Hostname: page-component-745bb68f8f-f46jp Total loading time: 0 Render date: 2025-01-13T12:27:47.926Z Has data issue: false hasContentIssue false
  • English
  • Français

Pharmacology of anthelmintic resistance

Published online by Cambridge University Press:  06 April 2009

N. Sangster
N. Sangster
Affiliation:
Department of Veterinary Pathology, University of Sydney, NSW 2006, Australia
Get access Rights & Permissions [Opens in a new window]

Summary

Anthelmintic resistance has compromised the control of nematode parasites in several animal-based industries. Studies of resistance have not only improved our understanding of this phenomenon but also shed light on physiological systems of parasitic helminths. In addition, research on molecular aspects of anthelmintic resistance may provide selectable markers for use in future transfection studies with helminths. Several anthelmintics act on helminth neuromuscular systems. Drugs such as levamisole are cholinergic agonists and, based on pharmacological studies, levamisole-resistant nematodes appear to have altered acetylcholine receptors. It is likely that anticholinesterase anthelmintics share cross resistance with levamisole. Ivermectin appears to be a glutamate agonist. In vitro studies of ivermectin-resistant nematodes suggest that IVM receptors are located on pharyngeal and somatic muscle. The free-living nematode Caenorhabditis elegans may provide a model for anthelmintic resistance. It has been useful in cloning drug receptors from parasites but differences between its life history and habitat compared with parasitic nematodes may limit its usefulness for studying resistance in these parasites.

Keywords

Levamisoleivermectinnematodesdrug resistance
Type
Research Article
Information
Parasitology , Volume 113 , supplement S1: Molecular biochemistry and physiology of helminth neuromuscular systems , January 1996 , pp. S201 - S216
Copyright
Copyright © Cambridge University Press 1996

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Arena, J. P., Liu, K. K., Paress, P. S. & Cully, D. F. (1991). Avermectin-sensitive currents induced by Caenorhabditis elegans RNA in Xenopus oocytes. Molecular Pharmacology 40, 368–74.Google ScholarPubMed
Arena, J. P., Liu, K. K., Paress, P. S., Schaeffer, J. M. & Cully, D. F. (1992). Expression of a glutamateactivated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin. Molecular Brain Research 15, 339–48.CrossRefGoogle ScholarPubMed
Atchison, W. D., Geary, T. G., Manning, B., Vandewaa, E. A., & Thompson, D. P. (1992). Comparative neuromuscular blocking actions of levamisole and pyrantel-type anthelmintics on rat and gastrointestinal nematode somatic muscle. Toxicology and Applied Pharmacology 112, 133–4.CrossRefGoogle ScholarPubMed
Avery, L. (1993). Motor neuron M3 controls pharyngeal muscle relaxation timing in Caenorhabditis elegans. Journal of Experimental Biology 175, 283–97.CrossRefGoogle ScholarPubMed
Avery, L. & Horwitz, H. R. (1990). Effects of starvation and neuroactive drugs on feeding in Caenorhabditis elegans. The Journal of Experimental Zoology 253, 263–70.CrossRefGoogle ScholarPubMed
Badger, S. B. & McKenna, P. B. (1990). Resistance to ivermectin in a field isolate of Ostertagia spp. in goats. New Zealand Veterinary Journal 38, 72–4.CrossRefGoogle Scholar
Bjorn, H., Roepstorff, A.Nansen, P. & Waller, P. J. (1989). A dose-response investigation on the level of resistance to pyrantel citrate in nodular worms of pigs. Veterinary Parasitology 31, 259–67.CrossRefGoogle ScholarPubMed
