Document Type : Review Paper
Authors
1 College of Veterinary Medicine, University of AL-Qadisiyah, Iraq
2 College of Biotechnology, University of AL-Qadisiyah, Iraq.
3 College of Pharmacy, University of AL-Qadisiyah, Iraq
10.29079/qjvms.2020.179345
Abstract
Haemonchus contortus is one of the world's major financial worms that attack ruminants. It is a blood-sucking parasite founded in the abomasum, particularly in cattle, sheep, and goats. Nematode infections may cause anemia, weight loss, or even death in animals that are severely affected. Current management practices against H. contortus largely depend on regular anthelmintic therapies in all countries with varying incidence across various regions. H. contortus thus aims to form new action techniques in order to overcome resistance to anthelmintic agents. One option is a logical approach focused on a thorough knowledge of the molecular pathways in growth and reproduction cycles in the manufacture in modern anti-parasite drugs and vaccines. Key molecules may be defined as potential drug targets by a simple description of molecular, biochemical functions. Besides, it is immediately essential to formulate immunological control of farm animal nematode infections. Important prevention has been accomplished after vaccination with native protein extracts, which shows that vaccination is possible. This paper explores the success of H. contortus science in the world. Particular fields of concern include epidemiological research, genetic analysis, and anthelmintic resistance identification using traditional and molecular techniques; morphological and chemical research of crucial molecules in mechanism expansion, parasitic organism-host interaction, and vaccine research. In the suggested form of these opinions, areas for potential exploration and alternatives for new or revised prevention strategies are described.
Keywords
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3. Blaxter M, Koutsovoulos G. The evolution of parasitism in Nematoda. Parasitology. 2015;142(Suppl 1):S26-39.https://doi.org/10.1017/S0031182014000791
4. Bundy DAP, Appleby LJ, Bradley M, Croke K, Hollingsworth TD, Pullan R, et al. 100 Years of Mass Deworming Programmes: A Policy Perspective From the World Bank's Disease Control Priorities Analyses. Adv Parasitol. 2018;127-54.https://doi.org/10.1016/bs.apar.2018.03.005
5. McKellar QA, Jackson F. Veterinary anthelmintics: Old and new. Trends Parasitol. 2004;20(10):456-61.https://doi.org/10.1016/j.pt.2004.08.002
6. Kaplan RM, Vidyashankar AN. An inconvenient truth: Global worming and anthelmintic resistance. Vet Parasitol. 2012;186(1-2):70-8.https://doi.org/10.1016/j.vetpar.2011.11.048
7. Hay SI, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1260-344.https://doi.org/10.1016/S0140-6736(17)32130-X
8. Hewitson JP, Maizels RM. Vaccination against helminth parasite infections. Expert Rev Vaccines. 2014;13(4):473-87.https://doi.org/10.1586/14760584.2014.893195
9. Sallé G, Laing R, Cotton JA, Maitland K, Martinelli A, Holroyd N, et al. Transcriptomic profiling of nematode parasites surviving vaccine exposure. Int J Parasitol. 2018;48(5):395-402.https://doi.org/10.1016/j.ijpara.2018.01.004
10. Laing R, Kikuchi T, Martinelli A, Tsai IJ, Beech RN, Redman E, et al. The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biol. 2013;14(8).https://doi.org/10.1186/gb-2013-14-8-r88
11. Doyle SR, Laing R, Bartley DJ, Britton C, Chaudhry U, Gilleard JS, et al. A Genome Resequencing-Based Genetic Map Reveals the Recombination Landscape of an Outbred Parasitic Nematode in the Presence of Polyploidy and Polyandry. Genome Biol Evol. 2018;10(2):396-409.https://doi.org/10.1093/gbe/evx269
12. Gilleard JS. Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance. Parasitology. 2013;140(12):1506-22.https://doi.org/10.1017/S0031182013001145
13. Coghlan A, Tyagi R, Cotton JA, Holroyd N, Rosa BA, Tsai IJ, et al. Comparative genomics of the major parasitic worms. Nat Genet. 2019;51(1):163-74.https://doi.org/10.1038/s41588-018-0262-1
14. Wang C, Li F, Zhang Z, Yang X, Ahmad AA, Li X, et al. Recent research progress in China on Haemonchus contortus. Front Microbiol. 2017;8:1509.https://doi.org/10.3389/fmicb.2017.01509
