Abstract
Thirty Haemonchus contortus male worms were collected from farmed red deer yearlings in order to determine whether routine administration of albendazole for a long-term period (17 years) could select anthelmintic resistance. PCR–RFLP method based on single-nucleotide polymorphism of codon 200 in isotype 1 ß-tubulin gene (Phe200Tyr) was applied. The results showed a significant frequency of either the resistant allele (85 %) or the homozygous resistant genotype (70 %). By chi-square test, Hardy–Weinberg equilibrium of the population was accepted (p = 0.334, power of test 0.01). True prevalence of the resistant genotype (RR) was estimated to be 46.5–87.2 % (confidence interval 95 %) calculated by Sterne’s exact method. These results confirmed that long-term use of benzimidazoles could change the relative allele frequency of genes associated with drug resistance and may cause a large-scale spread of the resistant allele. To our knowledge, this study supported benzimidazole resistance in Haemonchus contortus in red deer for the first time.
References
Barnes EH, Dobson RJ, Barger IA (1995) Worm control and anthelmintic resistance: adventures with a model. Parasitol Today 11(2):56–63. doi:10.1016/0169-4758(95)80117-0
Chintoan-Uta C, Morgan ER, Skuce PJ, Coles GC (2014) Wild deer as potential vectors of anthelmintic-resistant abomasal nematodes between cattle and sheep farms. Proc Biol Sci 281(1780):20132985. doi:10.1098/rspb.2013.2985
Coles GC, Jackson F, Pomroy WE, Prichard RK, von Samson-Himmelstjerna G, Silvestre A, Taylor MA, Vercruysse J (2006) The detection of anthelmintic resistance in nematodes of veterinary importance. Vet Parasitol 136(3–4):167–185. doi:10.1016/j.vetpar.2005.11.019
Delatour P, Garnier F, Benoit E, Caude I (1991) Chiral behaviour of the metabolite albendazole sulphoxide in sheep, goats and cattle. Res Vet Sci 50(2):134–138. doi:10.1016/0034-5288(91)90095-6
Dobson RJ, Hosking BC, Besier RB, Love S, Larsen JWA, Rolfe PF, Bailey JN (2011) Minimising the development of anthelmintic resistance, and optimising the use of the novel anthelmintic monepantel, for the sustainable control of nematode parasites in Australian sheep grazing systems. Aust Vet J 89(5):160–166. doi:10.1111/j.1751-0813.2011.00703.x
Dobson RJ, Hosking BC, Jacobson CL, Cotter JL, Besier RB, Stein PA, Reid SA (2012) Preserving new anthelmintics: a simple method for estimating faecal egg count reduction test (FECRT) confidence limits when efficacy and/or nematode aggregation is high. Vet Parasitol 186(1–2):79–92. doi:10.1016/j.vetpar.2011.11.049
Falzon LC, O’Neil TJ, Menzies PI, Peregrine AS, Jones-Bitton A, vanLeeuwen J, Mederos A (2014) A systematic review and meta-analysis of factors associated with anthelmintic resistance in sheep. Prev Vet Med 117(2):388–402. doi:10.1016/j.prevetmed.2014.07.003
Graffelman J (2010) The number of markers in the HapMap Project: some notes on chi-square and exact tests for Hardy–Weinberg equilibrium. Am J Hum Gen 86(5):813–818. doi:10.1016/j.ajhg.2009.11.019
Hennessy DR, Sangster NC, Steel JW, Collins GH (1993) Comparative pharmacokinetic behaviour of albendazole in sheep and goats. Int J Parasitol 23(3):3212–3325. doi:10.1016/0020-7519(93)90006-K
Hoste H, Chartier C, Etter E, Goudeau C, Soubirac F, Lefrileux Y (2000) A questionnaire survey on the practices adopted to control gastrointestinal nematode parasitism in dairy goat farms in France. Vet Res Commun 24(7):459–469. doi:10.1023/A:1006499522154
Jabbar A, Iqbal Z, Kerboeuf D, Muhammad G, Khan MN, Afaq M (2006) Anthelmintic resistance: the state of play revisited. Life Sci 79(26):2413–2431. doi:10.1016/j.lfs.2006.08.010
Kaplan RM, Vidyashankar AN (2012) An inconvenient truth: global worming and anthelmintic resistance. Vet Parasitol 186(1–2):70–78. doi:10.1016/j.vetpar.2011.11.048
