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PubMed2002

Effects of three anthelmintic treatment regimes against Fasciola and nematodes on the performance of ewes and lambs on pasture in the highlands of Kenya.

The efficacy of strategic anthelmintic control of liver flukes (Fasciola) and gastrointestinal (GI) nematodes on the performance of ewes and lambs on pasture was assessed on a farm in the highlands of Kenya. In May 1999, 45 Corriedale ewes, aged between 2 and 3 years, were ear-tagged, weighed and allocated randomly to three equal treatment groups based on body weight. Faecal samples taken at this time revealed low levels of strongyle-type eggs per gram of faeces (EPG) and the presence of liver fluke eggs in only a few of the animals. All the animals were then set stocked for 12 months on separate paddocks in an area endemic for both Fasciola and GI nematodes. The ewes in group 1 were given a combined anthelmintic treatment against Fasciola and GI nematodes during the periods recommended for the control of Fasciola in the area (February, June and October). The ewes in group 2 were given the combined treatments 3 weeks after the onset of both the short and long rainy seasons (November and April, respectively). Those in group 3 were given separate treatments for Fasciola (February, June and October) and nematodes (3 weeks after the onset of the rainy seasons). The anthelmintic treatment against Fasciola consisted of triclabendazole at 10 mg per kg body weight, and that against nematodes was levamisole at 10 mg per kg body weight. The nematode EPG for the ewes in group 1 were higher than in groups 2 and 3 during both rainy seasons. The nematode EPG did not differ significantly between groups 2 and 3. The prevalence of Fasciola eggs (number of ewes shedding eggs in a group) in the ewes in groups I and 3 remained very low throughout the study period compared to those in group 2. The highest birth weights and the weight gains of lambs were recorded for the group of ewes given separate anthelmintic treatments for Fasciola and nematodes (group 3). The results of this trial indicated that, in an area like Nyandarua District, where liver flukes and GI nematodes are important constraints to sheep production, the best practice is to give separate treatments for the two groups of parasites at the recommended times.

Aging↗
PubMed2002

Anthelmintic paraherquamides are cholinergic antagonists in gastrointestinal nematodes and mammals.

Oxindole alkaloids in the paraherquamide/marcfortine family exhibit broad-spectrum anthelmintic activity that includes drug-resistant strains of nematodes. Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs of these compounds rapidly induce flaccid paralysis in parasitic nematodes in vitro, without affecting adenosine triphosphate (ATP) levels. The mechanism of action of this anthelmintic class was investigated using muscle tension and microelectrode recording techniques in isolated body wall segments of Ascaris suum. None of the compounds altered A. suum muscle tension or membrane potential. However, PHQ blocked (when applied before) or reversed (when applied after) depolarizing contractions induced by acetylcholine (ACh) and the nicotinic agonists levamisole and morantel. These effects were mimicked by the nicotinic ganglionic blocker mecamylamine, suggesting that the anthelmintic activity of PHQ and marcfortines is due to blockade of cholinergic neuromuscular transmission. The effects of these compounds were also examined on subtypes of human nicotinic ACh receptors expressed in mammalian cells with a Ca2+ flux assay. 2DPHQ blocked nicotinic stimulation of cells expressing alpha3 ganglionic (IC50 approximately 9 microm) and muscle-type (IC50 approximately 3 microm) nicotinic cholinergic receptors, but was inactive at 100 microm vs. the alpha7 CNS subtype. PHQ anthelmintics are nicotinic cholinergic antagonists in both nematodes and mammals, and this mechanism appears to underlie both their efficacy and toxicity.

Animals↗
PubMedDate not supplied

Cattle nematodes resistant to anthelmintics: why so few cases?

The apparent lack of anthelmintic resistant nematodes in cattle is due to the management systems used with most cattle and the lack of surveys for resistance. With extensive beef grazing or with beef suckler herds a large percentage of worms are in refugia (not exposed to anthelmintic) and few anthelmintic treatments are used. With dairy replacement heifers resistance can become a problem unless only first year animals are treated and different fields are used for grazing the animals each year. Intensive beefproduction on grass is unsustainable and in New Zealand resistance is already becoming a serious problem. Individual farms require monitoring for resistance and steps taken to avoid the introduction of resistance. New validated tests and surveys for resistance are required as the extent of anthelmintic resistant bovine nematodes is not known.

Animal Husbandry↗
PubMed2001

Anthelmintic activity of the stem bark extracts of Berlina grandiflora and one of its active principles, Betulinic acid.

