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PubMed1990

Anthelmintic resistance in nematodes: extent, recent understanding and future directions for control and research.

Resistance has now been reported to all of the broad spectrum anthelmintic types currently available, namely to the benzimidazoles, levamisole/morantel and to ivermectin. The problem causes most concern for parasite control in sheep, but anthelmintic resistance has also been reported in nematodes of horses, goats, pigs and more recently cattle. Our understanding of the factors which select rapidly for resistance has increased and programmes of worm control which minimize selection for anthelmintic resistance are being developed and tested. One of the greatest problems encountered in attempting to reduce the selection for overt drug resistance is the need for more sensitive tests for developing resistance. In the long term, new approaches to chemotherapy and to overcoming anthelmintic resistance problems will arise from improving our understanding of the modes of action of, and mechanisms of resistance to, anthelmintics at the level of the receptor proteins and their genes.

Animals↗
PubMed1996

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Uruguay.

This survey was conducted on 252 farms randomly distributed over all the sheep raising areas in Uruguay. The study involved farms with more than 600 sheep, which represented 80% of the total sheep population of the country. Three anthelmintic groups were assessed, namely, benzimidazoles, levamisole and avermectins. Overall, the results showed 80% of sheep flocks had benzimidazole resistance, 71% had resistance to levamisole, and 1.2% of flocks showed resistance to avermectins. Approximately 28% of farms had resistance to one anthelmintic group, 64% to two anthelmintic groups, and 1% resistance to all three groups. Only 7.5% of farms had no detectable levels of anthelmintic resistance. More than 80% of farms had Trichostrongylus populations resistant to both benzimidazoles and levamisole. Resistance was recorded in all three anthelmintic groups for Haemonchus and resistance also occurred to benzimidazoles and levamisole in Ostertagia.

Agriculture↗
PubMed2001

Genetic variability following selection of Haemonchus contortus with anthelmintics.

Genetic diversity in nematodes leads to variation in response to anthelmintics. Haemonchus contortus shows enormous genetic diversity, allowing anthelmintic resistance alleles to be rapidly selected. Anthelmintic resistance is now a widespread problem, especially in H. contortus. Here, I compare the genes involved in anthelmintic resistance in H. contortus with those that confer susceptibility or resistance on the free living nematode Caenorhabditis elegans. I also discuss the latest knowledge of genes associated with resistance to benzimidazoles, levamisole and the macrocyclic lactones and the need for DNA markers for anthelmintic resistance.

Animals↗
PubMed2003

Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand.

AIM: To establish the efficacy of topical formulations of eprinomectin and abamectin against naturally acquired abomasal and small intestinal nematode infections in cattle purchased from a North Island bull-beef property. METHODS: A controlled slaughter trial, involving eighteen 6-8-month-old mixed breed calves, was conducted in May 2002.The animals were randomly allocated on the basis of faecal egg count to one of three equal-sized groups (n=6), consisting of an untreated control group and two treatment groups. One of the treatment groups was treated with a topical formulation of eprinomectin, the other with abamectin. Both anthelmintics were administered as a single topical treatment on an individual liveweight basis, at the manufacturer's recommended dose rates of 0.5 mg/kg. All calves were housed in separate groups with no access to pasture throughout the entire trial and were slaughtered 7-10 days after treatment. RESULTS: Both anthelmintic treatments were highly effective(worm count reduction >98%) against Ostertagia ostertagi, Trichostrongylus axei and Cooperia punctata, but were not effective at reducing worm counts significantly of either Cooperia oncophora or Trichostrongylus longispicularis. Against these latter two parasites, worm count reductions of only 72% and 79%, and 81% and 76%, respectively, were recorded following treatment with eprinomectin or abamectin, respectively (all p>0.05). CONCLUSIONS: These results demonstrate evidence of resistance to macrocyclic lactone anthelmintics by C. oncophora and probably T. longispicularis also. CLINICAL RELEVANCE: As well as perhaps providing the first record of resistance to any anthelmintic by T. longispicularis, the present findings may also represent the first case of resistance to macrocyclic lactone anthelmintics exhibited by more than one parasite species at a time in cattle in New Zealand.

Journal Article↗
PubMed1999

Economic evaluation of three anthelmintic strategies for lamb flocks affected by benzimidazole-resistant nematodes.

