The detection of anthelmintic resistance in nematodes of veterinary importance.

Direct anthelmintic effects of condensed tannins towards different gastrointestinal nematodes of sheep: in vitro and in vivo studies

Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.

http://jpkc.fudan.edu.cn/picture/article/84/6b37ad7f-5a34-40fe-9608-573fbaae51e0/926caa05-ccd1-4f93-815b-ab47a8a17456.pdf

A new class of anthelmintics effective against drug-resistant nematodes

Anthelmintic resistance now poses problems to sheep farmers throughout the world. In some Southern hemisphere countries multiple resistance has reached levels which make sheep farming non-sustainable. Evidence from studies in the UK and Europe suggests (a) that the selection process occurs over a longer time frame than in Southern tropical/temperate regions and (b) that for some of the key ovine species little or no reversion to susceptibility may occur for many years after the withdrawal of the selecting agent. The dynamics of the selection process are influenced by a number of host, parasite, drug, management and environment-dependent factors. Recent mechanistic studies on resistance against avermectins and milbemycins (AM) suggest that there may be a number of mechanisms associated with resistance at the different target sites for these drugs. Within Europe endectocides within the AM drug group have now become the crucial element in strategies aimed at controlling important diseases such as sheep scab and nematodoses. Given that there is little likelihood of a series of novel action compounds emerging in the immediate future to replace this family the conservation of efficacy of the AM group should be accorded the highest priority for research in this area.

The development of anthelmintic resistance in sheep nematodes.

Anthelmintic resistance involving particularly the gastrointestinal nematodes of small ruminants is escalating globally, to the extent that in certain countries, such as South Africa, it has already reached alarming proportions, and is affecting practically all the anthelmintics. In this paper it is argued that the high levels of resistance in nematodes of veterinary importance indicate that the drugs have been used incorrectly. It is suggested that the phenomenon of refugia plays a much more important role in the selection of anthelmintic resistance than other phenomena that are more frequently investigated and recommended for counteracting it, such as reduced drenching frequency and avoiding under-dosing. While refugia is commonly mentioned in passing in most papers on anthelmintic resistance, it is, almost without exception, not incorporated in the final control/ management proposals. On the strength of the conclusions arrived at in the present paper strategies such as the drench-and-move system in which all the animals in a flock are drenched before they are moved to pastures containing few or no worms in refugia, and the system of strategic drenching on safe pastures should be condemned and never recommended. If such strategies are indeed unavoidable, the farmer should be warned that the farming system would probably not be sustainable even in the short term, in view of the generally high levels of resistance already present in most of the important sheep-producing regions. Farmers should be educated to consider refugia above all else when designing worm management programmes. Finally there seems to be too much complacency concerning the possibility that anthelmintic resistance may also escalate in cattle, eventually to reach the proportions that it has in sheep.

Refugia--overlooked as perhaps the most potent factor concerning the development of anthelmintic resistance.

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).

IB Wood

Papers

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).

WAAVP second edition of guidelines for evaluating the efficacy of anthelmintics in ruminants ( bovine and ovine)