Effect of removing anthelmintic selection pressure on the benzimidazole resistance status of Haemonchus contortus and Trichostrongylus colubriformis in sheep.
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Animals↗
Biomedical subjects
J D Kelly
Publications and source records attributed to J D Kelly.
Tissue levels of ascorbic acid during rat gestation.
Maternal rat lung, liver, kidney and portions of small intestine lost up to 40% of their ascorbic acid between early pregnancy and the 15th day of gestation. From then to the end of pregnancy, the ascorbic acid content of the tissues increased by 30 to 60%. Ascorbic acid in fetal lung doubled in concentration on the 18th day of fetal life before a pre and post natal value of 200 micrograms/g tissue was established. Fetal liver had a minor rise in ascorbic acid concentration on the 18th day. Just prior to birth, the ascorbic acid content in fetal lung was 30% and fetal liver 50% higher than maternal.
Animals↗
Comparison of 111In-oxine and 111In-acetylacetone for the labeling of cells: in vivo and in vitro biological testing.
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Animals↗
Factors influencing the fate of 111indium-labelled lymphocytes after transfer to syngeneic rats.
Thoracic duct lymphocytes were labelled in vitro with 111indium-oxine or 111indium-acetylacetone in order to follow their migration after i.v. injection into syngeneic rats. Under certain conditions both preparations produced results with quantitatively confirmed data obtained by other approaches to the physiological pattern of lymphocyte recirculation. However, three significant difficulties were identified: (1) chemical toxicity by minor contaminants of the preparation; (2) radiation damage indicated by a progressive impairment of the recovery of radioactivity from lymph nodes. A labelling concentration of 20 microCi/10(8) cells was the highest compatible with survival of most lymphocytes for 24 h in vivo as confirmed by autoradiography; (3) rapid loss of 111In in vivo found at labelling concentrations below 1 microCi/10(8) cells. By one week after the injection of lymphocytes labelled at 20 Micro/Ci/10(8) cells most of the 111In had been transferred from lymphocytes to non-recirculating radioresistant cells within the spleen and lymph nodes.
Animals↗
The effect of iron and protein deficiency on plasma levels and parasite uptake of [14C] fenbendazole in rats infected with Nippostrongylus brasiliensis.
The Nippostrongylus brasiliensis-rat model was used to determine whether iron and protein deficiency, which are commonly associated with parasitic infections, affected the pharmacokinetic behaviour of fenbendazole as measured by plasma concentrations and uptake by worms. Plasma 14C concentrations after [14C] fenbendazole administration were higher in iron and protein-deficient rats than in sufficient rats. However, the uptake of 14C by N. brasiliensis in iron and protein-deficient rats was significantly less than in worms from diet-sufficient rats. The reduced anthelmintic uptake by worms in protein and iron-deficient hosts may account, in part, for reduced anthelmintic efficacy under these circumstances. These findings are relevant to understanding variations in response to chemotherapy in populations of parasitised hosts containing malnourished individuals.
Animals↗
Delayed expulsion of the nematode Nippostrongylus brasiliensis from rats on a low protein diet: the role of a bone marrow derived component.
Rats on a low protein diet, containing 10% casein as the only source of protein, have an impaired capacity to expel primary infections with the nematode Nippostrongylus brasiliensis and remain susceptible to reinfection. In the present study, the transfer of syngeneic bone marrow cells to rats on a low protein diet reconstituted the expulsion mechanism allowing parasite rejection to occur at the same rate as rats on a sufficient diet. Serum transfer, on the other hand, did not significantly alter the rate of worm expulsion. These results demonstrate that a bone marrow derived component plays an important role in the impaired immunity of rats fed a low protein diet.
Animals↗
Resistance to benzimidazole anthelmintics in equine strongyles. 1. Frequency, geographical distribution and relationship between occurrence, animal husbandry procedures and anthelmintic usage.
A survey was conducted to determine whether benzimidazole resistant populations of equine strongyles are present in New South Wales and north central Victoria; what is their frequency and geographical distribution; which species are involved; and whether different methods of parasite control could be related to the occurrence and frequency of anthelmintic resistant populations. Resistant populations of strongyles were found over wide areas of New South Wales and in north central Victoria. There was no relationship between geographical location and the occurrence of benzimidazole resistance. The species involved were small strongyles of the sub-family Cyathostominae. There was a direct correlation between the occurrence of resistance (including the level at which it is present) and the frequency of use of benzimidazole anthelmintics. Examination of management practices showed that resistance is not an important problem on farms where different chemical classes of anthelmintics were used in a slow rotation programme; combination anthelmintic therapy (for example, benzimidazole/piperazine/organophosphates) was used and anthelmintic treatment was given at intervals of not less than 16 weeks. Tentative suggestions are made for the control of small strongyles in the light of an emerging resistance problem.