OBJECTIVE: To compare the profitability of three anthelmintic strategies in growing lambs in flocks with nematodes resistant to benzimidazole anthelmintics. METHOD: A partial-budgeting analysis was carried out by means of a stochastic simulation model, which allows inputs to be described as distributions rather than as fixed values, and hence permits variation between farms to be considered in the analysis. RESULTS: The results show that control of nematode parasites by use of an effective anthelmintic provides the highest net returns, yielding a margin over ineffectively treated lambs of A$114 per 100 lambs on average. Suppressive treatment based on the administration of two controlled-release capsules and monthly with moxidectin resulted in an average loss of A$131 per 100 lambs in comparison with animals treated with an ineffective anthelmintic. Analysis of the results from capsule-treated lambs did not take into account the unmeasured benefits associated with less contamination of pastures. Sensitivity analysis using a stochastic model indicates that apart from the effect of treatment on weight gain variation in carcase price greatly influences the profitability of all the parasite control programs examined. CONCLUSION: The results suggest that it is economically important for farmers to adjust their strategy in the presence of anthelmintic resistance. But as a result of uncertainty in the factors influencing economic return, the expected economic benefit is likely to vary substantially.

Animals↗
PubMed1995

Anthelmintic sales in the highveld region of Eastern Transvaal.

Throughout a survey from 1991 to 1993 in the Highveld region of Eastern Transvaal, levamisole sales dominated in the sheep anthelmintic market. The macrocyclic lactone sales dominated in the cattle anthelmintic market, but were superseded by those of levamisole in 1993. The salicylanilides enjoyed the second highest demand in the sheep anthelmintic market. Anthelmintics were purchased throughout the year, but sales peaked in summer and autumn. When it rained in winter, sales increased during winter and peaked in spring. Eastern Transvaal Co-operative (OTK) sold 2,64 therapeutic doses per sheep during the driest year and 3,54 per sheep during the wettest year in the Highveld region. Only 24-29% of the cattle in the region could be treated with the anthelmintics sold by OTK for cattle. Total sales are estimated at double these figures.

Animals↗
PubMed2006

In vitro and In vivo anthelmintic activity of Nicotiana tabacum L. leaves against gastrointestinal nematodes of sheep.

The in vitro and in vivo anthelmintic activity of Nicotiana tabacum L. leaves was studied to rationalize its traditional use. Live Haemonchus contortus were used to assess the in vitro anthelmintic effect of a crude aqueous extract (CAE) and a methanol extract (CME) of N. tabacum. The in vitro inhibitory effect of both the extracts was evident from the paralysis and/or mortality of worms noted at 6 h post-exposure. For the in vivo studies, CAE and CME were administered in increasing doses (1.0-3.0 g/kg) to sheep naturally infected with mixed species of gastrointestinal nematodes. A maximum reduction of 73.6% in eggs per gram (EPG) of faeces was recorded on day 5 post-treatment with CME (3.0 g/kg) while the same dose of CAE showed a 49.4% reduction. Levamisole (7.5 mg/kg), a standard anthelmintic agent, showed a 99.6% reduction in EPG. These data show that the aqueous and methanol extracts of Nicotiana tabacum exhibit dose-dependent anthelmintic activity both in vitro and in vivo, thus justifying its use in the traditional medicine system of Pakistan.

Animals↗
PubMed1994

Effects of gabergic anthelmintics at higher concentrations on the guanidine-induced twitch responses in isolated frog rectus preparations.

Effects of various gabergic anthelmintics on the guanidine-induced twitch responses in isolated frog rectus preparations were examined. All gabergic anthelmintics such as milbemycin oxime, milbemycin D, avermectin B1a, ivermectin, and diethylcarbamazine (DEC) showed stimulatory effects on the guanidine-induced twitch responses at their higher concentrations. Only piperazine caused inhibitory effects on the twitch responses, even at higher concentrations. The stimulation of the twitch responses by the gabergic anthelmintics was antagonized with tetrodotoxin, hemicholinium-3, d-tubocurarine, and strychnine. These results suggest that all gabergic anthelmintics except piperazine stimulate the release of acetylcholine from the nerve endings and that all of them, including piperazine, have different effects on the gabergic mechanism at lower concentrations and on the cholinergic mechanism at higher concentrations.

Acetylcholine↗
PubMed2006

Anthelmintic resistance in trichostrongylid nematodes of sheep farms in Northwest Spain.

