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World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine and ovine).

During the 8th International Conference of the World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) held in Sydney, Australia, in 1977, President S. Gaafr appointed a committee to prepare international guidelines for evaluating the efficacy of anthelmintic products. The goal was to develop uniform testing standards and registration requirements to expedite the testing and approval of effective products with a minimum of labor, money, and experimental animals without sacrificing scientific validity. Achievement of such a goal would mean that data from investigators in one country could be used in registering drugs in another country. These guidelines, which were approved by the membership at the general meeting of the 9th International Conference of the W.A.A.V.P. on July 16, 1982 in Budapest, Hungary, are only a beginning in the development of uniform international methods for testing the efficacy of anthelmintics. We now propose that they be used by the scientific community recognizing that, at this time, these guidelines have not been officially reviewed or accepted by any government regulatory authority. Investigators are encouraged to evaluate this document critically and to recommend modifications promptly to the Committee so that they may be incorporated in these guidelines before the 10th International Conference to be held in Perth, Australia in 1983.

Animals↗

Response of young cattle to anthelmintic treatment during autumn in a mediterranean-type climatic environment.

A worm control programme in which heifers were treated with anthelmintic on three occasions during autumn, was tested in Mediterranean-type climatic environment of south-west Western Australia. The experiment aimed to determine if the treatments would prevent the heifers contaminating their pastures with worm eggs during autumn, thereby improving their growth performances the following winter. An attempt was made to measure the availability of infective larvae of abomasal worms on the heifers' pastures during early winter by counting the worms in steers, previously of low worm status, that grazed with the heifers from late autumn until the start of mating in mid-winter. The anthelmintic treatments reduced the contamination of pasture for most of the autumn. The treated heifers that grazed these pastures grew faster, and by the start of mating two months after the last treatment were about 22 kg heavier, than untreated heifers grazing contaminated pasture. At the end of mating six weeks later the difference was 45 kg in favour of the treated heifers. At this time the heifers grew faster than those left untreated, but by late November they had not attained the weight of the heifers grazing uncontaminated pasture. The heifers that grazed uncontaminated pasture produced more calves the following autumn than did those grazing contaminated pasture. The abomasal worm counts of the steers, with a mean of about 46,000 worms, failed to reveal any difference between treatments in the availability of larvae of abomasal worms on pasture. However, it was concluded that the treatments probably exerted their effect on growth rates by reducing the number of infective larvae ingested by heifers grazing the uncontaminated pasture during winter.

Administration, Oral↗

Chemotherapy of ovine fascioliasis: use of an analytical model to assess the impact of a series of discrete doses of anthelmintic on the prevalence and intensity of infection.

An analytical model of ovine fascioliasis is described. The model describes the essential features of the epidemiological patterns observed in the field and is used to assess the impact of a series of discrete doses of anthelmintic on the prevalence and intensity of infection in the flock. The reduction in prevalence after treatment with anthelmintics is shown to be critically dependent on the distribution of flukes amongst the ewes. The model is further used to define the optimum dosing times for a 2- or 3-dose regime. Model predictions concerning the optimum regime are in accord with usual treatment practices in the United Kingdom. The usefulness of analytical models of this kind in the assessment of disease control strategies is discussed.

Animals↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for evaluating the efficacy of anthelmintics in swine.

As a follow-up to a previous guideline publication on efficacy evaluation of anthelmintics in ruminants, an expert group of the World Association for the Advancement of Veterinary Parasitology presents similar guidelines for the testing of anthelmintics in swine. The goal of the guidelines is to develop uniform testing standards and registration requirements. Data obtained from investigations according to the guidelines should be internationally accepted in the registering of drugs. Further, the use of the guidelines may contribute towards reducing costs, labor and the number of experimental animals used for drug testing.

Animal Feed↗

Inhibition of malate dehydrogenase enzymes by benzimidazole anthelmintics.

Determinations were made of the inhibitory activities of four benzimidazole anthelmintics (Albendazole, Parbendazole, Mebendazole and Thiabendazole) on purified extracts of cytoplasmic and mitochondrial malate dehydrogenase obtained from Ascaris suum, Fasciola hepatica and Moniezia expansa. The highest percentage inhibitions were exhibited by Mebendazole. The results confirm that cytoplasmic MDH and mitochondrial MDH regulator enzymes of glycogen synthesis are the sites of mebendazole inhibitory activity, but the activity sites of the other anthelmintics in the study remain unclear.

Albendazole↗

Economics of a dry-cow anthelmintic drenching programme for dairy cows in New Zealand. Part 1. Overall response in 47 herds.