This study examines the anthelmintic activity of a methanol, hexane and ethylacetate extracts of Berlina grandiflora and purified betulinic acid, the major triterpenoid found in the extract. Caenorhabditis elegans, a free living soil nematode was used as in vitro model in the study. A suspension of worms was treated with the extracts. After seven days of incubation activity was assessed in terms of number of worms exhibiting motiliy. The results showed that methanol, hexane and ethylacetate fractions at 500 ppm showed anthelmintic activities in the order ethylacetate > methanol > hexane from the alcoholic crude extract. The isolated betulinic acid from the ethylacetate fraction at 100 and 500 ppm showed strong anthelmintic activities comparable to piperazine. These results confirm the traditional use of Berlina grandiflora as an anthelmintic and indicate that betulinic acid is the active component.

Animals↗
PubMed1990

Reduced efficacy of anthelmintics in young compared with adult horses.

Studies on a Thoroughbred breeding farm in Ohio from 1982 to 1988 demonstrated the value of three anthelmintic pastes (ivermectin, oxibendazole, pyrantel pamoate) in controlling benzimidazole resistant cyathostomes (small strongyles) in adult horses. However, a comparison of drug efficacy in suppressing faecal egg counts for the full period between treatments showed a significant reduction in efficacy of all drugs in yearling horses compared with adults. Mean faecal egg counts of adult horses were generally kept below 100 eggs per gram (epg) of faeces when using oxibendazole or pyrantel pamoate at four to five week intervals and ivermectin at eight week intervals. By contrast, mean counts of young horses rose as high as 655 epg (oxibendazole), 729 epg (pyrantel pamoate) and 852 epg (ivermectin) within the same time period after treatment. Individual counts of treated yearlings sometimes exceeded 3,000 epg. Three distinct mechanisms appeared to be involved in the poor results in young horses. These were 1) anthelmintic refuge, 2) anthelmintic resistance, and 3) anthelmintic avoidance.

Age Factors↗
PubMed1990

Effects of three anthelmintic schedules on the incidence of colic in horses.

Four privately owned herds (25 to 49 animals per herd) were used in a five-year trial designed to evaluate the effect of anthelmintic schedules on the incidence of colic. These herds had been treated bi-monthly with non-ivermectin, non-benzimidazole drugs for two years before the trial. Prior parasitological studies showed that they had substantial pre-treatment faecal egg counts (900 to 2200 eggs per gramme), and that they were infected with benzimidazole-resistant cyathostomes. In Years 1 and 2 of the trial, all herds (A, B, C, D) were treated bi-monthly with non-ivermectin anthelmintics (Schedule I). In Years 3 to 5, Herd A received monthly non-ivermectin anthelmintics (Schedule II) and Herd C was treated with bi-monthly ivermectin (Schedule III). Herd B was treated with Schedule II in Years 3 and 4 and Schedule III in Year 5. Herd D was maintained on Schedule I throughout the study period. In each herd, the incidence of colic, while on Schedule I, was compared to the incidence while on Schedule II or III. The risk of colic for horses on Schedule I was 2.61 to 13.04 times that of the same horses while on Schedule II and 2.27 to 9.64 times that of the same horses while on Schedule III. In Herd D, treated according to Schedule I for five years, the incidence of colic did not vary significantly throughout the study period. More effective anthelmintic treatment schedules decreased the incidence of colic in these herds, supporting the conclusion that bimonthly treatment with non-ivermectin drugs may not maximise horses' health in all management conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Nippostrongylus brasiliensis infection in the rat: effect of iron and protein deficiency on the anthelmintic efficacy of mebendazole, pyrantel, piperazine, and levamisole.

The benzimidazole anthelmintics mebendazole and fenbendazole have been shown to be much less effective against Nippostrongylus brasiliensis infections in the rat on a combined iron and protein deficient diet. In the present experiments it was shown that the anthelmintic efficacy of mebendazole was significantly impaired in the rat on either an iron deficient or a protein deficient diet. Furthermore, iron and protein deficiency reduced the efficacy of the anthelmintics pyrantel and piperazine but not levamisole. The finding that nutritional deficiencies reduce anthelmintic efficacy may well be relevant to worm eradication programmes in iron deficient and protein calorie malnourished populations.

Anemia, Hypochromic↗
PubMed1992

Slowing the spread of anthelmintic resistant nematodes of sheep and goats in the United Kingdom.

