Anthelmintic resistance in ruminants – a state report
Gastrointestinal worm populations that are resistant to our current anthelmintics are now a major worldwide problem facing small ruminant producers (see Table 1) and cattle farmers (see Table 2). The emergence of multiple anthelmintic resistance has provided a spur for research on alternative forms of control and recently served to prompt the search for new anthelmintics by the major pharmaceutical companies.
The three current broad-spectrum anthelmintic families (the benzimidazoles, imidazothiazoles/tetrahydropyrimidines and the macrocyclic lactones) together with some narrow spectrum anthelmintics have, for the last four decades, provided the major means of therapeutic and prophylactic control of nematodoses. The high mortality rates that can occur in young sheep, goats and calves infected with a range of pulmonary and gastrointestinal nematodes are the most obvious, costly consequence of infection however the morbid effects of these parasite infections, which reduce meat, fibre and milk production, are probably even more damaging economically. Unfortunately the key nematode species implicated in caprine and ovine parasitic gastroenteritis (Haemonchus, Teladorsagia and Trichostrongylus) as well as the most important nematodes in cattle as (Haemonchus, Cooperia, Trichostrongylus and Ostertagia) also have the capacity to develop resistance against both the broad and narrow spectrum anthelmintics.
Development of resistance
The pattern of development of resistance appears to be similar for all anthelmintics. The first case reports of resistance inevitably appear within a few years of the introduction of a new drug family onto the market. With small ruminants, these first reports of resistance quite often come from goats rather than sheep simply because of differences in pharmacology/bioavailability/presentation in the two species, which can result in worm populations in goats being less well exposed to the anthelmintics.
Anthelmintic resistance in nematodes appears to be a pre-adaptive phenomenon, with the mechanisms/genes that underpin resistance already existing within the worm population when the anthelmintics are first launched on the market. Under these circumstances, resistance arises from the process of selection, survivors of treatment carrying the genes for resistance, which are then passed onto their offspring. Resistance becomes evident as a clinical problem when there is a relatively high proportion of resistant individuals within the treated population leading to an apparent treatment failure. The rate at which resistance genes accumulate within the population as a whole varies depending upon a number of factors the most important of which is the size of the population in refugia (the population unexposed to anthelmintic). Treatments administered at a time when the majority of the population is within the host have been shown to rapidly select for resistance since the pasture becomes reinfected with resistant phenotypes. This is the key factor in explaining why resistance emerged very rapidly in the Southern hemisphere and why it has taken much longer for it to become a problem in the Northern hemisphere. Following the initial selection of resistance on farm resistance can also be widely disseminated through animal movement. Although the initial reports of resistance usually involve a single species and a single drench family inevitably over time multiple resistance becomes a problem and more than one species may be implicated in that resistance.
The production and welfare benefits afforded by chemotherapy and chemoprophylaxis have led to the development systems of ovine and caprine production that are almost wholly reliant upon the availability of effective anthelmintics. As the extent of resistance increases, it is possible in the short term to maintain control using combinations however there is now evidence that this may not be sustainable in the medium to long term. It is also now accepted that the whole flock treatments used within many of our production systems may not provide a sustainable approach to the control of nematodoses and that we need to reduce our reliance upon chemical control and develop means of focussing anthelmintic treatments towards those animals that most need them. The targeted selective treatment (TST) approach forms an important cornerstone of the PARASOL project.
Anthelmintic resistance has also been described in all the economically important gastrointestinal nematodes of cattle such as Haemonchus, Cooperia, Trichostrongylus and Ostertagia (see Table 2). Benzimidazole resistance is described in Cooperia spp., Haemonchus placei, Ostertagia ostertagi and Trichostrongylus axei in Australia, New Zealand, USA, South Africa and Europe. Reports of macrocyclic lactone (ML) resistance in nematodes of cattle have been less common. However, no detailed surveys have been performed to investigate the prevalence of resistance in nematodes of cattle, so we are left with clinical case reports. The first case of ML-resistant Cooperia species was reported in New Zealand, and later in the U.K, Brazil and Argentina, suggesting that ML-resistance in Cooperia species is starting to reach high levels. Avermectin-resistance has also been reported in H. placei and in Trichostrongylus spp. To date, reports of ivermectin-resistance in Ostertagia ostertagi are rare. Multi-drug resistance (to multiple anthelmintic classes) in cattle nematodes have been documented in New Zealand and South America and this will probably become more widespread. The full extent of the ML-resistance problem in bovine nematodes remains unknown and might be considerably more common than currently recognized in Europe and the USA.
