Plant-Based Solutions to Global Livestock Anthelmintic Resistance
Anthelmintic resistance in livestock is increasing globally. Livestock intestinal parasites now develop resistance to synthetic anthelmintics within 2–10 years, collectively costing billions of dollars annually in lost revenue around the world. Over-reliance on commercial drugs and dips and changes in livestock management practices are key drivers of this trend. To date, current research has focused on identifying new anthelmintics from bacterial and fungal sources or even synthesizing new drugs that target parasite metabolism or reproduction. Plant-derived anthelmintics are a promising alternative, yet to date major research funders and scientists have overlooked this option. Until the mid-20th century, rural communities relied on plant-based methods of controlling livestock parasites. These methods include feeding livestock specific medicinal plants and trees, grazing livestock on herbal leys, and changing where livestock grazed based on ecological factors (e.g., flooding) that increased parasite burdens. Many historic texts and ethnological accounts record the ethnobotanical knowledge of rural communities and the plants they used to control livestock intestinal parasites. Some traditions persist today yet the farmers, graziers, and shepherds who hold this knowledge are rapidly disappearing and with them perhaps a potential long-term solution to anthelmintic resistance. This short perspective piece will cover recent research using ethnobotanical data as a means to identifying potential new anthelmintics; the morphological, physiological, and metabolic effect of plant secondary metabolites on parasites; and an overview of “best practices” which can reduce bias in assessments of plant bioactivity and increase reproducibility of test results. This will hopefully bring recent advances in ethnobiology, chemistry, and ecology to new audiences, and, potentially, spark new interest in using medicinal plants to improve livestock health.
Abdel-Farid, I.B., M.G. Sheded, and E. A. Mohamed. 2014. Metabolomic Profiling and Antioxidant Activity of Some Acacia Species. Saudi Journal of Biological Science 21:400–408. DOI:10.1016/j.sjbs.2014.03.005.
Acevedo-Ramírez, P.M. del C., J.A. Figueroa-Castillo, R. Ulloa-Arvizú, L.G. Martínez-García, A. Guevara-Flores, J.L. Rendón, R.O. Valero-Coss, P.M. Gives, and H. Quiroz-Romero. 2015. Proteolytic Activity of Extracellular Products from Arthrobotrys musiformis and their Effect In Vitro Against Haemonchus contortus Infective Larvae. Veterinary Record Open 2, e000103. DOI:10.1136/vetreco-2014-000103.
Agnolet, S., S. Wiese, R. Verpoorte, and D. Staerk. 2012. Comprehensive Analysis of Commercial Willow Bark Extracts by New Technology Platform: Combined Use of Metabolomics, High-Performance Liquid Chromatography–Solid-Phase Extraction–Nuclear Magnetic Resonance Spectroscopy and High-Resolution Radical Scavenging Assay. Journal of Chromatography A 1262: 130–137. DOI:10.1016/j.chroma.2012.09.013.
Al-Tabini, R., K. Al-Khalidi, and M. Al-Shudiefat. 2012. Livestock, Medicinal Plants, and Rangeland Viability in Jordan’s Badia: Through the Lens of Traditional and Local Knowledge. Pastoralism Research, Policy, and Practice 2:4. DOI:10.1186/2041-7136-2-4.
Asami, D., J. Hong, D. Barrett, and A. Mitchell. 2003. Comparison of the Total Phenolic and Ascorbic Acid Content of Freeze-Dried and Air-Dried Marionberry, Strawberry, and Corn Grown Using Conventional, Organic, and Sustainable Agricultural Practices. Journal of Agricultural Food Chemistry 51:1237–1241. DOI:10.1021/jf020635c.
Athanasiadou, S., and I. Kyriazakis. 2004. Plant Secondary Metabolites: Antiparasitic Effects and their Role in Ruminant Production Systems. Proceedings of the Nutritional Society 63:631–639. DOI:10.1079/PNS2004396.
