Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2025-01-03T14:15:19.148Z Has data issue: false hasContentIssue false
  • English
  • Français

Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance

Published online by Cambridge University Press:  02 September 2013

JOHN S. GILLEARD
JOHN S. GILLEARD*
Affiliation:
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, 3280, Hospital Drive NW, University of Calgary, Calgary, Alberta, T2N 4Z6, Canada
*
*Corresponding author: Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, 3280, Hospital Drive NW, University of Calgary, Calgary, Alberta, T2N 4Z6, Canada. Tel: 403 210 6327. Fax: 403 210 6693. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Summary

Anthelmintic resistance is a major problem for the control livestock parasites and a potential threat to the sustainability of community-wide treatment programmes being used to control human parasites in the developing world. Anthelmintic resistance is essentially a complex quantitative trait in which multiple mutations contribute to the resistance phenotype in an additive manner. Consequently, a combination of forward genetic and genomic approaches are needed to identify the causal mutations and quantify their contribution to the resistance phenotype. Therefore, there is a need to develop genetic and genomic approaches for key parasite species identified as relevant models. Haemonchus contortus, a gastro-intestinal parasite of sheep, has shown a remarkable propensity to develop resistance to all the drugs used in its control. Partly because of this, and partly because of its experimental amenability, research on this parasite has contributed more than any other to our understanding of anthelmintic resistance. H. contortus offers a variety of advantages as an experimental system including the ability to undertake genetic crosses; a prerequisite for genetic mapping. This review will discuss the current progress on developing H. contortus as a model system in which to study anthelmintic resistance.

Keywords

Anthelmintic resistanceHaemonchus contortusnematodestrongylidgeneticsgenomicsIvermectinbenzimidazoles
Type
Research Article
Information
Parasitology , Volume 140 , Issue 12: Genetic and genomic approaches to understanding drug resistance in parasites , October 2013 , pp. 1506 - 1522
Copyright
Copyright © Cambridge University Press 2013 

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

Anderson, R. C. (2000). Nematode Parasites of Vertebrates: Their Development and Transmission. CABI, New York.CrossRefGoogle Scholar
Anderson, T., Nkhoma, S., Ecker, A. and Fidock, D. (2011). How can we identify parasite genes that underlie antimalarial drug resistance? Pharmacogenomics 12, 59–85. doi: 10.2217/pgs.10.165.CrossRefGoogle ScholarPubMed
Barrere, V., Alvarez, L., Suarez, G., Ceballos, L., Moreno, L., Lanusse, C. and Prichard, R. K. (2012). Relationship between increased albendazole systemic exposure and changes in single nucleotide polymorphisms on the beta-tubulin isotype 1 encoding gene in Haemonchus contortus. Veterinary Parasitology 186, 344–349. doi: 10.1016/j.vetpar.2011.11.068.CrossRefGoogle ScholarPubMed
Beech, R. N., Skuce, P., Bartley, D. J., Martin, R. J., Prichard, R. K. and Gilleard, J. S. (2011). Anthelmintic resistance: markers for resistance, or susceptibility? Parasitology 138, 160–174. doi: 10.1017/S0031182010001198.CrossRefGoogle ScholarPubMed
Blackhall, W. J., Liu, H. Y., Xu, M., Prichard, R. K. and Beech, R. N. (1998). Selection at a P-glycoprotein gene in ivermectin- and moxidectin-selected strains of Haemonchus contortus. Molecular and Biochemical Parasitology 95, 193–201. doi: S0166-6851(98)00087-5 [pii].CrossRefGoogle Scholar