A survey to determine the prevalence of anthelmintic resistance in nematode parasites of sheep against the three main families of anthelmintics (benzimidazoles, macrocyclic lactones and imidazothiazoles) was carried out from January 1999 to December 2003 involving 85 flocks in Northwest (NW) Spain. In the study on prevalence of resistance to benzimidazoles, faecal egg count reduction test (FECRT) showed there was resistance in 8 (12.7%) flocks, 1 (1.6%) was suspected, and 54 (85.7%) were susceptible. The results indicated that 9 flocks (34.61%) showed resistance, 1 (3.85%) showed suspected resistance, and 16 (61.54%) were susceptible to the imidazothiazoles. Against macrocyclic lactones, resistance was observed in 8 flocks (15.69%), 4 (7.84%) showed suspected resistance and 39 (76.47%) were susceptible. None of the flocks used in the study showed resistance to the three families of anthelmintics. Nevertheless, six were recorded as resistant or suspected of being resistant to two of these families of anthelmintics. Egg hatch assay (EHA) and FECRT were carried out jointly on 61 flocks, although EHA was done on a total of 83 farms. The results showed that 15 (18.07%) of the 83 flocks were resistant, with egg death 50 over 0.1 microg/ml thiabendazole, and 68 (81.93%) were susceptible to benzimidazoles. When the results between FECRT and EHA were compared, both techniques showed good correlation in field studies. Faecal cultures performed pre- and post-treatment indicated that Teladorsagia and Trichostrongylus were the main genera.

Animals↗
PubMed2004

Comparison of anthelmintic effects of two doses of ivermectin on intestinal strongyloidiasis in patients negative or positive for anti-HTLV-1 antibody.

Coinfection with HTLV-1 (T lymphotropic virus type I) has been observed in approximately 38% of cases of Strongyloides stercoralis infection in Japan. In the present study, we investigated whether the dose of ivermectin corresponding to approximately twice the conventional therapeutic dose could improve the anthelmintic rate without adverse effects in patients with intestinal strongyloidiasis, particularly in those positive for anti-HTLV-1 antibody. A single dose of 6 mg ivermectin (mean, 110 microg/kg) was administered and the same single dose was repeated 2 weeks later in 312 patients with intestinal strongyloidiasis during the period from 1990 to 1999. The long-term anthelmintic rate during the period of 12 months from 4 months after treatment was 77% (117/152) in all patients, and 92.7% (89/96) and 50% (28/56) in those negative and positive for anti-HTLV-1 antibody, respectively. Between 2000 and 2003, ivermectin was administered at 200 microg/kg in 97 patients, and repeated 2 weeks later. The long-term anthelmintic rate was 96.8% (60/62) in all patients, and 100% (42/42) and 90% (18/20) in those negative and positive for anti-HTLV-1 antibody, respectively. These results showed that the long-term anthelmintic rates in all patients in the 200 microg/kg dose group, and especially in those positive for anti-HTLV-1 antibody, were significantly higher than the respective rates of the 110 microg/kg dose group. Based on these results and the observed safety of the double dose of ivermectin, the recommended dose of ivermectin for treatment of intestinal strongyloidiasis should be 200 microg/kg in patients positive for anti-HTLV-1 antibody.

Administration, Oral↗
PubMed1995

The pharmacology of FMRFamide-related neuropeptides in nematodes: new opportunities for rational anthelmintic discovery?

The chemotherapeutic control of helminth parasites is compromised by the limited number of classes of anthelmintic drugs. Discovery of novel anthelmintics is impeded by the lack of novel screening technologies that overcome the difficulties inherent in screens based on whole organism toxicity. The development and implementation of mechanism-based screens for new anthelmintics offers great promise for the revitalization of antiparasitic drug discovery. However, mechanism-based screens must be based on a thorough understanding of the proteins or processes that offer the best chance for selective chemotherapeutic intervention. Basic research on the characterization of nematode FMRFamide-related peptides (FaRPs) has revealed that these peptides are ubiquitously distributed in helminths. Chemical identification of a number of nematode FaRPs has been achieved, and these peptides have potent and profound effects on the nematode neuromuscular system. Physiological processes mediated by nematode FaRPs (and other helminth neuropeptides) offer potential targets for the discovery of novel anthelmintics.

Amino Acid Sequence↗
PubMed1991

Effect of sustained release and pulse release anthelmintic intraruminal devices on development of pathophysiological changes and parasite populations in calves infected with Ostertagia ostertagi and Cooperia oncophora.

An experiment was conducted in calves to investigate the effect of sustained release and pulse release anthelmintic intraruminal boli on the development of pathophysiological changes following daily infection with Ostertagia ostertagi and Cooperia oncophora for six weeks. After infection various pathophysiological changes were detected including increases in serum pepsinogen concentration, enteric plasma protein losses and in the catabolic rate of albumin. Such changes developed rapidly in the unprotected calves following patency after 17 days and persisted until the termination of the study. There were indications that the sustained anthelmintic release device was more efficacious than the pulse anthelmintic release device in reducing the worm burdens and early pathophysiological changes associated with infection. It was found at necropsy that the release of anthelmintic by the oxfendazole pulse release bolus had been delayed in several calves.

Animals↗
PubMed1984

Analysis of anthelmintic trial protocols using sheep experimentally or naturally infected with Fasciola hepatica.

