Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-22T18:48:19.282Z Has data issue: false hasContentIssue false
  • English
  • Français

Population genetics of anthelmintic resistance in parasitic nematodes

Published online by Cambridge University Press:  03 July 2007

J. S. GILLEARD  and
R. N. BEECH
J. S. GILLEARD*
Affiliation:
Division of Infection and Immunity, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow, UKG61 1QH
R. N. BEECH
Affiliation:
Institute of Parasitology, Macdonald College, McGill University, 21,111 Lakeshore Road, Ste Anne de Bellevue, Quebec, CanadaH9X 3V9
*
*Corresponding author. Tel: (141) 330 5604. Fax: (141) 330 5603. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

A key aim of anthelmintic resistance research is to identify molecular markers that could form the basis of sensitive and accurate diagnostic tests. These would provide powerful tools to study the origin and spread of anthelmintic resistance in the field and to monitor strategies aimed at preventing and managing resistance. Molecular markers could also form the basis of routine diagnostic tests for use in surveillance and clinical veterinary practice. Much of the research conducted to date has focused on the investigation of possible associations of particular candidate genes with the resistance phenotype. In the future, as full parasite genome sequences become available, there will be an opportunity to apply genome-wide approaches to identify the genetic loci that underlie anthelmintic resistance. Both the interpretation of candidate gene studies and the application of genome-wide approaches require a good understanding of the genetics and population biology of the relevant parasites as well as knowledge of how resistance mutations arise and are selected in populations. Unfortunately, much of this information is lacking for parasitic nematodes. This review deals with a number of aspects of genetics and population biology that are pertinent to these issues. We discuss the possible origins of resistance mutations and the likely effects of subsequent selection on the genetic variation at the resistance-conferring locus. We also review some of the experimental approaches that have been used to test associations between candidate genes and anthelmintic resistance phenotypes and highlight implications for future genome-wide studies.

Keywords

Anthelmintic resistanceHaemonchus contortusgenetic linkageSNPgenetic marker
Type
Research Article
Information
Parasitology , Volume 134 , Special Issue 8: MARKERS FOR ANTHELMINTIC RESISTANCE , August 2007 , pp. 1133 - 1147
Copyright
Copyright © Cambridge University Press 2007

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

Alvarez-Sanchez, M. A., Perez Garcia, J., Bartley, D., Jackson, F. and Rojo-Vazquez, F. A. (2005). The larval feeding inhibition assay for the diagnosis of nematode anthelmintic resistance. Experimental Parasitology 110, 56–61.CrossRefGoogle ScholarPubMed
Anderson, T. J. (2004). Mapping drug resistance genes in Plasmodium falciparum by genome-wide association. Current Drug Targets – Infectious Disorders 4, 65–78.CrossRefGoogle ScholarPubMed
Anderson, T. J. C., Blouin, M. S. and Beech, R. N. (1998). Population biology of parasitic nematodes: applications of genetic markers. Advances in Parasitology 41, 219–283.CrossRefGoogle ScholarPubMed
Aquadro, C. F., Bauer DuMont, V. and Reed, F. A. (2001). Genome-wide variation in the human and fruitfly: a comparison. Current Opinions in Genetic and Development 11, 627–634.CrossRefGoogle ScholarPubMed
