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[The technology for manufacturing antiparasitic preparations. 6. The development of a technology for producing the anthelmintic Azinox (praziquantel) and the evaluation of its toxic and anthelmintic properties].

The paper outlines a procedure for manufacturing the anthelminthic Azinox (biltricide) using the new interfacial transfer catalyst benzyl-di-propyl (beta-hydroxyethyl)ammonium chloride. Azinox has been shown to be identical to biltricide (praziquantel) in its properties. Azinox tests on models of Opisthorchis felineus in golden hamsters and of Hymenolepis nana in albino outbred mice have indicated that the agent is not inferior to biltricide in its antitrematodal and anticestodal activities. Azinox displayed a high activity at the preimaginal stages of O. felineus and H. nana and at the larval stage of H.nana.

Animals↗

Worm control practices and anthelmintic usage in traditional and dairy cattle farms in the southern highlands of Tanzania.

Worm control practices and anthelmintic usage in 177 cattle farms in Iringa district in the southern highlands of Tanzania was determined through a questionnaire survey. A total of 76 traditional, 92 small-scale dairy and 9 large-scale dairy cattle farms were included in the survey. Results indicated that 87.7% traditional, 97.8% small-scale dairy and 100% large-scale farmers relied solely on the use of anthelmintics, 2.7% traditional farmers used traditional medicines while 9.6% traditional farmers had not any form of worm control practice. Worm infection was ranked the second most important constraint of productivity in cattle in the three production systems. Most farms (57.6% traditional, 35.8% small-scale dairy, 66.7% large-scale dairy) used anthelmintics with a combination of levamisole and oxyclozanide. Benzimidazoles were used only in traditional (25.4%) and small-scale dairy (32.1%) farms while nitroxynil (Trodax) was mostly used in large-scale dairy farms (33.3%). Generally, 40% of farmers treated three or four times a year and the frequency in some farms was surprisingly high for resource poor small-scale farmers. The frequency of anthelmintic treatment was mostly the same regardless of the management system. Treatments in most farms depended on availability of money and drugs and not the epidemiology of parasites. A significant proportion (46.3%, P=0.007) of farmers especially in rural areas failed to follow their pre-planned treatment schedules due to lack of money (86%) and unavailability of drugs (6.6%). Many farmers (58.9%) had used the same type of anthelmintic for four or more consecutive years and 85.3% of them would continue with the same anthelmintic. Farmers in all management systems mostly purchased anthelmintics from private veterinary drug shops and about 43% traditional and 33.3% small-scale dairy farmers mostly in rural areas obtained anthelmintics from village extension officers. Despite the fact that all farmers were aware of worm infection and the associated signs in cattle, 42.5% had poor knowledge on the source of worm infection. Small-scale dairy farmers allowed only a 1-day withdraw period for milk regardless of the type of anthelmintic used and there was no milk and slaughter clearance in traditional farms. It was concluded from this study that worm control in Iringa faces serious constrains and that education of farmers and farm hands is not adequate. Moreover, poor quality control and high price of potent anthelmintics, few extension workers, low income and low education among farmers contributed significantly to erratic worm control practices and anthelmintic usage in peri-urban and rural areas.

Animals↗

Anthelmintic resistance in South Africa: surveys indicate an extremely serious situation in sheep and goat farming.

Surveys to determine the prevalence and degree of resistance of Haemonchus spp. of sheep and goats to the available anthelmintics in South Africa indicate that small ruminant production is entering a crisis situation. Three surveys employing the faecal egg count reduction (FECR) test to determine resistance were conducted in some of the main sheep-producing areas in the summer rainfall region of South Africa, where H. contortus is the principal worm species in sheep. After analyzing the data recorded in the surveys by six different methods, including the RESO test at two different levels of confidence, the results obtained in the least stringent one (geometric mean reduction of the worm egg counts of drenched, vs untreated group of sheep) are reported in this paper, so that if any bias was obtained it would be in the favour of the anthelmintic. In Mpumalanga and KwaZulu-Natal there was anthelmintic resistance in Haemonchus spp. on all the 52 farms surveyed. Sixteen percent of the strains of H. contortus were < 60% susceptible to three of the four anthelmintics tested, and 8% of the strains were < 40% susceptible to all four of the anthelmintics. FECR tests of sheep in six localities in the Lebowa district of Northern Province indicated that even in previously disadvantaged communities where anthelmintic treatment is less intensive, anthelmintic resistance is developing, and is possibly at the level at which the situation on commercial sheep and goat farms in South Africa was 25 years ago. From the data it appears that the level of anthelmintic resistance of H. contortus in South Africa is possibly the highest that has so far been recorded in the world and that strains of it are emerging that may soon not be controllable by treatment with any of the existing anthelmintics. Farmers in the summer rainfall region, if not the whole country, must be alerted to the immediate need for testing the parasite burdens of their sheep for susceptibility to preparations in all four groups of anthelmintic compounds currently available. Alternative methods of integrated worm control, including biological, must be sought and implemented with urgency, to reduce further selection for resistance and to induce reversion of the resistance that has already developed.

