Anthelmintic resistance--the state of play

There is evidence that the incidence of anthelmintic resistance is increasing in livestock in countries throughout the world including the United Kingdom. Early detection of emerging drug resistance is important since reversion to susceptibility appears not to occur in highly selected homozygous strains. Because the current in vivo and in vitro assays, which generally determine the degree of disruption of normal physiological function of different parasite stages, are relatively insensitive, effort is being made to develop more direct genetic and biochemical diagnostic assays. Studies on the selection and genetics of resistance suggest that resistance is normally polygenic and arises from within the normal phenotypic range and that there are three phases in the selection process. An initial susceptible phase is followed by an intermediate one in which heterozygous resistant individuals are common within the population and finally homozygous resistant individuals predominate within the population. For these reasons low efficacy treatments, which enable the survival of heterozygous resistant individuals, and suppressive regimes, which only allow homozygous resistant individuals to survive, increase the rate of development of drug resistance. Strategies to delay the onset of resistance and control resistant strains usually incorporate minimal chemoprophylaxis, seek to maximize drug efficacy, and if possible include a 'slow' drug rotation and seek to limit host parasite contact by manipulation of the grazing environment. Although multi-species mathematical models of anthelmintic resistance appear to offer a means of assessing the long term impact of these and other control strategies, current models are limited by a lack of detailed biological knowledge. In particular, more information on the status and numbers of alleles associated with resistance to specific drugs, their frequencies within populations of different species and the fitness of resistant and susceptible populations is required. Anthelmintic resistance provides an example of the adaptability of metazoan parasites under intensive selection and suggests that sustainable control strategies will require an integrated approach in which both chemotherapy and immunotherapy, together with environmental management are used to control nematodoses.