Blouin, M. S., Dame, J. B., Tarrant, C. A. & Courtney, C. H. (1992). Unusual population genetics of a parasitic nematode: mtDNA variation within and among populations. Evolution 46, 470–6.CrossRefGoogle ScholarPubMed
Bottjer, K. P. & Bone, L. W. (1985). Trichostrongylus colubriformis: effect of anthelmintics on ingestion and oviposition. International Journal for Parasitology 15, 501–3.CrossRefGoogle ScholarPubMed
Cioli, D., Pica-Mattoccia, L. & Archer, S. (1995). Antischistosomal drugs: past, present… and future. Pharmacology and Therapeutics 68, 35–85.CrossRefGoogle ScholarPubMed
Coles, G. C., East, J. M. & Jenkins, S. N. (1975). The mechanism of action of the anthelmintic levamisole. General Pharmacology 6, 309–13.CrossRefGoogle Scholar
Coles, G. C., Folz, S. D. & IITritschler, J. P. (1989). Motility response of levamisole and benzimidazole resistant Haemonchus contortus larvae. Veterinary Parasitology 31, 253–7.CrossRefGoogle ScholarPubMed
Coles, G. C., IITritschler, J. P., Giordano, D. J., Laste, N. J. & Schmidt, A. L. (1988). Larval development test for detection of anthelmintic resistant nematodes. Research in Veterinary Science 45, 50–3.CrossRefGoogle ScholarPubMed
Conder, G. A., Johnson, S. S., Guimond, P. M., Geary, T. G., Lee, B. L.Winterrowd, C. A.Lee, B. H. & Diroma, P. J. (1991). Utility of a Haemonchus contortus/jird (Meriones unguiculatus) for studying resistance to levamisole. The Journal of Parasitology 77, 83–6.CrossRefGoogle ScholarPubMed
Conder, G. A., Thompson, D. P. & Johnson, S. S. (1993). Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin. The Veterinary Record 132, 651–2.CrossRefGoogle ScholarPubMed
Conder, G. A., Zielinski, R. J., Johnson, S. S., Kuo, M.-S. T., Cox, D. L., Marshall, V. P., Haber, C. L., Diroma, P. J., Nelson, S. J.Conklin, R. D.Lee, B. L., Geary, T. G., Rothwell, J. T. & Sangster, N. C. (1992). Anthelmintic efficacy of dioxapyrrolomycin. The Journal of Antibiotics 45, 977–83.CrossRefGoogle Scholar
Cooper, N. A. (1995). Naphthalophos combinations with white and clear drenches: an effective drench rotation alternative. In Australian Sheep Veterinary Society, Australian Veterinary Association Proceedings, pp. 137–140. Melbourne: Australian Veterinary AssociationGoogle Scholar
Craig, T. M. & Miller, D. K. (1990). Resistance by Haemonchus contortus to ivermectin in angora goats. The Veterinary Record 126, 580.Google ScholarPubMed
Cully, D. F., Vassilatis, D. K., Liu, K. K., Paress, P. S., Van Der Ploeg, L. H. T., Schaeffer, J. M. & Arena, J. P. (1994). Cloning of an avermectin-sensitive glutamategated chloride channel from Caenorhabditis elegans. Nature {London) 371, 707–10.CrossRefGoogle ScholarPubMed
Dash, K. M. (1985). Differential efficacy of levamisole and oxfendazole against resistant male and female Trichostrongylus colubriformis. The Veterinary Record 117, 502–3.CrossRefGoogle ScholarPubMed
Dobson, R. J., Le Jambre, L. F. & Gill, J. H. (1996). Management of anthelmintic resistance: inheritance of resistance and selection with persistent drugs. International Journal for Parasitology (in press).CrossRefGoogle Scholar
Douch, P. G. C. & Morum, P. E. (1994). The effects of anthelmintics on ovine larval nematode parasite migration in vitro. International Journal for Parasitology 24, 321–6.CrossRefGoogle ScholarPubMed
Egerton, J. R., Suhayda, D. & Eary, C. H. (1988). Laboratory selection of Haemonchus contortus for resistance to ivermectin. The Journal of Parasitology 74, 614–7.CrossRefGoogle ScholarPubMed
