CSIRO PUBLISHING
Animal Production Science, 2015, 55, 916–921 http://dx.doi.org/10.1071/AN14881
Review
Parasite control in pasture-grazed dairy cattle: are we at the edge of a precipice? I. A. Sutherland A,D and S. L. Bullen B,C A
AgResearch Ltd, Grasslands Research Centre, Palmerston North, New Zealand. Maffra Veterinary Centre, Maffra, Vic. 3860, Australia. C University of Melbourne, School of Veterinary Science, Werribee, Vic. 3030, Australia. D Corresponding author. Email:
[email protected] B
Abstract. Gastrointestinal nematode (GIN) parasites are one of the most production-limiting infections of pasture-based dairy cattle in Australasia. Intensification of dairy production systems in both countries has meant that farmers have come to rely heavily on anthelmintic drenches to control GIN parasitism. However, anthelmintic resistance is now widespread in New Zealand, particularly to the market-leading macrocyclic-lactones. Less work has been conducted on anthelmintic resistance in Australia but preliminary results of a study currently underway suggests that there are high levels of resistance on Victorian dairy farms. The identification and mitigation of risk factors for the development of resistance is crucial for long-term sustainability of control. These include the use of drenches with variable efficacy – particularly pour-on and injectable formulations. New Zealand studies suggest that this may be as a result of active not reaching parasites within the gut lumen as effectively as oral formulations. Also, the raising of young stock as monocultures is a risk factor for the development of resistance as it significantly reduces the numbers of unselected (and presumably susceptible) parasites on pasture. These risks can be mitigated: using effective drenches removes more resistant parasites. This often means the use of combination products containing more than one anthelmintic class. Combination products are more effective in the face of existing resistance, and can slow the development of resistance. Also, ensuring an adequate level of unselected parasites on pasture for ingestion by young stock will delay the development of resistance. While there are differences between dairying systems, both countries are likely to benefit from more active and collaborative research efforts to improving parasite control practices on dairy farms in their respective countries. Additional keywords: anthelmintic, gastrointestinal parasites, resistance. Received 16 October 2014, accepted 21 March 2015, published online 5 June 2015
Introduction Gastrointestinal nematode (GIN) parasitism is one of the most production-limiting diseases of pasture-based dairy cattle worldwide. Pathology and reduced dry matter intake result in impaired liveweight gain of young stock as well as reduced milk production and reproductive performance in lactating cattle (Shaw et al. 1998; Sanchez et al. 2004). In severely parasitised animals, profuse diarrhoea, loss of body condition and death if left untreated also pose a significant threat to animal welfare (Parkinson et al. 2010). Sustainable and effective parasite control will rely heavily on the availability and correct application of effective anthelmintics, something that is threatened by inefficacy of some treatments and the increase in the prevalence of drugresistant parasite populations. Overview of GIN parasites in Australasia Gastrointestinal parasitism typically occurs in mixed infections, whereby a large number of species may be present at any one time. In New Zealand, more than 23 different species of GIN have been recorded (Pomroy 1997). Of these, five have their preferred Journal compilation CSIRO 2015
site in the abomasum, 13 in the small intestine and five in the large intestine. The most economically important species affecting dairy cattle in New Zealand and temperate Australia include Ostertagia, Trichostrongylus and Cooperia spp. (Charleston and McKenna 2002; Taylor and Hodge 2014). In the summer-rainfall and northern regions of Australia, and also in some areas of Western Australia, Haemonchus placei and Cooperia spp. play a more significant role in GIN parasitism of dairy cattle (Taylor and Hodge 2014). The presence of numerous species of GIN at any one time poses a challenge for both developing and implementing parasitecontrol programs, as well as for predicting the impact of mixed parasite burdens on animal productivity. For example, measuring the number of eggs in faeces (faecal egg count; FEC) provides an indication of the level of parasitism, but may fail to provide an accurate picture of the productivity effects when used alone. This occurs in part as a result of marked variation in the pathogenicity and fecundity of various parasite species. For example, Ostertagia spp. are not particularly fecund, yet pose a significant threat as they are highly pathogenic and can lead to www.publish.csiro.au/journals/an
Dairy parasitism
severe clinical disease and deaths in dairy cattle of all ages. In contrast, Cooperia spp. are the most prevalent parasites in young stock and are highly fecund, but relatively non-pathogenic compared with Ostertagia, Trichostrongylus and Haemonchus spp. (Stromberg et al. 2012). The relatively benign effect of low to moderate levels of Cooperia spp. on live-weight gain was demonstrated in field trials in eastern Victoria in early 2014 (S. Swaney, pers. comm.) but heavy burdens were associated with pronounced production effects in both New Zealand studies and in northern Australia (Lyndal-Murphy et al. 2010; Sutherland and Leathwick 2011). This may be attributed to some extent to variable pathogenicity among species, with subtropical Cooperia pectinata and C. punctata being more commonly associated with production loss and clinical disease in Australia than is C. oncophora (Keith 1967; Coop et al. 1979; Lyndal-Murphy et al. 2010). Nonetheless, it is prudent to include larval culture and morphological speciation when submitting samples for parasitological examination. Interestingly, there appears to be some potential for sharing of GIN among livestock species. Trichostrongylus axei readily infects both small ruminants and cattle, and typical small ruminant parasites such as Haemonchus contortus have been recorded in cattle (Pomroy 1997). Therefore, co-grazing and grazing of dairy cattle on pasture previously grazed by small ruminants should be considered as a risk factor for transmission of GIN parasites.
