Anthelmintic resistance: The state of play revisited

doi:10.1016/j.lfs.2006.08.010

Life Sciences

Volume 79, Issue 26, 25 November 2006, Pages 2413-2431

https://doi.org/10.1016/j.lfs.2006.08.010 Get rights and content

Abstract

Helminthosis is one of the major constraints in the successful wool and mutton industry throughout the world. Anthelmintic Resistance (AR) is said to have been established when previously effective drug ceases to kill exposed parasitic population at the therapeutically recommended dosages. Anthelmintic resistance is almost cosmopolitan in distribution and it has been reported in almost all species of domestic animals and even in some parasites of human beings. Some of the most important species of parasites of small ruminants in which AR has been reported include: Haemonchus spp., Trichostrongylus spp. Teladorsagia spp., Cooperia spp. Nematodirus spp., and Oesophagostomum spp. All the major groups of anthelmintics have been reported for development of variable degrees of resistance in different species of gastrointestinal nematodes. This paper describes the global scenario of prevalence and methods used for detection of AR in small ruminants. Different mechanisms and contributory factors for the development of AR are discussed. Various options and alternate strategies for the control and/or delay in the onset of AR are suggested in the light of available information.

Introduction

Despite remarkable achievements in the discovery and development of anthelmintic drugs, nematode parasitic disease remains one of the greatest limiting factors to successful, and sustainable ruminant livestock production, worldwide (Perry and Randolph, 1999). Nematodosis can cause direct losses due to drop in production and deaths of animals. Furthermore, most of the economic losses are due to sub-clinical effects which are not immediately noticed by the owner. Lanusse and Prichard (1993) estimated that about 1.7 billion US$ is spent annually worldwide to combat helminth parasites in cattle. Although, the amount spent on small ruminants is much less, it is still quite substantial. In Australia, the estimated cost to control worms in sheep is between 220 (McLeod, 1995) to 500 millions US$ (Emery and Wagland, 1991). Considering the reported large problems in the sheep industry in South and Central America plus South Africa due to AR, the costs of treatment in these countries would be very high.

The anthelmintic resistant gastro-intestinal (GI) nematode populations constitute a major problem especially in small ruminants not only in the subtropics and tropics, but also in a serious threat to livestock in rest of the world (Conder and Campbell, 1995, Waller, 1997, Sangster, 1999). Anthelmintic resistance in nematode parasites of almost all species of animals is now a firmly established phenomenon, particularly in warm temperate or tropical regions of the world (Waller and Prichard, 1985). Resistance is considered to have been established when previously effective drug ceases to kill exposed parasitic population at the therapeutically recommended dosages (Prichard et al., 1980, Jackson, 1993). The existence of AR came to light in the mid-1950s as a result of the failure of phenothiazine to control haemonchosis in a flock of sheep kept at a research farm in Kentucky, USA (Drudge et al., 1957). The development of resistance by nematodes to broad-spectrum anthelmintics is of particular concern. Currently, three different chemical groups, i.e., benzimidazole (BZs), imidazothiazoles and avermectins are commonly used for deworming. A varying degree of resistance in nematode populations against these anthelmintics has been widely reported throughout the world (Prichard et al., 1980, Jackson et al., 1987, Prichard, 1990, Jackson, 1993, Besier and Love, 2003, Coles, 2005). The development of AR, therefore, has resulted in lowered animal productivity due to heavy nematode burden.

This paper reviews prevalence of AR in gastrointestinal nematodes (GINs) of small ruminants against commonly used anthelmintics. It also describes the factors contributing towards AR, mechanisms of development of AR, methods for the detection of resistance and some possible solutions to control the development of AR.

Section snippets

Prevalence of anthelmintic resistance

Many of the earliest reports of ruminant nematode strains resistant to broad-spectrum anthelmintics emanated from the southern hemisphere and usually involved species with a high biotic potential such as Haemonchus (H.) contortus and Trichostrongylus (T.) colubriformis. The rate of emergence of resistance appears to vary geographically in accordance with the prevailing climate, parasite species and treatment regimes adopted in the region. Although the rate of emergence of resistant strains has

Factors contributing towards development of resistance

Modern anthelmintics are used at an efficiency of around 99% against susceptible strains. A small number of surviving worms, which are the most resistant component of the population, then contaminate the pasture with a majority of resistant offsprings for subsequent generations which lead to development of AR due to selection pressure. The rate of development of resistance is influenced by many factors which can be classified as genetic, biological or operational. The most important are the

Benzimidazoles

The best known mechanism of resistance is the one to BZs. The BZs exert their anthelmintic activity by binding to β-tubulin, which interferes with the polymerization of the microtubuli. Some authors (Beech et al., 1994, Roos et al., 1995) have shown that there is an extensive polymorphism of the β-tubulin gene in susceptible H. contortus populations. Roos et al. (1995) proved that selection for resistance to BZs is accompanied by a loss of alleles at the locus of β-tubulin isotype-1. It has

Genetics of nematodes and anthelmintic

Nematode parasite populations are genetically heterogeneous and thus able to respond to selective pressures, i.e., anthelmintic drugs (Grant, 1994). Widespread drug pressure will favour and select parasite lines carrying tolerance or resistance alleles. The rate at which resistance spreads in the parasite population depends on many factors. One key factor is the proportional contribution of genetic material that helminths surviving therapy will make to the next generation. This contribution is

Detection of resistance

A wide range of tests has been developed to detect AR for research and diagnostic purposes (Presidente, 1985). The growing importance of AR has led to an increased need for reliable and standardized detection methods (Coles et al., 1992) some of which have been previously described and reviewed (Presidente, 1985, Johansen, 1989, Hazelby et al., 1994, Taylor et al., 2002). Most of the methods described have drawbacks either in terms of cost, applicability and interpretation or reproducibility of

Control of resistance

Environmentally and/or immunologically based parasite control strategies which seek to limit host/parasite contact have an obvious application in the avoidance and management of AR along with chemotherapy. Work to overcome AR has been going on with increased intensity for more than a decade. The reason for this interest is multi-facetted but primarily driven by the serious development of AR in parasite populations. The fact that very few producers routinely screen for AR, coupled with the

Conclusion

AR is a threatening problem to livestock industry posing very threats to the future welfare and production of livestock throughout the world. The factors considered most significant have been an excessive frequency of treatments and the administration of an inadequate dose (underdosing) particularly latter is true for developing countries. However, these factors may not be completely true in all cases. Although some factors like quality of drugs, education of farmers, modifications to treatment

Acknowledgements

This paper was prepared during the work on anthelmintic resistance in the authors' laboratories which was supported by the Pakistan Science Foundation and Higher Education Commission of Pakistan.