Křížová-Forstová V, Lamka J, Cvilink V, Hanušová V, Skálová L (2011) Factors affecting pharmacokinetics of benzimidazole anthelmintics in food-producing animals: the consequences and potential risks. Res Vet Sci 91(3):333–341. doi:10.1016/j.rvsc.2010.12.013
Lichtenfels JR, Pilitt PA, Hoberg EP (1994) New morphological characters for identifying individual specimens of Haemonchus spp. (Nematoda: Trichostrongyloidea) and a key to species in ruminants in North America. J Parasitol 80(1):107–119. doi:10.2307/3283353
Mackintosh CG, Cowie C, Fraser K, Johnstone P, Mason PC (2014) Reduced efficacy of moxidectin and abamectin in young red deer (Cervus elaphus) after 20 years of moxidectin pour-on use on a New Zealand deer farm. Vet Parasitol 199(1–2):81–92. doi:10.1016/j.vetpar.2013.09.028
Mottier ML, Prichard RK (2008) Genetic analysis of a relationship between macrocyclic lactone and benzimidazole anthelmintic selection on Haemonchus contortus. Pharmacogenet Genom 18:129–140. doi:10.1097/FPC.0b013e3282f4711d
Mylrea GE, Mulley RC, English AW (1991) Gastrointestinal helminthosis in fallow deer (Dama dama) and their response to treatment with anthelmintics. Aust Vet J 68(2):74–75. doi:10.1111/j.1751-0813.1991.tb03144.x
Pfeiffer DU (2002) Veterinary epidemiology—an introduction. Royal Veterinary College, North Mymms, UK, http://ww3.panaftosa.org.br/Comp/MAPA/431857.pdf
Prichard RK (1985) Interaction of host physiology and efficacy of antiparasitic drugs. Vet Parasitol 18(2):103–110. doi:10.1016/0304-4017(85)90060-3
Reiczigel J (2003) Confidence intervals for the binomial parameter: some new considerations. Stat Med 22(4):611–621. doi:10.1002/sim.1320
Silvestre A, Leignel V, Berrag B, Gasnier N, Humbert JF, Chartier C, Cabaret J (2002) Sheep and goat nematode resistance to anthelmintics: pro and cons among breeding management factors. Vet Res 33(5):465–480. doi:10.1051/vetres:2002033
Smith G, Grenfell BT, Isham V, Cornell S (1999) Anthelmintic resistance revisited: under-dosing, chemoprophylactic strategies, and mating probabilities. Int J Parasitol 29(1):77–91. doi:10.1016/S0020-7519(98)00186-6
Tiwari J, Kumar S, Kolte AP, Swarnkar CP, Singh D, Pathak KML (2006) Detection of benzimidazole resistance in Haemonchus contortus using RFLP-PCR technique. Vet Parasitol 138(3–4):301–307. doi:10.1016/j.vetpar.2006.02.003
Várady M, Papadopoulos E, Dolinská M, Königová A (2011) Anthelmintic resistance in parasites of small ruminants: sheep versus goats. Helminthologia 48(3):137–144. doi:10.2478/s11687-011-0021-7
Velík J, Baliharová V, Skálová L, Szotáková B, Wsól V, Lamka J (2005) Liver microsomal biotransformation of albendazole in deer, cattle, sheep and pig some related wild breeds. J Vet Pharmacol Ther 28(4):377–384. doi:10.1111/j.1365-2885.2005.00671.x
Virkel G, Lifschitz A, Sallovitz J, Pis A, Lanusse C (2004) Comparative hepatic and extrahepatic enantioselective sulfoxidation of albendazole and fenbendazole in sheep and cattle. Drug Metab Dispos 32(5):536–544. doi:10.1124/dmd.32.5.536
Waller PJ, Donald AD, Dobson RJ, Lacey E, Hennessy DR, Allerton GR, Prichard RK (1989) Changes in anthelmintic resistance status of Haemonchus contortus and Trichostrongylus colubriformis exposed to different anthelmintic selection pressures in grazing sheep. Int J Parasitol 19(1):99–110. doi:10.1016/0020-7519(89)90027-1
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The authors are very thankful to Prof. Colin Mackintosh for his professional advice and linguistic proposals, and to the anonymous reviewer for the helpful criticism.
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Nagy, G., Csivincsik, Á., Zsolnai, A. et al. Benzimidazole resistance in Haemonchus contortus recovered from farmed red deer. Parasitol Res 115, 3643–3647 (2016). https://doi.org/10.1007/s00436-016-5155-6
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DOI: https://doi.org/10.1007/s00436-016-5155-6