G. H. Collins

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.

Comparative pharmacokinetic behaviour of albendazole in sheep and goats

Albendazole (ABZ) containing a trace of [14C]-ABZ was administered intraruminally at 4.75 mg kg-1 to Merino sheep and Angora goats and the pharmacokinetic behaviour of ABZ and its metabolites in plasma nd abomasal fluid compared. The systemic availability (area under the curve, AUC) for total [14C]-labelled metabolites was significantly lower in goats than in sheep. This was largely attributable to the disposition of ABZ sulphoxide (ABZ.SO) which had a significantly lower maximum concentration (Cmax) in goats (0.94 +/- 0.04 micrograms ml-1) than in sheep (1.41 +/- 0.24 micrograms ml-1). The AUC of [14C] in abomasal fluid was similar in goats and sheep, with approximately 35 and 45% of the dose passing the pylorus in the two species, respectively. ABZ, ABZ.SO and ABZ sulphone (ABZ.SO2) were present in the abomasal fluid of both species but between-species differences were only evident with ABZ.SO which had a lower Cmax in goats compared with sheep. The relative proportions of the [14C] dose excreted in urine and faeces were similar between species. It is suggested that ABZ may be sequestered to a greater extent in the liver of goats than of sheep which would result in lower concentrations of ABZ.SO in plasma and abomasal fluid. This behaviour might be compensated for by administering ABZ to goats at a proportionally higher dose rate.

Epidemiology of paramphistomosis in cattle

The epidemiology of paramphistomosis in cattle was studied using tracer calves in a subtropical location in eastern Australia. Two species of paramphistomes were present; Calicophoron calicophorum and Paramphistomum ichikawai. The former species was the most abundant. Gyraulus scottianus and Helicorbis australiensis acted as intermediate hosts, respectively. Paramphistome burdens varied seasonally and were dependent upon the number of infected host snails. Peak fluke burdens and clinical paramphistomosis occurred in late summer in year 1 and early winter in year 2. The peak fluke burdens coincided with prolonged inundation of the grazing areas resulting in rapid multiplication and infection of host snails, and the period after the inundated areas dried out. The prevalence of infection in snails was high in both years, peaking at 98% in year 1 and 58% in year 2. The main host snail, G. scottianus, aestivated and retained infection for at least 24 weeks in soil, and in vegetable debris on the surface of the soil, resulting in rapid reappearance of host snails and infective metacercariae after the onset of seasonal rain. Metacercariae survived on herbage for up to 12 weeks, depending on the environmental conditions. Paramphistome burdens in calves could be predicted from the prevalence of infection in the host snail, the water levels and an index of surface water on the grazing site. Control of paramphistomosis during and after flooding may be achieved by removal of susceptible cattle from pasture or regular treatment during these periods. Strategic treatment during the dry season may reduce contamination of snail habitats and infectivity of the pasture in the following wet season.

Investigation of the mechanism of levamisole resistance in trichostrongylid nematodes of sheep

Abstract Uptake and metabolism of levamisole by adult worms and the effects of levamisole, morantel and other cholinergic agonists on egg hatching were investigated. A susceptible strain, a levamisole/morantel resistant strain and a morantel-only resistant strain of Trichostrongylus colubriformis all took up levamisole to the same extent. In all three strains 45–52% of the levamisole absorbed was converted to an unidentified metabolite. Levamisole, morantel and some of their analogues and other cholinergic agonists, carbachol, dimethylphenyl piperazinium, BAY d8815 and bephenium Br − were all less effective inhibitors of egg hatching in levamisole resistant strains of T. colubriformis and Haemonchus contortus than in susceptible strains of the same species. These data suggest that resistance is due to a reduction in the number of levamisole receptors in resistant trichostrongylids or a reduction in the affinity of these receptors for levamisole.

Effects of cholinergic drugs on longitudinal contraction in levamisole-susceptible and -resistant Haemonchus contortus

A novel force transducer was used to measure the effects of cholinergic agonists on longitudinal contraction in Haemonchus contortus. Drugs were applied to whole worms or injected via a cannula in the pseudocoelomic cavity. A number of agonists, including nicotine and the anthelmintics m-aminolevamisole, levamisole and morantel, caused contractions in whole worms. Four- to 25-fold increases in concentration of the active compounds were required to cause contractions in each of two levamisole-resistant strains of H. contortus. Of the other compounds tested, bephenium had equivalent activity against susceptible and resistant strains. Anticholinesterase compounds caused contractions after a slight delay in susceptible, but not resistant worms. Numerous cholinergic agonists and other compounds did not cause contraction when applied to whole worms. One of these, acetylcholine, caused contractions in cannulated worms. Compared with the susceptible strain, five- to six-fold higher concentrations of acetylcholine were required to cause equivalent contractions in the resistant strains. Levamisole resistance in adult H. contortus is likely to be due to a change in the characteristics of the cholinergic receptor(s).

Pathology of infection with Paramphistomum ichikawai in sheep

Lambs were given 40,000 or 50,000 metacercariae of Paramphistomum ichikawai by injection into the rumen and necropsied at 21, 42 and 84 days after infection. Pathological changes were observed grossly and confirmed histologically in the small intestine and rumen. The numbers of flukes and their location in the gastrointestinal tract were recorded and the populations of eosinophils, mast cells and globule leucocytes estimated. Changes varied, according to the numbers of flukes present, from a localised enteritis and villous atrophy in the duodenum in light infections to severe destruction of the mucosa extending into most of the jejunum in heavy infections. As the infection progressed changes were characterised by extensive thickening and fibroplasia in the mucosa and submucosa. Severe damage to the mucosa of the rumen was also observed in heavy infections. Heavy infections were associated with increased infiltration with eosinophils. Mast cells were generally depleted and globule leucocytes only appeared after the flukes had left the small intestine. Migration of the flukes from the small intestine was delayed in heavy infections exacerbating the effect of the infection. It is suggested that the presence of 20,000 to 25,000 flukes would result in clinical disease; smaller numbers would cause significant subclinical disease.

Haematological and pathological responses to experimental Trixacarus caviae infection in guinea pigs

Outbred guinea pigs became infected with the mite Trixacarus caviae (Acarina, Sarcoptidae) when introduced into an infected colony. Mite numbers were highest after one month, then fell progressively. Infected guinea pigs developed a neutrophilia, monocytosis, eosinophilia and basophilia. Despite pronounced reactive changes in the superficial lymph nodes, infected guinea pigs developed only a mild dermatitis. In contrast, home bred animals, susceptible to T. caviae acquired many mites and developed a severe chronic dermatitis. Trixacaral manage in guinea pigs offers considerable potential for the study of mite infections in man and animals.

Trixacarus caviae infection of guinea pigs with genetically determined differences in susceptibility to Trichostrongylus colubriformis infection

Guinea pigs with genetically determined resistance or susceptibility to infection with the nematode parasite Trichostrongylus colubriformis were allowed to become infected with the sarcoptid mite Trixacarus caviae. Compared with nematode-susceptible guinea pigs, nematode-resistant animals had larger populations of mites and developed a more severe dermatitis, with greater mast cell hyperplasia and many more infiltrating eosinophils. The results suggest that animals bred for resistance to one parasite may have greater susceptibility to other parasites.