Animal Production Science
917
fenbendazole). The imidazothiazoles/tetrahydropyrimidines (LEV; ‘clear drenches’) were introduced a few years later and include levamisole and morantel tartrate (Turton 1969). As with the benzimidazoles, products containing levamisole are still commercially available but are not widely used on a global basis due to their lower efficacy against Ostertagia spp. and a narrower safety margin. Ivermectin, the first of the macrocyclic lactones (MLs), further revolutionised worm control (Chabala et al. 1980). The MLs (including doramectin, moxidectin, eprinomectin and avermectin) are highly effective at low dosages against not only GIN but also a range of ectoparasites and are available in convenient injectable and pour-on formulations that have since come to dominate the cattle anthelmintic market (Sutherland and Leathwick 2011). Recently, a further two anthelmintic families have been commercialised for use in sheep in New Zealand (derquantal; Startect, Zoetis Ltd, Auckland, New Zealand) and Australia (monepantel; Zolvix, Novartis Animal Health Ltd, Sydney, NSW, Australia) (Kaminsky et al. 2008; Little et al. 2010); however, these products are not currently available for use in cattle. As a consequence, worm control in cattle in Australasia has relied heavily on the BZ, LEV and MLs, so it is not surprising that GIN populations have developed resistance to one or more classes. In hindsight, it is quite surprising that the efficacy of these classes of drenches has persisted as long as it has. Anthelmintic resistance in cattle GIN
Control of GIN parasites There is a variety of worm-control strategies available to farmers, such as grazing management and nutritional supplementation, but by far the most common is the regular application of anthelmintic drenches. Anthelmintics are drugs that are effective in either removing existing burdens and/or preventing the establishment of ingested infective-stage larvae. Several peer-reviewed studies have described the productivity benefits of drenching young dairy cattle (Fisher et al. 1995; Dorny et al. 2000), while early work suggested that the regular use of anthelmintics could provide between 20% and 65% improvement in liveweight gain (Entrocasso et al. 1986; Somers et al. 1987). More recently, a study (Forbes et al. 2000) found that Holstein heifers naturally infected with gastrointestinal-nematode parasites spent significantly less time grazing, and had lower dry matter intakes and mean liveweight gain than did uninfected controls, while Larsson et al. (2011) showed that weight-gain penalties incurred as a result of parasitism in the first grazing season persisted in subsequent seasons (Larsson et al. 2011). Therefore, the quality of parasitecontrol practices implemented in the first year or two of a heifer’s life may have lasting impacts on future productivity in the herd (Charlier et al. 2009). Despite this, there have been surprisingly few anthelmintics commercialised for use in livestock. Thiabendazole was the first commercially viable broadspectrum anthelmintic, and the new found ability for farmers to control GIN parasites was an instrumental means by which livestock production could be intensified (Brown 1969). Thiabendazole was the first member of the benzimidazole family (BZ; ‘white drenches’) and its development was quickly followed by several related products that are still commercially available today (e.g. albendazole, oxfendazole,
Anthelmintic resistance in GIN of cattle is now widespread in New Zealand, particularly to the market-leading macrocycliclactones (ML). A national survey of anthelmintic resistance found that over 90% of farms raising young beef animals had resistance to MLs (Waghorn et al. 2006b). These findings were published at a time when anthelmintic resistance in cattle GINs were limited to isolated reports and so revolutionised our thinking about drench resistance as a threat to cattle production across Australasia. The majority of the cases of ML resistance involved the relatively non-pathogenic Cooperia spp., although there were reports of resistance in other species to the other drench families (Waghorn et al. 2006a). There has been less emphasis on anthelmintic resistance on dairy farms, although McAnulty and Gibbs (2010) identified anthelmintic resistance in at least one class of anthelmintic and involving three economically important species (Ostertagia spp., Trichostrongylus spp. and Cooperia spp.) on four largescale dairy farms on the South Island, New Zealand. Macrocyclic lactone-resistant Ostertagia spp. was present on three of four properties surveyed. Given the pathogenicity of this species, and the limited range of alternative treatment options available, this is a very important development. On two farms, a combination of albendazole and levamisole failed to reduce faecal egg count by greater than 95% for Ostertagia spp. and Trichostrongylus spp., indicating the presence of multipleanthelmintic resistance (McAnulty and Gibbs 2010). Interestingly, none of these farms had previously tested their current anthelmintics for efficacy and drenching decisions were made by the calendar and labour availability, usually monthly, rather than using any parasitological monitoring or epidemiological evidence. Australian farms appear to present