Ayers, S., D.L. Zink, K. Mohn, J.S. Powell, C.M. Brown, G. Bills, A. Grund, D. Thompson, and S. B. Singh. 2010. Anthelmintic Constituents of Clonostachys candelabrum. Journal of Antibiotics 63:119–122. DOI:10.1038/ja.2009.131.
Bartha, S.G., C.L. Quave, L. Balogh, and N. Papp. 2015. Ethnoveterinary Practices of Covasna County, Transylvania, Romania. Journal of Ethnobiology and Ethnomedicine 11: 35. DOI:10.1186/s13002-015-0020-8.
Beinart, W., and K. Brown. 2013. African Local Knowledge and Livestock Health: Traditional, Environmental & Biomedical Approaches in South Africa. James Currey, Oxford, UK.
Boik, J.C., R.A. Newman, and R. J. Boik. 2008. Quantifying Synergism/Antagonism Using Nonlinear Mixed-Effects Modeling: A Simulation Study. Statistical Medicine 27:1040–1061. DOI:10.1002/sim.3005.
Buckingham, S.D., F.A. Partridge, and D. B. Sattelle. 2014. Automated, High-Throughput, Motility Analysis in Caenorhabditis elegans and Parasitic Nematodes: Applications in the Search For New Anthelmintics. International Journal of Parasitology, Drugs, and Drug Resistance 4:226–232. DOI:10.1016/j.ijpddr.2014.10.004.
Burke, J.M., A. Wells, P. Casey, and R.M. Kaplan. 2009. Herbal Dewormer Fails to Control Gastrointestinal Nematodes in Goats. Veterinary Parasitology 160:168–170. DOI:10.1016/j.vetpar.2008.10.080.
Cappello, M., R.D. Bungiro, L.M. Harrison, L.J. Bischof, J.S. Griffitts, B.D. Barrows, and R. V. Aroian. 2006. A Purified Bacillus thuringiensis Crystal Protein with Therapeutic Activity Against the Hookworm Parasite Ancylostoma ceylanicum. Proceedings of the National Academy of Sciences 103:15154–15159. DOI:10.1073/pnas.0607002103.
Cooke, A.S., E.R. Morgan, and J.A.J. Dungait. 2017. Modelling the Impact of Targeted Anthelmintic Treatment of Cattle on Dung Fauna. Environmental Toxicology and Pharmacology 55:94–98. DOI:10.1016/j.etap.2017.07.012.
Cowan, M.M.1999. Plant Products as Antimicrobial Agents. Clin. Microbiol. Rev. 12:564–582.
de Macedo, M., S. Clais, E. Lanckacker, L. Maes, E. Lima, and P. Cos. 2015. Anti-Infective Agents: The Example of Antibacterial Drug Leads. In Ethnopharmacology, edited by M. Heinrich and A. Jäger, pp. 111–123. Wiley-Blackwell, Chichester, West Sussex.
de Torres, C., M.C. Díaz-Maroto, I. Hermosín-Gutiérrez, and M.S. Pérez-Coello. 2010. Effect of Freeze-Drying and Oven-Drying on Volatiles and Phenolics Composition of Grape Skin. Analytica Chimica Acta 660:177–182. DOI:10.1016/j.aca.2009.10.005.
Demeler, J., N. Krüger, J. Krücken, V.C. von der Heyden, S. Ramünke, U. Küttler, S. Miltsch, M.L. Cepeda, M. Knox, J. Vercruysse, P. Geldhof, A. Harder, and G. von Samson-Himmelstjerna. 2013. Phylogenetic Characterization of β-Tubulins and Development of Pyrosequencing Assays for Benzimidazole Resistance in Cattle Nematodes. PLoS one 8:e70212. DOI:10.1371/journal.pone.0070212.
Duke, J.A. 1992. Handbook of Phytochemical Constituent Grass, Herbs, and Other Economic Plants. CRC Press, Boca Raton, FL.