Anthelmintic resistant nematodes pose an increasing threat to animal welfare and lamb production on lowland sheep farms in the United Kingdom. Based on published information on anthelmintic resistance in nematodes and insecticide resistance in arthropods, seven recommendations are made for reducing the development and spread of anthelmintic resistant nematodes. The two most important are probably to prevent the introduction of resistant worms through the purchase of stock and to reduce the reliance on frequent anthelmintic treatments by using epidemiological principles of nematode control.

Animals↗
PubMed2004

Adverse drug reactions to anthelmintics.

BACKGROUND: Anthelmintics are commonly used in tropical areas, but are also prescribed in Western countries with other climates. However, pharmacoepidemiologic studies of these drugs are rare. OBJECTIVE: To investigate adverse drug reactions (ADRs) due to anthelmintics. METHODS: All spontaneous reports of ADRs associated with albendazole, diethylcarbamazine, flubendazole, ivermectin, mebendazole, niclosamide, praziquantel, pyrantel pamoate, and thiabendazole were identified in the French Pharmacovigilance Database from January 1, 1985, to August 31, 1999. For each case, the following data were recorded: age, gender, weight, ADRs, drug, dosage, and indication. RESULTS: A total of 243 cases were found corresponding to 291 ADRs. Serious ADRs (hematologic or hepatic injury) to albendazole most often occurred when the drug was used for the treatment of echinococcosis or cysticercosis, thus requiring both high dosage and long duration of therapy. Our data show that the profile and seriousness of anthelmintic-induced ADRs vary according to their use. Furthermore, the low number of spontaneous reporting of ADRs suggests a high rate of underreporting for these drugs, which are often considered in France as orphan drugs. CONCLUSIONS: The improvement of reporting of serious or unrecognized (unlabeled) anthelmintic-induced ADRs will increase our knowledge of the benefit/risk ratio associated with these agents and optimize their use.

Adolescent↗
PubMed2002

PF1022A and related cyclodepsipeptides - a novel class of anthelmintics.

Parasitic nematodes are a major cause of morbidity and mortality in man and also cause widespread loss of food production by infection of livestock. A milestone in the chemotherapy of nematode infections, especially in animals, was the discovery of the avermectins and milbemycins during the 1970s. Since the discovery of these highly active macrolides, reports of potent new classes of anthelmintics have been scarce. One of the most outstanding recently reported anthelmintics is the cyclooctadepsipeptide PF1022A, the most active member of a novel class of anthelmintic agents. During the past years several total syntheses of PF1022A and manifold structure-activity relationships have been established. Additionally, the biosynthesis of PF1022A has been elucidated and intensive investigations into the mode of action of this novel anthelmintic are underway. Comprehensive studies including cyclodepsipeptides with smaller ring-sizes, such as the enniatins, proved the PF1022 family and related cyclodepsipeptides to be the most promising follow-up candidates for the avermectins and milbemycins, which suffer from increasing nematode resistance.

Animals↗
PubMed1997

A survey of anthelmintic resistance on ten sheep farms in Mashonaland East Province, Zimbabwe.

A survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 10 randomly-distributed farms in the Chivhu District, Mashonaland East Province, Zimbabwe. Before the survey, a questionnaire was circulated to the farmers concerning nematode parasite control. Results showed that parasite control using anthelmintic treatment was the only method practised and that the benzimidazoles were the most frequently used anthelmintic drugs. The faecal egg count reduction test was used to detect resistance. The anthelmintic groups tested were benzimidazoles, levamisole and ivermectin. Resistance to benzimidazoles was detected on 6 of 10 farms and levamisole resistance on 2 of 3 farms. Ivermectin resistance was not observed on the farms surveyed. Post-treatment larval cultures indicated that Haemonchus contortus survived administration of fenbendazole, albendazole, oxfendazole and levamisole. A Cooperia sp. strain resistant to albendazole was detected and this is the first report in Zimbabwe of a resistant parasite in this genus.

Animals↗
PubMed2003

Little anthelmintic drenching required for lambs finished over winter and spring on annually re-established irrigated pasture on the Highveld of Gauteng Province, South Africa.

