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Absorption, distribution and excretion of the anthelmintic praziquantel (Droncit) in rainbow trout (Salmo gairdneri R.).

Prazquantel is an anthelmintic active against trematodes and cestodes. The absorption, distribution and excretion of the drug was studied in serum, muscles, liver, bile fluid and kidneys of rainbow trout at two temperatures, 12 degrees C and 18 degrees C, after a single oral dose of 500 mg/kg body wt. A bioassay, using cercaria larvae of the trematode Diplostomum spathaceum as the test organism, was employed to measure the drug levels in tissues of the fish. The cercariae were very sensitive to praziquantel; their mobility was significantly reduced within 20 min in a 0.01 micrograms/ml solution. Praziquantel was readily absorbed from the gastrointestinal tract of the fish. Absorption was more rapid at 18 degrees C than at 12 degrees C. Only in the liver, however, did the peak values reach significantly higher levels at the higher temperature. The peak values in different tissues (10.2-31.8 micrograms/g) were reached 4-16 h after administration of the drug. The elimination of the drug from the tissues was less dependent on temperature than absorption. By 32 h p.a., 67%-96% of the maximum amounts had been eliminated from the tissues. Praziquantel was excreted partly with bile fluid and partly as water-soluble metabolites through the kidneys.

Animals↗

The effect of peri-parturient anthelmintic treatment on the productivity of dairy cattle in subtropical western India.

Trials with fenbendazole (Panacur, Hoechst India Ltd) were carried out on two commercial farms in subtropical western India to study the response and economics of nematode treatment in adult dairy cows. Milk yield, lactation length, time to first oestrus and worm egg output were monitored in treated and control groups. Treatment reduced the egg count considerably. Treated cows produced 142 litres more milk over 100 days (p < 0.05), with extension of lactation length and advancement of time to first oestrus. The economic gain in terms of milk yield far outweighed the cost of anthelmintic used.

Animals↗

Effect of anthelmintic treatment on the performance of Awassi sheep in Iraq.

Studies are reported on the effect of anthelmintic treatment on the body weight gain and wool growth of ewes with subclinical helminth infections. The parasites involved were Fasciola gigantica and Ostertagia spp., together with some Haemonchus contortus, Trichostrongylus spp., and Dictyocaulus filaria. In 1 group, 5 sheep, which were treated twice with tetramisole at an interval of 4 weeks to remove gastro-intestinal nematodes and lungworms, showed an increase of 41% in weight gain and 3.2% in wool growth compared with an untreated group. Another group, which was treated with both tetramisole and rafoxanide to remove nematode and fluke infections, had a 143% increase in weight gain and 81% in wool growth compared with the control.

Animals↗

Use of anthelmintics to control fascioliasis in sheep in the Yemen Arab Republic.

Repeated use of modern anthelmintics gave good control of fascioliasis in sheep in a village in the inter-montane plain of the Yemen Arab Republic despite the presence on the same pasture of untreated animals. The sheep mainly acquired the infection during the drier winter season and it is probable that effective control could be achieved by regular treatment of all animals over that period.

Animals↗

Population-S benzimidazole- and tetrahydropyrimidine-resistant small strongyles in a pony herd in Kentucky (1977-1999): effects of anthelmintic treatment on the parasites as determined in critical tests.

Population-S small strongyles have been studied since 1974 in central Kentucky in a closed Shetland pony breeding herd. The ponies were treated approximately every 8 weeks with cambendazole (1974-1978), oxibendazole (OBZ) (1978-1992), or pyrantel pamoate (PRT) (1992-1999). Small strongyles in the ponies have shown resistance to these compounds in field and critical tests. One purpose of this presentation was to compare different parameters for determination of effects on the small strongyle species in ponies after treatment, mainly with OBZ or PRT, from data in critical tests (n=112). Also, the objective was to report on relative changes in the composition of species of small strongyles during the period 1977 through 1999. The following entities were compared to evaluate the effect of OBZ- or PRT-treatment on the small strongyles: (1) numbers of specimens with eggs in utero--there were less gravid worms passed in the feces than recovered at necropsy for OBZ but the numbers of gravid worms were similar in both categories for PRT, (2) pre- and posttreatment counts of eggs per gram of feces (EPGs) and larvae per gram of feces (LPGs)--the reductions were greater for the counts of EPGs than LPGs for OBZ but not for PRT, and (3) pre- and posttreatment counts of EPGs versus % of worms removed--reductions of the former were greater than the latter for both compounds. As shown from data in this study, reduction of EPG counts post treatment indicated much greater drug activity than was actually demonstrated by removal of worms. One evident factor was the value of doing critical tests to verify posttreatment counts of EPGs as indicators of anthelmintic activity. Twenty-eight species of small strongyles were found. For the 20 most prevalent species in the study, two decreased, five remained unchanged, three increased and then became stationary, five increased but then decreased, and five increased progressively. Numbers of small strongyles were highest in 1987 and 1999.