Ardelli, B. F., Guerriero, S. B. and Prichard, R. K. (2006 a). Characterization of a half-size ATP-binding cassette transporter gene which may be a useful marker for ivermectin selection in Onchocerca volvulus. Molecular and Biochemical Parasitology 145, 94–100.CrossRefGoogle ScholarPubMed
Ardelli, B. F., Guerriero, S. B. and Prichard, R. K. (2006 b). Ivermectin imposes selection pressure on P-glycoprotein from Onchocerca volvulus: linkage disequilibrium and genotype diversity. Parasitology 132, 375–386.CrossRefGoogle ScholarPubMed
Barnes, T. M., Kohara, Y., Coulson, A. and Hekimi, S. (1995). Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. Genetics 141, 159–179.CrossRefGoogle ScholarPubMed
Bartley, D., Jackson, F., Coop, R. L., Jackson, E., Johnston, K. and Mitchell, G. B. (2001). Anthelmintic-resistant nematodes in sheep in Scotland. Veterinary Record 149, 94–95.Google ScholarPubMed
Bartley, D. J., Donnan, A. A., Jackson, E., Sargison, N., Mitchell, G. B. and Jackson, F. (2006). A small scale survey of ivermectin resistance in sheep nematodes using the faecal egg count reduction test on samples collected from Scottish sheep. Veterinary Parasitology 137, 112–118.CrossRefGoogle ScholarPubMed
Beech, R. N., Prichard, R. K. and Scott, M. E. (1994). Genetic variability of the β-tubulin genes in benzimidazole-susceptible and -resistant strains of Haemonchus contortus. Genetics 138, 103–110.CrossRefGoogle ScholarPubMed
Blackhall, W. (1999). Genetic Variation and Ivermectin Resistance in Haemonchus contortus. Ph.D. Thesis, Institute of Parasitology, McGill University, Montreal.Google Scholar
Blackhall, W., Liu, H. Y., Xu, M., Prichard, R. K. and Beech, R. N. (1998 a). Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus. Molecular and Biochemical Parasitology 95, 193–201.CrossRefGoogle Scholar
Blackhall, W. J., Pouliot, J. F., Prichard, R. K. and Beech, R. N. (1998 b). Haemonchus contortus: selection at a glutamate-gated chloride channel gene in ivermectin- and moxidectin-selected strains. Experimental Parasitology 90, 42–48.CrossRefGoogle Scholar
Blackhall, W. J., Prichard, R. K. and Beech, R. N. (2003). Selection at a gamma-aminobutyric acid receptor gene in Haemonchus contortus resistant to avermectins/milbemycins. Molecular and Biochemical Parasitology 131, 137–145.CrossRefGoogle Scholar
Blouin, M., Yowell, C., Courtney, C. and Dame, J. (1995). Host movement and the genetic structure of populations of parasitic nematodes. Genetics 141, 1007–1014.CrossRefGoogle ScholarPubMed
Blouin, M. S. (1998). Mitochondrial DNA diversity in nematodes. Journal of Helminthology 72, 285–289.CrossRefGoogle ScholarPubMed
Blouin, M. S. (2000). Neutrality tests on mtDNA: unusual results from nematodes. Journal of Heredity 91, 156–158.CrossRefGoogle ScholarPubMed
Blouin, M. S., Dame, J. B., Tarrant, C. A. and Courtney, C. H. (1992). Unusual population genetics of a parasitic nematode: mtDNA variation within and among populations. Evolution 46, 470–476.CrossRefGoogle ScholarPubMed
Braisher, T. L., Gemmell, N. J., Grenfell, B. T. and Amos, W. (2004). Host isolation and patterns of genetic variability in three populations of Teladorsagia from sheep. International Journal for Parasitology 34, 1197–1204.CrossRefGoogle ScholarPubMed
Cabaret, J. and Gasnier, N. (1994). Farm history and breeding management influences on the intensity and specific diversity of nematode infection of dairy goats. Veterinary Parasitology 53, 219–232.CrossRefGoogle ScholarPubMed
Campbell, W. C., Fisher, M. H., Stapley, E. O., Albers-Schonberg, G. and Jacob, T. A. (1983). Ivermectin: a potent new antiparasitic agent. Science 221, 823–828.CrossRefGoogle ScholarPubMed