As part of a trial to test the profitability of finishing weaner lambs over winter and spring on the Highveld of Gauteng province, an investigation was carried out over 4 consecutive years as to whether or not worm control was necessary while the lambs were on irrigated, improved pastures. Pastures that had not been grazed by sheep or other livestock for at least 5 years were planted to annual ryegrass (Lolium multiflora) that was ploughed under and replanted annually. Weaner lambs were randomly divided into either 2 (A and B) or 3 (A, B and C) groups and finished from April/May to November/December on a separate pasture per group. While Group A lambs were dewormed before being placed on pasture, those in Groups B and C were not. Faecal egg counts were performed at irregular intervals, and when the lambs were sold at the conclusion of each year's trial, the gastrointestinal tracts of 4-5 lambs per trial group were processed for worm recovery. Haemonchus contortus was the dominant worm species, while Trichostrongylus colubriformis, Ostertagia circumcincta and Trichuris spp. were encountered sporadically. From the results obtained it seems unlikely that there is appreciable 'carry-over' of the various worm species from year to year on pastures that are ploughed and replanted annually; thus it is improbable that there will be a build-up of anthelmintic-resistant worms. While on pasture, no drenching was required for the Group A lambs (dewormed before placing on the pasture), nor in 2 of the 4 years in Groups B or B+C that were not drenched and were lightly infected at the start. In the remaining 2 years Groups B or B+C were drenched once only during the course of each trial. Thus, under the conditions as in this study, little worm control is necessary, provided faecal worm egg counts are done to gauge the levels of infection before the lambs are placed on pasture, and to guard against the possibility of an increase in worm burdens thereafter in some years. Also, because of the apparent lack of carry-over between years, anthelmintic treatment at the time of introduction of the lambs or during the period of finishing should be safe as regards progressive selection for anthelmintic resistance. It is also likely to be cost-effective, considering the low cost of anthelmintics in relation to the price of lambs, to counter the possibility of a loss in production if lambs were to harbour relatively heavy worm burdens when introduced.

Animals↗
PubMed1995

Anthelmintic profile of the cyclodepsipeptide PF1022A in in vitro and in vivo models.

A novel cyclodepsipeptide of fungal origin, PF1022A, recently was reported to have anthelmintic activity. To supplement published reports and determine potential utility of PF1022A as a ruminant anthelmintic, the compound was examined in in vitro and in vivo models. Assays used measured motility of Haemonchus contortus (intrinsic drug potency), ATP levels (parasite death), and activity against H. contortus, Ostertagia ostertagi, and Trichostrongylus colubriformis in the jird (spectrum, potency, and efficacy by various routes). The potency of PF1022A in reducing motility is greater than commercial anthelmintics. Examination of ATP levels in PF1022A-paralyzed H. contortus indicates that worms are not killed, suggesting the compound acts as a neurotoxin in nematodes. In the jird, PF1022A has activity orally against each of the parasites studied and at doses comparable to all commercial anthelmintics, except the macrocyclic lactones which are more potent. Unfortunately, for some nematode species, parenteral delivery is ineffective at realistic doses.

Adenosine Triphosphate↗
PubMed2002

A survey on the occurrence of resistance to anthelmintics of gastrointestinal nematodes of goats in Mozambique.

A survey to study the extent of anthelmintic resistance was conducted in Maputo and Gaza, two of the ten provinces of Mozambique, during February and March, 1999. A total of 12 flocks, six in Maputo and six in Gaza, was surveyed. The faecal egg count reduction test was used to assess the efficacy of three anthelmintics most often used in Mozambique, namely albendazole, fenbendazole and levamisole. The degree of resistance was calculated using two different methods, and varied according to the method used. Using the formula of Coles, Bauer, Borgsteede, Geerts, Klei, Taylor & Waller (1992), resistance to the benzimidazoles was detected in one flock in Maputo and one in Gaza, and to levamisole in three flocks in Maputo and one in Gaza. When the formula of Dash, Hall & Barger (1988) was used, however, resistance to the benzimidazoles was detected in only one flock in Maputo, and no resistance to levamisole was detected. The 12 farms surveyed were too few for conclusions to be made on the prevalence of anthelmintic resistance in goats in Mozambique as a whole. Therefore, an extensive survey at national level is needed. This study gives evidence, however, that anthelmintic resistance in nematode parasites of goats is an emerging problem, to which special attention should be paid.

Albendazole↗
PubMed1991

Overberg Research Projects. XI. First stage larval reduction test to assess anthelmintic efficacy ante mortem in sheep.

Two field trials, one with suckling Merino ewe lambs and the other with yearling Dohne Merino rams, are described. In these the anthelmintic efficacy of febantel (a benzimidazole), ivermectin, levamisole and morantel are compared, using the 1st stage larval reduction test. The mean natural log (+1 for zero values) of the post treatment larval counts of the treated groups was compared with that of the untreated controls and the percentage reduction used to assess anthelmintic efficacy. Febantel was only 87.4% effective against Teladorsagia in suckling lambs but the other anthelmintics were more than 99% effective against this genus. Efficacy against Haemonchus and Trichostrongylus ranged from 93.2%-100% for all 4 compounds. In the rams all compounds were 100% effective against Trichostrongylus, with the exception of morantel which was only 87.5% effective. None of the compounds were effective against Teladorsagia, particularly morantel, animals treated with which having more larvae than the controls. The interpretation of anthelmintic efficacy; the advantages of the first stage larval reduction test, compared with the faecal egg count reduction test; and the importance of incubating cultures at 30 degrees C for 24 h, in order to harvest first stage larvae, are discussed.