Analytical models of the common anthelmintic trial protocols for ovine fascioliasis are used to investigate the way in which the conventional measure of anthelmintic efficiency (percentage reduction in mean fluke burden) depends on factors other than the additional fluke death rate due to chemotherapy. In prophylactic protocols where infection and dosing are coincident, the natural death rate of the parasites (both flukes and metacercariae) is an important factor. Numerical simulations indicate that the between-trial variations in anthelmintic efficiency due to fluctuations in natural parasite mortality may be substantial, especially for anthelmintic trials in the field.

Animals↗
PubMed1984

The impact of repeated doses of anthelmintic on the intensity of infection and age structure of Fasciola hepatica populations in sheep.

A mathematical model of ovine fascioliasis is used to assess the likely impact of repeated doses of 2 anthelmintic types on the intensity of infection in the ewes. When chemotherapy is applied in the autumn and early winter, the type of anthelmintic that kills proportionately more of the immature parasites brings about a greater reduction in the predicted overall mean intensity of infection than the type of anthelmintic that kills proportionately more of the mature parasites, and leads to a lower predicted burden of mature flukes. In both cases, each dose of flukicide has proportionately less effect on the predicted mean intensity of infection than the preceding one. It is argued that analytical models of the kind described here provide a more informative pre-trial comparison of anthelmintic properties than tabulation of age-dependent kill rates.

Age Factors↗
PubMed1993

Model predictions for anthelmintic resistance amongst Haemonchus contortus populations in southern Brazil.

A computer model developed to study Ostertagia circumcincta resistance to anthelmintics in UK sheep flocks has been adapted for use with Haemonchus contortus under southern Brazilian conditions. The model simulates the effect of different anthelmintic control regimens on the year-to-year pattern of resistance in breeding ewes. The nematode control regimen most used by Brazilian sheep farmers was found to increase the frequency of genes which confer resistance from approximately 3% to 14% in an H. contortus population over a 20 year period. The effect of early versus late season anthelmintic treatment was investigated. This indicated that early season treatment would select for resistance rapidly, whereas late season treatments would not, owing to large numbers of untreated parasites accumulating at the beginning of the season. A model which can predict the development of anthelmintic resistance in parasites of ewes is a valuable tool in the understanding of the effect of different strategies on nematode control programmes and merits further consideration.

Animals↗
PubMed1996

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: Brazil.

This survey was conducted in the southern Brazilian state of Rio Grande do Sul and involved 182 farms located in 26 counties. In addition to the three major broad-spectrum anthelmintic groups (viz. benzimidazole, levamisole and ivermectin) the combination benzimidazole and levamisole and the H. contortus specific anthelmintic, closantel, were tested by the faecal egg count reduction method for the prevalence of anthelmintic resistance. Resistance was found to be 90%, 84%, 13%, 73% and 20%, respectively. This is a crisis situation. Immediate, drastic action needs to be implemented, otherwise the sheep industry in this region (approx. 10 million head) will soon face a lack of any effective anthelmintics with the inevitable consequences of major restructuring or abandonment.

Animals↗
PubMed1996

The prevalence of anthelmintic resistance in nematode parasites of sheep in southern Latin America: general overview.

South America has a large population of small ruminants. Currents estimates are approximately 100 million sheep and 23 million goats. A large percentage of these flocks are raised in the humid tropics/sub-tropics. Nematode parasitism is singly the most important disease of these animals and typically farmers resort to frequent anthelmintic treatment in attempts to control this problem. Because of this reliance on drugs, price consideration is an important determinant in a farmer's choice of anthelmintic. In some circumstances, this has led to unethical practices of drug adulteration and substitution, or the offering to farmers of cheap, sub-standard generic products. The prevalence of anthelmintic resistance has not been investigated in any widespread sense in South America, although some of the first reports of resistance were made in southern Brazil almost 30 years ago. The following series of papers outline surveys conducted in the humid topics/sub-tropics of southern Latin America to assess the significance of resistance to the broad-spectrum anthelmintic groups in nematode parasites of sheep flocks.

Animals↗
PubMed2006

Anthelmintic resistance and alternative control methods.

Anthelmintic resistance has been a problem almost from the first use of the drugs introduced during the past 50 years. Evaluation of anthelmintics on a specific farm is essential to determine which drugs may be used in controlling parasite numbers. Treatment of livestock during the season in which parasite transmission is unfavorable lessens pasture contamination. Targeting treatment places less pressure on susceptible worms, diluting the resistant parasite population. Pasture management and using safe pastures for animals at highest risk lower pasture exposure. Selection for individual animals resistant to the effects of parasites lessens the need for use of anthelmintics. Alternatives to anthelmintics include cryptic antigen vaccines, copper wires, and biologic compounds.

Animals↗