Trials were conducted on 47 seasonal supply dairy farms (greater than 5500 cows) to assess the economics of a dry-cow anthelmintic drenching programme. The programme was administered during the autumn/winter of 1983 and consisted of two treatments, the first shortly after drying off (late April-early June) and the second shortly before calving (mid-July-late August). The effects of the programme on the body condition of cows over winter and their subsequent milk production and reproductive performance were assessed. Overall, the treatment did not result in a worthwhile improvement in cow condition over winter. However, there was a small, but significant overall increase in milk production (2.24 kg milkfat/cow/lactation = 51.5 l milk; P less than 0.01). Young cows (3 years old) did not respond significantly better than mature cows, but high quality cows (as assessed on the basis of the previous season's milk production) responded significantly better than those of poorer quality. The pre-calving condition of cows did not significantly influence the magnitude of their response. Calving data for the year following the trials indicated that conception rates and time of conception were unaffected by the drench programme. At prices prevailing at the time of the trials, the programme proved to be only marginally economic overall (approximately 1 kg milkfat/cow was required simply to cover the cost of the anthelmintic used). However, levels of response in the individual herds involved varied considerably.

Animals↗

Efficacy of three broad-spectrum anthelmintics against gastrointestinal nematode infections of goats.

Groups of 10 goats, harbouring both naturally acquired and experimental infections of gastrointestinal nematodes, were drenched with either levamisole (5 mg kg-1), albendazole (3.8 mg kg-1) or parbendazole (15 mg kg-1), or remained untreated. Haemonchus contortus was the numerically dominant infection, with Strongyloides papillosus, Trichostrongylus colubriformis and Oesophagostomum columbianum also present. At 5-6 days post-treatment, goats were killed and necropsied. Post-mortem worm counts showed that the reduction in mean total worm burdens was 57.4% in levamisole-treated animals, 71.1% in the albendazole group and 85.1% in the parbendazole group. Reductions for H. contortus were 80.2, 87.9 and 83.9% in the levamisole-, albendazole- and parbendazole-treated groups, respectively. These data indicate that the anthelmintics in question are not being applied at an adequate dose rate for goats, and/or resistance to anthelmintics is occurring in the field in Pernambuco State, northeast Brazil.

Albendazole↗

Relationship of the prevalence of swine helminths to management practices and anthelmintic treatment in Danish sow herds.

During 1982-1984, the occurrence of helminths in 66 sow herds in Denmark was examined by means of faecal samples. The correlations between the prevalences of Ascaris suum and Oesophagostomum spp. and management practices were analysed for fatteners and sows, respectively, resulting in four multivariate models. The helminth prevalences were in general low in large herds, specific pathogen-free (SPF) herds and herds with low weaning age. The multivariate analyses showed that only the two latter correlations were significant. The helminth prevalences of the fatteners were not correlated with anthelmintic treatment. In the sows, anthelmintic treatment was significantly correlated with low prevalences of both helminths, despite samples from recently dewormed sows indicating a rather transitory effect. The prevalences of Oesophagostomum in both fatteners and sows were significantly higher on solid floors with straw bedding than on slatted floors without straw, while this was not the case for Ascaris. Tethering of sows was not significantly correlated with helminth prevalences. Daily cleaning was significantly correlated with low helminth prevalences in fatteners, but not in the sows, while disinfection of the pens was only significantly correlated with low prevalences of Oesophagostomum in fatteners. No correlations to washing of the pens were found. The epidemiology of Ascaris and Oesophagostomum is discussed, especially why the latter is the most sensitive to intensive management.

Animal Husbandry↗

A field evaluation of anthelmintics for control of cyathostomes of horses in Brazil.

The anthelmintic efficacy of ivermectin (IVM), piperazine citrate (PPZ) and fenbendazole (FBZ) alone, and combinations of FBZ with varying dosages of PPZ, was evaluated for the control of strongyles of Mangalarga equids. In all cases of positive strongly egg counts per gram of faeces (EPG) before and after treatment, pure populations of cyathostome larvae with eight gut cells were consistently observed in faecal cultures. The faecal egg count reductions (FECR) were evaluated between Day 7 and Day 56 post-treatment. Significant differences (P less than or equal to 0.05) were found between Day 7 and Day 49 when comparing the mean EPG values of IVM with those of the other anthelmintics. PPZ alone and the combination of FBZ (7.5 mg kg-1) and PPZ (55 mg base kg-1) did not show significant differences during the trial; both groups exhibiting an FECR of greater than 90% between Day 7 and Day 30. Horses treated with the combinations of FBZ (7.5 mg kg-1) and PPZ at either 40 or 25 mg base kg-1, and with FBZ alone at either 7.5 or 15 mg kg-1, showed an FECR of less than 90% 2 weeks after treatment. The emergence of a degree of resistance of strongyles to FBZ and PPZ in a segment of the cyathostomes in this population is suggested.