Chabala, J. C., Mrozik, H., Tolman, R. L., Eskola, P., Lusi, A., Peterson, L. H., Woods, M. F., Fisher, M. H., Campbell, W. C., Egerton, J. R. and Ostlind, D. A. (1980). Ivermectin, a new broad-spectrum antiparasitic agent. Journal of Medical Chemistry 23, 1134–1136.CrossRefGoogle ScholarPubMed
Chehresa, A., Beech, R. N. and Scott, M. E. (1997). Life history variation among lines isolated from a laboratory population of Heligmosomoides polygyrus bakeri. International Journal for Parasitology 27, 541–551.CrossRefGoogle ScholarPubMed
Coles, G. C. (1999). Anthelmintic resistance and the control of worms. Journal of Medical Microbiology 48, 323–325.CrossRefGoogle ScholarPubMed
Coles, G. C., Rhodes, A. C. and Wolstenholme, A. J. (2005). Rapid selection for ivermectin resistance in Haemonchus contortus. Veterinary Parasitology 129, 345–347.CrossRefGoogle ScholarPubMed
Cully, D., Vassilatis, D., Liu, K., Paress, P., Van, D. P. L., Schaeffer, J. and Arena, J. (1994). Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans. Nature 371, 707–711.CrossRefGoogle ScholarPubMed
Daborn, P. J., Yen, J. L., Bogwitz, M. R., Le Goff, G., Feil, E., Jeffers, S., Tijet, N., Perry, T., Heckel, D., Batterham, P., Feyereisen, R., Wilson, T. G. and ffrench-Constant, R. H. (2002). A single p450 allele associated with insecticide resistance in Drosophila. Science 297, 2253–2256.CrossRefGoogle ScholarPubMed
Davidse, L. C. and Flach, W. (1977). Differential binding of methyl benzimidazole-2-yl-carbamate to fungal tubulin as a mechanism of resistance to this antimitotic agent in mutant strains of Aspergillus nidulans. Journal of Cell Biology 72, 174–189.CrossRefGoogle Scholar
Dent, J. A., Smith, M. M., Vassilatis, D. K. and Avery, L. (2000). The genetics of ivermectin resistance in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 97, 2674–2679.CrossRefGoogle ScholarPubMed
Denver, D. R., Morris, K., Lynch, M. and Thomas, W. K. (2004). High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome. Nature 430, 679–682.CrossRefGoogle ScholarPubMed
Denver, D. R., Morris, K., Lynch, M., Vassilieva, L. L. and Thomas, W. K. (2000). High direct estimate of the mutation rate in the mitochondrial genome of Caenorhabditis elegans. Science 289, 2342–2344.CrossRefGoogle ScholarPubMed
Denver, D. R., Morris, K., Streelman, J. T., Kim, S. K., Lynch, M. and Thomas, W. K. (2005). The transcriptional consequences of mutation and natural selection in Caenorhabditis elegans. Nature Genetics 37, 544–548.CrossRefGoogle ScholarPubMed
Egerton, J., Suhayda, D. and Eary, C. (1988). Laboratory selection of Haemonchus contortus for resistance to ivermectin. Journal of Parasitology 74, 614–617.CrossRefGoogle ScholarPubMed
Eng, J. K., Blackhall, W. J., Osei-Atweneboana, M. Y., Bourguinat, C., Galazzo, D., Beech, R. N., Unnasch, T. R., Awadzi, K., Lubega, G. W. and Prichard, R. K. (2006). Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and Haemonchus contortus. Molecular and Biochemical Parasitology 150, 229–235.CrossRefGoogle ScholarPubMed
Feng, X. P., Hayashi, J., Beech, R. N. and Prichard, R. K. (2002). Study of the nematode putative GABA type-A receptor subunits: evidence for modulation by ivermectin. Journal of Neurochemistry 83, 870–878.CrossRefGoogle ScholarPubMed
ffrench-Constant, R., Daborn, P. and Feyereisen, R. (2006). Resistance and the jumping gene. Bioessays 28, 6–8.CrossRefGoogle ScholarPubMed
ffrench-Constant, R. H., Daborn, P. J. and Le Goff, G. (2004). The genetics and genomics of insecticide resistance. Trends in Genetics 20, 163–170.CrossRefGoogle ScholarPubMed
