Anthelmintics Resistance; How to Overcome it?


Many parasitic helminthes of veterinary importance have genetic features that favor development of anthelmintic resistance, this becoming a major worldwide constrain in livestock production. The de-velopment of anthelmintic resistance poses a large threat to future production and welfare of grazing animals. Development of variable degrees of resistance among different species of gastrointestinal nematodes has been reported for all the major groups of anthelmintic drugs. It has been observed that frequent usage of the same group of anthelmintic; use of anthelmintics in sub-optimal doses, prophylactic mass treatment of domestic animals and frequent and continuous use of a single drug have contributed to the widespread development of anthelmintic resistance in helminthes. The de-gree and extent of this problem especially with respect to multidrug resistance in nematode popula-tions is likely to increase. Maintaining parasites in refugia and not exposed to anthelmintics, seems to be a key point in controlling and delaying the development of resistance, because the susceptible genes are preserved. Targeted selective treatments attract the interest of scientists towards this direc-tion. Additionally, adoption of strict quarantine measures and a combination drug strategy are two important methods of preventing of anthelmintic resistance. Experience from the development of anthelmintic resistance suggests that modern control schemes should not rely on sole use of anthelmintics, but employ other, more complex and sustainable recipes, including parasite resistant breeds, nutrition, pasture management, nematode-trapping fungi, antiparasitic vaccines and botanical dewormers. Most of them reduce reliance on the use of chemicals and are environmental friendly. Finally, if new anthelmintic products are released, an important question will be raised about how they should be used. It is suggested that slowing the development of resistance to a new class are likely to be gained by releasing it in combination with one or more of the older anthelmintic classes, especially where efficacy of the older active(s) remains high.

Kaplan RM. Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology. 2004; 20: 477-481.

Hotez PJ, Brindley PJ, Bethony JM, King CH, Pearce EJ, Jacobson J. Helminth in-fections: the great neglected tropical diseases. J Clin Invest. 2008; 118: 1311-1321.

Wolstenholme AJ, Fairweather I, Prichard R, von Samson- Himmelstjerna G, Sangster NC. Drug resistance in veterinary hel-minthes. Trends in Parasitology. 2004; 20: 469-476.

Bartram DJ, Leathwick DM, Taylor MA, Geurden T, Maeder SJ. The role of combi-nation anthelmintic formulations in the sus-tainable control of sheep nematodes. Vet Parasitol. 2012; 186: 151-158.

Coles GC. Drug resistance and drug toler-ance in parasites. Trends in Parasitology. 2006; 22: 348.

Prichard RK. Markers for benzimidazole re-sistance in human parasitic nematodes? Par-asitology. 2007; 134: 1087-1092.

Fojo T. Multiple paths to a drug resistance phenotype: mutations, translocations, dele-tions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Update. 2007; 10: 59-67.

Jackson F, Coop RL. The development of anthelmintic resistance in sheep nematodes. Parasitology. 2000; 120: S95–S107.

Besier RB, Love SCJ. Anthelmintic resistance in sheep nematodes in Australia: the need for new approaches. Aus J Exp Agricul. 2003; 43: 1383-1391.

Sangster NC, Gill J. Pharmacology of an-thelmintic resistance. Parasitology Today. 1999; 15: 141-146.

Mejia ME, Fernandez Iqartua BM, Schmidt E.E., Cabaret J. Multispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance? Vet Res. 2003; 34: 461-467.

Loveridge B, McArthur M, McKenna P.B., Mariadass B. Probable multigeneric re-sistance to macrocyclic lactone anthelmintics in cattle in New Zealand. N Z Vet J. 2003; 51: 139-141.

Borovsky M, Langrova I, Jankovska I., Na-vratil J., Slavik V. The benzimidazole re-sistance of cyathostomes on five horse farms in the Czech Republic. Helminthologia. 2002; 39: 211-216.

Wirtherle N, Schnieder T, von Samsom-Himmelstjerna G. Prevalence of benzimi-dazole resistance on horse farms in Germa-ny. Vet Rec. 2004; 154:39-41.

Fairweather I., Boray JC. Fasciolicides: effi-cacy, actions, resistance and its management. Vet J. 1999; 158: 81-112.

Overend DJ, Bowen FL. Resistance of Fas-ciola hepatica to triclabendazole. Aust Vet J. 199; 72: 275-276.

Mitchell G.B.B. Update on fasciolosis in cat-tle and sheep. In Pract. 2002; 24 378-385.

Lalchhandama K. Anthelmintic resistance: the song remains the same. Sci Vis. 2010; 10: 111-122.

