily dose of pindone, administered for 5 days, ranged from 0.3 mg/kg for dogs to 2.5 mg/kg for chickens. This range of dose rates was considered to be indicative of the worst possible case that could arise following a campaign of baiting for rabbits. Although significant elevations in PT (more than double baseline values) were noted in all species other than horses, clinical signs of anticoagulant poisoning were not observed in any of the species tested. From the observed PT, cattle and cats appeared to be the most susceptible, and horses the least susceptible, to pindone toxicity. The half-lives of the elevated PT were calculated as 3.1 days for cattle, 2.8 days for goats and chickens, 1.9 days for horses and dogs and less than one day for cats. It is proposed that these half-lives can be used as a guide for determining the duration of treatment of pindone-affected animals.     

Use of phenytoin to treat horses with Australian stringhalt

Five horses with Australian stringhalt were treated with 15 mg/kg phenytoin orally for 2 weeks. During the second week of the trial, 3 of the horses were given an additional dose of 10 mg/kg phenytoin. The response to treatment was clinically assessed by grading the severity of the gait abnormality at the walk, trot, turning and backing twice daily. There was a significant (P less than 0.05) improvement in the gait abnormality when pre-treatment values were compared with the mean of the last 3 assessments before treatment stopped. When reassessed 2 weeks after treatment ceased, there remained a significant (P less than 0.05) improvement compared with pre-treatment values at the trot and on backing, but not at the walk or turning. Surface electromyographic recordings were made weekly from the long digital extensor muscle, and there was a change to a near normal recording by the end of treatment. Plasma phenytoin concentrations were monitored during the trial, and the dose rates used achieved a steady state with a mean plasma level of 37 +/- 7 mumol/l. There was wide variability between plasma concentrations in different horses, although there was no difference in absorption between administration of the phenytoin as a paste, or when it was mixed in the feed. Although mild tranquilization was seen after treatment, there were no clinical, haematological or biochemical signs of toxicity from the phenytoin therapy.     

Postmortem diagnosis of preclinical and clinical scrapie in sheep by the detection of disease-associated PrP in their rectal mucosa

Samples of tissue from the central nervous system (cns), the lymphoreticular system (lrs) and the rectal mucosa of a large number of scrapie-exposed sheep, with and without signs of clinical disease, were examined immunohistochemically for evidence of disease-associated prion protein (PrP(d)). The rectal mucosa has received almost no attention so far in scrapie diagnosis, despite its abundant rectoanal mucosa-associated lymphoid tissue, and its accessibility. The scrapie-confirmed cases included 244 with clinical disease, of which 237 (97.1 per cent) were positive in the rectal mucosa, and 121 apparently healthy sheep, of which 104 (86 per cent) were positive in the rectal mucosa. PrP(d) was detected in 86.4 to 91.5 per cent of the other lrs tissues of the healthy sheep examined and in 77.7 per cent of their cns tissues. The stage of infection, therefore, affected the probability of a positive result in the rectal mucosa, whereas the breed, PrP genotype, age and sex had little or no independent effect. Accumulations of PrP(d) were observed in the rectal mucosa and other lrs tissues of vrq/arr sheep with preclinical and clinical scrapie, albeit with a lower frequency and magnitude than in sheep of other PrP genotypes. Western immunoblotting analyses of samples of rectal mucosa gave the characteristic PrP glycoprofile, with a sensitivity similar to that of immunohistochemistry.     

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.     

Preliminary findings on the experimental transmission of chronic wasting disease agent of mule deer to cattle.

To determine the transmissibility of chronic wasting disease (CWD) to cattle and to provide information about clinical course, lesions, and suitability of currently used diagnostic procedures for detection of CWD in cattle, 13 calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Between 24 and 27 months postinoculation, 3 animals became recumbent and were euthanized. Gross necropsies revealed emaciation in 2 animals and a large pulmonary abscess in the third. Brains were examined for protease-resistant prion protein (PrP(res)) by immunohistochemistry and Western blotting and for scrapie-associated fibrils (SAFs) by negative-stain electron microscopy. Microscopic lesions in the brain were subtle in 2 animals and absent in the third case. However, all 3 animals were positive for PrP(res) by immunohistochemistry and Western blot, and SAFs were detected in 2 of the animals. An uninoculated control animal euthanized during the same period did not have PrP(res) in its brain. These are preliminary observations from a currently in-progress experiment. Three years after the CWD challenge, the 10 remaining inoculated cattle are alive and apparently healthy. These preliminary findings demonstrate that diagnostic techniques currently used for bovine spongiform encephalopathy (BSE) surveillance would also detect CWD in cattle should it occur naturally.     

Characterisation of Pasteurella multocida isolated from fowl cholera outbreaks on turkey farms

SUMMARY: Biochemical profiles, restriction endonuclease analysis (REA) and ribotyping were used to investigate Pasteurella multocida isolates from outbreaks of fowl cholera on 7 turkey farms in New South Wales. While only a single isolate was available from 5 of the farms, multiple isolates, 4 and 12 respectively, were available from the other 2 farms. The available field evidence suggested that 8 outbreaks had occurred with one farm suffering 2 outbreaks. The isolates obtained were all confirmed as Pasteurella multocida . Biochemical profiles allocated the isolates to 4 groups, 3 being variants of P multocida subsp multocida and the fourth being P multocida subsp septica . REA performed with Hpall established 7 groups. Ribotyping using the Hpall digests probed with the 16S rRNA operon of Haemophilus paragallinarum recognised the same 7 groups as REA. Unlike the biochemical profiles, both REA and ribotyping provided a fine subdivision that identified outbreaks as either related or unrelated. The REA and ribotyping patterns as well as biochemical profiles were stable for all isolates from the outbreaks in which multiple isolates were obtained from either the same bird or from different birds. REA and ribotyping were found to be superior to biotyping methods for the investigation of fowl cholera outbreaks.     

Transmission of sheep scrapie to elk (Cervus elaphus nelsoni) by intracerebral inoculation: final outcome of the experiment.

This is a final report of an experimental transmission of sheep scrapie agent by intracerebral inoculation to Rocky Mountain elk (Cervus elaphus nelsoni). It documents results obtained in experimental (n = 6) and control (n = 2) elk. During the first 2 years postinoculation (PI), 3 animals died or were euthanized because of infection or injuries other than spongiform encephalopathy (SE). In years 3 and 4 PI, 3 other inoculated elk died after brief terminal neurological episodes. Necropsy of these animals revealed moderate weight loss but no other gross lesions. Microscopically, characteristic lesions of SE were seen throughout the brain and spinal cord, and the tissue was positive for proteinase K-resistant prion protein (PrPres) by immunohistochemistry (IHC) and by Western blot. Scrapie-associated fibrils (SAF) were observed by negative-stain electron microscopy in the brain of elk with neurologic signs. PrPres and SAF were not detected in the 3 inoculated elk necropsied during the first 2 years or in the 2 control animals. Retrospective analysis of the gene-encoding cervid PrP revealed a polymorphism at codon 132. The elk with SE were either homozygous (MM) or heterozygous (LM). These findings confirm that intracerebral inoculation of sheep scrapie agent results in SE with accumulations of PrPres in the central nervous system of elk. Based on morphologic and IHC findings, the experimentally induced SE cannot be distinguished from chronic wasting disease of elk with currently available diagnostic techniques.