Falbo, M.K., V.T. Soccol, I.E. Sandini, J.H. Novakowiski, and C. R. Soccol. 2015. Effect of Spraying Arthrobotrys conoides Conidia on Pastures to Control Nematode Infection in Sheep. Semina: Ciências Agrárias 36:239–252. DOI:10.5433/1679-0359.2015v36n1p239.
Fayer, R. 2000. Global Change and Emerging Infectious Diseases. Journal of Parasitology 86: 1174–1181. DOI:10.1645/0022-3395(2000)086[1174:GCAEID]2.0.CO;2.
Fox, N.J., P.C.L. White, C.J. McClean, G. Marion, A. Evans, and M.R. Hutchings. 2011. Predicting Impacts of Climate Change on Fasciola hepatica Risk. PLoS one 6:e16126. DOI:10.1371/journal.pone.0016126.
French, K.E. 2017. Species Composition Determines Forage Quality and Medicinal Value of High Diversity Grasslands in Lowland England. Agriculture, Ecosystems, and the Environment 241:193–204. DOI:10.1016/j.agee.2017.03.012.
Garvis, S., A. Munder, G. Ball, S. de Bentzmann, L. Wiehlmann, J.J. Ewbank, B. Tümmler, and A. Filloux. 2009. Caenorhabditis elegans Semi-Automated Liquid Screen Reveals a Specialized Role for the Chemotaxis Gene cheB2 in Pseudomonas aeruginosa Virulence. PLoS Pathogens 5:e1000540. DOI:10.1371/journal.ppat.1000540.
Githiori, J.B., J. Höglund, P.J. Waller, and R. Leyden Baker. 2003. Evaluation of Anthelmintic Properties of Extracts from Some Plants Used as Livestock Dewormers by Pastoralist and Smallholder Farmers in Kenya Against Heligmosomoides polygyrus Infections in Mice. Veterinary Parasitology 118:215–226. DOI:10.1016/j.vetpar.2003.10.006.
Hoste, H., F. Jackson, S. Athanasiadou, S.M. Thamsborg, and S.O. Hoskin. 2006. The Effects of Tannin-Rich Plants on Parasitic Nematodes in Ruminants. Trends in Parasitology 22:253–261. DOI:10.1016/j.pt.2006.04.004.
Hotez, P.J., J.M. Bethony, D.J. Diemert, M. Pearson, and A. Loukas. 2010. Developing Vaccines to Combat Hookworm Infection and Intestinal Schistosomiasis. Nature Reviews in Microbiology 8:814–826. DOI:10.1038/nrmicro2438.
Hu, Y., and R.V. Aroian. 2012. Bacterial Pore-Forming Proteins as Anthelmintics. Invertebrate Neuroscience 12:37–41. DOI:10.1007/s10158-012-0135-8.
Jr, J.F.U., Y. Hu, M.M. Miller, U. Scheib, Y.Y. Yiu, and R. V. Aroian. 2013. Bacillus thuringiensis-Derived Cry5B Has Potent Anthelmintic Activity against Ascaris suum. PLOS Neglected Tropical Diseases 7:e2263. DOI:10.1371/journal.pntd.0002263.
Kaminsky, R., P. Ducray, M. Jung, R. Clover, L. Rufener, J. Bouvier, S.S. Weber, A. Wenger, S. Wieland-Berghausen, T. Goebel, N. Gauvry, F. Pautrat, T. Skripsky, O. Froelich, C. Komoin-Oka, B. Westlund, A. Sluder, and P. Mäser. 2008. A New Class of Anthelmintics Effective Against Drug-Resistant Nematodes. Nature 452:176–180. DOI:10.1038/nature06722.
Kaplan, R.M. and A.N. Vidyashankar. 2012. An Inconvenient Truth: Global Worming and Anthelmintic Resistance. Veterinary Parasitology Special Issue: Novel Approaches to the Control of Helminth Parasites of Livestock 186:70–78. DOI:10.1016/j.vetpar.2011.11.048.