15. Kwa MSG, Veenstra JG, Roos MH. Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in β-tubulin isotype 1. Mol Biochem Parasitol. 1994;63(2):299-303.https://doi.org/10.1016/0166-6851(94)90066-3
16. Prichard RK. Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends Parasitol. 2001;17(9):445-53.https://doi.org/10.1016/S1471-4922(01)01983-3
17. Rufener L, Kaminsky R, Mäser P. In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of β-tubulin. Mol Biochem Parasitol. 2009;168(1):120-2.https://doi.org/10.1016/j.molbiopara.2009.07.002
18. Kwa MSG, Veenstra JG, Van Dijk M, Roos MH. β-Tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. J Mol Biol. 1995;246(4):500-10.https://doi.org/10.1006/jmbi.1994.0102
19. Silvestre A, Cabaret J. Mutation in position 167 of isotype 1 β-tubulin gene of Trichostrongylid nematodes: Role in benzimidazole resistance? Mol Biochem Parasitol. 2002;120(2):297-300.https://doi.org/10.1016/S0166-6851(01)00455-8
20. Ghisi M, Kaminsky R, Mäser P. Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Vet Parasitol. 2007;144(3-4):313-20.https://doi.org/10.1016/j.vetpar.2006.10.003
21. Zhang Z, Gasser RB, Yang X, Yin F, Zhao G, Bao M, et al. Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China. Int J Parasitol Drugs Drug Resist. 2016;6(3):199-206.https://doi.org/10.1016/j.ijpddr.2016.10.001
22. Roeber F, Jex AR, Gasser RB. Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants. Biotechnol Adv. 2013;31(8):1135-52.https://doi.org/10.1016/j.biotechadv.2013.01.008
23. Kotze AC, Prichard RK. Anthelmintic Resistance in Haemonchus contortus. History, Mechanisms and Diagnosis. Adv Parasitol. 2016;93:397-428.https://doi.org/10.1016/bs.apar.2016.02.012
24. Redman E, Sargison N, Whitelaw F, Jackson F, Morrison A, Bartley DJ, et al. Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing. PLoS Pathog. 2012;8(2).https://doi.org/10.1371/journal.ppat.1002534
25. Luo X, Shi X, Yuan C, Ai M, Ge C, Hu M, et al. Genome-wide SNP analysis using 2b-RAD sequencing identifies the candidate genes putatively associated with resistance to ivermectin in Haemonchus contortus. Parasites and Vectors. 2017;10(1).https://doi.org/10.1186/s13071-016-1959-6
26. Lespine A, Ménez C, Bourguinat C, Prichard RK. P-glycoproteins and other multidrug resistance transporters in the pharmacology of anthelmintics: Prospects for reversing transport-dependent anthelmintic resistance. Int J Parasitol Drugs Drug Resist. 2012;2:58-75.https://doi.org/10.1016/j.ijpddr.2011.10.001
27. Khan S, Nisar A, Yuan J, Luo X, Dou X, Liu F, et al. A whole genome re-sequencing based GWA analysis reveals candidate genes associated with ivermectin resistance in Haemonchus contortus. Genes (Basel). 2020;11(4).https://doi.org/10.3390/genes11040367
28. Laing R, Maitland K, Lecová L, Skuce PJ, Tait A, Devaney E. Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use. Int J Parasitol. 2016;46(10):621-30.https://doi.org/10.1016/j.ijpara.2016.03.010
29. Alam MBB, Omar AI, Faruque MO, Notter DR, Periasamy K, Mondal MMH, et al. Single nucleotide polymorphisms in candidate genes are significantly associated with resistance to Haemonchus contortus infection in goats. J Anim Sci Biotechnol. 2019;10(1):30.https://doi.org/10.1186/s40104-019-0327-8
30. Becker GM, Davenport KM, Burke JM, Lewis RM, Miller JE, Morgan JLM, et al. Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep. Anim Genet. 2020;51(2):330-5.https://doi.org/10.1111/age.12895
31. Luo X, Shi X, Yuan C, Ai M, Ge C, Hu M, et al. Genome-wide SNP analysis using 2b-RAD sequencing identifies the candidate genes putatively associated with resistance to ivermectin in Haemonchus contortus. Parasit Vectors. 2017;10(1):31.https://doi.org/10.1186/s13071-016-1959-6
32. Li FC, Gasser RB, Lok JB, Korhonen PK, He L, Di W Da, et al. Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1). Parasites and Vectors. 2016;9(1).https://doi.org/10.1186/s13071-016-1351-6
33. Li FC, Gasser RB, Lok JB, Korhonen PK, Wang YF, Yin FY, et al. Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus. Parasites and Vectors. 2014;7(1).