Animals↗

Efficacy of six anthelmintics against luminal stages of Baylisascaris procyonis in naturally infected raccoons (Procyon lotor).

The efficacy of six anthelmintics against natural infections of Baylisascaris procyonis in raccoons (n = 7 per drug) was determined in a series of critical tests. The drugs were given via moist cat food as a single dose or once daily for three consecutive days. Raccoons treated with pyrantel embonate (1 x 20 mg base kg-1 bodyweight (bwt.)), ivermectin (1 x 1 mg kg-1 bwt.), moxidectin (1 x 1 mg kg-1 bwt.), albendazole (3 x 50 mg kg-1 bwt.), fenbendazole (3 x 50 mg kg-1 bwt.) or flubendazole (3 x 22 mg kg-1 bwt.) expelled 1-198, 2-24, 2-14, 3-80, 2-70, or 2-35 B. procyonis stages, respectively, within the faeces. No roundworm was detected in any raccoon at post mortem examinations 7 days after the end of treatment. These results suggest that any of the six anthelmintics can be used at the dose rates tested in a deworming programme for captive raccoons.

Albendazole↗

Anthelmintic resistance in goats in peninsular Malaysia.

Ninety-six randomly selected farms, located throughout peninsular Malaysia, were surveyed for goat nematodes resistant to benzimidazoles (BZ). On 33 farms BZ resistance was demonstrated by means of an egg hatch assay. Haemonchus contortus was found to be the main species involved in anthelmintic resistance. There was a positive association between the frequency of anthelmintic treatments on a farm and the presence of benzimidazole resistance. To assess the value of the egg hatch assay, faecal egg count reduction (FECR) tests were also performed on 20 farms. On six farms the LD50 of thiabendazole (TBZ) was less than 0.10 micrograms ml-1 and the FECR higher than 95% and on ten farms with an LD50 TBZ of over 0.10 micrograms ml-1 a FECR of less than 95% was measured. On four farms the FECR was less than 95%, although the egg hatch assay showed LD50 TBZ values of less than 0.10 micrograms ml-1 and on two of these three farms a controlled efficacy test confirmed the presence of BZ resistant H. contortus. From these results it can be concluded that the egg hatch assay underestimated the true incidence of benzimidazole resistance. Levamisole resistance was detected with a FECR test on two of ten farms investigated.

Animal Husbandry↗

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bovine, ovine, caprine)

The first edition of the W.A.A.V.P. anthelmintic guidelines for ruminants was published in 1982. Since then improved parasitological procedures have been developed, new therapeutic and prophylactic products have appeared requiring different test methods, and registration authorities are requesting more detailed record keeping and data validation. This second edition addresses these developments and fulfills the original goal of publishing guidelines for high quality, scientifically valid testing standards for trials that would be accepted as proof of efficacy by registration authorities regardless of country of origin. This second edition includes updated guidance on standard parasitological procedures, dose titration, dose confirmation and clinical trials, and provides guidelines for evaluating products for efficacy against anthelmintic resistant parasites, persistence of activity and prophylactic activity. Tests for efficacy against nematodes, trematodes and cestodes are included.

Animals↗

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

This survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 11 farms in the Occidental and 26 farms in the Oriental Regions of Paraguay using the faecal egg count reduction test (FECRT). The anthelmintic groups tested were the benzimidazoles, levamisole and avermectins (both oral and injectable). Overall the levels of resistance were 73%, 68%, 73% and 47%, respectively. Levels of resistance were similar for all three important nematode genera, viz. Haemonchus contortus, Ostertagia and Trichostrongylus. This survey clearly indicates that a large, and ever increasing, proportion of sheep farmers are rapidly approaching the time when they will have exhausted all chemotherapeutic options to control parasites. Unless they face having to abandon their sheep farming operations, radical changes will need to be implemented with urgency.

Animals↗

The value of bulk milk ELISA Ostertagia antibody titres as indicators of milk production response to anthelmintic treatment in the dry period.