Blaxter, M. L., De Ley, P., Garey, J. R., Liu, L. X., Scheldeman, P., Vierstraete, A., Vanfleteren, J. R., Mackey, L. Y., Dorris, M., Frisse, L. M., Vida, J. T. and Thomas, W. K. (1998). A molecular evolutionary framework for the phylum Nematoda. Nature 392, 71–75.CrossRefGoogle ScholarPubMed
Blouin, M. S., Yowell, C. A., Courtney, C. H. and Dame, J. B. (1995). Host movement and the genetic structure of populations of parasitic nematodes. Genetics 141, 1007–1014.CrossRefGoogle ScholarPubMed
Borges, S., Cravo, P., Creasey, A., Fawcett, R., Modrzynska, K., Rodrigues, L., Martinelli, A. and Hunt, P. (2011). Genomewide scan reveals amplification of mdr1 as a common denominator of resistance to mefloquine, lumefantrine, and artemisinin in Plasmodium chabaudi malaria parasites. Antimicrobial Agents and Chemotherapy 55, 4858–4865. doi: 10.1128/AAC.01748-10.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
Coles, G. C., Jackson, F., Pomroy, W. E., Prichard, R. K., von Samson-Himmelstjerna, G., Silvestre, A., Taylor, M. A. and Vercruysse, J. (2006). The detection of anthelmintic resistance in nematodes of veterinary importance. Veterinary Parasitology 136, 167–185.CrossRefGoogle ScholarPubMed
Couthier, A., Smith, J., McGarr, P., Craig, B. and Gilleard, J. S. (2004). Ectopic expression of a Haemonchus contortus GATA transcription factor in Caenorhabditis elegans reveals conserved function in spite of extensive sequence divergence. Molecular and Biochemical Parasitology 133, 241–253.CrossRefGoogle ScholarPubMed
Coyne, M. J. and Smith, G. (1992). The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections. International Journal for Parasitology 22, 315–325.CrossRefGoogle ScholarPubMed
Culleton, R., Martinelli, A., Hunt, P. and Carter, R. (2005). Linkage group selection: rapid gene discovery in malaria parasites. Genome Research 15, 92–97. doi: 10.1101/gr.2866205.CrossRefGoogle ScholarPubMed
Demeler, J., Kuttler, U., El-Abdellati, A., Stafford, K., Rydzik, A., Varady, M., Kenyon, F., Coles, G., Hoglund, J., Jackson, F., Vercruysse, J. and von Samson-Himmelstjerna, G.Standardization of the larval migration inhibition test for the detection of resistance to ivermectin in gastro intestinal nematodes of ruminants. Veterinary Parasitology 174, 58–64. doi: S0304-4017(10)00461-9 [pii] 10.1016/j.vetpar.2010.08.020.CrossRefGoogle Scholar
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., Wilhelm, L. J., Howe, D. K., Gafner, K., Dolan, P. C. and Baer, C. F. (2012). Variation in base-substitution mutation in experimental and natural lineages of Caenorhabditis nematodes. Genome Biology and Evolution 4, 513–522. doi: 10.1093/gbe/evs028.CrossRefGoogle ScholarPubMed
Diawara, A., Schwenkenbecher, J. M., Kaplan, R. M. and Prichard, R. K. (2013). Molecular and biological diagnostic tests for monitoring benzimidazole resistance in human soil-transmitted helminths. American Journal of Tropical Medicine and Hygiene 88, 1052–1061. doi: 10.4269/ajtmh.12-0484.CrossRefGoogle ScholarPubMed
Durette-Desset, M. C. (1985). Trichostrongyloid nematodes and their vertebrate hosts: reconstruction of the phylogeny of a parasitic group. Advances in Parasitology 24, 239–306.CrossRefGoogle ScholarPubMed
Ehrenreich, I. M., Torabi, N., Jia, Y., Kent, J., Martis, S., Shapiro, J. A., Gresham, D., Caudy, A. A. and Kruglyak, L. (2010). Dissection of genetically complex traits with extremely large pools of yeast segregants. Nature 464, 1039–1042. doi: 10.1038/nature08923.CrossRefGoogle ScholarPubMed
Eng, J. K. and Prichard, R. K. (2005). A comparison of genetic polymorphism in populations of Onchocerca volvulus from untreated- and ivermectin-treated patients. Molecular and Biochemical Parasitology 142, 193–202.CrossRefGoogle ScholarPubMed
Epe, C. and Kaminsky, R. (2013). New advancement in anthelmintic drugs in veterinary medicine. Trends in Parasitology 29, 129–134. doi: 10.1016/j.pt.2013.01.001.CrossRefGoogle ScholarPubMed