34. Li F, Lok JB, Gasser RB, Korhonen PK, Sandeman MR, Shi D, et al. Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation. Int J Parasitol. 2014;44(7):485-96.https://doi.org/10.1016/j.ijpara.2014.03.005
35. Hu M, Lok JB, Ranjit N, Massey HC, Sternberg PW, Gasser RB. Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). Int J Parasitol. 2010;40(4):405-15.https://doi.org/10.1016/j.ijpara.2009.09.005
36. Mohandas N, Hu M, Stroehlein AJ, Young ND, Sternberg PW, Lok JB, et al. Reconstruction of the insulin-like signalling pathway of Haemonchus contortus. Parasites and Vectors. 2016;9(1):64.https://doi.org/10.1186/s13071-016-1341-8
37. Hartman D, Donald DR, Nikolaou S, Savin KW, Hasse D, Presidente PJA, et al. Analysis of developmentally regulated genes of the parasite Haemonchus contortus. Int J Parasitol. 2001;31(11):1236-45.https://doi.org/10.1016/S0020-7519(01)00248-X
38. Yang Y, Ma Y, Chen X, Guo X, Yan B, Du A. Screening and analysis of Hc-ubq and Hc-gst related to desiccation survival of infective Haemonchus contortus larvae. Vet Parasitol. 2015;210(3-4):179-85.https://doi.org/10.1016/j.vetpar.2015.03.020
39. Guo X, Zhang H, Zheng X, Zhou Q, Yang Y, Chen X, et al. Structural and functional characterization of a novel gene, Hc-daf-22, from the strongylid nematode Haemonchus contortus. Parasites and Vectors. 2016;9(1).https://doi.org/10.1186/s13071-016-1704-1
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2. O'Connor LJ, Walkden-Brown SW, Kahn LP. Ecology of the free-living stages of major trichostrongylid parasites of sheep. Vet Parasitol. 2006;142(1-2):1-15.https://doi.org/10.1016/j.vetpar.2006.08.035
3. Blaxter M, Koutsovoulos G. The evolution of parasitism in Nematoda. Parasitology. 2015;142(Suppl 1):S26-39.https://doi.org/10.1017/S0031182014000791
4. Bundy DAP, Appleby LJ, Bradley M, Croke K, Hollingsworth TD, Pullan R, et al. 100 Years of Mass Deworming Programmes: A Policy Perspective From the World Bank's Disease Control Priorities Analyses. Adv Parasitol. 2018;127-54.https://doi.org/10.1016/bs.apar.2018.03.005
5. McKellar QA, Jackson F. Veterinary anthelmintics: Old and new. Trends Parasitol. 2004;20(10):456-61.https://doi.org/10.1016/j.pt.2004.08.002
6. Kaplan RM, Vidyashankar AN. An inconvenient truth: Global worming and anthelmintic resistance. Vet Parasitol. 2012;186(1-2):70-8.https://doi.org/10.1016/j.vetpar.2011.11.048
7. Hay SI, Abajobir AA, Abate KH, Abbafati C, Abbas KM, Abd-Allah F, et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1260-344.https://doi.org/10.1016/S0140-6736(17)32130-X
8. Hewitson JP, Maizels RM. Vaccination against helminth parasite infections. Expert Rev Vaccines. 2014;13(4):473-87.https://doi.org/10.1586/14760584.2014.893195
9. Sallé G, Laing R, Cotton JA, Maitland K, Martinelli A, Holroyd N, et al. Transcriptomic profiling of nematode parasites surviving vaccine exposure. Int J Parasitol. 2018;48(5):395-402.https://doi.org/10.1016/j.ijpara.2018.01.004
10. Laing R, Kikuchi T, Martinelli A, Tsai IJ, Beech RN, Redman E, et al. The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery. Genome Biol. 2013;14(8).https://doi.org/10.1186/gb-2013-14-8-r88