Galazzo, D. (2004). A comparison of laboratory and field resistance to macrocyclic lactones in Haemonchus contortus. MSc. thesis, Institute of Parasitology, McGill University, Montreal.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. and Thompson, D. P. (1993). Haemonchus contortus: ivermectin-induced paralysis of the pharynx. Experimental Parasitology 77, 88–96.CrossRefGoogle ScholarPubMed
Ghisi, M., Kaminsky, R. and Maser, P. (2007). Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Veterinary Parasitology 144, 313–320.CrossRefGoogle ScholarPubMed
Gill, J. H., Redwin, J. M., van Wyk, J. A. and Lacey, E. (1991). Detection of resistance to ivermectin in Haemonchus contortus. International Journal for Parasitology 21, 771–776.CrossRefGoogle ScholarPubMed
Gilleard, J. S. (2006). Understanding anthelmintic resistance: The need for genomics and genetics. International Journal for Parasitology 36, 1227–1239.CrossRefGoogle ScholarPubMed
Grant, W. N. and Mascord, L. J. (1996). Beta-tubulin gene polymorphism and benzimidazole resistance in Trichostrongylus colubriformis. International Journal for Parasitology 26, 71–77.CrossRefGoogle ScholarPubMed
Grillo, V., Jackson, F., Cabaret, J. and Gilleard, J. S. (2007). Population genetic analysis of the ovine parasitic nematode Teladorsagia circumcincta and evidence for a cryptic species. International Journal for Parasitology 37, 435–447.CrossRefGoogle ScholarPubMed
Grillo, V., Jackson, F. and Gilleard, J. S. (2006). Characterisation of Teladorsagia circumcincta microsatellites and their development as population genetic markers. Molecular and Biochemical Parasitology 148, 181–189.CrossRefGoogle ScholarPubMed
Haag-Liautard, C., Dorris, M., Maside, X., Macaskill, S., Halligan, D. L., Charlesworth, B. and Keightley, P. D. (2007). Direct estimation of per nucleotide and genomic deleterious mutation rates in Drosophila. Nature 445, 82–85.CrossRefGoogle ScholarPubMed
Hermisson, J. and Pennings, P. S. (2005). Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169, 2335–2352.CrossRefGoogle ScholarPubMed
Hill, W. G. (1975). Linkage disequilibrium among multiple neutral alleles produced by mutation in finite population. Theoretical Population Biology 8, 117–126.CrossRefGoogle ScholarPubMed
Hudson, R. R. (2001). Two-locus sampling distributions and their application. Genetics 159, 1805–1817.CrossRefGoogle ScholarPubMed
Jensen-Seaman, M. I., Furey, T. S., Payseur, B. A., Lu, Y., Roskin, K. M., Chen, C. F., Thomas, M. A., Haussler, D. and Jacob, H. J. (2004). Comparative recombination rates in the rat, mouse, and human genomes. Genome Research 14, 528–538.CrossRefGoogle ScholarPubMed
Kaplan, R. M. (2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477–481.CrossRefGoogle ScholarPubMed
Kindahl, E. (1994). Recombination and DNA polymorphism on the third chromosome of Drosophila melanogaster. Ph.D. Thesis, Cornell University, Ithaca, NY.Google Scholar
Kohn, M. H., Pelz, H. J. and Wayne, R. K. (2000). Natural selection mapping of the warfarin-resistance gene. Proceedings of the National Academy of Sciences, USA 97, 7911–7915.CrossRefGoogle ScholarPubMed
Kong, A., Gudbjartsson, D. F., Sainz, J., Jonsdottir, G. M., Gudjonsson, S. A., Richardsson, B., Sigurdardottir, S., Barnard, J., Hallbeck, B., Masson, G., Shlien, A., Palsson, S. T., Frigge, M. L., Thorgeirsson, T. E., Gulcher, J. R. and Stefansson, K. (2002). A high-resolution recombination map of the human genome. Nature Genetics 31, 241–247.CrossRefGoogle ScholarPubMed