Falzon, L. C., Menzies, P. I., Shakya, K. P., Jones-Bitton, A., Vanleeuwen, J., Avula, J., Stewart, H., Jansen, J. T., Taylor, M. A., Learmount, J. and Peregrine, A. S. (2013). Anthelmintic resistance in sheep flocks in Ontario, Canada. Veterinary Parasitology 193, 150–162. doi: 10.1016/j.vetpar.2012.11.014.CrossRefGoogle ScholarPubMed
Fay, D. and Bender, A. (2008). SNPs: introduction and two-point mapping. WormBook: The Online Review of C. elegans Biology 1–10. doi: 10.1895/wormbook.1.93.2.Google 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
Geary, T. G. (2012). Are new anthelmintics needed to eliminate human helminthiases? Current Opinion in Infectious Diseases 25, 709–717. doi: 10.1097/QCO.0b013e328359f04a.CrossRefGoogle ScholarPubMed
Geldhof, P., Murray, L., Couthier, A., Gilleard, J. S., McLauchlan, G., Knox, D. P. and Britton, C. (2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801–810. doi: S0020-7519(05)00422-4 [pii] 10.1016/j.ijpara.2005.12.004.CrossRefGoogle ScholarPubMed
Ghosh, R., Andersen, E. C., Shapiro, J. A., Gerke, J. P. and Kruglyak, L. (2012). Natural variation in a chloride channel subunit confers avermectin resistance in C. elegans. Science 335, 574–578. doi: 10.1126/science.1214318.CrossRefGoogle Scholar
Gilleard, J. S. (2004). The use of Caenorhabditis elegans in parasitic nematode research. Parasitology 128(Suppl. 1), S49–S70. doi: S003118200400647X [pii] 10.1017/S003118200400647X.CrossRefGoogle ScholarPubMed
Gilleard, J. S. (2006). Understanding anthelmintic resistance: the need for genomics and genetics. International Journal for Parasitology 36, 1227–1239.CrossRefGoogle ScholarPubMed
Gilleard, J. S. and Beech, R. N. (2007). Population genetics of anthelmintic resistance in parasitic nematodes. Parasitology 134(Pt 8), 1133–1147.CrossRefGoogle ScholarPubMed
Glendinning, S. K., Buckingham, S. D., Sattelle, D. B., Wonnacott, S. and Wolstenholme, A. J. (2011). Glutamate-gated chloride channels of Haemonchus contortus restore drug sensitivity to ivermectin resistant Caenorhabditis elegans. PLoS ONE 6, e22390. doi: 10.1371/journal.pone.0022390.CrossRefGoogle ScholarPubMed
Goddard, M. E. and Hayes, B. J. (2009). Mapping genes for complex traits in domestic animals and their use in breeding programmes. Nature Reviews Genetics 10, 381–391. doi: 10.1038/nrg2575.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
Heckel, D. G. (2012). Ecology. Insecticide resistance after Silent spring. Science 337, 1612–1614. doi: 10.1126/science.1226994.CrossRefGoogle ScholarPubMed
Hoberg, E. P., Kocan, A. A. and Rickard, L. G. (2001). Gastrointestinal strongyles in wild ruminants. In Parasitic Diseases of Wild Animals (ed. Samuel, W. M., Pybus, M. J. and Kocan, A. A.), pp. 193–227. Manson Publishing Ltd, London.CrossRefGoogle Scholar
Hoberg, E. R., Lichtenfels, J. R. and Gibbons, L. (2004). Phylogeny for species of Haemonchus (Nematoda: Trichostrongyloidea): considerations of their evolutionary history and global biogeography among Camelidae and Pecora (Artiodactyla). Journal of Parasitology 90, 1085–1102.CrossRefGoogle ScholarPubMed
Hoekstra, R., Criado-Fornelio, A., Fakkeldij, J., Bergman, J. and Roos, M. H. (1997). Microsatellites of the parasitic nematode Haemonchus contortus: polymorphism and linkage with a direct repeat. Molecular and Biochemical Parasitology 89, 97–107.CrossRefGoogle ScholarPubMed
Hunt, P. W., Knox, M. R., Le Jambre, L. F., McNally, J. and Anderson, L. J. (2008). Genetic and phenotypic differences between isolates of Haemonchus contortus in Australia. International Journal for Parasitology 38, 885–900. doi: S0020-7519(07)00390-6 [pii] 10.1016/j.ijpara.2007.11.001.CrossRefGoogle ScholarPubMed
Hunt, P. W., Kotze, A. C., Knox, M. R., Anderson, L. J., McNally, J. and LF, L. E. J. (2010). The use of DNA markers to map anthelmintic resistance loci in an intraspecific cross of Haemonchus contortus. Parasitology 137, 705–717. doi: 10.1017/S0031182009991521.CrossRefGoogle Scholar