11. Doyle SR, Laing R, Bartley DJ, Britton C, Chaudhry U, Gilleard JS, et al. A Genome Resequencing-Based Genetic Map Reveals the Recombination Landscape of an Outbred Parasitic Nematode in the Presence of Polyploidy and Polyandry. Genome Biol Evol. 2018;10(2):396-409.https://doi.org/10.1093/gbe/evx269
12. Gilleard JS. Haemonchus contortus as a paradigm and model to study anthelmintic drug resistance. Parasitology. 2013;140(12):1506-22.https://doi.org/10.1017/S0031182013001145
13. Coghlan A, Tyagi R, Cotton JA, Holroyd N, Rosa BA, Tsai IJ, et al. Comparative genomics of the major parasitic worms. Nat Genet. 2019;51(1):163-74.https://doi.org/10.1038/s41588-018-0262-1
14. Wang C, Li F, Zhang Z, Yang X, Ahmad AA, Li X, et al. Recent research progress in China on Haemonchus contortus. Front Microbiol. 2017;8:1509.https://doi.org/10.3389/fmicb.2017.01509
15. Kwa MSG, Veenstra JG, Roos MH. Benzimidazole resistance in Haemonchus contortus is correlated with a conserved mutation at amino acid 200 in β-tubulin isotype 1. Mol Biochem Parasitol. 1994;63(2):299-303.https://doi.org/10.1016/0166-6851(94)90066-3
16. Prichard RK. Genetic variability following selection of Haemonchus contortus with anthelmintics. Trends Parasitol. 2001;17(9):445-53.https://doi.org/10.1016/S1471-4922(01)01983-3
17. Rufener L, Kaminsky R, Mäser P. In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of β-tubulin. Mol Biochem Parasitol. 2009;168(1):120-2.https://doi.org/10.1016/j.molbiopara.2009.07.002
18. Kwa MSG, Veenstra JG, Van Dijk M, Roos MH. β-Tubulin genes from the parasitic nematode Haemonchus contortus modulate drug resistance in Caenorhabditis elegans. J Mol Biol. 1995;246(4):500-10.https://doi.org/10.1006/jmbi.1994.0102
19. Silvestre A, Cabaret J. Mutation in position 167 of isotype 1 β-tubulin gene of Trichostrongylid nematodes: Role in benzimidazole resistance? Mol Biochem Parasitol. 2002;120(2):297-300.https://doi.org/10.1016/S0166-6851(01)00455-8
20. Ghisi M, Kaminsky R, Mäser P. Phenotyping and genotyping of Haemonchus contortus isolates reveals a new putative candidate mutation for benzimidazole resistance in nematodes. Vet Parasitol. 2007;144(3-4):313-20.https://doi.org/10.1016/j.vetpar.2006.10.003
21. Zhang Z, Gasser RB, Yang X, Yin F, Zhao G, Bao M, et al. Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China. Int J Parasitol Drugs Drug Resist. 2016;6(3):199-206.https://doi.org/10.1016/j.ijpddr.2016.10.001
22. Roeber F, Jex AR, Gasser RB. Advances in the diagnosis of key gastrointestinal nematode infections of livestock, with an emphasis on small ruminants. Biotechnol Adv. 2013;31(8):1135-52.https://doi.org/10.1016/j.biotechadv.2013.01.008
23. Kotze AC, Prichard RK. Anthelmintic Resistance in Haemonchus contortus. History, Mechanisms and Diagnosis. Adv Parasitol. 2016;93:397-428.https://doi.org/10.1016/bs.apar.2016.02.012
24. Redman E, Sargison N, Whitelaw F, Jackson F, Morrison A, Bartley DJ, et al. Introgression of ivermectin resistance genes into a susceptible Haemonchus contortus strain by multiple backcrossing. PLoS Pathog. 2012;8(2).https://doi.org/10.1371/journal.ppat.1002534
25. Luo X, Shi X, Yuan C, Ai M, Ge C, Hu M, et al. Genome-wide SNP analysis using 2b-RAD sequencing identifies the candidate genes putatively associated with resistance to ivermectin in Haemonchus contortus. Parasites and Vectors. 2017;10(1).https://doi.org/10.1186/s13071-016-1959-6
