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Anthelmintic treatment in horses: the extra-label use of products and the danger of under-dosing.

Anthelmintic products form the basis of helminth control practices on horse stud farms at present. Regular evaluation of the efficacy of these products is advisable, as it will provide information on the worm egg reappearance period and the resistance status in the worm population. The aim of this study was to evaluate the efficacy of doramectin, pyrantel pamoate, ivermectin and moxidectin on a Thoroughbred stud farm in the Western Cape Province, South Africa. The study also compared the anthelmintic efficacy of two moxidectin formulations administered at their recommended dosages (an injectable, at 0.2 mg/kg, not registered for horses, and an oral gel at 0.4 mg/kg, registered for horses). Two mixed-sex groups of 30 yearlings and 40 weaners were tested in 2001 and 2002, respectively, divided into 3 and 4 groups of equal size. In 2001, moxidectin was one of 3 drugs administered orally and at a dose rate of 0.4 mg/kg. In 2002, pyrantel pamoate and ivermectin were orally administered at 19 and 0.2 mg/kg. Moxidectin and doramectin (the latter not registered for horses) were administered by intramuscular injection at a dose of 0.2 mg/kg, the dosage registered for other host species. The faecal egg count reduction test was used to determine the anthelmintic efficacies in both years. Each animal acted as its own control and the arithmetic mean faecal egg count and lower 95% confidence limit was calculated for each of the groups. A 100% reduction in the faecal egg counts and a 100% lower 95% confidence limit was recorded for moxidectin (0.4 mg/kg) in 2001. In 2002, a 99% and 96% reduction was recorded for pyrantel pamoate and ivermectin, respectively. In the same year doramectin and moxidectin (both injectable and given at 0.2 mg/kg) did not have any effect on worm egg counts. Of the 4 drugs tested in 2002, only pyrantel pamoate recorded lower 95% confidence limits above 90%.

Administration, Oral↗

Anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area of South Africa.

A survey was conducted on the occurrence of anthelmintic resistance of nematodes in communally grazed goats in a semi-arid area in South Africa. In herds belonging to 10 small-holder goat farmers, the efficacies of fenbendazole, levamisole and rafoxanide were tested by faecal egg count reduction (FECR) tests. Efficacies of 80% were considered a threshold for anthelmintic resistance. The FECR tests showed that all drugs tested more than 80% effective in most instances, but there were notable exceptions. In 1 case, rafoxanide was only 31% effective and in another case fenbendazole was only 47% effective. The occurrence of anthelmintic resistance in this farming sector is of concern. Steps should be taken to prevent its further spread and to avoid the development of a situation as on numerous commercial sheep farms in South Africa where resistance is very common.

Albendazole↗

Synthesis and in vitro anthelmintic properties of some new dithiaarsanes.

Fifteen new trivalent organoarsenicals were synthesized and evaluated for anthelmintic properties on three in vitro models, infective larvae of the filaria Molinema dessetae, infective larvae of an intestinal nematode, Nippostrongylus brasiliensis and adults and larvae of Rhabditis pseudoelongata a free living nematode. On the M. dessetae model, the most active compound after a 24 h incubation period had an EC50 of 0.02 mumol/l (compound 3a). Twelve compounds had an EC50 lower than 1 mumol/l whereas potassium melarsonyl exhibited an EC50 of 45.6 mumol/l. After 7 days incubation time, compound 1d had an EC50 of 2 nmol/l. On the N. brasiliensis model, compound 1d was also the most efficient after a 4 day incubation period (EC50 of 1 mumol/l). This compound was 100 times more active than potassium melarsonyl used as a reference compound. Nevertheless, no compound had an EC50 less than 100 mumol/l on Rhabditis pseudoelongata. Concerning the effect of dithiol ligands on the anthelmintic activity of these trivalent organoarsenicals on M. dessetae and N. brasiliensis, 2,2'-dimercaptodiethyloxide was more efficient as dithiol ligand than 1,3-dimercaptopropane which was more efficient than 1,2-dimercaptoethane. Moreover, the para-amino haptophore was more efficient than the melaminyl haptophore. These results showed that the use of new dithiol ligands for trivalent arsenicals enhanced greatly the anthelmintic activity compared with potassium melarsonyl.