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Identification of strongyle eggs from anthelmintic-treated horses using a PCR-ELISA based on intergenic DNA sequences.

The efficacy of five daily fenbendazole (FBZ) treatments was tested against benzimidazole-resistant cyathostomins in naturally infected horses (n=13). Horses were treated with pyrantel embonate (PYR) to remove adult strongyles followed, 7 days later, by a 5-day course of FBZ. The PYR treatment produced an average faecal egg count reduction of 98%. All samples were negative by faecal egg count 7 days after the start of the FBZ treatment. Positive egg counts were observed from 28 days after the start of FBZ treatment and all horses displayed positive faecal egg counts by 77 days after treatment. Strongyle eggs were harvested from the faeces of the horses prior to treatment and then weekly from 42 to 70 days post-treatment. DNA was obtained from eggs in groups of ten. A PCR-ELISA, based on species-specific differences in intergenic DNA sequences, was used to identify the presence of six cyathostomin species. In pre-treatment samples, Cyathostomum catinatum was detected in nine out of the 13 horses and Cylicostephanus longibursatus, Cylicostephanus goldi and Cylicocyclus nassatus, were found in samples from eight animals. Cylicocyclus ashworthi and Cylicocyclus insigne were not detected pre-treatment. After anthelmintic treatment, C. catinatum and C. longibursatus were most frequently detected, followed by C. nassatus, C. goldi and C. ashworthi. C. insigne was detected at only one time point in a sample from a single horse.

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Anthelmintic activity of Spigelia anthelmia extract against gastrointestinal nematodes of sheep.

In vitro (larval development assay) and in vivo studies were conducted to determine possible direct anthelmintic effect of ethanolic and aqueous extracts of Spigelia anthelmia towards different ovine gastrointestinal nematodes. The effect of extracts on development and survival of infective larvae stage (L(3)) was assessed. Best-fit LC(50) values were computed by global model of non-linear regression curve fitting (95% confidence interval). Therapeutic efficacy of the ethanolic extracts administered orally at a dose rate of 125, 250, and 500 mg/kg, relative to a non-medicated control group of sheep harbouring naturally acquired infection of gastrointestinal nematodes, was evaluated in vivo.The presence of S. anthelmia extracts in the cultures decreased the survival of L(3) larvae. The LC(50) of aqueous extract (0.714 mg/ml) differ significantly from the LC(50) of the ethanolic extract (0.628 mg/ml) against the strongyles (p < 0.05, paired t-test). Faecal egg counts on day 12 after treatment showed that the extract is effective, relative to control (one-way analysis of variance [ANOVA], Dunnett's multiple comparison test) at 500 mg/kg against Strongyloides spp. (p < 0.01), 250 mg/kg against Oesophagostomum spp., Trichuris spp. (p < 0.05), and 125 mg/kg against Haemonchus spp. and Trichostrongylus spp. (p < 0.01). The effect of the doses is significant in all cases, the day after treatment is also extremely significant in most cases, whereas interaction between dose and day after treatment is significant (two-way ANOVA). S. anthelmia extract could, therefore, find application in the control of helminth in livestock, by the ethnoveterinary medicine approach.

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Unexpected increased thiabendazole tolerance in Haemonchus contortus resistant to anthelmintics by modulation of glutathione activity.

The effect of several modulators of the synthesis or activity of glutathione (GSH) on the susceptibility of Haemonchus contortus eggs susceptible or resistant to anthelmintics was investigated using in vitro egg-hatch assays. Diethylmaleate, D,L-buthionine-[S,R]-sulfoximine, and patulin induced an unexpected decrease in the susceptibility of resistant eggs to thiabendazole, which was chosen as a reference for resistance to benzimidazole compounds. The results demonstrate that the level of GSH or SH analog plays an important role in the toxicity of thiabendazole to nematode eggs. Comparison with changes observed in the cytotoxicity of antitumor or antiprotozoal drugs after GSH modulation suggests that in H. contortus eggs this increased thiabendazole tolerance might depend on different factors, whether associated or not, including the ability of thiabendazole to conjugate with parasitic GSH or analog, the potential toxicity of such conjugates, their cellular distribution, and their role in the expression of glutathione S-transferase activities, and, perhaps, in the regulation of apoptosis.

