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. Gaafar 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, 1981 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.     

World association for the advancement of veterinary parasitology (WAAVP): second edition of guidelines for evaluating the efficacy of anthelmintics in swine

Guidelines are provided for evaluating the efficacy of anthelmintics in swine which, in conjunction with other sets of guidance such as those of the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH GL7 and VICH GL16), should encourage the adoption of uniform registration requirements globally. Testing of efficacy should be carried out according to the principles of "Good Clinical Practice" (VICH GL9, 2000). Data obtained according to these guidelines should be internationally acceptable for the registration of anthelmintics for swine. Further, the use of the guidelines should expedite development, government review, and approval of anthelmintics for swine, as well as contribute towards reducing costs and the number of experimental animals used for drug testing.     

International harmonisation of anthelmintic efficacy guidelines (Part 2).

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.     

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.     

International harmonisation of anthelmintic efficacy guidelines

The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan, and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics: specific recommendations for caprines (VICH GL14). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities.     

The occurrence of anthelmintic-resistant sheep nematodes in the southern North Island of New Zealand

An analysis of veterinary diagnostic cases submitted to the Batchelar Animal Health Laboratory for faecal egg count reduction testing in sheep between 1986 and 1992 showed that 63% of them originated from properties carrying anthelmintic-resistant worms. Most of these cases involved resistance to a single drench type only, with the benzimidazoles being implicated most frequently. Overall, the figures suggested a frequency of occurrence of resistance to benzimidazole anthelmintics of 74%, to levamisole-type anthelmintics of 23% and to benzimidazo-lelevamisole combinations of 30%. No cases of resistance to milbemycin/avermectin-type drenches were recorded.     

A survey on anthelmintic resistance in nematode parasites of sheep in the Slovak Republic

The prevalence of anthelmintic resistance on 27 sheep farms in Slovakia was investigated in 2003 and 2004 using the faecal egg count reduction test (FECRT) according to the WAAVP guidelines. Resistance to albendazole was detected on one farm (3.7%) and suspected on two farms (7.4%) out of 27 sheep flocks. Resistance to ivermectin was tested on 26 farms. On six (23.1%) farms, results indicated the presence of ivermectin resistance. Resistance to ivermectin was suspected on eight farms (30.8%). However, it is also possible that generic ivermectin anthelmintics used in survey have a lower efficacy against sheep nematodes.     

The prevalence of anthelmintic resistance in ovine case submissions to animal health laboratories in New Zealand in 1993

An analysis was undertaken of 177 veterinary diagnostic case submissions to two North Island and two South Island animal health laboratories for faecal egg count reduction testing in sheep during 1993 to provide some comparative data on the frequency of occurrence of anthelmintic resistance. The results suggest that resistance to anthelmintics in sheep nematodes may be more common in the South Island than the North. In both instances this mainly involved resistance to a single drench type, the benzimidazoles. The data indicated a frequency of occurrence of resistance to benzimidazole anthelmintics of 61 and 72%, to levamisole-type anthelmintics of 29 and 29% and to benzimidazole-levamisole combinations of 11 and 22% for submissions to North and South Island laboratories, respectively. In submissions from the South Island, resistance to benzimidazoles involved infections of Nematodirus spp. alone much more frequently than those from the North.     

The prevalence of anthelmintic resistance in ovine case submissions to animal health laboratories in New Zealand in 1993

An analysis was undertaken of 177 veterinary diagnostic case submissions to two North Island and two South Island animal health laboratories for faecal egg count reduction testing in sheep during 1993 to provide some comparative data on the frequency of occurrence of anthelmintic resistance. The results suggest that resistance to anthelmintics in sheep nematodes may be more common in the South Island than the North. In both instances this mainly involved resistance to a single drench type, the benzimidazoles. The data indicated a frequency of occurrence of resistance to benzimidazole anthelmintics of 61 and 72%, to levamisole-type anthelmintics of 29 and 29% and to benzimidazole-levamisole combinations of 11 and 22% for submissions to North and South Island laboratories, respectively. In submissions from the South Island, resistance to benzimidazoles involved infections of Nematodirus spp. alone much more frequently than those from the North.     

Principles for the use of macrocyclic lactones to minimise selection for resistance

OBJECTIVE: To provide principles for the appropriate use of avermectin/milbemycin or macrocyclic lactone (ML) anthelmintics in sheep, to ensure effective worm control and to minimise selection for ML resistance. STRATEGY: The principles were based on an assessment of the information currently available. The MLs were categorised into three groups (ivermectin [IVM], abamectin [ABA] and moxidectin [MOX]) based on structural differences, persistence and efficacy against ML resistant strains. The reported order of activity or efficacy against ML resistant worm strains was IVM相似文献   

Treatment and prevention of intestinal parasite-associated disease.