Silvestre A., Humbert JF. Diversity of ben-zimidazoleresistance alleles in populations of small ruminant parasites. Int J Parasitol. 2002; 32:921-928.

Taylor MA, Hunt KR. Anthelmintic drug re-sistance in the UK. Vet Rec. 1989; 125: 143-147.

Dorny P, Claerebout E, Vercruysse J, Sani R, Jalila A. Anthelmintic resistance in goats in peninsular Malaysia. Vet Parasitol. 1994; 55: 327-342.

Coles GC, Papadopoulos E, Himonas CA. Tubulin, resistance and worms. Parasitol Today. 1995; 11: 183-185.

Smith G. Hookworm Disease: Current Sta-tus and New Directions, in Chemotherapy: future problems, Schad GA, Warren KS, (Eds.), Taylor & Francis, London, UK, 1990 pp. 291-303.

Hoekstra R, Visser A, Wiley LJ, et al. Char-acterisation of an acetylcholine receptor gene of Haemonchus contortus in relation to levamisole resistance. Mol Biochem Parasitol. 1997; 84: 179-187.

Hennessy DR. The disposition of antipara-sitic drugs in relation to the development of resistance by parasites of livestock. Acta Trop. 1994; 56: 125-141.

Warren KS, Bundy DAP, Anderson RM, Davis AR, Henderson DA, Jamison DT, Prescott N, Senft A. Disease Control Prior-ities in Developing Countries, in Helminth infection, Jamison DT, Mosley WH, Measham AR, Bobadilla JL, (Eds.), Oxford University Press, Oxford, 1993, pp. 131.

van Wyk JA, Refugia-overlooked as perhaps the most potent factor concerning the de-velopment of anthelmintic resistance. Onderstepoort J Vet Res. 2001; 68: 55-67.

Pal RA, Qayyum M. A review of anthel-mintic resistance in small ruminants: preva-lence, recent understanding and future pro-spects for the nematodes control. Pakistan Veterinary Journal. 1996; 16: 107-114.

Reinemeyer CR, Rohrbach BW, Grant VM, Radde GL. A survey of ovine parasite con-trol practices in Tennessee. Vet Parasitol. 1992; 42: 111-122.

Geerts S, Brandt J, Kumar V, Biesemans L. Suspected resistance of Ostertagia ostertagi in cattle to levamisole. Vet Parasitol. 1987; 23: 77-82.

vanWyk JA, Malan FS, Gerber HM, Alves RMR. The problem of escalating resistance to H. contortus to the modern anthelmintics in South Africa. Onderstepoort J Vet Res. 1989; 56: 41-49.

Shoop WL. Ivermectin resistance. Parasitol Today. 1993; 9: 154-159.

Várady M, Paraslicka J, Čorba J. Treatment of multiple resistant field strain of Ostertagia spp. in Cashmere and Angora goats. Int J Parasitol. 1994; 24: 335-340.

Anderson TJC, Blouin MS, Beech RN. Population biology of parasitic nematodes: Applications of genetic markers. Adv Parasi-tol. 1998; 41: 219-283.

Sreter T, Molnar V, Kassai T. The distribu-tion of nematode egg counts and larval counts in grazing sheep and their im-plications for parasite control. Int J Parasitol. 1994; 24: 103-108.

Sangster NC, Gill J. Pharmacology of an-thelmintic resistance. Parasitol Today. 1999; 15: 141-146.

Fleming SA, Craig T, Kaplan RM, Miller JE, Navarre C, Rings M. Anthelmintic resistance of gastrointestinal parasites in small rumi-nants. J Vet Intern Med. 2006; 20: 435-444.

Barnes EH, Dobson RJ, Barger IA. Worm control and anthelmintic resistance: adven-tures with a model. Parasitol Today. 1995; 11: 56-63.

Utzinger J, Keiser J, Shuhua X, Tanner M, Singer BH. Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials. Antimicrob Agents Chemoth. 2003; 47: 1487-1495.

Utzinger J, Keiser J. Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control. Expert Opin Pharmacother. 2004; 5: 263-285.

Bennet EV, Behm C, Bryant C, Chevis RAF. Synergistic action of mebendazole and levamisole in the treatment of a benzi-midazole-resistant Haemonchus contortus in sheep. Vet Parasitol. 1980; 7: 207-214.

Hopkins TJ, Gyr P. Synergismus einer kombination von febantel und pyrantelem-bonat gegen Ancylostoma caninum beim hund. Vet Med Nachr. 1991; 62: 3-9.

Mehlhorn H, Harder A. Effects of the syn-ergistic action of febantel and pyrantel on the nematode Heterakis spumosa: a light and transmission electron microscopy study. Parasitol Res. 1997; 83: 419-434.