Animal Husbandry↗
Resistance to benzimidazole anthelmintics in equine strongyles. 2. Evidence of side-resistance, and susceptibility of benzimidazole-resistant strongyles to non-benzimidazole compounds.
The susceptibility of a known thiabendazole-resistant population of small strongyles to anthelmintics of both benzimidazole and non-benzimidazole groups, was determined. In the first study, 42 horses infected with thiabendazole-resistant small strongyles were allocated to 6 groups. Treatment groups received one of the following anthelmintics: mebendazole, febantel, febantel plus trichlorphon, morantel tartrate, or a combination of thiabendazole, piperazine and trichlorphon. Morantel tartrate and the thiabendazole/piperazine/trichlorphon combination produced highly significant (p less than 0.001) reductions in faecal strongyle egg counts 20 days post-treatment. Mebendazole, febantel and febantel plus trichlorphon failed to reduce strongyle egg counts significantly. Larval culture and differentiation indicated that in all cases of anthelmintic failure, small strongyles of the sub-family Cyathostominae were involved. Eighteen horses from groups in which treatment had failed were re-allocated to 3 groups. Treatment with either morantel tartrate or haloxon was highly efficient in reducing faecal strongyle egg counts. In the final study, fifty-four horses, infected with benzimidazole-resistant small strongyles were allocated to 10 groups. On day zero, each treatment group received one of the following anthelmintics: thiabendazole, cambendazole, mebendazole, oxibendazole, piperazine, thiabendazole/piperazine, cambendazole/piperazine, mebendazole/piperazine or oxibendazole/piperazine. Oxibendazole, piperazine and the benzimidazole/piperazine combinations produced highly significant reductions in faecal strongyle egg counts 20 days post-treatment (p less than 0.001). When administered alone, benzimidazole anthelmintics failed to reduce strongyle egg counts significantly, with the exception of oxibendazole. Larval culture and differentiation indicated that in all cases of anthelmintic failure, the species involved were small strongyles of subfamily Cyathostominae. There was no significant increase in benzimidazole resistance level (based on in vitro assay) as a result of drug treatment, over one generation.
Animals↗
Use of guniea pigs to assay anthelmintic resistance in ovine isolates of Trichostrongylus colubriformis.
Guinea pigs infected with Trichostrongylus colubriformis were used to develop an assay for anthelmintic resistance by determination of worm burdens following treatment with test anthelmintics. To achieve comparable efficacy with the recommended dose of thiabendazole and levamisole in sheep, dose rates in guinea pigs had to be increased two to four fold. For example, thiabendazole at 100 mg/kg in guinea pigs was 96.6 per cent effective against a thiabendazole susceptible (GS) strain of T colubriformis, but had no effect against a thiabendazole-resistant (VRSG) strain. In sheep 50 mg/kg of thiabendazole would have a similar efficacy against each strain respectively. Morantel tartrate at 10 mg/kg in guinea pigs was 99 to 100 per cent effective against the GS strain but only 54 per cent effective against a morantel resistant (PF4) strain. A slope ratio assay was used to calculate the relative potency of anthelmintics by comparing efficacies against resistant strains with efficacy against the GS strain. Resistance of the VRSG strain to thiabendazole was confirmed with a relative potency for this drug of 0.047 in guinea pigs. The PF4 strain was resistant to both thiabendazole and levamisole which had relative potencies of 0.168 and 0.255 respectively. The advantages of this statistical treatment together with the cost and time savings of the guinea pig model over a conventional critical anthelmintic assay in sheep are discussed.
Animals↗
Five generations of selection with benzimidazole and non-benzimidazole anthelmintics against benzimidazole resistant strains of Haemonchus and Ostertagia spp in sheep.
Benzimidazole resistant strains of Haemonchus contortus and Ostertagia spp were subjected to selection pressure over five laboratory generations with the recommended dose rates of either cambendazole, oxfendazole or morantel. A change in response, with larger residual worm burdens remaining after treatment at the fifth generation, was shown for both cambendazole and oxfendazole against both species of nematode. No change in response against either species are shown for morantel. The results are discussed in terms of the problem associated with inefficient removal of the adult parasites after treatment.
Animals↗
Changes in response of a benzimidazole resistant strain of Haemonchus contortus from sheep after passing through calves.