Fleming, J. T., Tornoe, C., Riina, H. A., Coadwell, J., Lewis, J. A. & Sattelle, D. B. (1993). Acetylcholine receptor molecules of the nematode Caenorhabditis elegans. Comparative Molecular Neurobiology 63, 65–80.CrossRefGoogle ScholarPubMed
Geary, T. G., Sims, S. M., Thomas, E. M., Vanover, L., Davis, J. P., Winterrowd, C. A., Klein, R. D., Ho, N. F. H. & Thompson, D. P. (1993). Haemonchus contortus: Ivermectin-induced paralysis of the pharynx. Experimental Parasitology 77, 88–96.CrossRefGoogle ScholarPubMed
Gill, J. H., Redwin, J. M., Van Wyk, J. A. & Lacey, E. (1991). Detection of resistance to ivermectin in Haemonchus contortus. International Journal for Parasitology 21, 771–6.CrossRefGoogle ScholarPubMed
Gill, J. H., Redwin, J. M., Van Wyk, J. A. & Lacey, E. (1995). Avermectin inhibition of larval development in Haemonchus contortus – effects of Ivermectin resistance. International Journal for Parasitology 25, 463–70.CrossRefGoogle ScholarPubMed
Giordano, D. J., IITritschler, J. P. & Coles, G. C. (1988). Selection of ivermectin-resistant Trichostrongylus colubriformis in lambs. Veterinary Parasitology 30, 139–48.CrossRefGoogle ScholarPubMed
Grant, W. N. (1992). Transformation of Caenorhabditis elegans with genes from parasitic nematodes. Parasitology Today 8, 344–6.CrossRefGoogle ScholarPubMed
Grant, W. N. (1994). Genetic variation in parasitic nematodes and its implications. International Journal for Parasitology 24, 821–30.CrossRefGoogle ScholarPubMed
Green, P. E., Forsyth, B. A., Rowan, K. J. & Payne, G. (1981). The isolation of a field isolate of Haemonchus contortus in Queensland showing multiple anthelmintic resistance. Australian Veterinary Journal 57, 79–84.CrossRefGoogle ScholarPubMed
Harrow, I. D. & Gration, K. A. F. (1985). Mode of action of the anthelmintics morantel, pyrantel and levamisole on muscle cell membrane of the nematode Ascaris suum. Pesticide Science 16, 662–72.CrossRefGoogle Scholar
Hazelby, C. A., Probert, A. J. & Rowlands, D. Ap T. (1994). Anthelmintic resistance in nematodes causing parasitic gastroenteritis of sheep in the UK. Journal of Veterinary Pharmacology and Therapeutics 17, 245–52.CrossRefGoogle ScholarPubMed
Hubert, J. & Kerboeuf, D. (1992). A microlarval development assay for the detection of anthelmintic resistance in sheep nematodes. The Veterinary Record 130, 442–6.CrossRefGoogle ScholarPubMed
Jackson, F., Coop, R. L., Jackson, E., Scott, E. W. & Russel, A. J. F. (1992). Multiple anthelmintic resistant nematodes in goats. The Veterinary Record 130, 210–11.CrossRefGoogle ScholarPubMed
Kelly, J. D., Sangster, N. C., Porter, C. J., Martin, I. C. A. & Gunawan, M. (1981). Use of guinea pigs to assay anthelmintic resistance in ovine isolates of Trichostrongylus colubriformis. Research in Veterinary Science 30, 131–7.CrossRefGoogle ScholarPubMed
Lacey, E. (1988). The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resisatnce to benzimidazoles. International Journal for Parasitology 18, 885–936.CrossRefGoogle Scholar
Lacey, E., Redwin, J. M., Gill, J. H., Demargheriti, V. M. & Waller, P. J. (1990). A larval development assay for the simultaneous detection of broad spectrum anthelmintic resistance. In Resistance of Parasites to Antiparasitic Drugs (ed. Boray, J. C., Martin, P. J. & Roush, R. T.), pp. 129–139. New Jersey: MSD Agvet.Google Scholar
Laughton, D. L., Wheeler, S. V., Lunt, G. G. & Wolstenholme, A. J. (1995). The β-subunit of Caenorhabditis elegans avermectin receptor responds to glycine and is encoded by chromosome 1. Journal of Neurochemistry 64, 2354–7.CrossRefGoogle ScholarPubMed