Since 1917, only 11 new endoparasiticides have been developed for the horse, of which five chemical classes are in common use. The selection pressure of frequent administration of deworming doses for parasite control programs has been associated with the development of resistance of small strongyle parasites to the effects of benzimidazoles and pyrantel salts. Against the background of the inevitability of the occurrence of ivermectin/moxidectin resistance, responsible use of equine anthelmintics based on the clinical pharmacology of the compounds and the biology/epidemiology of intestinal parasites is a major issue for equine clinicians. The evidence base for the recommendations for treatment and control of equine intestinal parasites is sparse, however, and few robust data exist from controlled clinical trials to validate current guidelines.     

Pyrantel resistance in two herds of donkey in the UK

Resistance to currently available anthelmintics is a serious phenomenon which is prevalent globally. Cyathostomins are one of the major parasites, and are of primary concern in donkeys. There have been reports of emerging resistance to pyrantel, but the status of pyrantel resistance in donkey populations in the UK is largely unknown. This report investigates pyrantel resistance in two geographically isolated donkey herds in the South West of England. The first herd had suspected pyrantel resistance, with already established resistance to other anthelmintics. In the second herd the efficacy of pyrantel was not suspected at the time the study took place. Faecal Egg Count Reduction Test (FECRT) was carried out, revealing large scale resistance. Eighty one percent of the first herd and 73% of the second herd had a FEC of less than 95% after treatment, and anthelmintic resistance was confirmed using the World Association for the Advancement of Veterinary Parasitology guidelines. These findings indicate that anthelmintic resistance to pyrantel exists in both tested donkey populations and illustrate the continuing development of resistance through different classes of chemotherapeutics.     

Factors affecting pharmacokinetics of benzimidazole anthelmintics in food-producing animals: the consequences and potential risks

Benzimidazoles are frequently and widely used veterinary anthelmintics. Unfortunately, an administration of these anthelmintics does not always result in the expected therapeutic success. Many host-related factors modify pharmacokinetic behavior and efficacy of a chosen anthelmintic. Pharmacokinetics of anthelmintics varies among animals of different species, sex and age. Also diseases, medication, feed and environmental conditions can significantly affect behavior of anthelmintics and resultant drug efficacy in animals. The presented review gathers information, gained in last 20 years, on factors which bring about the variability in performance of benzimidazole anthelmintics in food-producing animals. It is focused particularly on differences in absorption and metabolism of these anthelmintics as these stages of the pharmacokinetic process seem to be the most important for the overall anthelmintic efficacy. The consequences of abnormalities and alterations in pharmacokinetics of benzimidazole anthelmintics are summarized and discussed.     

Larval development assay for detection of anthelmintic resistance in cyathostomins of Swedish horses

The aim of this study was to investigate the suitability of a larval development assay (LDA) for the determination of anthelmintic resistance in cyathostomin nematode populations of the horse. In addition, comparison of results between geographic regions, types of horse establishment, and the use of anthelmintics in Sweden, was established. Seventy horse herds from different parts of Sweden were sampled, and strongyle eggs from the faeces of 54 of those were investigated by an LDA (DrenchRite). The following anthelmintics were tested: thiabendazole (TBZ), levamisole (LEV), ivermectin monosaccharide (IVM-MS), ivermectin aglycone (IVM-AG) and pyrantel (PYR). The LC50 values for TBZ and LEV were generally lower than those previously reported in other LDA studies on horse nematodes. This could be related to the infrequent use of these compounds for the past 20 years in Sweden. In this study, there was a great variation within and between assay plates that could not be explained. Still the LC50 values differed significantly between the regions for all anthelmintics, except for pyrantel. The highest LC50s were observed in parasite populations from the south of Sweden. There were no significant differences between riding schools and studs. Limitations of this technique exist, namely the lack of established cut-off values for susceptible and resistant populations and interpretation problems related to multi-species infections. Although there are advantages with LDA such as the possibility of testing several compounds simultaneously without interference with the deworming programmes on the farms, we conclude that LDA currently is not a reliable alternative to the faecal egg count reduction test (FECRT).     

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.     

The epidemiology and control of gastrointestinal nematode infestation of sheep and cattle in South Africa. I. The historic role of Onderstepoort and a short discussion of present research priorities

The research activities of the Veterinary Research Institute, Onderstepoort, from its inception in 1908 until recent times are reviewed in this first article of a series on nematode epidemiology of sheep and cattle. While the taxonomic and certain biological aspects of the subject and the testing of anthelmintic compounds have been well covered on the whole in various parts of the country, the testing of control methods under field conditions has largely been neglected. It is suggested that all known methods of integrated worm control should be scrutinized and the most promising methods be tested under practical farming conditions in the country to reduce our dependence on anthelmintic compounds for worm control. Furthermore, unless we are able to employ the available anthelmintics to better advantage and thus reduce the tempo of selection for resistance, the situation may well develop where highly effective remedies are no longer available for worm control.     

