Levamisole is commonly used to treat nematode parasite infections but therapy is limited by resistance. The purpose of this study was to determine the mechanism of resistance to this selective nicotinic drug. Levamisole receptor channel currents in muscle patches from levamisole-sensitive and levamisole-resistant isolates of the parasitic nematode Oesophagostomum dentatum were compared. The number of channels present in patches of sensitive and resistant isolates was similar at 10 microM levamisole, but at 30 microM and 100 microM the resistant isolate contained fewer active patches, suggesting desensitization. Mean Po and open times were reduced in resistant isolates. The distribution of conductances of channels in the sensitive isolate revealed a heterogeneous receptor population and the presence of G25, G35, G40, and G45 subtypes. A G35 subtype was missing in the resistant isolate. Resistance to levamisole was produced by changes in the averaged properties of the levamisole receptor population, with some receptors from sensitive and resistant isolates having indistinguishable characteristics.

This paper reviews sites of action of anthelmintic drugs including: (1) levamisole and pyrantel, which act as agonists at nicotinic acetylcholine receptors of nematodes; (2) the avermectins, which potentiate or gate the opening of glutamate-gated chloride channels found only in invertebrates; (3) piperazine, which acts as an agonist at GABA gated chloride channels on nematode muscle; (4) praziquantel, which increases the permeability of trematode tegument to calcium and results in contraction of the parasite muscle; (5) the benzimidazoles, like thiabendazole, which bind selectively to parasite β-tubulin and prevents microtubule formation; (6) the proton ionophores, like closantel, which uncouple oxidative phosphorylation; (7) diamphenethide and clorsulon, which selectively inhibit glucose metabolism of Fasciola and; (8) diethylcarbamazine, which appears to interfere with arachidonic acid metabolism of filarial parasites and host. The review concludes with brief comments on the development of anthelmintics in the future.

An experiment was carried out to investigate the anthelmintic activity of papaya latex (Carica papaya) against natural infection of Ascaris suum in pigs. Sixteen naturally infected pigs were, on the basis of faecal egg counts and body weight, allocated into four groups, each of four pigs. Three groups (groups B, C, and D) were given papaya latex per os at dose levels of 2, 4, and 8 g of papaya latex per kg body weight, respectively. The fourth group (group A) served as a non-treated control. Results of post mortem counts on day 7 post treatment revealed worm count reductions of 39.5, 80.1 and 100% in groups B, C, and D, respectively. Some of the pigs receiving the highest dose of the latex showed mild diarrhoea on the day following treatment. Otherwise, no clinical or pathological changes were observed in the treated animals. The possible future use of this traditional herbal medicine for livestock and humans is discussed.

Summary This study reports on the prevalence of anthelmintic resistance in strongyles of horses in Denmark. Of 5 methods used for the calculation of faecal egg count reduction (FECR) the method recommended by the World Association for the Advancement of Veterinary Parasitology, for the detection of resistance in sheep was the most sensitive procedure for detecting resistance. Using this method benzimidazole resistance was detected on 33 of 42 farms (79%) examined. Pyrantel was tested on 15 farms and FECR tests indicate resistance on 3 (30%) farms. On 2 farms on which resistance to pyrantel was detected resistance to benzimidazoles was also detected. On one of 16 farms examined ivermectin resistance was indicated at Day 14 but not at Day 19. On the 15 remaining farms ivermectin was effective. Due to the high prevalence of anthelmintic resistance in Danish horse herds it is recommended that tests of anthelmintic efficacy be conducted routinely to monitor the effectiveness of the strongyle control programmes.

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Macrocyclic lactones are characterized by their long persistence in animals because of their extensive distribution into fat. This study examined the influence of body condition on the disposition of ivermectin (IVM) and moxidectin (MXD) in blood and fat following subcutaneous (s.c.) drug administration. 'Fat' and 'thin' lines of pigs were established using two different diets. All animals were then injected with either MXD or IVM at 300 microg/kg and blood samples were taken at regular intervals until slaughter. Two IVM-treated animals from each diet group were slaughtered at either 3 days or 3 weeks posttreatment. Two MXD-treated animals from each diet group were slaughtered at 3 days, 3, 6 or 9 weeks after treatment. Samples of backfat were taken from all animals at slaughter. Fluorescence HPLC was used to determine the concentrations of MXD or IVM in the plasma and fat samples. The plasma IVM concentration peaked more rapidly in the thin IVM treated pigs compared with the fat pigs. The concentration of IVM in backfat was significantly lower in the thin animals slaughtered 3 weeks after treatment. The MXD plasma concentration peaked within the first hour in both the thin and fat groups, but from 12 h posttreatment there was a higher MXD concentration in the plasma of the fat pigs resulting in MXD being detectable in these pigs for 28 days compared with only 17 days in the thin pigs. Despite this difference in plasma persistence no differences were seen in the MXD concentration of backfat between fat and thin animals. Body condition influenced the kinetic disposition of IVM and MXD following s.c. drug administration with both drugs being less persistent in thin compared with fat animals.

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