Kwa, M., Veenstra, J., Van, D. M. and Roos, M. (1995). Beta-tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. Journal of Molecular Biology 246, 500–510.CrossRefGoogle ScholarPubMed
Kwa, M. S. G., Jetty, V. S. and Roos, M. H. (1994). Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in β-tubulin isotype 1. Molecular and Biochemical Parasitology 63, 299–303.CrossRefGoogle ScholarPubMed
Kwa, M. S. G., Kooyman, F. N. J., Boersema, J. H. and Roos, M. H. (1993). Effect of selection for benzimidazole resistance in Haemonchus contortus on β-tubulin isotype 1 and isotype 2 genes. Biochemical and Biophysical Research Communications 191, 413–419.CrossRefGoogle ScholarPubMed
Langley, C. H., Lazzaro, B. P., Phillips, W., Heikkinen, E. and Braverman, J. M. (2000). Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome. Genetics 156, 1837–1852.CrossRefGoogle Scholar
Leignel, V., Cabaret, J. and Humbert, J. F. (2002). New molecular evidence that Teladorsagia circumcincta (Nematoda: Trichostrongylidea) is a species complex. Journal of Parasitology 88, 135–140.CrossRefGoogle ScholarPubMed
Leignel, V. and Humbert, J. F. (2001). Mitochondrial DNA variation in benzimidazole-resistant and -susceptible populations of the small ruminant parasite Teladorsagia circumcincta. Journal of Heredity 92, 503–506.CrossRefGoogle ScholarPubMed
Lubega, G. W. and Prichard, R. K. (1990). Specific interaction of benzimidazole anthelmintics with tubulin: high-affinity binding and benzimidazole resistance in Haemonchus contortus. Molecular and Biochemical Parasitology 38, 221–232.CrossRefGoogle ScholarPubMed
Lubega, G. W. and Prichard, R. K. (1991 a). Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. Experimental Parasitology 73, 203–213.CrossRefGoogle ScholarPubMed
Lubega, G. W. and Prichard, R. K. (1991 b). Specific interaction of benzimidazole anthelmintics with tubulin from developing stages of thiabendazole-susceptible and -resistant Haemonchus contortus. Biochemical Pharmacology 41, 93–101.CrossRefGoogle ScholarPubMed
Maynard Smith, J. and Haigh, J. (1974). The hitchhiking effect of a favoured gene. Genetical Research 23, 23–35.CrossRefGoogle Scholar
Mes, T. H. (2004). Purifying selection and demographic expansion affect sequence diversity of the ligand-binding domain of a glutamate-gated chloride channel gene of Haemonchus placei. Journal of Molecular Evolution 58, 466–478.CrossRefGoogle ScholarPubMed
Molento, M. B., Wang, G. T. and Prichard, R. K. (1999). Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations. Veterinary Parasitology 86, 77–81.CrossRefGoogle ScholarPubMed
Nachman, M. W. (2002). Variation in recombination rate across the genome: evidence and implications. Current Opinions in Genetic and Development 12, 657–663.CrossRefGoogle ScholarPubMed
Nadler, S. A. (1987). Genetic variability in endoparasitic helminths. Parasitology Today 3, 154–155.CrossRefGoogle ScholarPubMed
Nair, S., Nash, D., Sudimack, D., Jaidee, A., Barends, M., Uhlemann, A. C., Krishna, S., Nosten, F. and Anderson, T. J. (2007). Recurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites. Molecular Biology and Evolution 24, 562–573.CrossRefGoogle ScholarPubMed
Nair, S., Williams, J. T., Brockman, A., Paiphun, L., Mayxay, M., Newton, P. N., Guthmann, J. P., Smithuis, F. M., Hien, T. T., White, N. J., Nosten, F. and Anderson, T. J. (2003). A selective sweep driven by pyrimethamine treatment in Southeast Asian malaria parasites. Molecular Biology and Evolution 20, 1526–1536.CrossRefGoogle ScholarPubMed
Nei, M. and Tajima, F. (1981). DNA polymorphism detectable by restriction endonucleases. Genetics 97, 145–163.CrossRefGoogle ScholarPubMed