Lee, R. M. & Hodsden, M. R. (1963). Cholinersterase activity in Haemonchus contortus and its inhibition by organophosphorus compounds. Biochemical Pharmacology 12, 1241–52.CrossRefGoogle Scholar
Le Jambre, L. F. (1993). Ivermectin-resistant Haemonchus contortus in Australia. Australian Veterinary Journal 70, 357.CrossRefGoogle ScholarPubMed
Le Jambre, L. F., Gill, J. H., Lenane, I. J. & Lacey, E. (1995). Characterisation of an avermectin resistant isolate of Australian Haemonchus contortus. International Journal for Parasitology 25, 691–8.CrossRefGoogle ScholarPubMed
Le Jambre, L. F. & Martin, P. J. (1979). Effectiveness of morantel tartrate and naphthalophos against levamisole resistant Ostertagia in sheep. Veterinary Science Communications 3, 153–8.CrossRefGoogle Scholar
Lewis, J. A. & Berberich, S. (1992). A detergentsolubilized nicotinic acetylcholine receptor of Caenorhabditis elegans. Brain Research Bulletin 29, 667–4.CrossRefGoogle ScholarPubMed
Lewis, J. A., Elmer, J. S., Skimming, J., McLafferty, S., Fleming, J. & McGee, T. (1987 a). Cholinergic receptor mutants of the nematode Caenorhabditis elegans. The Journal of Neuroscience 7, 3059–71.CrossRefGoogle ScholarPubMed
Lewis, J. A., Fleming, J. T., McLafferty, S., Murphy, H. & Wu, C. (1987 b). The levamisole receptor, a cholinergic receptor of the nematode Caenorhabditis elegans. Molecular Pharmacology 31, 185–93.Google ScholarPubMed
Lewis, J. A., Wu, C.-H., Levine, J. H. & Berg, H. (1980). Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors. Neuroscience 5, 967–89.CrossRefGoogle ScholarPubMed
McKenna, P. B. (1985). The efficacy of levamisole and ivermectin against a morantel-resistant isolate of Trichostrongylus colubriformis. New Zealand Veterinary Journal 33, 198–9.CrossRefGoogle Scholar
Marriner, S. E., McKinnon, I. & Bogan, J. A. (1987). Pharmacokinetics of ivermectin after oral and subcutaneous administration of sheep and horses. Journal of Veterinary Pharmacology and Therapeutics 10, 175–9.CrossRefGoogle ScholarPubMed
Martin, P. J. (1990). Ecological genetics of anthelmintic resistance. In Resistance of Parasites to Antiparasitic Drugs (ed. Boray, J. C., Martin, P. J. & Roush, R. T.), pp. 129–139. New Jersey: MSD Agvet.Google Scholar
Martin, P. J., Anderson, N. & Jarrett, R. G. (1989). Detecting benzimidazole resistance with faecal egg count reduction tests and in vitro assays. Australian Veterinary Journal 66, 236–40.CrossRefGoogle ScholarPubMed
Martin, P. J. & Le Jambre, L. F. (1979). Larval paralysis as an in vitro assay of levamisole and morantel tartrate resistance in Ostertagia. Veterinary Science Communications 3, 159–64.CrossRefGoogle Scholar
Martin, P. J. & McKenzie, J. A. (1990). Levamisole resistance in Trichostrongylus colubriformis: a sexlinked recessive character. International Journal for Parasitology 20, 867–72.CrossRefGoogle ScholarPubMed
Martin, R. J. & Pennington, A. J. (1989). A patch clamp study of effects of dihydroavermectin on Ascaris muscle. British Journal of Pharmacology 98, 747–56.CrossRefGoogle ScholarPubMed
Maule, A. G., Shaw, C., Bowman, J. W., Halton, D. W., Thompson, D. P., Geary, T. G. & Thim, L. (1994). KSAYMRFamide: a novel FMRFamide-related heptapeptide from the free-living nematode, Panagrellus redivivus, which is myoactive in the parasitic nematode Ascaris suum. Biochemical and Biophysical Research Communications. 200, 973–80.CrossRefGoogle ScholarPubMed
Natoff, I. L. (1969). The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum. British Journal of Pharmacology 37, 251–7.CrossRefGoogle ScholarPubMed