A benzimidazole resistant strain of Haemonchus contortus was passaged through lambs only or from lambs to calves and back into lambs. Changes in response to thiabendazole were monitored by using an egg hatch test at each animal passage and by a controlled experiment on adult worms at the final passage in lambs. An increased level of resistance was shown for the isolate during its passage through calves by the egg hatch test, although this was not supported on the adult worms in sheep using a single dose rate of 66 mg/kg of thiabendazole.
Animals↗
Anthelmintic efficacy of low-dose phenothiazine against strains of sheep nematodes susceptible or resistant to thiabendazole, levamisole and morantel tartrate: effect on patent infections.
The anthelmintic efficacy of low-dose phenothiazine therapy, administered as a 1:40 phenothiazine: molasses mixture, was tested against patent infections of strains of Haemonchus contortus, Trichostrongylus colubriformis and Ostertagia spp susceptible or resistant to thiabendazole (an other benzimidazoles), levamisole and morantel tartrate. Phenothiazine reduced faecal egg output for both susceptible and resistant strains of all three nematodes. In daily doses of 0.25 g per sheep per day and above it completely inhibited larval production in susceptible strains. Against resistant strains, there was a reduced efficiency with 82.3 per cent inhibition of egg hatch at the 0.25 g per sheep per day level. Phenothiazine treatment had no significant effect on worm numbers for either susceptible or resistant worms. It is suggested that benzimidazole-resistant strains may be cross-resistant to phenothiazine.
Animals↗
Anthelmintic efficacy of low-dose phenothiazine against strains of sheep nematodes susceptible or resistant to thiabendazole, levamisole and morantel tartrate: efficiency against sequentially administered infections.
Low-dose daily phenothiazine therapy, administered as a 1:40 phenothiazine:molasses mixture, was tested against sequential infections of strains of Haemonchus contortus. Trichostrongylus colubriformis and Ostertagia spp susceptible or resistant to thiabendazole, levamisole and morantel tartrate. Phenothiazine at a dose rate of 0.5 g per sheep per day significantly reduced the numbers of worm eggs per gram of faeces in both susceptible and resistant strains by an average of 48 per cent and 60 per cent respectively. Phenothiazine completely inhibited larval production in susceptible strains. With resistant worms, larval production was depressed by up to 85.7 per cent. Treatment with phenothiazine : molasses mixture reduced the numbers of worms which became established in resistant Ostertagia spp and susceptible T colubriformis but had no effect on the establishment of susceptible H contortus and Ostertagia spp or resistant H contortus and T colubriformis.
Administration, Oral↗
Prolonged anthelmintic effect of closantel and disophenol against a thiabendazole selected resistant strain of Haemonchus contortus in sheep.
Two long-acting anthelmintics, closantel and disophenol, were tested by treatment 90, 60 and 30 days before challenge with a thiabendazole selected laboratory strain of Haemonchus contortus. The sheep were slaughtered 28 days after infection for total worm counts. A significant reduction in the number of adults remaining at autopsy was recorded after treatment with both anthelmintics 30 and 60 days before challenge but there was zero efficacy when the animals were treated 90 days before challenge. No significant difference was exhibited between the two compounds. Variability in response was recorded between animals on the 60 day period of treatment, which for disophenol may be dose related because animals receiving the lower volumes showed higher worm counts. For both anthelmintics a variability in the rate of metabolism may be responsible. The possibility offered by both anthelmintics for treating benzimidazole resistant strains of H contortus is discussed.
Animals↗
Use of disophenol for the control of Haemonchus contortus in sheep in West Java, Indonesia.
The result of a field trial investigating the anthelmintic effect of disophenol against H. contortus in sheep raised under Asian small farming practice is reported. it was clearly shown that a single injection of disophenol suppressed the numbers of H. contortus to very low levels for periods up to 3 months despite the presence of large populations of H. contortus infective larvae available on pasture and herbage grasses.
Animals↗
The segregation of lambs into 'responders' and 'non-responders': response to vaccination with irradiated Trichostrongylus colubriformis larvae before weaning.
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Animals↗
The problem of anthelmintic resistance in nematodes.
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Animals↗
High performance liquid chromatographic determination of phenothiazine residues in sheep tissues.
A high performance liquid chromatographic (HPLC) technique is described for the determination of residue levels of the anthelmintic drug phenothiazine in sheep tissues. Phenothiazine was administered to sheep which were slaughtered after withholding periods of 24, 48, and 72 h. Residues of phenothiazine were then extracted from tissue samples by homogenization in methanol. The HPLC analysis of the extracts involved separation on a 10 micrometer silica column using a mobile phase of 0.3% n-propanol in cyclohexane. The lower limit of detection by ultraviolet absorption at 254 nm was 0.05 ppm.
Animals↗