Njue, A. I., Hayashi, J., Kinne, L., Feng, X. P. and Prichard, R. K. (2004). Mutations in the extracellular domains of glutamate-gated chloride channel alpha3 and beta subunits from ivermectin-resistant Cooperia oncophora affect agonist sensitivity. Journal of Neurochemistry 89, 1137–1147.CrossRefGoogle ScholarPubMed
Njue, A. I. and Prichard, R. K. (2004). Genetic variability of glutamate-gated chloride channel genes in ivermectin-susceptible and -resistant strains of Cooperia oncophora. Parasitology 129, 741–751.CrossRefGoogle ScholarPubMed
Pennings, P. S. and Hermisson, J. (2006 a). Soft sweeps II – molecular population genetics of adaptation from recurrent mutation or migration. Molecular Biology and Evolution 23, 1076–1084.CrossRefGoogle ScholarPubMed
Pennings, P. S. and Hermisson, J. (2006 b). Soft sweeps III: The signature of positive selection from recurrent mutation. PLoS Genetics 2, e186.CrossRefGoogle ScholarPubMed
Pomroy, W. E. (2006). Anthelmintic resistance in New Zealand: a perspective on recent findings and options for the future. New Zealand Veterinary Journal 54, 265–270.CrossRefGoogle ScholarPubMed
Prichard, R. K. (1970). Mode of action of the anthelmintic thiabendazole in Haemonchus contortus. Nature 228, 684–685.CrossRefGoogle ScholarPubMed
Prichard, R. K., Eng, F. J., Ardelli, B., Halstead, M. and Beech, R. N. (2001). DNA-based diagnostic tool for ivermectin-resistance in Onchocerca volvulus. In WHO-TDR Workshop on Non-responders to Ivermectin Treatment in Onchocerciasis, Noguchi Memorial Institute, Accra, Ghana.Google Scholar
Roos, M. H., Boersema, J. H., Borgsteede, F. H. M., Cornelissen, J., Taylor, M. and Ruitenberg, E. J. (1990). Molecular analysis of selection for benzimidazole resistance in the sheep parasite Haemonchus contortus. Molecular and Biochemical Parasitology 43, 77–88.CrossRefGoogle ScholarPubMed
Silvestre, A. and Cabaret, J. (2002). Mutation in position 167 of isotype 1 beta-tubulin gene of Trichostrongylid nematodes: role in benzimidazole resistance? Molecular and Biochemical Parasitology 120, 297–300.CrossRefGoogle ScholarPubMed
Silvestre, A. and Humbert, J. F. (2002). Diversity of benzimidazole-resistance alleles in populations of small ruminant parasites. International Journal for Parasitology 32, 921–928.CrossRefGoogle ScholarPubMed
Taillon-Miller, P., Bauer-Sardina, I., Saccone, N. L., Putzel, J., Laitinen, T., Cao, A., Kere, J., Pilia, G., Rice, J. P. and Kwok, P. Y. (2000). Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nature Genetics 25, 324–328.CrossRefGoogle ScholarPubMed
Thomas, W. K. and Wilson, A. C. (1991). Mode and tempo of molecular evolution in the nematode Caenorhabditis: cytochrome oxidase II and calmodulin sequences. Genetics 128, 269–279.CrossRefGoogle ScholarPubMed
Troell, K., Engstrom, A., Morrison, D. A., Mattsson, J. G. and Hoglund, J. (2006). Global patterns reveal strong population structure in Haemonchus contortus, a nematode parasite of domesticated ruminants. International Journal for Parasitology 36, 1305–1316.CrossRefGoogle ScholarPubMed
Urquhart, G., Duncan, J., Armour, J., Dunn, A., Jennings, F. and Jennings, F. W. (1996). Veterinary Parasitology, Blackwell Science, Inc., Oxford, UK.Google Scholar
Wagland, B. M., Jones, W. O., Hribar, L., Bendixsen, T. and Emery, D. L. (1992). A new simplified assay for larval migration inhibition. International Journal for Parasitology 22, 1183–1185.CrossRefGoogle ScholarPubMed
Zhou, S. (2005). Role of the HG1 gene in larval movement and response to moxidectin in Haemonchus contortus. MSc. thesis, Institute of Parasitology, McGill University, Montreal.Google Scholar