Jones, C. M., Liyanapathirana, M., Agossa, F. R., Weetman, D., Ranson, H., Donnelly, M. J. and Wilding, C. S. (2012). Footprints of positive selection associated with a mutation (N1575Y) in the voltage-gated sodium channel of Anopheles gambiae. Proceedings of the National Academy of Sciences, USA 109, 6614–6619. doi: 10.1073/pnas.1201475109.CrossRefGoogle ScholarPubMed
Jones, N., Ougham, H., Thomas, H. and Pasakinskiene, I. (2009). Markers and mapping revisited: finding your gene. The New Phytologist 183, 935–966. doi: 10.1111/j.1469-8137.2009.02933.x.CrossRefGoogle ScholarPubMed
Kaminsky, R., Ducray, P., Jung, M., Clover, R., Rufener, L., Bouvier, J., Weber, S. S., Wenger, A., Wieland-Berghausen, S., Goebel, T., Gauvry, N., Pautrat, F., Skripsky, T., Froelich, O., Komoin-Oka, C., Westlund, B., Sluder, A. and Maser, P. (2008). A new class of anthelmintics effective against drug-resistant nematodes. Nature 452, 176–180. doi: nature06722 [pii] 10.1038/nature06722.CrossRefGoogle ScholarPubMed
Kaplan, R. M. (2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology 20, 477–481.CrossRefGoogle ScholarPubMed
Kwa, M. S., Kooyman, F. N., Boersema, J. H. and Roos, M. H. (1993). Effect of selection for benzimidazole resistance in Haemonchus contortus on beta-tubulin isotype 1 and isotype 2 genes. Biochemical and Biophysical Research Communications 191, 413–419.CrossRefGoogle ScholarPubMed
Kwa, M. S., Veenstra, J. G. and Roos, M. H. (1994). Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in beta-tubulin isotype 1. Molecular and Biochemical Parasitology 63, 299–303.CrossRefGoogle ScholarPubMed
Kwa, M. S., Veenstra, J. G., Van Dijk, M. and Roos, M. H. (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
Laing, R., Hunt, M., Protasio, A. V., Saunders, G., Mungall, K., Laing, S., Jackson, F., Quail, M., Beech, R., Berriman, M. and Gilleard, J. S. (2011). Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans. PLoS ONE 6, e23216. doi: 10.1371/journal.pone.0023216.CrossRefGoogle ScholarPubMed
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. and Baker, P. (2000). Inheritance of avermectin resistance in Haemonchus contortus. International Journal for Parasitology 30, 105–111.CrossRefGoogle ScholarPubMed
Le Jambre, L. F., Gill, J. H., Lenane, I. J. and Lacey, E. (1995). Characterisation of an avermectin resistant strain of Australian Haemonchus contortus. International Journal for Parasitology 25, 691–698.CrossRefGoogle ScholarPubMed
Le Jambre, L. F., Lenane, I. J. and Wardrop, A. J. (1999). A hybridisation technique to identify anthelmintic resistance genes in Haemonchus. International Journal for Parasitology 29, 1979–1985.CrossRefGoogle ScholarPubMed
Le Jambre, L. F., Royal, W. M. and Martin, P. J. (1979). The inheritance of thiabendazole resistance in Haemonchus contortus. Parasitology 78, 107–119.CrossRefGoogle ScholarPubMed
Lustigman, S., Geldhof, P., Grant, W. N., Osei-Atweneboana, M. Y., Sripa, B. and Basanez, M. G. (2012). A research agenda for helminth diseases of humans: basic research and enabling technologies to support control and elimination of helminthiases. PLoS Neglected Tropical Diseases 6, e1445. doi: 10.1371/journal.pntd.0001445.CrossRefGoogle ScholarPubMed
Mackay, T. F., Stone, E. A. and Ayroles, J. F. (2009). The genetics of quantitative traits: challenges and prospects. Nature Reviews Genetics 10, 565–577. doi: 10.1038/nrg2612.CrossRefGoogle ScholarPubMed
Martin, P. J. and McKenzie, J. A. (1990). Levamisole resistance in Trichostrongylus colubriformis: a sex-linked recessive character. International Journal for Parasitology 20, 867–872.CrossRefGoogle ScholarPubMed