Animals↗

[Marketing study of the Russian market of anthelmintics. Assortment analysis].

The range of anthelmintics was studied at the first stage of marketing research. It has shown that there is a small number of their synonyms, a wide range of manufacturing countries, and a predominance of anthelmintics as tablets. Import anthelmintics have been prevalent on the market. However, there is a tendency for the share of anthelminitics made in Russia to increase, which will provide an indubitable economic effect while making health-promoting measures and supporting Russian pharmaceutical industry.

Anthelmintics↗

[Use of anthelmintics for nematode control in sheep in West Germany: results of a survey].

A survey by questionnaires was performed on 543 (0.9% of all) sheep flocks in western Germany in 1988/89 to obtain informations about deworming practices against gastrointestinal nematodes. The major informations are: Anthelmintic treatments were associated with the reproductive status of ewes and the breeding of lambs in most of the flocks. They were performed at an epidemiologically appropriate time in many cases but were not accompanied by essential management practices. (Pro)benzimidazole compounds were the anthelmintics most frequently used by more than 95% of the farmers; 22% and 13% of the farmers additionally or exclusively administered levamisole/pyrantel and ivermectin, respectively. On average, treatment of ewes and lambs against nematodes was performed 2.5 times and 2.8 times a year, respectively. The mean frequency of deworming differed regionally and was generally greater in pedigree breeding flocks than in commercial breeding flocks; it was significantly affected by the husbandry system, the number of ewes per flock, the size of available pasture and the class of anthelmintics employed. The results of this survey revealed that many German sheep farmers obviously lack an awareness of the rationale of preventive and economic control practices against gastrointestinal nematodes.

Animals↗

[Transplanted infections with Toxocara canis as a model for the effectiveness testing of anthelmintics].

Patent infections of adult dogs with Toxocara canis induced by transplantation of immature, intestinal stages were examined for their suitability for testing of anthelmintics. Each of 5 dogs were infected four times by transplantation of 80 immature, intestinal stages of Toxocara canis. The dogs were treated with various anthelmintics of well established efficacy (pyrantel, nitroscanate, mebendazole, piperazine) 20 dpi. All anthelmintics tested showed the same efficacy as had been assessed earlier by treatment of dogs infected prenatally with Toxocara canis.

Animals↗

[New anthelmintics and new treatment systems for the control of parasitic diseases of cattle in pastures].

Advanced knowledge of the epizootiology of parasitic gastroenteritis and the introduction of new anthelmintics and new application systems allow new strategies to control parasites of cattle on pastures. Ideally, parasitic gastro-enteritis is prevented by evasive grazing, i.e. the animals are driven every two weeks to new and not yet contaminated pastures, and the application of anthelmintics is not necessary. Midsummer treatment is most effective when combined with a move to non-contaminated pastures (Weybridge dose and move system). Following the introduction of the slow-release-devices, the prophylaxis of parasitic gastro-enteritis became much easier. The device, which is usually called bolus, is administered before turnout and it results in an effective reduction of the infection risk throughout the grazing season. Treatment following 3, 6 and 9 weeks after turnout prevents the development of dangerous numbers of infective larvae on the pasture in the second half of the grazing season. This system is known as Glasgow model. The pulse-release boluses follow the same principle and they offer the advantage of application at turnout and of releasing the anthelmintic in full doses at intervals. Treatment at the beginning of housing is only necessary when measures to prevent parasitic gastro-enteritis during the grazing season were not sufficient. All strategic measures reduce the risk of lung worm disease, but they do not prevent lung worm infection completely. On farms with a high lung worm pressure, additional control measures may be necessary. In areas with high risk of liver fluke infection, treatment in July may reduce pasture contamination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative effects of anthelmintics on motility in vitro of Onchocerca gutturosa, Brugia pahangi and Acanthocheilonema viteae.