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Anthelmintic efficacy of tinidazole against the progression of Toxocara canis larvae to the brain in mice.

The anthelmintic effect of tinidazole (100 mg/kg per day for 3 successive days) was tested in male Swiss CF-1 mice infected with second-stage Toxocara canis larvae at challenge doses of 250, 500, 1000, and 1500 embryonated eggs per mouse. The drug was given orally on days 3-5 postinfection (p.i.) to one-half of the animals, and all mice were killed on day 40 p.i. The number of larvae recovered from each mouse's brain and skeletal muscle was then scored in both groups. Tinidazole yielded a highly significant reduction in the total recovery of larvae from the test animals' brains at the second and third inoculum levels but no statistically significant reduction at the highest larval dose as compared with the values obtained in the untreated control animals.

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Anthelmintic effects of cyclosporin A on protoscoleces and secondary hydatid cysts of Echinococcus granulosus in the mouse.

Cyclosporin A (CsA), employed primarily as an immunosuppressant during the management of organ and graft transplants, exhibits anthelmintic properties. However, its efficacy against tapeworm infections in laboratory models is variable. A preliminary investigation has been undertaken to assess the action of CsA on the establishment and growth of protoscoleces and secondary hydatid cysts of ovine Echinococcus granulosus in mice. Administration of CsA in five consecutive daily doses, beginning 2 days prior to infection, resulted in significant reduction in cyst establishment (measured in terms of cyst masses, cyst numbers and cyst wet weights), when mice were autopsied 20 weeks post-infection. None of these parameters were significantly reduced when the drug was administered 18 weeks post-infection, although wet weight decreased by 42%. Ultrastructural examination of the germinal membrane and laminated layer of late-treated E. granulosus revealed abnormalities in all cysts studied whereas control and early-treated hydatids were normal. A case is made for the consideration of a clinical use for CsA for post-operative control of secondary hydatidosis and its efficacy against hydatid cysts is discussed.

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Evaluation of immune dependence of anthelmintic treatment of Heligmosomoides polygyrus in CBA/Ca mice.

The efficacy of anthelmintic treatment of adult Heligmosomoides polygyrus was evaluated in immunologically intact and immune-incompetent (T-cell-deprived) CBA/Ca mice. There was no statistically significant difference in the cure rate, in terms of percentage reduction in worm burden, following treatment with pyrantel pamoate and levamisole between normal (57-71% reduction) and immune-incompetent mice (69-78% reduction). The rate of expulsion, and the total number, of worms expelled from infected mice following drug treatment were comparable in normal and deprived mice. The activity of 2 drugs against adult H. polygyrus has been shown to be independent of the immune status of the host. The significance of the mode of actions of drugs and the site of residence of a parasite within the host are discussed.

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Chronic infections with Trichostrongylus colubriformis in lambs: influence of anthelmintic treatment on intestinal morphology and mucosal cell populations.

Intestinal mucosal morphology, topography and populations of crypt intraepithelial globule leucocytes (IGLs), goblet cells and mucosal mast cells were compared in 4 groups of 3-month-old lambs which had been reared worm-free from birth. Groups 1 and 2 were infected daily on 5 days per week with 2500 Trichostrongylus colubriformis larvae for 18 weeks. Group 2 lambs were treated with fenbendazole (5 mg per kg) at week 10 and week 15. Group 3 lambs were infected as above with T. colubriformis for 10 weeks, dosed with fenbendazole and given no further larvae. A fourth group of 4 lambs (Group 4) was maintained worm-free throughout the experiment as controls. All lambs were killed at week 20. Worm populations (range 410 to 30460) and mucosal damage varied considerably between individuals in the untreated Group 1 lambs, but damage was severe, with total villous atrophy, in lambs with large worm burdens. In 3 lambs with moderate worm burdens, worms were seen only in circumscribed flat "finger-print" lesions in the jejunal mucosa. There was no correlation between IGL numbers, mast cell numbers and final worm burdens in Group 1 lambs, though there was a trend towards an association between high worm populations and low IGL numbers. Only trivial pathological changes were detected in the re-infected Group 2 lambs. Low worm egg counts were found in this group 4 weeks after the first anthelmintic treatment, and virtually no eggs were present after the second treatment. Mucosal morphology in Group 3 lambs, which were not re-infected, resembled the controls at the end of the experiment. IGL numbers were greater in both treated groups than in controls, and numbers in the re-infected Group 2 lambs were greater than those in Group 3 lambs. Mucosal mast cell numbers did not differ significantly between groups, but crypt goblet cell numbers were increased in all 3 infected groups, compared with controls.