An experiment was done to study whether estimation of the herd infection level, by assessing Ostertagia antibodies in bulk milk samples can serve to predict the effect of anthelmintic treatment on milk production. Bulk milk samples were collected from 134 farms at monthly intervals on three occasions prior to the start of the study. The ELISA titres to Ostertagia found in October at the end of the grazing season served as a basis to select 16 and 18 farms as having high and low levels of parasitism respectively. Heifers and cows within each herd were ranked by expected calving date, paired and randomly allocated to be treated with ivermectin or a placebo. Records of milk production and composition were collected for all the trial animals. The response to treatment expressed as the 305 day corrected milk yield of anthelmintic treated animals minus that of placebo treated animals was not statistically significant and amounted to 78 kg for multiparous cows and 124 kg for heifers. For cows as well as heifers the response to treatment was larger in the high antibody level herds than in low antibody level herds, but these differences also lacked statistical significance.

Animals↗

Antibacterial, antifungal and anthelmintic activities of root barks of Uvaria hookeri and Uvaria narum.

On a pharmacological screening, substantial antibacterial, antifungal and anthelmintic activities were observed for the hexane and ethyl acetate extracts of the root barks of Uvaria narum Wall. and Uvaria hookeri King. Chromatographic fractionation of these extracts led to the isolation of the triterpenes glutinol, glutinone, taraxerol, beta-sitosterol and Annonaceous acetogenins uvariamicins-I, II and III mixture, isodesacetyluvaricin, squamocin-28-one, narumicins-I and II stereoisomeric mixture, squamocin and panalicin. The acetogenins exhibited antimicrobial and anthelmintic activities in their individual screening comparable with standard drugs and hence their presence could be attributed to a great extent for the biocidal properties of U. narum and U. hookeri extracts.

Animals↗

Anthelmintic activity of papaya latex against patent Heligmosomoides polygyrus infections in mice.

The purpose of this experiment was to study the possible anthelmintic activity of papaya latex (Carica papaya) against Heligmosomoides polygyrus in experimentally infected mice. Five groups of BALB/C mice were infected with 100 Heligmosomoides polygyrus infective larvae/mouse. After patency (day 22) four groups of mice (groups B, C, D and E) were given papaya latex suspended in water at dose levels of 2, 4, 6 and 8 g of papaya latex/kg body weight, respectively. One group of mice (group A) served as non-treated controls. All animals were necropsied on day 25, i.e. 3 days after treatment, for post-mortem worm counts. The papaya latex showed an antiparasitic efficacy of 55.5, 60.3, 67.9 and 84.5% in groups B, C, D and E, respectively. The results may suggest a potential role of papaya latex as an anthelmintic against patent intestinal nematodes of mammalian hosts.

Animals↗

Anthelmintic usage of extracts of Embelia schimperi from Tanzania.

Embelia schimperi Vatke, belonging to the family Myrsinaceae, is used among the traditional Masai people of Tanzania and Kenya since it is believed to eliminate adult Taenia saginata, the beef tapeworm. In the present study, the anthelmintic effect of an extract of the dried fruits of Embelia schimperi was studied in experimental parasite/rodent models. In two experiments, rats with 10 adult tapeworms of Hymenolepis diminuta were treated with a diammonium salt of embelin (DE), isolated from the fruits. Significant lower numbers and total worm biomass of Hymenolepis diminuta were observed in rats treated with 100 mg DE/kg. Furthermore, clear indications of the occurrence of destrobilation was observed in faeces after treatment and in 16% of the worms found at autopsy. The killing effect shown in vivo was corroborated by in vitro studies, which showed that all adult Hymenolepis diminuta were killed when incubated in a culture medium containing as little as 0.08 mg DE/ml. No significant in vivo effect of DE was observed against Hymenolepis microstoma, the trematode Echinostoma caproni and the nematode Heligmosomoides polygyrus in mice, although the worms could be killed in vitro. These results indicate that the crushed seeds of Embelia schimperi taken orally by the Masai people indeed have an anthelmintic effect against human intestinal tapeworms.

Animals↗

Chimeric cyclodepsipeptides as mimetics for the anthelmintic PF1022A.

In the anthelmintic cyclooctadepsipeptide PF1022A (1) didepsipeptide units have been exchanged for the beta-turn mimetics (D)-Pro-(L)-Pro and BTD (7) in order to elucidate the functional role of the depsipeptide backbone. Compounds 12 and 14 are the first PF1022A analogues in which a substantial part of the PF1022A backbone has been replaced with an improvement of anthelmintical activity. Preliminary structure-activity relationships suggest a symmetric conformation to be the biological active one.

Anthelmintics↗