26. Lespine A, Ménez C, Bourguinat C, Prichard RK. P-glycoproteins and other multidrug resistance transporters in the pharmacology of anthelmintics: Prospects for reversing transport-dependent anthelmintic resistance. Int J Parasitol Drugs Drug Resist. 2012;2:58-75.https://doi.org/10.1016/j.ijpddr.2011.10.001
27. Khan S, Nisar A, Yuan J, Luo X, Dou X, Liu F, et al. A whole genome re-sequencing based GWA analysis reveals candidate genes associated with ivermectin resistance in Haemonchus contortus. Genes (Basel). 2020;11(4).https://doi.org/10.3390/genes11040367
28. Laing R, Maitland K, Lecová L, Skuce PJ, Tait A, Devaney E. Analysis of putative resistance gene loci in UK field populations of Haemonchus contortus after 6 years of macrocyclic lactone use. Int J Parasitol. 2016;46(10):621-30.https://doi.org/10.1016/j.ijpara.2016.03.010
29. Alam MBB, Omar AI, Faruque MO, Notter DR, Periasamy K, Mondal MMH, et al. Single nucleotide polymorphisms in candidate genes are significantly associated with resistance to Haemonchus contortus infection in goats. J Anim Sci Biotechnol. 2019;10(1):30.https://doi.org/10.1186/s40104-019-0327-8
30. Becker GM, Davenport KM, Burke JM, Lewis RM, Miller JE, Morgan JLM, et al. Genome-wide association study to identify genetic loci associated with gastrointestinal nematode resistance in Katahdin sheep. Anim Genet. 2020;51(2):330-5.https://doi.org/10.1111/age.12895
31. Luo X, Shi X, Yuan C, Ai M, Ge C, Hu M, et al. Genome-wide SNP analysis using 2b-RAD sequencing identifies the candidate genes putatively associated with resistance to ivermectin in Haemonchus contortus. Parasit Vectors. 2017;10(1):31.https://doi.org/10.1186/s13071-016-1959-6
32. Li FC, Gasser RB, Lok JB, Korhonen PK, He L, Di W Da, et al. Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1). Parasites and Vectors. 2016;9(1).https://doi.org/10.1186/s13071-016-1351-6
33. Li FC, Gasser RB, Lok JB, Korhonen PK, Wang YF, Yin FY, et al. Exploring the role of two interacting phosphoinositide 3-kinases of Haemonchus contortus. Parasites and Vectors. 2014;7(1).
34. Li F, Lok JB, Gasser RB, Korhonen PK, Sandeman MR, Shi D, et al. Hc-daf-2 encodes an insulin-like receptor kinase in the barber's pole worm, Haemonchus contortus, and restores partial dauer regulation. Int J Parasitol. 2014;44(7):485-96.https://doi.org/10.1016/j.ijpara.2014.03.005
35. Hu M, Lok JB, Ranjit N, Massey HC, Sternberg PW, Gasser RB. Structural and functional characterisation of the fork head transcription factor-encoding gene, Hc-daf-16, from the parasitic nematode Haemonchus contortus (Strongylida). Int J Parasitol. 2010;40(4):405-15.https://doi.org/10.1016/j.ijpara.2009.09.005
36. Mohandas N, Hu M, Stroehlein AJ, Young ND, Sternberg PW, Lok JB, et al. Reconstruction of the insulin-like signalling pathway of Haemonchus contortus. Parasites and Vectors. 2016;9(1):64.https://doi.org/10.1186/s13071-016-1341-8
37. Hartman D, Donald DR, Nikolaou S, Savin KW, Hasse D, Presidente PJA, et al. Analysis of developmentally regulated genes of the parasite Haemonchus contortus. Int J Parasitol. 2001;31(11):1236-45.https://doi.org/10.1016/S0020-7519(01)00248-X
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