Anthelmintic Resistance

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1 Anthelmintic Resistance H. H. Jody Wade, DVM Introduction Controlling internal parasites in grazing cattle has a significant positive return on investment; in most cases greater than any other management practice. However, there is increasing concern about resistance of cattle parasites to dewormers (anthelmintic resistance) and the ability of cattlemen to continue to have cost effective parasite control. Worldwide there is documented anthelmintic resistance to all commercially available products in all of the important cattle parasites. But the extent of the resistance varies from country to country and from ranch to ranch. Anthelmintic resistance is a very complex and serious issue. Cattlemen need a basic understanding of parasite biology and control measures so they can work with their veterinarian to develop parasite control programs that balance the short term economic benefits of deworming with the long term impact of anthelmintic use on resistance. Parasitology Basics Adult parasites live in the gastrointestinal tract of cattle and lay eggs that are shed in manure. These eggs hatch and develop into infective larvae. These larvae crawl onto the grass and are ingested when cattle graze. The larvae then develop into adults in the gastrointestinal tract and lay more eggs. Many factors, including rainfall, environmental temperatures, pasture type, grazing management, age and immune status of the cattle, previous product use and anthelmintic resistance patterns all determine the severity of parasite problems on an individual ranch in a given year. A unique parasite control program must be developed for each. The parasite load in the animal and on the pasture must both be considered. Ostertagia ostertagi is an important cattle parasite in the Southeast. It can impact both young and mature animals. Ostertagia likes cool weather, and infective larvae do not survive well in the heat of Southeastern summers. Cooperia sp. and Haemonchus placei are common parasites of calves. They are warm season parasites, so large numbers build up in summer months. Cattle usually develop immunity to these parasites by the time they are yearlings, but adult cattle will continue to have low numbers that will contaminate pastures for calves. Anthelmintic Resistance Anthelmintic resistance is an inevitable consequence of the use of anthelmintics over time. Resistant parasites have genes that protect them from the effects of the anthelmintic. The parasites may be resistant to one or multiple products at the same time. Ranches can also acquire anthelmintic resistant parasites with herd additions. Anthelmintic resistance is usually suspected when a deworming fails to give the expected production responses. But poor performance or clinical signs of parasitism that don t improve following deworming should not immediately be interpreted as a failure of the product. Other factors to check include:

2 Proper product storage Proper product administration Dose Route Diagnostic testing is required to determine the existence and extent of parasite problems and anthelmintic resistance on each ranch. Quantitative fecal egg counts are essential in determining the magnitude of parasite problems, and the fecal egg count reduction test (FECRT) can be used to estimate anthelmintic resistance. Parasite Control: A Balancing Act One of the key concepts in slowing down the development of resistance is the maintenance of refugia. Parasitesin refugia do not have genes for anthelmintic resistance they are still susceptible to anthelmintics. The more refugia in a population, the more the resistance genes in a population are diluted and the more effective anthelmintics will be. Parasites in refugia can be on pasture or in animals. When an entire group of cattle is dewormed, we eliminate refugia in the animals. The only parasites that survive the deworming are the few that are resistant. These resistant parasites then mate and multiply and soon take over. Eventually, there is failure of the dewormer to work as expected. The overall level of infective larval contamination of pasture is influenced by pasture management practices and environmental pressures. These influences will impact larvae from both resistant parasites and refugia. Examples of differing levels of pasture contamination: * Contaminated pastures Permanent pastures used continuously for grazing Overseeded pastures that have recently been grazed * Clean pastures Environmental temperature impacts on pastures left fallow for a season * Ostertagia larvae don t survive well in summer * Cooperia and Haemonchus don t survive well in winter Pastures grazed by other livestock species Stocker pastures grazed by cows (cleaner) * Cleanest pastures Non permanent pastures * Tilled and planted * Used for harvesting hay The quickest way to get widespread anthelmintic resistance is to deworm an entire group of cattle and then put them on a clean pasture. In this way we have no refugia left on pasture and we eliminate refugia in the animals. The only parasites left in the animals are resistant. When they reproduce, they will contaminate the pasture with an almost pure population of resistant parasites. There are no refugia on pasture to dilute the resistant worms. Another common scenario for development of resistance is grazing stocker calves on permanent pastures combined with frequent use of dewormers. This is especially true of the macrocyclic lactones that may have a residual effect for weeks. Initially there is a mix of refugia and resistant parasite larvae on the pasture, but as the calves graze day after day, the refugia larvae are killed by the residual product, and only the resistant parasites survive. Egg shedding is then only by resistant parasites,

3 which eventually shifts the population to mostly resistant parasites both in the animals and on the pastures. The above situation can be avoided by trying not to eliminate all parasites on a ranch. Cattlemen should work with their veterinarian to find a balance between keeping overall parasite levels low enough to prevent economic losses while at the same time retaining some refugia to slow the progression of anthelmintic resistance. Principles of Control The following principles can be incorporated into an overall parasite control program: * Increase overall herd immunity Proper nutrition will help cattle fight the effects of parasites * Use cows as vacuum cleaners for calf parasites by grazing cows after calves * Use other grazing livestock species as vacuum cleaners Horses, goats * Don t bring resistant worms to the farm with herd additions Deworm with multiple classes of anthelmintics on arrival according to Vet recommendations Drylot for hours Turn out onto contaminated pasture * Cull poor doers They may not be as resistant to parasites as cattle that maintain themselves under the same management system * Use and store products properly Avoid generics unless there are data to prove their efficacy Dose adult cows with dose for heaviest cow Dose calves with dose for heaviest calf Don t store products at the processing area * Follow label directions for storage Seek advice from a Vet to select the right product for right time of year and right age of animal * Keep refugia Avoid deworming all animals before turnout onto clean pastures * This is especially critical with macrocyclic lactones and other long acting products For example: * In cow/calf operation, don t deworm cows 5 years old and over as older cows then have refugia and younger, more susceptible cattle are dewormed Avoid deworming older cows going into summer * Deworming combined with environmental impact on pasture larvae eliminates Ostertagia refugia For replacement heifers where deworming the whole group may be desirable * Turn out onto contaminated pasture following deworming Avoid keeping replacement heifers that have all been dewormed and then put on clean pasture for grazing * They will likely have only resistant parasites in the gut * If unavoidable, treat like new herd additions above Avoid using the same pastures for young stock year after year * For example, don t raise replacement heifers in the same pasture year after year move the heifer pasture around on the ranch