The effects of standard anthelmintics on the motor activity in vitro of adult Onchocerca gutturosa, Brugia pahangi and Acanthocheilonema viteae were determined using a micromotility meter. Fresh adult males dissected from bovine tissues were the best source for observations on O. gutturosa. Parasites liber-ated by collagenase digestion showed poor viability and motility. Only segments of O. gutturosa females were obtainable by dissection and these were not able to sustain motility in vitro. Adult males and females of O. volvulus were active after collagenase digestion of human nodular tissue, but behaved so irregularly that satisfactory monitoring of their movements with the meter was not possible on a regular enough basis to permit quantitation of drug-induced changes. Inhibitory effects on motility of O. gutturosa, B. pahangi and A. viteae were produced by anthelmintics which showed macrofilaricidal effects in vivo in a laboratory rodent model, with the exception of the benzimidazoles. O. gutturosa was, however, much more sensitive than B. pahangi or A. viteae to the temporary paralyzing effects of levamisole and pyrantel. The utility of in vitro screening against O. gutturosa and B. pahangi was evaluated by determining the discriminatory capacity of the tests in detecting novel compounds with reproducible in vivo activity in the jird-B. pahangi/A. viteae model. The results suggested that this would be a valuable selective screening procedure. Although false positives were detected at the rate of 15-17% of the novel anthelmintic chemical series tested, no false negatives were allowed through the screen provided both O. gutturosa and B. pahangi were included.2=

Animals↗

The response of adult and free-living stages of Necator americanus, in vitro, to anthelmintics.

The in vitro response of adults (males and females) and free-living stages of Necator americanus one of the human hookworms, to a wide variety of 20 broad and narrow spectrum anthelmintics was tested. Almost all the broad spectrum anthelmintics influenced males, females and free-living stages at different levels and showed good activity with EC50 values varying from about 0.0002 and 0.0007 mg/l for pyrantel pamoate and tricofenol piperazine respectively to about 8.47 and 7.6 mg/l for morantel tartrate and amoscanate respectively. Certain drugs (emetine, praziquantel and suramin) exerted their effect either on male or female or free-living stages at 10.0 mg/l level. It is concluded that either sex or life-cycle stage alone may not be an effective criteria for screening of anthelmintics which have been employed at large; and females of nematodes (in particular those of N. americanus) should be taken into account for proposing EC50 as they were found to require relatively highest EC50 level in almost all the instances studied presently.

Animals↗

[Pros and cons of anthelmintic treatment of lambing ewes].

The advantages, prevention of gastro-intestinal worm infections in lambs, the improvement in the condition of the ewes during lactation, and the disadvantages, the costs, a possible interference with the build-up of immunity and the risks of the occurrence of anthelmintic resistance are discussed. It is concluded that the advantages more than counterbalance the disadvantages. Providing that the dosage of anthelmintics is correct, that is to say that an overdosage is preferable to too low a dosage, and safe pastures are used, post-lambing anthelmintic treatment of ewes is an effective procedure in preventing gastro-intestinal infections in lambs. Moreover, treatment will eventually improve the condition of the ewes so that, for instance, as the result of a slightly higher milk yield, the gain in weight of the lambs will be promoted.

Animals↗

Screen for anthelmintics, using larvae of Ascaris suum.

A multiwell culture system was used to assay the effects of 12 known anthelmintic compounds on Ascaris suum larval development from 2nd-stage (L2; hatched from eggs) to early 3rd-stage (L3) and from in vivo-derived late L3 to early 4th-stage (L4). Larval survival, development, and motility were monitored for drug effects. Development of L2 to L3 was sensitive to thiabendazole, albendazole (ABZ), ABZ/sulfoxide, ABZ/sulfone (SO), mebendazole, L-tetramisole, D-tetramisole, piperazine, or closantel at a concentration of 0.01 microgram/ml; however, the effects of these drugs on larval development did not correlate well with known effects in vivo. The development of L3 to L4 was blocked by ABZ or mebendazole at 0.01 microgram/ml, by thiabendazole or ABZ/sulfoxide at 0.1 microgram/ml, and by ABZ/SO at 1.0 microgram/ml; however, except for ABZ/SO, most larvae were viable at these concentrations. In contrast, L-tetramisole or morantel appeared to inhibit development of L3 to L4 and to reduce survival at concentrations of greater than or equal to 1 microgram/ml; however, D-tetramisole was at least 10 times less effective. Haloxon, ivermectin, and closantel blocked development of L3 to L4 at 0.1, 1, and 10 micrograms/ml, respectively, in the absence of serum, but their activity was reduced by the presence of serum. Seemingly, in vitro development of A suum larvae was a convenient and sensitive bioassay for anthelmintic activity and could serve as a screen for anthelmintic residues in edible tissues.