Michelmore, R. W., Paran, I. and Kesseli, R. V. (1991). Identification of markers linked to disease-resistance genes by bulked segregant analysis: a rapid method to detect markers in specific genomic regions by using segregating populations. Proceedings of the National Academy of Sciences, USA 88, 9828–9832.CrossRefGoogle ScholarPubMed
Mu, J., Ferdig, M. T., Feng, X., Joy, D. A., Duan, J., Furuya, T., Subramanian, G., Aravind, L., Cooper, R. A., Wootton, J. C., Xiong, M. and Su, X. Z. (2003). Multiple transporters associated with malaria parasite responses to chloroquine and quinine. Molecular Microbiology 49, 977–989.CrossRefGoogle ScholarPubMed
Mu, J., Myers, R. A., Jiang, H., Liu, S., Ricklefs, S., Waisberg, M., Chotivanich, K., Wilairatana, P., Krudsood, S., White, N. J., Udomsangpetch, R., Cui, L., Ho, M., Ou, F., Li, H., Song, J., Li, G., Wang, X., Seila, S., Sokunthea, S., Socheat, D., Sturdevant, D. E., Porcella, S. F., Fairhurst, R. M., Wellems, T. E., Awadalla, P. and Su, X. Z. (2010). Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs. Nature Genetics 42, 268–271. doi: 10.1038/ng.528.CrossRefGoogle ScholarPubMed
Parra, G., Bradnam, K. and Korf, I. (2007). CEGMA: a pipeline to accurately annotate core genes in eukaryotic genomes. Bioinformatics 23, 1061–1067. doi: 10.1093/bioinformatics/btm071.CrossRefGoogle ScholarPubMed
Perry, B. D., Randolph, T. F., McDermott, J. J., Sones, K. R. and Thornton, P. K. (2002). Investing in Animal Health Research to Alleviate Poverty. ILRI (International Livestock Research Institute), Nairobi, Kenya, 148 pp.Google Scholar
Perry, T., Batterham, P. and Daborn, P. J. (2011). The biology of insecticidal activity and resistance. Insect Biochemistry and Molecular Biology 41, 411–422. doi: 10.1016/j.ibmb.2011.03.003.CrossRefGoogle ScholarPubMed
Prichard, R. (2001). Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends in Parasitology 17, 445–453.CrossRefGoogle ScholarPubMed
Redman, E., Grillo, V., Saunders, G., Packard, E., Jackson, F., Berriman, M. and Gilleard, J. S. (2008 a). Genetics of mating and sex determination in the parasitic nematode Haemonchus contortus. Genetics 180, 1877–1887. doi: genetics.108.094623 [pii] 10.1534/genetics.108.094623.CrossRefGoogle ScholarPubMed
Redman, E., Packard, E., Grillo, V., Smith, J., Jackson, F. and Gilleard, J. S. (2008 b). Microsatellite analysis reveals marked genetic differentiation between Haemonchus contortus laboratory isolates and provides a rapid system of genetic fingerprinting. International Journal for Parasitology 38, 111–122.CrossRefGoogle ScholarPubMed
Redman, E., Sargison, N., Whitelaw, F., Jackson, F., Morrison, A., Bartley, D. J. and Gilleard, J. S. (2012). Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing. PLoS Pathogens 8, e1002534. doi: 10.1371/journal.ppat.1002534.CrossRefGoogle ScholarPubMed
Roos, M. H., Otsen, M., Hoekstra, R., Veenstra, J. G. and Lenstra, J. A. (2004). Genetic analysis of inbreeding of two strains of the parasitic nematode Haemonchus contortus. International Journal for Parasitology 34, 109–115.CrossRefGoogle ScholarPubMed
Rowe, A., Gondro, C., Emery, D. and Sangster, N. (2009). Sequential microarray to identify timing of molecular responses to Haemonchus contortus infection in sheep. Veterinary Parasitology 161, 76–87. doi: 10.1016/j.vetpar.2008.12.023.CrossRefGoogle ScholarPubMed
Samarasinghe, B., Knox, D. P. and Britton, C. (2011). Factors affecting susceptibility to RNA interference in Haemonchus contortus and in vivo silencing of an H11 aminopeptidase gene. International Journal for Parasitology 41, 51–59. doi: 10.1016/j.ijpara.2010.07.005.CrossRefGoogle ScholarPubMed
Sangster, N. C., Redwin, J. M. and Bjorn, H. (1998). Inheritance of levamisole and benzimidazole resistance in an isolate of Haemonchus contortus. International Journal for Parasitology 28, 503–510.CrossRefGoogle Scholar