Karesh, W.B., A. Dobson, J.O. Lloyd-Smith, J. Lubroth, M.A. Dixon, M. Bennett, S. Aldrich, T. Harrington, P. Formenty, E.H. Loh, C.C. Machalaba, M.J. Thomas, and D.L. Heymann. 2012. Ecology of Zoonoses: Natural and Unnatural Histories. The Lancet 380:1936–1945. DOI:10.1016/S0140-6736(12)61678-X.
King, K.C., R.B. Stelkens, J.P. Webster, D.F. Smith, and M.A. Brockhurst. 2015. Hybridization in Parasites: Consequences for Adaptive Evolution, Pathogenesis, and Public Health in a Changing World. PLOS Pathog 11:e1005098. DOI:10.1371/journal.ppat.1005098.
Landau, S.Y., H. Muklada, A. Abu-Rabia, S. Kaadan, and H. Azaizeh. 2014. Traditional Arab Ethno-Veterinary Practices in Small Ruminant Breeding in Israel. Small Ruminant Research 119:161–171. DOI:10.1016/j.smallrumres.2014.01.004.
Lans, C., N. Turner, T. Khan, G. Brauer, and W. Boepple. 2007. Ethnoveterinary Medicines Used for Ruminants in British Columbia, Canada. Journal of Ethnobiology and Ethnomedicine 3:11. DOI:10.1186/1746-4269-3-11.
Larsen, M. 2000. Prospects for Controlling Animal Parasitic Nematodes by Predacious Micro Fungi. Parasitology 120:S121–S131.
Liu, W., Y. Han, B. Wang, L. Sun, M. Chen, K. Cai, X. Li, M. Zhao, C. Xu, Q. Xu, L. Yi, H. Wang, D. Xie, X. Li, J. Wu, J. Yang, S. Wei, D. Li, C. Chen, T. Zheng, Q. Li, and J. Peng. 2015. Isolation, Identification, and Characterization of the Nematophagous Fungus Monacrosporium salinum from China. Journal of Basic Microbiology 55:992–1001. DOI:10.1002/jobm.201400909.
Lopes, S.G., L.B.G. Barros, H. Louvandini, A.L. Abdalla, and L.M. Costa Junior. 2016. Effect of Tanniniferous Food from Bauhinia pulchella on Pasture Contamination with Gastrointestinal Nematodes from Goats. Parasitology Vectors 9:102. DOI:10.1186/s13071-016-1370-3.
Marcellino, C., J. Gut, K.C. Lim, R. Singh, J. McKerrow, and J. Sakanari. 2012. WormAssay: A Novel Computer Application for Whole-Plate Motion-Based Screening of Macroscopic Parasites. PLoS Neglected Tropical Diseases 6. DOI:10.1371/journal.pntd.0001494.
Nabukenya, I., C. Rubaire-Akiiki, D. Olila, K. Ikwap, and J. Höglund. 2014. Ethnopharmacological Practices by Livestock Farmers in Uganda: Survey Experiences from Mpigi and Gulu Districts. Journal of Ethnobiology and Ethnomedicine 10:9. DOI:10.1186/1746-4269-10-9.
Numa, C., J.R. Verdú, C. Rueda, and E. Galante. 2012. Comparing Dung Beetle Species Assemblages between Protected Areas and Adjacent Pasturelands in a Mediterranean Savanna Landscape. Rangeland Ecology and Management 65:137–143. DOI:10.2111/REM-D-10-00050.1.
Patz, J.A, T.K. Graczyk, N. Geller, and A.Y. Vittor. 2000. Effects of Environmental Change on Emerging Parasitic Diseases. International Journal for Parasitology 30:1395–1405.
