Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-07-01T16:04:09.212Z Has data issue: false hasContentIssue false
  • English
  • Français

Measuring the effect of avermectins and milbemycins on somatic muscle contraction of adult Haemonchus contortus and on motility of Ostertagia circumcincta in vitro

Published online by Cambridge University Press:  27 February 2014

JANINA DEMELER ,
GEORG VON SAMSON-HIMMELSTJERNA  and
NICHOLAS C. SANGSTER
JANINA DEMELER*
Affiliation:
Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany Faculty of Veterinary Science, University of Sydney, 2006 NSW, Australia
GEORG VON SAMSON-HIMMELSTJERNA
Affiliation:
Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany
NICHOLAS C. SANGSTER
Affiliation:
Faculty of Veterinary Science, University of Sydney, 2006 NSW, Australia School of Animal and Veterinary Sciences, Charles Sturt University, Locked Bag 588, Wagga Wagga, 2678 NSW, Australia
*
*Corresponding author: Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany. E-mail: janina.demeler@fu-berlin.de
Get access Rights & Permissions [Opens in a new window]

Summary

The mechanism of anthelmintic resistance against the widely used macrocyclic lactones (MLs) is still not fully understood. Pharyngeal, somatic body muscles and the ovijector have been proposed as putative sites of action as well as resistance. In the present study the effects of three avermectins and three milbemycins on adult parasitic nematodes were evaluated in vitro. The Muscle Transducer system was used to investigate the effects of MLs on muscle contraction in female Haemonchus contortus and effects on motility were measured in Ostertagia (Teladorsagia) circumcincta using the Micromotility Meter. Concentration-response curves for all substances in both systems shifted to the right in the resistant isolates. Resistance was present to ivermectin (IVM) and its components IVM B1a and IVM B1b, suggesting that both components are involved in the mode of action and resistance. No consistent patterns of potency and resistance of the substances were observed except that milbemycins generally showed lower resistance ratios (RRs) than IVM. IVM and IVM B1b were the most potent inhibitors of contraction and motility in both susceptible isolates and also showed the highest RR in both species. Low RRs for milbemycins recorded in vitro for highly resistant isolates in vivo suggest that other factors such as pharmacokinetics influence drug potency in vivo.

Keywords

anthelmintic resistancemotilitysheep nematodesin vitro assaysmuscle transducercontraction
Type
Research Article
Information
Parasitology , Volume 141 , Issue 7 , June 2014 , pp. 948 - 956
Check for updates
Copyright
Copyright © Cambridge University Press 2014 