Animals↗

Anthelmintic effect of levamisole, ivermectin, albendazole and fenbendazole on larval Toxocara canis infection in mice.

The anthelmintic effects of levamisole (100-50 mg kg-1 live bodyweight), ivermectin (2 mg kg-1 bodyweight), albendazole and fenbendazole (both 100 mg kg-1 bodyweight), were tested against second stage Toxocara canis larvae in mice. Anthelmintic treatment on days 2 to 7 after infection inclusive resulted in significant (P less than 0.05) retention of larvae in the liver, and fewer larvae migrated subsequently to the brain and the musculature of treated mice compared to untreated controls. Most of the larvae retained in the liver subsequently died there and were not recoverable by day 35 after infection, causing significant (P less than 0.05) reduction in the total larval recoveries compared to the controls. The oral route of drug administration caused higher larval retention in the liver than the subcutaneous route. All infected levamisole treated mice survived for four months, whereas half the similarly infected but untreated mice died within the same period. Treatment on days 8 to 13 inclusive after infection had no effect on second stage T canis larvae suggesting that once the larvae have reached the brain and musculature they are not susceptible to anthelmintic agents.

Albendazole↗

[Two cases of Ostertagia spp. in sheep showing resistance to benzimidazole anthelmintics].

Two field isolates of Ostertagia spp. of sheep from the Swellendam and Malmesbury districts in the south-western Cape were shown to be resistant to benzimidazole anthelmintics. At therapeutic dosage rates albendazole was 32,5%, thiabendazole 0%, oxfendazole 14,9% and morantel 91,4% effective against the adult stage of Ostertagia spp. in naturally infested lambs at Swellendam. Efficacy against the adult stage of the same isolate of Ostertagia spp. in artificially infested sheep in the laboratory was tested at dosage rates of albendazole 3,8% mg/kg or 7,6 mg/kg, mebendazole 15 mg/kg, levamisole 7,5 mg/kg and morantel 14,5 mg/kg and varied from 0%, 0%, 1,9% 53,9% and 87,0% respectively. Albendazole, the only anthelmintic tested against the Malmesbury strain of Ostertagia spp. was 9,8% effective against the adult stage in naturally infested lambs. Trichostrongylus spp. and Nematodirus spp. simultaneously present in these animals were fully susceptible to all the anthelmintics tested.

Abomasum↗

Effect of anthelmintic treatment on the milk yield of dairy cows in England, Scotland and Wales.

One hundred and twenty dairy herds collaborated in a trial to determine the effect on milk yield of anthelmintic treatment given at calving. Cows and heifers were divided into five groups. Three were each given a different anthelmintic: thiabendazole, fenbendazole or levamisole. One group was given a placebo and the fifth was untreated. Analysis of data from 9000 lactations showed a treatment effect just significant at the 5 per cent level, of 42 kg milk, 1.8 kg fat and 1.4 kg protein. There was no evidence that the three anthelmintics differed in their effect on yield. The effect of treatment was not greater in heifers than in cows, nor was there a difference between spring and autumn calvers. There was no indication that the effect of treatment was markedly greater in some herds than others and it was not related to periparturient faecal egg count.

Animals↗

Anthelmintic treatments against digestive-tract nematodes in grazing dairy goats with high or low levels of milk production.

The effect of a regular anthelmintic treatment during the grazing period on milk production and milk composition was measured in a dairy goat farm. One month before turnout, 92 goats were given 10 mg.kg-1 febantel and then allocated to 2 equivalent groups according to their levels of milk production. The first group was given febantel monthly, the second group was kept as an untreated control. Parasitological, haematological and serological data were collected monthly from March to September. Milk production data were recorded from March to August, goats being dried up in September. Results of strongyle egg counts, serum inorganic phosphate concentrations and 4 necroscopic examinations indicated a low level of nematode infection composed almost exclusively with Trichostrongylus colubriformis in untreated goats. No significant changes in milk yield, fat and protein content were detected between treated and untreated groups. Moreover, the impact of monthly anthelmintic treatment on milk production was different depending on the initial level of milk yield. Anthelmintic treatment induced a 4-8% increase in milk production for goats with the highest milk yield at the start of the experiment, whereas no beneficial effects were recorded for goats with the lowest milk yield.