918
Animal Production Science
I. A. Sutherland and S. L. Bullen
a similar picture, with often haphazard drenching practices and high levels of BZ-resistant Ostertagia spp. and ML-resistant Cooperia spp. detected on south-eastern Victorian dairy farms Alarmingly, ML-resistant Ostertagia spp. also appears to be commonplace, although not to the same extent as resistant Cooperia spp. (S. L. Bullen, pers. comm.). The overwhelming majority of cases of resistance in GIN infecting cattle have been reported since 2000 (Sutherland and Leathwick 2011). However, diagnosis remains difficult by the limitations of diagnostic tests for anthelmintic resistance in cattle. The ability to accurately assess the economic impact of drench resistance on dairy farms is difficult. Depending on the severity of the resistance, it is intuitive that any productivity gains made through the use of drenches will be progressively lost. One study, which did quantify productivity impacts of resistance in New Zealand, measured a 17-kg reduction in liveweight of beef cattle by 12 months of age due to the presence of ML-resistant Cooperia spp. (D. M. Leathwick, pers. obs.), and it is likely that the impact of resistance will become more pronounced as more pathogenic parasite species become involved.
cattle is highly influenced by parasite density inside the host, that is, the more adult worms present the lower the number of eggs each female produces (Smith et al. 1987). Despite this, there are currently no other validated means by which to detect anthhelmintic resistance in cattle.
Development of resistance
Identification and mitigation of risk factors
Typically, when resistance emerges, it involves only a single parasite and a single class of anthelmintic (Hall et al. 1979; Vlassoff and Brunsdon 1981). However, as anthelmintic use has continued and resistant worms become more prevalent, cases have emerged in which multiple species of GIN are found to be resistant to more than one anthelmintic family (Le Jambre 1976; Wrigley et al. 2006; Gasbarre et al. 2009). An alarming difference between small ruminants and cattle is that the appearance of multiple-active resistance seems to have occurred at an earlier stage in cattle. Although the exact reason for this phenomenon is unclear, it is reasonable to hypothesise that selection for resistance in GIN of each host may be occurring in a different manner and may be a reflection of the manner in which anthelmintics are used in the respective species (see below).
Anthelmintics are often used in young cattle, regardless of known parasitic burden (McAnulty and Gibbs 2010). While the correlation between the number of treatments and selection for resistance is not straightforward, it is intuitive that regular exposure greatly increases the likelihood of anthelmintic resistance. In addition, frequent short-interval drenching or the use of long-acting products typical of the pour-on and injectable MLs prevent the re-establishment of susceptible worms, further exacerbating selection pressure (Sutherland and Leathwick 2011). The period of extended activity also invariably ends with a ‘tail’, whereby anthelmintic levels become subtherapeutic, and allows the survival and re-establishment of resistant but not susceptible parasites. In sheep, a reduction in the duration of efficacy of the ‘tail’ became evident as resistance began to build up (Sutherland et al. 1999).
The detection of resistance in GIN infecting cattle The gold-standard method for determining either anthelmintic efficacy or resistance status is by controlled efficacy in slaughter trials. However, this is costly, both in terms of animal usage and in diagnostic testing. Therefore, the FEC reduction test (FECRT), in which FECs of treated animals are compared with pretreatment samples or with an untreated control group is the most commonly employed technique for diagnosis of anthelmintic resistance. Resistance is defined as less than 95% reduction in FEC, and a lower 95% confidence interval of less than 90%, provided a minimum parasitic burden is present in the first place. However, even with a reduction of