Piluzza, G., L. Sulas, and S. Bullitta. 2014. Tannins in Forage Plants and their Role in Animal Husbandry and Environmental Sustainability: A Review. Grass Forage Science 69:32–48. DOI:10.1111/gfs.12053.
Ridsdill-Smith, T.J. 1993. Effects of Avermectin Residues in Cattle Dung on Dung Beetle (Coleoptera: Scarabaeidae) Reproduction and Survival. Veterinary Parasitology 48:127-37.
Sabatelli, L. 2010. Effect of Heterogeneous Mixing and Vaccination on the Dynamics of Anthelmintic Resistance: A Nested Model. PLOS ONE 5:e10686. DOI:10.1371/journal.pone.0010686.
Semenza, J.C. and B. Menne. 2009. Climate Change and Infectious Diseases in Europe. Lancet Infectious Diseases 9:365–375. DOI: 10.1016/S1473-3099(09)70104-5.
Shalaby, H.A. 2013. Anthelmintics Resistance: How to Overcome it? Iranian Journal of Parasitology 8:18–32.
Silva, F. dos S., U.P. Albuquerque, L.M. Costa Júnior, A. da S. Lima, A.L.B. do Nascimento, and J.M. Monteiro. 2014. An Ethnopharmacological Assessment of the Use of Plants Against Parasitic Diseases in Humans and Animals. Journal of Ethnopharmacology 155:1332–1341. DOI:10.1016/j.jep.2014.07.036.
Sinott, M.C., N.A. Cunha Filho, L.L.D. Castro, L.B. Lorenzon, N.B. Pinto, G.A. Capella, and F.P.L. Leite. 2012. Bacillus spp. Toxicity Against Haemonchus contortus Larvae in Sheep Fecal Cultures. Experimental Parasitology 132:103–108. DOI:10.1016/j.exppara.2012.05.015.
Smith, J.F., K.T. Jagusch, L.F.C. Brunswick, and R.W. Kelly. 1979. Coumestans in Lucerne and Ovulation in Ewes. New Zealand Journal of Agricultural Research 22:411–416. DOI:10.1080/00288233.1979.10430768.
Soelberg, J. and A.K. Jäger. 2016. Comparative Ethnobotany of the Wakhi Agropastoralist and the Kyrgyz Nomads of Afghanistan. Journal of Ethnobiology and Ethnomedicine 12:2. DOI:10.1186/s13002-015-0063-x.
Spratt, D.M. 1997. Australian and New Zealand Societies for Parasitology Scientific Meeting Endoparasite Control Strategies: Implications for Biodiversity of Native Fauna. International Journal of Parasitology 27:173–180. DOI: 10.1016/S0020-7519(96)00147-6.
Storey, B., C. Marcellino, M. Miller, M. Maclean, E. Mostafa, S. Howell, J. Sakanari, A. Wolstenholme, and R. Kaplan. 2014. Utilization of Computer Processed High Definition Video Imaging for Measuring Motility of Microscopic Nematode Stages on a Quantitative Scale: “The Worminator.” International Journal of Parasitology, Drugs, and Drug Resistance 4:233–243. DOI:10.1016/j.ijpddr.2014.08.003.
Strong, L. 1993. Overview: The Impact of Avermectins on Pastureland Ecology. Veterinary Parasitology 48:3–17. DOI:10.1016/0304-4017(93)90140-I.
Taylor, C.M., Q. Wang, B.A. Rosa, S.C.-C. Huang, K. Powell, T. Schedl, E.J. Pearce, S. Abubucker, and M. Mitreva. 2013. Discovery of Anthelmintic Drug Targets and Drugs Using Chokepoints in Nematode Metabolic Pathways. PLOS Pathology 9:e1003505. DOI:10.1371/journal.ppat.1003505.