Mehlhorn H, Hanser E, Harder A, Hansen O, Mencke N, Schaper RA. light and elec-tron microscopic study on the synergistic ef-fect of pyrantel and the febantel metabolite febendazole on adult Toxocara canis in vitro. Parasitol Res. 2003; 90: 305-313.

Leathwick DM. Modelling the benefits of a new class of anthelmintic in combination. Vet Parasitol. 2012; 186: 93-100.

Bartram DJ, Leathwick DM, Taylor MA, Geurden T, Maeder SJ. The role of combi-nation anthelmintic formulations in the sus-tainable control of sheep nematodes. Vet Parasitol. 2012; 186: 151-158.

Fairweather I. Triclabendazole: new skills to unravel an old(ish) enigma. J Helminthol. 2005; 79: 227-234.

Fairweather I, Boray JC. Fasciolicides: effi-cacy, actions, resistance and its management. Vet J. 1999; 158 81-112.

Boray JC. Drug resistance in Fasciola hepatica in: Resistance of Parasites to Antiparasitic Drugs. Boray JC, Martin PJ, Roush RT. (Eds), MSD AGVET, Rahway, New Jersey, 1990, pp. 51-60.

Rolfe PF, Boray JC, Fitzgibbon C, Parsons G, Kemsley P, Sangster N. Closantel re-sistance in Haemonchus contortus from sheep. Aust Vet J. 1990; 67: 29-31.

Shalaby HA, Abu El Ezz N M T, Farag T K, Abou-Zeina H A A. In vitro efficacy of a combination of ivermectin and Nigella sativa oil against helminth parasites. Global Veterinaria. 2012; 9: 465-473.

Gasbarre LC, Miller JE. Genetics of hel-minth resistance in Breeding for Disease Re-sistance in Farm Animals, Axford RXE, Bishop SC, Nicholas FW, Owen JB (Eds), New York, NY: CABI Publishing, 1999, pp. 129-152.

Bisset SA, Morris CA, McEwan JC, Vlassoff A. Breeding sheep in New Zealand that are less reliant on anthelmintics to maintain health and productivity. N Z Vet J. 2001; 49: 236-246.

Coop RL, Kyriazakis I. Influence of host nu-trition on the development and conse-quences of nematode parasitism in rumi-nants. Trends Parasitol. 2001; 17: 325-330.

Sykes AR, Coop RL. Interaction between nutrition and gastrointestinal parasitism in sheep N Z Vet J. 2001; 49: 222-226.

Barger IA. The role of epidemiological knowledge and grazing management for helminth control in small ruminants. Int J Parasitol. 1999; 29: 41-47.

Athanasiadou S, Kyriazakis I, Jackson F, Coop RL. Direct anthelmintic effects of condensed tannins towards different ga-strointestinal nematodes of sheep: In vitro and in vivo studies. Vet Parasitol. 2001; 99: 205-219.

Niezen JH, Waghorn GC, Graham T, Carter JL, Leathwick DM. The effect of diet fed to lambs on subsequent development of Trichostrongylus colubriformis larvae in vitro and on pasture. Vet Parasitol. 2002; 105: 269-283.

Waller PJ, Faedo M, Ellis K. The potential of nematophagous fungi to control the free-living stages of nematode parasites of sheep: Towards the development of a fungal con-trolled release device. Vet Parasitol. 2001; 102: 299-308.

Larsen M. Prospects for controlling animal parasitic nematodes by predacious micro fungi. Parasitol. 2000; 120: S121-S131.

Larsen M. Biological control of nematodes in sheep. J Anim Sci. 2006; 84: E133-E139.

Bain RK, Urquhart GM. Parenteral vacci-nation of calves against the cattle lungworm Dictyocaulus viviparous. Res Vet Sci. 1988; 45: 270-271.

Bain RK. Irradiated vaccines for helminth control in livestock. Int J Parasitol. 1999; 29: 185-191.

Knox DP, Redmond DL, Newlands GF, Skuce PJ, Pettit D, Smith WD The nature and prospects for gut membrane proteins as vaccine candidates for Haemonchus contortus and other ruminant trichostrongyloids. Int J Parasitol. 2003; 33: 1129-1137.

Haroun EM, Hillyer GV. Resistance to fas-cioliasis – a review. Vet Parasitol. 1986; 20: 63-93.

Bitakaramire PK. Preliminary studies on the immunization of cattle against fascioliasis us-ing gamma-irradiated metacercariae of Fasciola gigantic,” in Isotopes and Radiation in Parasitology III, pp. 23–32, International Atomic Energy Agency, Vienna, 1973.