A review of some modern equine anthelmintics

Thiabendazole was the first of several benzimidazole anthelmintics and was superior to previously available drugs in both-efficiency and safety. Of the “second generation” of benzimidazoles, mebendazole and cambendazole are widely used inhorses and provide wider efficacy spectra and lowerdose rates compared with thiabendazole. Thiabendazole has proven activity against larval strongyles, but requires high dose rates. Two organophosphates, dichlorvos and haloxon have been formulated as horse anthelmintics. Pyrantel and its analogue morantel, are reported as efficient equine anthelmintics, but only in-feed and pasteformulations are recommended by the manufacturer as suitable for horses. Strains of small strongyles tolerant to benzimidazoles have been reported in U.S.A. and U.K. The addition of a piperazine salt to approximately half recommended dose rate, or the use of pyrantel, removed the tolerant nematodes.     

Primary anthelminthic screening on the L4 and L5 developmental stages of the lungworm, Dictyocaulus viviparus, in guinea pigs

The study was aimed at expanding the primary anthelmintic screening to cover a model of the group of pulmonary nematodes; in this particular case to introduce the lungworm, D. viviparus, in laboratory animals. A method of primary screening for the fourth and fifth larval states of D. viviparus in guinea-pigs was worked out after the selection of a suitable laboratory host. In the primary screening, three well-known anthelmintics of the benzimidazol series, including fenbendazole, mebendazole and levamisol, were tested by the method of controlled test. The anthelmintics were administered at the recommended doses of 7.5 and 10.0 mg per kg of live weight for two days in succession. The effectiveness of the control of the 4th and 5th larval states of D. viviparus was 93.4% in fenbendazole, 89.0% in mebendazole, and 89.9% in levamisol. It is confirmed by the results of the trials that guinea-pigs can be used for the testing model of the lungworm, D. viviparus, in anthelmintic screening.     

Anthelmintic resistance in non-strongylid parasites of horses

Since 2002, selected populations of Parascaris equorum in several countries have been reported to survive treatment with macrocyclic lactone (M/L) anthelmintics. Clinical treatment failures are characterized by negligible fecal egg count reduction, but M/L resistance has been confirmed in ascarids by controlled efficacy testing. Resistance was selected by current parasite control practices for foals, which often include exclusive and excessively frequent use of M/L dewormers, thereby minimizing refugia within the host and in the environment. Chemical control of M/L-resistant isolates can be accomplished with pyrimidine and/or benzimidazole anthelmintics, but a few M/L-resistant populations have recently exhibited resistance to pyrantel pamoate as well. Some specimens of Oxyuris equi regularly survive treatment with macrocyclic lactones, but it is uncertain whether this constitutes resistance or merely confirms the incomplete oxyuricidal efficacy of virtually all broad spectrum equine anthelmintics. Variations in other biological parameters of Oxyuris and Parascaris, specifically atypical infection of older hosts and shorter prepatent periods, have been reported anecdotally. These changes may represent genetic modifications that have evolved in parallel with resistance as a result of anthelmintic selection pressure.     

The veterinary and public health significance of hookworm in dogs and cats in Australia and the status of A. ceylanicum

There is no current information regarding the prevalence of hookworm in Australian dogs and cats and based on the results of studies conducted over 20 years ago, where high prevalences of helminths were recorded, the prophylactic administration of broad spectrum anthelmintics has been advocated. During this study, faecal samples were collected from dogs (n=1391) and cats (n=1027) across Australia. Samples were examined by microscopy and information regarding the demographics of each animal, and the management practices they experienced were recorded. A highly sensitive and species-specific PCR-RFLP technique was utilized to differentiate the various hookworm species which can infect dogs and cats directly from eggs in faeces. The prevalence of hookworm in dogs and cats was found to be 6.9% and 1.4%, respectively. Ancylostoma ceylanicum was detected for the first time in Australia in 10.9% of the dogs found positive for hookworm. Significantly, A. ceylanicum is capable of causing a patent infection in humans. After adjusting for other factors with multiple logistic regression, dogs from refuges, dogs originating from a tropical climatic zone, dogs aged 1 year or less, and those dogs which had not received anthelmintics were significantly more likely to be parasitized. Only univariate analysis was conducted for the cats as there were too few samples positive for hookworm. Cats were more likely to be infected with hookworm if they were from refuges, originated from a tropical climatic zone, and had not received treatment with anthelmintics. The results of this study demonstrates the importance of having current information regarding the prevalence of parasites of dogs and cats and the risk factors associated with infection, as well as the need to reassess the veterinary and public health concerns regarding hookworm infection and its control, which are currently based on out-dated information.