Taylor, M.A., J. Learmount, E. Lunn, C. Morgan, and B.H. Craig. 2009. Multiple Resistance to Anthelmintics in Sheep Nematodes and Comparison of Methods Used for Their Detection. Small Ruminant Research Special Issue: Keynote Lectures of the 7th International Sheep Veterinary Congress 86:67–70. DOI:10.1016/j.smallrumres.2009.09.020
Traversa, D. and G. von Samson-Himmelstjerna. 2016. Anthelmintic Resistance in Sheep Gastro-Intestinal Strongyles in Europe. Small Ruminant Research Special Issue: Advances in Sheep and Goats Research: A Holistic Approach. Selected Papers from SIPAOC 2014 Meeting, Italy 135:75–80. DOI:10.1016/j.smallrumres.2015.12.014.
Vatta, A.F. and A.L.E. Lindberg. 2006. Managing Anthelmintic Resistance in Small Ruminant Livestock of Resource-Poor Farmers in South Africa: Review Article. Journal of South African Veterinary Association 77:2–8. DOI:10.4102/jsava.v77i1.331.
Vieira, M.E.D., C. Costa, A.C. Silveira, and M.D. Arrigoni. 2001. Saponins and Tannins in Twenty-Eight Alfalfa (Medicago sativa L.) Cultivates Grown in Botucatu SP. Brazilian Journal of Animal Science 30: 1432–1438. DOI:10.1590/S1516-35982001000600007.
Vilela, V.L.R., T.F. Feitosa, F.R. Braga, J.V. de Araújo, S.C. de Lucena, E.S. Dantas, A.C.R. Athayde, and W.W. Silva. 2013. Efficacy of Monacrosporium thaumasium in the Control of Goat Gastrointestinal Helminthiasis in a Semi-Arid Region of Brazil. Parasitology Research 112: 871–877. DOI:10.1007/s00436-012-3078-4.
Waghorn, T.S., D.M. Leathwick, L.-Y. Chen, and R.A. Skipp. 2003. Efficacy of the Nematode-Trapping Fungus Duddingtonia flagrans against Three Species of Gastro-Intestinal Nematodes in Laboratory Faecal Cultures from Sheep and Goats. Veterinary Parasitology 118: 227–234. DOI:10.1016/j.vetpar.2003.09.018.
Waller, P.J. 2006. From Discovery to Development: Current Industry Perspectives for the Development of Novel Methods of Helminth Control in Livestock. Veterinary Parasitology 139:1–14. DOI:10.1016/j.vetpar.2006.02.036.
Waller, P.J., G. Bernes, S.M. Thamsborg, A. Sukura, S.H. Richter, K. Ingebrigtsen, and J. Höglund. 2001. Plants as De-Worming Agents of Livestock in the Nordic Countries: Historical Perspective, Popular Beliefs, and Prospects for the Future. Acta Veterinaria Scandanavia 42:31. DOI:10.1186/1751-0147-42-31.
Wei, J.-Z., K. Hale, L. Carta, E. Platzer, C. Wong, S.-C. Fang, and R.V. Aroian. 2003. Bacillus thuringiensis Crystal Proteins that Target Nematodes. Proceedings of the National Academy of Sciences 100:2760–2765. DOI:10.1073/pnas.0538072100.
Williams, A.R., C. Fryganas, A. Ramsay, I. Mueller-Harvey, and S.M. Thamsborg. 2014. Direct Anthelmintic Effects of Condensed Tannins from Diverse Plant Sources Against Ascaris suum. PLOS ONE 9, e97053. DOI:10.1371/journal.pone.0097053.
Wink, M. 2010. Introduction. In Functions and Biotechnology of Plant Secondary Metabolites, edited by M. Wink, pp. 1–20. Blackwell Publishing Ltd., Oxford, UK.
Wink, M. and O. Schimmer. 2010. Molecular Modes of Action of Defensive Secondary Metabolites. In Functions and Biotechnology of Plant Secondary Metabolites, edited by M. Wink, pp. 21–161. Blackwell Publishing Ltd., Oxford, UK.
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