Saunders, G. I., Wasmuth, J. D., Beech, R., Laing, R., Hunt, M., Naghra, H., Cotton, J. A., Berriman, M., Britton, C. and Gilleard, J. S. (2013). Characterization and comparative analysis of the complete Haemonchus contortus beta-tubulin gene family and implications for benzimidazole resistance in strongylid nematodes. International Journal for Parasitology 43, 465–475. doi: 10.1016/j.ijpara.2012.12.011.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
Skuce, P., Stenhouse, L., Jackson, F., Hypsa, V. and Gilleard, J. (2010). Benzimidazole resistance allele haplotype diversity in United Kingdom isolates of Teladorsagia circumcincta supports a hypothesis of multiple origins of resistance by recurrent mutation. International Journal for Parasitology 40, 1247–1255. doi: S0020-7519(10)00151-7 [pii] 10.1016/j.ijpara.2010.03.016.CrossRefGoogle ScholarPubMed
Stromberg, B. E. and Gasbarre, L. C. (2006). Gastrointestinal nematode control programs with an emphasis on cattle. Veterinary Clinics of North America Food Animal Practice 22, 543–565. doi: S0749-0720(06)00055-7 [pii] 10.1016/j.cvfa.2006.08.003.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
Tyrrell, K. L., Dobson, R. J., Stein, P. A. and Walkden-Brown, S. W. (2002). The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus. Veterinary Parasitology 107, 85–93.CrossRefGoogle ScholarPubMed
Urquhart, G. M., Armour, J., Duncan, J. L., Dunn, A. and Jennings, F. (1996). Veterinary Parasitology, 2nd edn. Blackwell, Oxford.Google Scholar
Valderramos, S. G., Valderramos, J. C., Musset, L., Purcell, L. A., Mercereau-Puijalon, O., Legrand, E. and Fidock, D. A. (2010). Identification of a mutant PfCRT-mediated chloroquine tolerance phenotype in Plasmodium falciparum. PLoS Pathogens 6, e1000887. doi: 10.1371/journal.ppat.1000887.CrossRefGoogle ScholarPubMed
Van Wyk, J. A. and Van Wyk, L. (2002). Freezing of sheep faeces invalidates Haemonchus contortus faecal egg counts by the McMaster technique. Onderstepoort Journal of Veterinary Research 69, 299–304.Google ScholarPubMed
Volkman, S. K., Neafsey, D. E., Schaffner, S. F., Park, D. J. and Wirth, D. F. (2012). Harnessing genomics and genome biology to understand malaria biology. Nature Reviews Genetics 13, 315–328. doi: 10.1038/nrg3187.CrossRefGoogle ScholarPubMed
von Samson-Himmelstjerna, G., Walsh, T. K., Donnan, A. A., Carriere, S., Jackson, F., Skuce, P. J., Rohn, K. and Wolstenholme, A. J. (2009). Molecular detection of benzimidazole resistance in Haemonchus contortus using real-time PCR and pyrosequencing. Parasitology 136, 349–358. doi: 10.1017/S003118200800543.CrossRefGoogle ScholarPubMed
Waller, P. J., Rudby-Martin, L., Ljungstrom, B. L. and Rydzik, A. (2004). The epidemiology of abomasal nematodes of sheep in Sweden, with particular reference to over-winter survival strategies. Veterinary Parasitology 122, 207–220.CrossRefGoogle ScholarPubMed
Witzig, C., Wondji, C. S., Strode, C., Djouaka, R. and Ranson, H. (2013). Identifying permethrin resistance loci in malaria vectors by genetic mapping. Parasitology, 1–10. doi: 10.1017/S0031182013000024.Google ScholarPubMed
Wolstenholme, A. J., Fairweather, I., Prichard, R., von Samson-Himmelstjerna, G. and Sangster, N. C. (2004). Drug resistance in veterinary helminths. Trends in Parasitology 20, 469–476.CrossRefGoogle ScholarPubMed
Wolstenholme, A. J. and Kaplan, R. M. (2012). Resistance to macrocyclic lactones. Current Pharmaceutical Biotechnology 13, 873–887.CrossRefGoogle ScholarPubMed
Yates, D. M., Portillo, V. and Wolstenholme, A. J. (2003). The avermectin receptors of Haemonchus contortus and Caenorhabditis elegans. International Journal for Parasitology 33, 1183–1193.CrossRefGoogle ScholarPubMed
Zawadzki, J. L., Kotze, A. C., Fritz, J. A., Johnson, N. M., Hemsworth, J. E., Hines, B. M. and Behm, C. A. (2012). Silencing of essential genes by RNA interference in Haemonchus contortus. Parasitology 139, 613–629. doi: 10.1017/S0031182012000121.CrossRefGoogle ScholarPubMed