Albendazole↗

Use of anthelmintics by New England sheep producers.

Six hundred and sixty-five New England sheep producers responded to a postal survey on management practices, anthelmintic use, and the perceived failure of anthelmintics to control nematodes. Although the average farm had 34.8 lambs and 29.8 stock sheep, 59.8% and 50.3% of the total number of lambs and stock sheep were on 16.5% of the farms, which had greater than 50 lambs. About 54% of the lambs were born in January and February. Spring markets and confinement rearing were popular, as only 45.7% of the total lambs grazed summer pasture. Most producers (81.5%) treated their stock sheep (and lambs) for nematodiasis 2 to 4 times per year (mean, 3.3), generally before lambing, before pasturing, midsummer, and/or before breeding. Only 27.5% of the producers indicated distinct drenching management for grazing lambs. There was little use of preventive control, such as spring prophylaxis (0.5%) or dosing in midsummer and moving animals to safe pasture (2.9%). More than one anthelmintic class was used on 59.6% of the farms, with a mean of 1.88 anthelmintics per farm. Though 53.7% of the producers had a policy of alternating anthelmintic classes within a year, only 11.6% alternated anthelmintics annually. Levamisole and thiabendazole were the anthelmintics most frequently used by 81.8% and 61.6% of producers, respectively. However, 26.5% and 16.2% of the farms used fenbendazole and phenothiazine, respectively. The presence of gastrointestinal nematode resistance to anthelmintics was suggested, because 35.4% of the producers had discontinued using at least one anthelmintic that they considered to be ineffective. The anthelmintic that was most frequently discontinued was thiabendazole.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Observations on the emergence of multiple anthelmintic resistance in sheep flocks in the south-east of Scotland.

Multiple resistance to benzimidazole, imidazothiazole and macrocyclic lactone anthelmintics is an emerging problem in the south-east of Scotland. The general management and nematode control strategies employed in four affected flocks (flocks 1-4) were investigated in an attempt to identify the risk factors which might have led to the appearance of production limiting disease associated with anthelmintic resistance. The important risk factors for multiple anthelmintic resistance could not be confirmed and it proved easier to criticise nematode control practices on theoretical grounds, than to propose practical solutions. It seems likely that different risk factors were involved in the four flocks. Lambs in flocks 1 and 2 had been treated with an anthelmintic at 3-4 weekly intervals with the aim of achieving suppressive nematode control, while sheep in flock 1 had been treated with an anthelmintic after they were moved onto clean grazing. Recently lambed ewes had been treated with moxidectin in three of the four flocks, with the aim of controlling their periparturient rise in faecal nematode egg output. All of these factors might have contributed to the emergence of multiple anthelmintic resistance, because they could have led to anthelmintic treatments at times when the nematode population in refugia was small, compared to that in the sheep. Annual rotation of the anthelmintic group was compromised by the emergence of benzimidazole resistance and did not prevent the emergence of multiple resistance in any of the flocks described, although the practice may have slowed the development of resistance. Underdosing may have selected for benzimidazole and imidazothiazole resistance in flock 2, associated with inaccurate estimation of the weights of terminal sire lambs. These investigations also highlighted problems associated with the diagnosis of anthelmintic resistance, in particular the confounding effects of the onset of host immunity to nematode parasites, the possible influence of the age of the adult nematode population, and the insensitivity of the undifferentiated faecal egg count reduction test in situations where resistance is emerging.

Animals↗

Anthelmintic treatment strategies: current status and future.

Despite the array of anthelmintics and endectocides and delivery systems available for use in the prevention and control of nematode parasites of ruminants, the number of highly effective control programs that have been developed and even the number of such programs that have been successfully implemented in commercial animal production, there have been no recent innovations or discoveries in regard to strategies, new anthelmintics, or systems for controlling nematode parasites through anthelmintic use. In the traditional sense of chemotherapy-chemoprophylaxis, we have probably achieved the maximum effect of what is possible from excellent anthelmintics developed by the pharmaceutical industry over the last 35 years, i.e. from thiabendazole through levamisole and morantel tartrate, to more advanced benzimidazoles and to the avermectins and milbemycins. At the core of all anthelmintic treatment-related problems is the lingering conception among a large body of animal producers that anthelmintic treatment is the only effort needed to control parasitism and its effects on host animals. This concept has given rise to the long-standing difficulty of drug resistance in sheep nematodes and the not remote possibility of its development in nematodes of cattle. Along with this are serious concerns over environmental toxicity, tissue residues and enormous financial investment to develop new and novel anthelmintic compounds. Progress is being made in current and intensive searches for development and testing of control approaches alternative to anthelmintics, e.g. helminth vaccines, biological control agents such as fungi, selection of resistant sires, alternative chemicals and nematode growth regulators. A timetable for when alternative controls can be developed fully and put into practical use cannot be predicted. It is universally acknowledged among parasitologists that existing anthelmintics must be preserved and utilized judiciously to ensure continued effectiveness. A major example is to be found in strategic or integrated control programs in Australia developed over the last 10 years to combat widespread drug resistance in sheep. Major imperatives for future programs and systems of controlling nematode parasites of ruminants are improved means of getting producers to adopt proven and sustainable methods.