Analysis of Variance↗

[Differential diagnosis of delayed encephalopathy induced by anthelmintic imidazoles].

Anthelmintic imidazoles induced delayed encephalopathy (AIIDE) is frequently encountered and has usually been misdiagnosed as sporadic encephalitis of unknown cause (SEU). This study was carried out to facilitate differentiation of the two diseases. The records of 202 cases of AIIDE were reviewed and the clinical features analyzed. As a results, 7 diagnostic criteria for AIIDE were proposed as follows: (1) history of exposure to anthelmintic before the onset; (2) presence of a latent period of of 2 to 5 weeks; (3) onset of the disease acute or subacute; (4) presence of neuropsychiatric symptoms and signs resulted from multifocal cerebral damage; (5) Fulfillment of two of the following conditions; (a) subinflammatory change in CSF with elevation of IgG; (b) diffuse slow waves in EEG during early stage; (c) characteristics of acute demyelinating encephalopathy in brain biopsy; (6) good therapeutic effect of adrenal corticosteroids; (7) exclusion of other neuropsychiatric disorders in a fallow-up period of one year. AIIDE is a new disease entity and its diagnosis is mainly based on the clinical features. EEG, CT or MRI are important diagnostic measures, but history of exposure to anthelmintic is the most important criterion. Multifocal hemorrhagic leukoencephalopathy is its main pathologic feature.

Adult↗

[Structural disorders in the tissues of nematodes of the suborder Ascaridata after exposure to anthelmintics].

The paper analyzes the authors' original findings and the data available in the literature concerning the structural changes in the tissue of Ascaridae after exposure to anthelmintics. The subject of the study of structural changes occurring in the digestive and genital systems represented As. canis lumbricoides, Toxocara mystax, Ascaridia galli. All the anthelmintics under study were found to greatly affect their hypodermis, the wall of the middle intestine and the epithelium of various parts of the genital tubes. All the agent differently caused vacuolization and impaired the integrity of cellular organoids. The middle intestine displayed a local or complete destruction of the brush border, as well as the swelling or pyknosis of epithelial nuclei. Each anthelminthic affected the same tissue of different helminths in a different manner. The nature and magnitude of structural derangements in the digestive and genital systems of Ascaridae depended on the properties of an agent and species-specific responses of nematodes. The used anthelmintics caused only insignificant structural changes in the excretory system.

Animals↗

Ascaris lumbricoides aggregation in relation to child growth status, delayed cutaneous hypersensitivity, and plant anthelmintic use in Madagascar.

The relationships between Ascaris lumbricoides worm burden, growth status, general delayed cutaneous hypersensitivity (DCH) response, and plant anthelmintic use were investigated in a 12-mo prospective survey of 663 children, 4-10 yr old, living in the Ranomafana rainforest, Madagascar. Initial fecal examinations revealed prevalences of 93% for A. lumbricoides, 55% for Trichuris trichuria, and 27% for hookworm. After anthelmintic treatment and a 12-mo reinfection period, 428 of the children participated in worm expulsion studies using pyrantel pamoate, revealing an overdispersed A. lumbricoides worm population, mean = 19.2 (SD = 20.4). Malnutrition was common with 72% of the children growth stunted, 61% underweight, and 6% wasted. The children were also skin tested to recall antigens for DCH, with 94% reacting. The DCH immune response was significantly decreased in the malnourished children; however, DCH was not reduced in relation to increasing worm intensity. Growth status, growth velocity, and triceps skinfold did not vary significantly in relation to A. lumbricoides worm burden. Traditional plant anthelmintic treatment was effective in significantly reducing worm intensity. This study indicates that, in human communities where the children are predominately stunted, A. lumbricoides does not aggregate in the most malnourished or immunodepressed children.

Analysis of Variance↗