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The anthelmintic action of praziquantel.

Although fairly expensive (around US$4.00 per single dose) praziquantel is now the most favoured drug against all forms of schistosomiasis, and against many other helminth infections. It is now marketed by four companies: E. Merck and Bayer (F.R.G.), Ames-Myers (USA), and Shin-Poon Pharmaceuticals (S. Korea). Administration of praziquantel typically causes paralysis of susceptible worms, or damage to their tegument, making them more vulnerable to host enzymes or antibody-dependent immune effector mechanisms. Other effects may also be involved. Here, Bill Harnett reviews the range of anthelmintic effects displayed by this remarkable drug.

Journal Article↗

Worm control and anthelmintic resistance: adventures with a model.

There are three common questions asked of parasitologists about anthelmintic resistance. Does it matter? How do you prevent it? Can you help me (it's here!)? In short, the respective answers are yes, read on the read on. Elizabeth Barnes, Robert Dobson and Ian Barger examine these issues in the context of nematode parasite control in grazing sheep. With the aid of a model, they examine some important factors that influence drug resistance and how farm management decisions and worm genetics modify these factors. They also explore the likely impact of new technologies on drug resistance and how efficient they need to be to sustain good worm control.

Journal Article↗

Intestinal enzyme activity in lambs chronically infected with Trichostrongylus colubriformis: effect of anthelmintic treatment.

After twenty weeks of continuous dosing with Trichostrongylus colubriformis larvae substantial, but declining, numbers of worms had persisted in most of the lambs examined, although there were wide inter-individual variations. Mucosal lesions were found in the proximal small intestines of all the infected animals, their severity being directly related to worm burden. Representative brush border enzyme activities analysed in intestinal mucosal extracts from the same lambs showed differing responses. Alkaline phosphatase and glycyl-L-leucine dipeptidase were significantly depleted, whereas maltase activity was only marginally reduced, and leucine aminopeptidase activity was normal. Mucosal acetylcholinesterase activity was significantly elevated in the parasitised animals and, interestingly in view of the postulated role of this enzyme in nematode pathogenicity, the level of activity was directly correlated with individual worm burdens. Intestinal trypsin and chymotrypsin activities were unaffected and the level of superoxide dismutase, an enzyme associated with the inflammatory response, was normal. There were also no consistent changes in the mucosal activities of several enzymes including lactic dehydrogenase, creatine phosphokinase, aldolase, and glutamic oxaloacetate transaminase, whose leakage from damaged or necrotic tissues has been well defined in terms of the concomitant increase in their activity in the circulation. Lambs treated orally with fenbendazole five and/or ten weeks before slaughter either in the presence or absence of continued larval intake, had negligible worm burdens, and showed little evidence of intestinal damage at post mortem. Brush border enzyme levels, with the exception of alkaline phosphatase and, in two cases dipeptidase, were normal in these animals. The activity of alkaline phosphatase was approximately double that in the continuously infected, untreated lambs, but remained markedly lower than in the uninfected controls. The activities of the other enzymes studied, including acetylcholinesterase, were within the control range. In summary, in chronic trichostrongylosis even relatively low nematode burdens were associated with marked pathological and biochemical damage in the intestine with both lesion severity and mucosal acetylcholinesterase activity being directly related to worm numbers. Although morphological integrity was completely restored after anthelmintic treatment, the persistent low activity of brush border alkaline phosphatase coupled with the enzymological findings in untreated, infected animals suggests that recovery of the full functional capability of the intestinal mucosa may take longer.

Acetylcholinesterase↗

Anthelmintic evaluation of a thiabendazole-resistant strain of Ostertagia circumcincta recovered from sheep in England.

A total of 35 worm-free lambs were infected with a strain of Ostertagia circumcincta isolated earlier from sheep in Cheshire, England, and found to be resistant to thiabendazole (TBZ). When patency was established the sheep were divided into groups of six, and dosed orally with either TBZ (44 mg kg-1, 88 mg kg-1), fenbendazole (FBZ; 5 mg kg-1) or levamisole (7.5 mg kg-1) or not treated. Three of the remaining five animals were dosed with FBZ at 10 mg kg-1. Egg hatch tests, post-dosing faecal egg counts and post-mortem worm counts confirmed resistance to TBZ, and a degree of side-resistance to FBZ was also revealed. Only levamisole gave the clearance expected of modern anthelmintics.

Animals↗