Animal Husbandry↗

Anthelmintic resistance and management of nematode parasites on beef cattle-rearing farms in the North Island of New Zealand.

AIM: To provide information on current farmers' opinions and farming practices thought to be related to anthelmintic resistance, and to test for associations between the presence of anthelmintic resistance and management practices on beef-cattle rearing farms in the North Island of New Zealand. METHODS: A study using an interview-based questionnaire about management of internal parasites was conducted on 62 beef cattle-rearing farms in the North Island of New Zealand, using case-control analyses to test for associations between management practices and the presence or absence of resistance to ivermectin or albendazole. Resistance was inferred from faecal nematode egg count (FEC) reduction (FECR) tests (FECRTs) when there was <90% reduction in FEC 7-10 days after treatment of calves <12 months of age. RESULTS: Of the 59 farmers who completed the questionnaire, most (n=40) ranked parasites highly, and at about the same level as quality and quantity of feed, as important production-limiting factors for their enterprises. In contrast, anthelmintic resistance was not perceived to be a problem on 13 farms, and its importance was rated low on 24, moderate on 15, and high on only six farms. Despite all farms having planned parasite control programmes, there was heavy reliance on clinical signs of parasitism to determine frequency of treatments. About one in three farmers with beef breeder cows routinely treated their calves at marking, one in five treated mixed-age cows, and almost half treated rising 2-year-old cows before calving. One in four farmers used anthelmintics on calves on 8-12 occasions in their first year of life. Co-grazing with other species was rare, but follow-on grazing within 3 months after older cattle or sheep was common. On most farms, grazing cattle was restricted to part of the farm, a finding with implications for parasite control and persistence of larvae in refugia. Macrocyclic lactone (ML) anthelmintics or their combinations with other action families were currently, and for the past 5 years, used more frequently than benzimidazoles and levamisole, and benzimidazole-levamisole combinations. The prevalence of resistance to ivermectin was high (82%) and no plausible model of associations could be constructed from the data. The prevalence of resistance to albendazole was 60%, and the risk of resistance increased as the number of rising 1-year-old cattle present mid-winter increased, and decreased as the number of breeding cows >2 years old present mid-winter increased. CONCLUSION: It is clear that in practice anthelmintic resistance is a secondary consideration to obtaining productivity advantages from the use of anthelmintics in beef cattle. Farmers' opinions were divided on many issues and the overall impression was of confused and diverse thinking regarding the principles of the use of anthelmintics. The overall outlook regarding anthelmintic resistance in cattle is bleak unless the need for integrated and long-term research activities is acted upon soon.

Animal Husbandry↗

Anthelmintic resistance.

Anthelmintic resistance is widespread in nematode parasites of sheep, goats and horses. Resistance is also developing in nematode parasites of cattle and has been detected in pig parasites. Benzimidazole, levamisole/morantel and ivermectin resistances occur in nematodes of sheep and goats and closantel resistance has been found in Haemonchus contortus. Anthelmintic resistance is likely to develop wherever anthelmintics are frequently used and be detected if it is investigated. Worm count or egg count reduction after treatment are useful for the detection of all types of anthelmintic resistances. More economical, faster and more sensitive in vitro assays for the detection of anthelmintic resistance have been developed. Some, such as the egg hatch assay are specific for a particular class of anthelmintic, whilst others such as larval development assays can be used with most anthelmintics. Improvements in our understanding of the biochemistry and molecular genetics of anthelmintic actions should lead to the development of more sensitive assays for the detection of anthelmintic resistance in individual nematodes. Levamisole/morantel resistance appears to be associated with alterations in cholinergic receptors in resistant nematodes. Ivermectin appears to act by binding to a glutamate receptor of a membrane chloride channel. This receptor has been expressed in vitro so that further studies of the interaction of ivermectin with this receptor and its possible alteration in ivermectin resistance will be feasible. Benzimidazole resistance in nematodes and fungi appears to be associated with an alteration in beta-tubulin genes which reduces or abolishes the high affinity binding of benzimidazoles for tubulin in these organisms. This knowledge can be exploited for DNA probes for benzimidazole resistance/susceptibility in individual organisms.

Animals↗