4 For stocker calves where deworming the whole group may be desirable * Avoid permanent pastures used only for young stock combined with long acting products * This is certain to produce a pure anthelmintic resistant population of parasites over time * If long acting products are used, all stockers should go to feedyards for eventual harvest, and pastures should be tilled, used for hay or left fallow for several months * Do not bring replacement heifers back to a cow/calf operation from this type of grazing system Concomitant Therapy Concomitant anthelmintic therapy, sometimes referred to as concurrent therapy, is the practice of administering more than one dewormer product at the same time to an animal. The combination therapy practice that has gained favor of late utilizes a benzimidazole oral dewormer along with either an injectable or topical endectocide. A published feedlot field trial evaluating animal performance when concomitant anthelmintic therapy was compared to single dewormer therapy demonstrated that the concomitant therapy treatment group out performed the ivermectin-based endectocide only treatment group(1). A conclusion that could be drawn from that study is that the ivermectin-based endectocide product did not remove performance robbing parasites from the animal s system that the oral dewormer did control. It has been suggested that Cooperia spp., a family of small intestine parasites of cattle, are not well controlled by macrocyclic lactone endectocides(2,3). Those same intestinal parasite species appear to be well controlled by the oral, purge dewormer benzimidazoles(2,3,4). Inclusion of generic ivermectin products in concomitant anthelmintic therapy further clouds the issue since trial work suggests that generic products are less effective than pioneer products against multiple species of parasites(5,6). Therefore, cost savings alone is not justification for exposing parasite populations to sub-lethal formulations of anthelmintic compounds. Proponents of concomitant anthelmintic therapy in cattle cite added performance, expressed as increased weight gain, improved feed efficiency, and sometimes improved health parameters, as legitimate reasons to utilize more than one anthelmintic. When feed costs are high, those performance advantages can be compelling. Opponents of concomitant anthelmintic therapy are primarily concerned with the creation of so called super worms. It is logical to conclude that if parasites are not eliminated from the animal when exposed to two anthelmintic compounds administered at the same time, the surviving parasites have developed resistance to both of those products. Surviving parasites pass on their resistance genetic profile to their offspring, offspring that populate the environment and pose a potentially serious threat to other animals. The greatest potential threat of resistant super worms is in the non-confined cattle segment due to the risk of parasite transmission and the propagation of anthelmintic resistant parasites in cattle on pasture or other grazing facilities. Feedlot environments with bare dirt floors are not

5 conducive to parasite transmission, therefore terminal feedlot animals are not a source for spreading resistant parasites. Implementation of a sound deworming program varies in different geographic regions of this country. A variety of host and environmental conditions must be considered as well. Predominant species of parasite to control may differ depending on the location and season of the year. Ostertagia is a good example of how arrested, or inhibited, developmental stages of a parasite alter the time treatment should be administered for optimal control and which product would be most effective. An additional factor is age of the host animal. Cattle past their second grazing season limit populations of Cooperia effectively on their own. New deworming compounds for use in cattle do not appear to be on the horizon. Judicious use of anthelmintic products available today is crucial to insuring currently available products will continue to be efficacious. Strategic timing of administration with potent anthelmintics targeting the parasite species present should be an important consideration. Evaluating internal parasite infestations with fecal egg count tests is a good starting point. Coproculture provides added value to the diagnosis with identification of parasite species involved. Fecal egg count reduction tests are also needed to assess the effectiveness of products being used. Livestock producers and their veterinary consultants may need to utilize one or more of these diagnostic tools to effectively control cattle internal parasites. In summary, the decision to incorporate concomitant anthelmintic therapy into a beef cattle production system should be based on diagnostic procedures that indicate anthelmintic resistance does in fact exist on that farm or ranch. If it is determined that anthelmintic resistance is present, knowledge of parasite species involved will aid in judicious use of anthelmintic products. References: 1) Reinhardt, C.D, et al., A fenbendazole oral drench in addition to an ivermectin pour-on reduces parasite burden and improves feedlot and carcass performance of finishing heifers compared with endectocides alone. J Anim Sci Aug;84(8): ) Yazwinski, T.A., et al., Fecal egg count reduction and control trial determinations of anthelmintic efficacies for several parasiticides utilizing a single set of naturally infected calves. Vet. Parasitology. (2009). 3) Edmonds, M.D., et al., Anthelmintic resistance of Ostertagia ostertagi and Cooperia oncophora to macrocyclic lactones in cattle from the western United States. Vet. Parasitol. (2010). 4) Stromberg, B., et al., Cooperia punctata: Effect on cattle productivity? 5) Yazwinski, T.A., et al., A field trial evaluation of several commercial ivermectin pour-on products in cattle. 6) Yazwinski, T.A., et al., Treatment and progression of nematode parasitisms in feedlot cattle. Proceedings 23 rd WAAVP. (2011).

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