References for nematode resistance in cattle:
Anziani O.S., Zimmermann G., Guglielmone A.A., Vazquez R. en Suarez V. (2001). Avermectin resistance in Cooperia pectinata in cattle in Argentina. The Veterinary Record 149, 58-59.
Coles G.C., Stafford K.A. en MacKay P.H. (1998). Ivermectin-resistant Cooperia species from calves on a farm in Somerset. Veterinary Record 142, 255-256.
Coles G.C., Watson C.L. en Anziani O.S. (2001). Ivermectin-resistant Cooperia in cattle. Veterinary Record 148, 283-284.
Echevarria F. en Pinheiro A. (1999). Eficiência de anti-helmínticos em bovinos. XI Seminário Brasileiro de Parasitologia Veterinária, October 24-28, Abstract TL-HB-274.
Familton A.S., Mason P. en Coles G.C. (2001). Anthelmintic-resistant Cooperia in New Zealand cattle. Veterinary Record 149, 719-720.
Fiel C.A., Saumell C.A., Steffan P.E., Rodrigues E.M. en Salaberry G. (2000). Resistance of Cooperia and Trichostrongylus species to ivermectin treatments in grazing cattle of the Humid Pampa-Argentina. Revista de Medicina Veterinaria (Buenos Aires) 81, 310-315.
Fiel C.A., Saumell C.A., Steffan P.E., Rodrigues E.M.. (2001). Resistance of Cooperia to ivermectin treatments in grazing cattle of the Humid Pampa-Argentina. Veterinary Parasitology 97, 213-219.
Gasbarre L.C., Smith L.L. and Pilitt P.A. (2005). The identification of cattle nematode parasites resistant to multiple classes of anthelmintics in a commercial cattle population in the U.S. In the Proceedings of the American Association of Veterinary Parasitologists 50th Meeting, Minneapolis, MN (abstract 46).
http://www.wormwise.co.nz/main.cfm?id=260&spid=238
Kaplan, Ray M. (2004). Drug resistance in nematodes of veterinary importance: a status report. Trends in Parasitology, Vol. 20 No.10, 477-481.
Loveridge B., McArthur M., McKenna P.B. en Mariadass B. (2003) Probable multigeneric resistance to macrocyclic lactone anthelmintics in cattle in New Zealand. New Zealand Veterinary Journal 51(3), 139-141
Mejia M.E., Fernandez Igartua B.M.F., Schmidt E.E. en Cabaret J. Multispecies and multiple anthelmintic resistance on cattle nematodes in a farm in Argentina: the beginning of high resistance? Veterinary Research 34, 461-467.
Paiva F. en Menz I. (2000). In vitro evaluation of ivermectin resistant field strains of Haemonchus placei and Cooperia punctata infective larvae. 21st World Buiatrics Congress, Punta el Este, Uruguay, December 4-8.
Rhodes, A.P., Leathwick, D.M., Pomroy, W.E., West, D.M., Jackson R., Lawrence, K., Moffat, J., & Waghorn, T.S., 2006. A profile of anthelmintic resistance and parasite control practices in New Zealand - results from a 2005 survey. Proceedings of the New Zealand Society of Animal Production, 66: 14-19.
Sangster N.C. and Dobson R.J. (2002). Anthelmintic Resistance. From The Biology of nematodes (ed. Donald L.Lee) Taylor & Francis, London and New York
Sutherland I.A., Leathwick D.M., Moen I.C. en Bisset S.A. (2002). Resistance to therapeutic treatment with macrocyclic lactone anthelmintics in Ostertagia ostertagi. Veterinary Parasitology 109, 91-99.
Vermunt J.J., West D.M. en Pomroy W.E. (1996). Inefficacy of moxidectin and doramectin against ivermectin-resistant Cooperia spp. of cattle in New Zealand. New Zealand Veterinary Journal 44, 188-193.