Animals↗
PubMed1990

Structure-activity relationships of benzothiazole and benzimidazole anthelmintics: a molecular modeling approach to in vivo drug efficacy.

An investigation of the biochemical effects of an anthelmintic, tioxidazole (TIOX, methyl 6-[n-propoxy]benzothiazole-2-carbamate), on Hymenolepis diminuta in experimentally infected rats is reported. The chemotherapeutic actions of TIOX on H. diminuta in vivo were accompanied by marked changes in worm weight and chemical composition. Tapeworms recovered from rats that had received a therapeutically effective dose of TIOX 24 hr earlier were significantly smaller and contained much less glycogen (as a percentage of the wet weight) than worms from untreated controls. In TIOX-treated worms, protein concentrations rose at a rate sufficient to offset the decline in glycogen concentration. Glycogen/protein ratios in TIOX-treated worms were considerably lower than the corresponding control-values. Differences in the absolute amounts of glycogen and protein between control and drug-treated worms were even more pronounced. Administration of a subcurative dose of TIOX to the rat produced in H. diminuta another change, the onset of which preceded the gross alterations in worm weight and chemical composition. In vitro studies, carried out 18 hr after treatment, revealed that TIOX-treated worms absorbed and metabolized much smaller quantities of exogenous glucose than did the controls and that the ability of the worm to accumulate glucose against a concentration difference was significantly depressed. A mode of action common to the structurally related benzothiazole and benzimidazole anthelmintics is indicated by the similarity of their biochemical and physiological effects on the tapeworms and their time course of action when administered to rats infected with H. diminuta. Molecular modeling revealed that the benzothiazole and benzimidazole anthelminitics are congruent electronically and structurally. In vivo drug efficacy depends upon the magnitude of the molecular dipole moment and the percentage of polar surface area. Within the benzimidazole series, structural and electronic congruence is found between the 2-thiazolyl and 2-methyl carbamate groups, suggesting that these groups behave similarly in transport to, and binding at, the active site. Finally, anthelmintics that have the 5' substituents twisted out-of-plane were more active than those anthelminitics with 5' substituents in-plane. All of these factors implicate a highly polar, L-shaped cleft to which the anthelmintics bind at the active site.

Animals↗
PubMed1990

Overberg research projects. V. Anthelmintic sales in the Bredasdorp area of the southern Cape.

In the Bredasdorp anthelmintic market segment with its 327,764 sheep and goats and 19,818 cattle, 1,323,770 therapeutic doses of anthelmintic for sheep and goats and 6,622 therapeutic doses for cattle, worth R456,800.46 and R22,548.31, respectively, were sold during 1988. Fewer than 4 market segment therapeutic doses of nematocide, with an annual total average cost of R1.40 per animal, were sold for sheep and goats, while only an estimated 33 1/3% of the cattle received an anthelmintic, at an annual average cost of R3.41 per animal. Anthelmintic prices fluctuated by -12 to +42% in 16 months. Benzimidazoles were responsible for 38.5%, ivermectins for 22.1% and combination products for 19.4% of sales. The injectable formulation of ivermectin was responsible for 38.5% of ivermectin sales and probably used primarily in the control of sheep scab.

Animals↗
PubMed1990

A novel anthelmintic model utilizing jirds, Meriones unguiculatus, infected with Haemonchus contortus.

Currently, no in vivo laboratory model is available for evaluating anthelmintics against the important ruminant helminth Haemonchus contortus. This report outlines a novel anthelmintic assay utilizing immunosuppressed (0.02% hydrocortisone in feed) jirds, Meriones unguiculatus, infected with H. contortus. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus, treated per os on day 10 postinoculation (PI), and necropsied on day 13 PI. Each stomach was removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Stomach contents were examined using a stereomicroscope (15-45x). A variety of standard anthelmintics has been evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses (mg/kg) comparable to those required for efficacy against H. contortus in ruminants. This model provides an important new tool to assess preliminarily the activity of experimental drugs against H. contortus in vivo prior to studies in ruminants and also may provide a useful tool for studying host-parasite interactions for H. contortus.

Animals↗