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

Anziani, O. S., Suarez, V. H., Guglielmone, A. A., Warnke, O., Grande, H. and Coles, G. C. (2004). Resistance to benzimidazole and macrocyclic lactone anthelmintics in cattle nematodes in Argentina. Veterinary Parasitology 122, 303–306.CrossRefGoogle ScholarPubMed
Bennet, J. L. and Pax, R. A. (1987). Micromotility Meter: an instrumentation to analyse helminth motility. Parasitology Today 3, 159–160.Google Scholar
Conder, G. A., Thompson, D. P. and Johnson, S. S. (1993). Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin. Veterinary Record 132, 651–652.Google Scholar
Demeler, J., Van Zeveren, A. M., Kleinschmidt, N., Vercruysse, J., Hoglund, J., Koopmann, R., Cabaret, J., Claerebout, E., Areskog, M. and von Samson-Himmelstjerna, G. (2009). Monitoring the efficacy of ivermectin and albendazole against gastro intestinal nematodes of cattle in Northern Europe. Veterinary Parasitology 160, 109–115.CrossRefGoogle ScholarPubMed
Demeler, J., Gill, J. H., von Samson-Himmelstjerna, G. and Sangster, N. C. (2013). The in vitro assay profile of macrocyclic lactone resistance in three species of sheep trichostrongyloids. International Journal for Parasitology – Drugs and Drug Resistance 3, 109–118.Google Scholar
Folz, S. D., Pax, R. A., Thomas, E. M., Bennett, J. L., Lee, B. L. and Conder, G. A. (1987 a). Detecting in vitro anthelmintic effects with a micromotility meter. Veterinary Parasitology 24, 241–250.Google Scholar
Folz, S. D., Pax, R. A., Thomas, E. M., Bennett, J. L., Lee, B. L. and Conder, G. A. (1987 b). Development and validation of an in vitro Trichostrongylus colubriformis motility assay. International Journal for Parasitology 17, 1441–1444.Google Scholar
Geary, T. G., Sims, S. M., Thomas, E. M., Vanover, L., Davis, J. P., Winterrowd, C. A., Klein, R. D., Ho, N. F. H. and Thompson, D. P. (1993). Haemonchus contortus: ivermectin-induced paralysis of the pharynx. Experimental Parasitology 77, 88–96.Google Scholar
Gill, J. H. and Lacey, E. (1998). Avermectin/milbemycin resistance in trichostrongyloid nematodes. International Journal for Parasitology 28, 863–877.Google Scholar
Gill, J. H., Redwin, J. M., Van Wyk, J. A. and Lacey, E. (1995). Avermectin inhibition of larval development in Haemonchus contortus – effects of ivermectin resistance. International Journal for Parasitology 25, 463–470.CrossRefGoogle ScholarPubMed
Jackson, R., Rhodes, A. P., Pomroy, W. E., Leathwick, D. M., West, D. M., Waghorn, T. S. and Moffat, J. R. (2006). Anthelmintic resistance and management of nematode parasites on beef cattle-rearing farms in the North Island of New Zealand. New Zealand Veterinary Journal 54, 289–296.CrossRefGoogle ScholarPubMed
Kass, I. S., Stretton, A. O. W. and Wang, C. C. (1984). The effects of avermectin and drugs related to acetylcholine and 4-aminobutyric acid on neurotransmission in Ascaris suum . Molecular and Biochemical Parasitology 13, 213–225.Google Scholar
Kohler, P. (2001). The biochemical basis of anthelmintic action and resistance. International Journal for Parasitology 31, 336–345.Google Scholar
Kotze, A. C., Hines, B. M. and Ruffell, A. P. (2012). A reappraisal of the relative sensitivity of nematode pharyngeal and somatic musculature to macrocyclic lactone drugs. International Journal for Parasitology: Drugs and Drug Resistance 2, 29–35.Google Scholar
Le Jambre, L., Geoghegan, J. and Lyndal-Murphy, M. (2005). Characterization of moxidectin resistant Trichostrongylus colubriformis and Haemonchus contortus . Veterinary Parasitology 128, 83–90.Google Scholar
Marks, N. J., Sangster, N. C., Maule, A. G., Halton, D. W., Thompson, D. P., Geary, T. G. and Shaw, C. (1999). Structural characterisation and pharmacology of KHEYLRamide (AF2) and KSAYMRFamide (PF3/AF8) from Haemonchus contortus . Molecular and Biochemical Parasitology 100, 185–194.Google Scholar
McCavera, S., Walsh, T. K. and Wolstenholme, A. J. (2007). Nematode ligand-gated chloride channels: an appraisal of their involvement in macrocyclic lactone resistance and prospects for developing molecular markers. Parasitology 134, 1111–1121.Google Scholar
Mejía, M. E., Fernandez Igartúa, B. M., Schmidt, E. E. and Cabaret, J. (2003). Multispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance. Veterinary Research 34, 461–467.Google Scholar
Moreno, Y., Nabhan, J. F., Solomon, J., Mackenzie, C. D. and Geary, T. G. (2010). Ivermectin disrupts the function of the excretory-secretory apparatus in microfilariae of Brugia malayi . Proceedings of the National Academy of Sciences USA 107, 20120–20125.Google Scholar
Portillo, V., Jagannathan, S. and Wolstenholme, A. J. (2003). Distribution of glutamate-gated chloride channel subunits in the parasitic nematode Haemonchus contortus . Journal of Comparative Neurology 462, 213–222.Google Scholar
Richards, J. C., Behnke, J. M. and Duce, I. R. (1995). In vitro studies on the relative sensitivity to ivermectin of Necator americanus and Ancylostoma ceylanicum . International Journal for Parasitology 25, 1185–1191.Google Scholar
Sangster, N. C. and Bjorn, H. (1995). Levamisole resistance in Haemonchus contortus selected at different stages of infection. International Journal for Parasitology 25, 343–348.CrossRefGoogle ScholarPubMed
Sangster, N. C., Davis, C. W. and Collins, G. H. (1991). Effects of cholinergic drugs on longitudinal contraction in levamisole-susceptible and-resistant Haemonchus contortus . International Journal for Parasitology 21, 689–695.Google Scholar
Sangster, N. C., Song, J. and Demeler, J. (2005). Resistance as a tool for discovering and understanding targets in parasite neuromusculature. Parasitology 131 (Suppl.), S179–190.Google Scholar
Sheriff, J. C., Kotze, A. C., Sangster, N. C. and Martin, R. J. (2002). Effects of macrocyclic lactone anthelmintics on feeding and pharyngeal pumping in Trichostrongylus colubriformis in vitro . Parasitology 125, 477–484.Google Scholar
Sheriff, J. C., Kotze, A. C., Sangster, N. C. and Hennessy, D. R. (2005). Effect of ivermectin on feeding by Haemonchus contortus in vivo . Veterinary Parasitology 128, 341–346.Google Scholar
Shoop, W. L. (1993). Ivermectin resistance. Parasitology Today 9, 154–159.Google Scholar
Soutello, R. V. G., Seno, M. C. Z. and Amarante, A. F. T. (2007). Anthelmintic resistance in cattle nematodes in northwestern São Paulo State, Brazil. Veterinary Parasitology 148, 360–364.Google Scholar
Suarez, V. H. and Cristel, S. L. (2007). Anthelmintic resistance in cattle nematode in the western Pampeana Region of Argentina. Veterinary Parasitology 144, 111–117.Google Scholar
Sutherland, I. A., Leathwick, D. M., Moen, I. C. and Bisset, S. A. (2002). Resistance to therapeutic treatment with macrocyclic lactones anthelmintic in Ostertagia circumscripta . Veterinary Parasitology 109, 91–99.Google Scholar
Waghorn, T. S., Leathwick, D. M., Rhodes, A. P., Jackson, R., Pomroy, W. E., West, D. M. and Moffat, J. R. (2006). Prevalence of anthelmintic resistance in 62 beef cattle farms in the North Island of New Zealand. New Zealand Veterinary Journal 54, 278–282.Google Scholar
Wolstenholme, A. J. and Rogers, A. T. (2005). Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics. Parasitology 131 (Suppl.), S85–S95.Google Scholar