Ochoa, E. L. M., Chattopadhyay, A. & McNamee, M. G. (1989). Desensitisation of the nicotinic acetylcholine receptor: molecular mechanisms and effect of modulators. Cellular and Molecular Neurobiology 9, 141–78.CrossRefGoogle ScholarPubMed
Okimoto, R., Macfarlane, J. L., Clary, D. O. & Wolstenholme, D. R. (1992). The mitochondrial genomes of two nematodes, Caenorhabditis elegans and Ascaris suum. Genetics 130, 471–98.CrossRefGoogle ScholarPubMed
Overend, D. J., Phillips, M. L., Poulton, A. L. & Foster, C. E. D. (1994). Anthelmintic resistance in Australian sheep nematode populations. Australian Veterinary Journal! 1, 117–21.CrossRefGoogle Scholar
Pomroy, W. E. & Whelan, N. C. (1993). Efficacy of moxidectin against an ivermectin-resistant isolate of Ostertagia circumcincta in young sheep. The Veterinary Record 132, 416.CrossRefGoogle Scholar
Raizen, D. M. & Avery, L. (1994). Electrical activity and behaviour in the pharynx of Caenorhabditis elegans. Neuron 12, 483–95.CrossRefGoogle ScholarPubMed
Robertson, S. J. & Martin, R. J. (1993). Levamisoleactivated single-channel currents from muscle of the nematode parasite Ascaris suum. British Journal of Pharmacology 108, 170–8.CrossRefGoogle ScholarPubMed
Roepstorff, A., Bjorn, H. & Nansen, P. (1987). Resistance of Oesophagostomum spp. in pigs to pyrantel citrate. Veterinary Parasitology 24, 229–39.CrossRefGoogle ScholarPubMed
Rohrer, S. P., Birzin, E. T., Eary, C. H., Schaeffer, J. M. & Shoop, W. L. (1994). Ivermectin binding sites in sensitive and resistant Haemonchus contortus. The Journal of Parasitology 80, 493–7.CrossRefGoogle ScholarPubMed
Rohrer, S. P., Meinke, P. T., Hayes, E. C., Mrozik, H. & Schaeffer, J. M. (1992). Photoaffinity labeling of avermectin binding sites from Caenorhabditis elegans and Drosophila melanogaster. Proceedings of the National Academy of Sciences, USA 89, 4168–72.CrossRefGoogle ScholarPubMed
Roos, M. H., Kwa, M. S. G., Veenstra, J. G.Kooyman, F. N. J. & Boersema, J. P. (1993). Molecular aspects of drug resistance in parasitic helminths. Pharmacology and Therapeutics 60, 331–6.CrossRefGoogle ScholarPubMed
Rothwell, J. T. & Sangster, N. C. (1993). An in vitro assay utilising parasitic larval Haemonchus contortus to detect resistance to closantel and other anthelmintics. International Journal for Parasitology 23, 573–8.CrossRefGoogle Scholar
Sangster, N. C. (1995). Ivermectin and moxidectin: just different names? In Australian Sheep Veterinary Society, Australian Veterinary Association Proceedings, pp. 144–150. Melbourne: Australian Veterinary Association.Google Scholar
Sangster, N. C. & Bjorn, H. (1995). Levamisole resistance in Haemonchus contortus selected at different stages of infection. International Journal for Parasitology 25, 343–8.CrossRefGoogle ScholarPubMed
Sangster, N. C., Davis, C. W. & Collins, G. H. (1991). Effect of cholinergic drugs on longitudinal contraction on levamisole-susceptible and -resistant Haemonchus contortus. International Journal for Parasitology 21, 689–95.CrossRefGoogle ScholarPubMed
Sangster, N. C., Lacey, E., Than, C. & Long, M. A. (1989). Synthesis of deuterium and tritium labelled maminolevamisole and levamisole. Journal of Labelled Compounds and Radiopharmaceuticals. 27: 1069–78.CrossRefGoogle Scholar
Sangster, N. C., Riley, F. L. & Collins, G. H. (1988). Investigation of the mechanism of levamisole resistance in trichostrongylid nematodes of sheep. International Journal for Parasitology 18, 813–18.CrossRefGoogle ScholarPubMed