Younis SA, Yagi AI, Haroun EM, Gameel AA, Taylor MG. Immunisation of zebu calves against Fasciola gigantica using irradiated metacercariae. J Helminthol. 1986; 60: 123-134.

El Sanhouri AA, Haroun EM, Gameel AA, Bushara HO. Protective effect of irradiated metacercariae of Fasciola gigantica and irradiat-ed cercariae of Schistosoma bovis against fascioliasis in goats. Trop Anim Health Pro. 1987; 19: 245-249.

Yadav SC, Gupta SC. Immune responses of goats against Fasciola gigantica induced by irra-diated metacercariae. J Vet Parasitol. 1989; 3: 121-123.

Boyce WM, Courtney CH, Loggins PE. Re-sistance to experimental infection with Fasciola hepatica in exotic and domestic breeds of sheep. Int J Parasitol. 1987; 17: 1233-1237.

A’Gadir H, Haroun EM, Gameel AA. The protective effect of irradiated metacercariae of Fasciola gigantica against homologous chal-lenge in sheep. J Helminthol. 1987; 61: 137-142.

Spithill TW, Smooker PM, Sexton JL, Bozas E, Morrison CA, Creaney J, Parsons JC. De-velopment of vaccines against Fasciola hepatica, in Fasciolosis, Dalton JP (Ed.), CAB Interna-tional, New York, 1999, pp. 377.

Morrison CA, Colin T, Sexton JL, Bowen F, Wicker J, Friedel T, Spithill TW. Protection of cattle against Fasciola hepatica infection by vaccination with glutathione S-transferase. Vaccine. 1996; 14: 1603–1612.

Rossjohn J, Feil SC, Wilee MCL, Sexton JL, Spithill TW, Parker MW. Crystallization, structural determination and analysis of a novel parasite vaccine candidate F. hepatica GST. J Mol Biol. 1997; 273: 857-872.

Brophy PM, Pritchard DL. Parasitic helminth glutathione S-transferase: an update on their potential as targets for immuno- and chemo-therapy. Exp Parasitol. 1994; 79: 89-96.

Howell MJ, Board PG, Boray JC. Glutat-hione S-transferase in Fasciola hepática. J Para-sitol. 1988; 74: 715-718.

Sexton JL, Milner AR, Panaccio M, Wad-dington J, Wijfels G, Chandler D., Thomp-son C, Wilson L, Spithill TW, Mitchell GF, Campbell NJ. Glutathione S-transferase, novel vaccine against Fasciola hepatica infec-tion in sheep. J Immunol. 1990; 145: 3905-3910.

Deghiedy NS, Awad WS, Shalaby HA, Ghazy AA, Abdel Hamid AF, Evaluation of some Fasciola gigantica antigens as vaccines against fasciolosis in goats. Global Veterinaria. 2008; 2: 169-174.

Satyavati GV, Raina MK, Sharma M. Medi-cinal Plants of India, vol. I, Indian Council of Med. Res., New Delhi, India, 1976, pp. 201-206.

Akhtar MS, Iqbal Z, Khan MN, Lateef M. Anthelmintic activity of medicinal plants with particular reference to their use in ani-mals in Indo-Pakistan subcontinent. Small Ruminant Research. 2000; 38: 99-107.

Shalaby HA, El Namaky AH, Kamel ROA. In vitro effect of artemether and tric-labendazole on adult Fasciola gigantica. Vet Parasitol. 2009; 160: 76-82.

Shalaby HA, El Namaky AH, Kamel ROA, Derbala AA. Tegumental surface changes in adult Paramphistomum microbothrium (Fischoeder 1901) following in vitro admin-istration of artemether. J Helminthol.2010; 85: 115-122.

Shalaby HA, El Namaky AH, Khalil FA, Kandil OM. Efficacy of methanolic extract of Balanites aegyptiaca fruit on Toxocara vitulorum. Vet Parasitol. 2012; 183: 386-392.

Massoud AM, Shalaby HA, El Khateeb RM, Mahmoud MS, Kutkat MA. Effects of Mirazid and myrrh volatile oil on adult Fasciola gigantic under laboratory conditions. Asian Pacific J Trop Biomed. 2012; 2: 875.

Niezen JH, Charleston WAG, Hodgson J, Mackay AD, Leathwick DM. Controlling in-ternal parasites in grazing ruminants without recourse to anthelmintics: approaches, expe-riences and prospects. Int J Parasitol. 1996; 26: 983-992.

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Anthelmintic Control Helminths Resistance

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Shalaby HA. Anthelmintics Resistance; How to Overcome it?. Iran J Parasitol. 1;8(1):18-32.