Sangster, N. C., Whitlock, H. V., Russ, I. G., Gunawan, M., Griffin, D. L. & Kelly, J. D. (1979). Trichostrongylus colubriformis and Ostertagia circumcincta resistant to levamisole, morantel tartrate and thiabendazole: occurrence of field isolates. Research in Veterinary Science 27, 106–10.CrossRefGoogle Scholar
Schaeffer, J. M. & Haines, H. W. (1989). Avermectin binding in Caenorhabditis elegans a two-state model for the avermectin binding site. Biochemical Pharmacology 38, 2329–38.CrossRefGoogle ScholarPubMed
Shoop, W. L., Haines, H. W., Michael, B. F. & Eary, C. H. (1993) Mutual resistance to avermectin and milbemycins: oral activity of ivermectin and moxidectin against ivermectin-resistant and susceptible nematodes. The Veterinary Record 133, 445–7.CrossRefGoogle ScholarPubMed
Swan, N., Gardner, J. J., Besier, R. B. & Wroth, R. (1994). A field case of ivermectin resistance in Ostertagia of sheep. Australian Veterinary Journal 71, 302–3.CrossRefGoogle ScholarPubMed
Taylor, M. A. (1990). A larval development test for the detection of anthelmintic resistance in nematodes of sheep. Research in Veterinary Science 49, 198–202.CrossRefGoogle ScholarPubMed
Van Nueten, J. M. (1976). Pharmacological aspects of tetramisole. In Biochemistry of Parasites and Hostparasite Relationships. (Ed. Bossche, H. Van den) pp. 101–115. North-Holland, Amsterdam.Google Scholar
Van Wyk, J. A. & Malan, F. S. (1988). Resistance of field isolates of Haemonchus contortus to ivermectin, closantel, rafoxanide and the benzimidazoles in South Africa. The Veterinary Record 123, 226–8.CrossRefGoogle Scholar
Van Wyk, J. A., Van Schalkwyk, P. C., Gerger, H. M., Visser, E. L., Alves, R. M. R. & Van Schalkwyk, L. (1989). South African field isolates of Haemonchus contortus resistant to the levamisole/morantel group of anthelmintics. Onderstepoort Journal of Veterinary Research 56, 257–62.Google Scholar
Varady, M., Petersen, M. B., Bjorn, H. & Nansen, P. (1996). The efficacy of ivermectin against nodular worms of pigs. International Journal for Parasitology 26, 369–74CrossRefGoogle ScholarPubMed
Waller, P. J. (1994). The development of anthelmintic resistance in ruminant livestock. Ada Tropica 56, 233–43.CrossRefGoogle ScholarPubMed
Waller, P. J., Dash, K. M., Barger, I. A., Le Jambre, L. F. & Plant, J. (1995). Anthelmintic resistance in nematode parasites of sheep: learning from the Australian experience. The Veterinary Record 136, 411–13.CrossRefGoogle ScholarPubMed
Waller, P. J., Dobson, R. J., Obendorf, D. L. & Gillham, R. J. (1986). Resistance of Trichostrongylus colubriformis to levamisole and morantel: differences in relation to selection history. Veterinary Parasitology 21, 255–63.CrossRefGoogle ScholarPubMed
Waller, P. J., Echevarria, F., Eddi, C., Maciel, S., Nari, A. & Hansen, J. W. (1996). Anthelmintic resistance of nematodes in sheep flocks in South America. The Veterinary Record 136, 620.CrossRefGoogle Scholar
Ward, S. (1988). Caenorhabditis elegans: a model for parasitic nematodes. In The Biology of Parasitism: A Molecular and Biochemical Approach (ed. Englund, P. T. & Sher, A.), pp. 503–516. New York: Liss.Google Scholar
Wiley, L. J. (1994). Biochemical and molecular investigation into levamisole-resistance in trichostrongylid nematodes of sheep. PhD thesis, University of Sydney.Google Scholar
Wiley, L. J., Weiss, A. S., Sangster, N. C. & Li, Q. (1996). Cloning and sequence analysis of the candidate nicotinic acetylcholine receptor alpha subunit gene tarl from Trichostrongylus colubriformis. Gene (in press).Google Scholar