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Anthelmintic Control Strategies for Horses
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The goals or objectives for a comprehensive parasite control program designed for horses residing in developed countries of the world, with temperate climates, are focused principally on control of the cyathostomes, or small strongyles. Variations of these programs will exist between regions of the world, between horse farms of different management practices, even between calendar years due to weather differences, but the underlying objectives will remain intact. A parasite-free horse farm is neither realistic nor desirable; the goal is to control the level of parasitism rather than the unrealistic goal of elimination. The nature of the horse industry is one of movement between sites for events, races, rodeos, trail rides, etc., virtually guaranteeing eventual exposure to parasites. The goal is to provide horses with exposure to parasitism in order to engender an acquired resistance to clinical disease. With this in mind, the objectives of a comprehensive control program for horses can be outlined as:
- Reduce the number of infective cyathostome larvae on pasture by reducing the number of cyathostome eggs passed in the feces of resident horses.
- Reduce as well the number of anthelmintic treatments required to achieve this egg reduction, as a means of delaying or avoiding drug resistance in the cyathostome population.
- Control the secondary parasitic infections as needed by shifting the anthelmintics employed for the primary focus to include the secondary parasite of interest within the spectrum of activity of the selected antiparasitic compound.
The costs for a parasite control program include the direct costs of anthelmintics, the veterinary costs for designing and monitoring the progress of the program, and the labor needed not only for anthelmintic administration, but for ancillary practices such as pasture management, additional fencing or manure composting. The benefits, however, are not as obvious to the horse owner or farm manager but include improved performance by the resident horses, better feed utilization as well as decreased incidence of diseases, such as colic. An important aspect of today's equine practice that differs from years past with regards to parasite control is that today's veterinarians will not build their practice through selling anthelmintics; they will succeed through their advice on what to use, and how or when to use it. The change in delivery of anthelmintics via nasogastric tube to paste dewormers has altered the profession. Any horse owner can purchase anthelmintics more cheaply from a feed supply or tack store than from a veterinarian. The veterinarian can, however, provide an indispensable service by designing a control strategy, then implementing and monitoring the effectiveness of that strategy. To accomplish this goal, the veterinarian must know the biology of the parasites as well as the pharmacology of the drugs employed. The purpose of this article is to highlight features that are relevant to the practitioner.
The number of anthelmintic drug classes and products available to veterinary practitioners and horse owners has increased during the last 40 years, although most anthelmintic programs use just 3: avermectins, benzimidazoles, or pyrantel salts. The compounds within the class of avermectins/milbemycins (AM) have moved to the forefront due to their spectrum of activity, potency and relative safety. Within this broader class are subcategories of the avermectins, most notably ivermectin (IVM), or the milbemycins, most notably moxidectin(MO1), for use in control programs of horse parasites. These compounds share a basic chemical structure and mechanism of action , but differ somewhat in the spectrum of activity, and differ greatly in relevant pharmacological parameters .
The advent of the avermectins in the early 1980s brought about a profound change in anthelmintic programs for horses. By introducing control of both adult and migrating larvae of the large strongyles, the efficacy of IVM shifted the concern of horse owners away from the threat posed by the large strongyles to focus today on control of the small strongyles, or cyathostomes. A comprehensive control program must also address other important parasitic infections besides the small strongyles, but these can be treated on an "as need" basis. Some examples include: Strongyloides westeri or Parascaris equorum, which are age-related parasitic problems restricted to foals or yearlings; botfly larvae (Gasterophilus spp.), which have a distinct seasonal component for control; treatments for tapeworms (principally Anoplocephala perfoliata), or pinworms (Oxyuris equi), which are parasitic concerns but not the focus of a control program. These secondary parasitic infections can be treated within the framework of a program directed towards the cyathostomes by employing antiparasitic compounds that include any specific secondary parasite within the spectrum of activity.
Regional variations on this theme exist, principally as pertains to the timing of peak parasitic transmission or timing of drug administrations, yet the focus across the modern horse industry remains on the cyathostomes. A comprehensive control program must be designed, implemented and monitored by a local practitioner familiar with the locale, and tailored to the individual client. By doing so, the practitioner can incorporate any regional influences such as climate and weather, any age-related needs of the horse population (breeding farm versus boarding stable), as well as by the management practices of the horse farm.
Rote memorization of treatment schedules and antiparasitic drugs without understanding the biology of the worms to be controlled concedes any intellectual advantage to the worms. Total reliance on anthelmintics for parasite control also places more faith in pharmaceuticals than is warranted. A sustainable control program must also implement some ancillary practices as a means of reducing the parasite population prior to anthelmintic treatment. In this manner, a comprehensive program will ease the pressure on anthelmintic performance and, perhaps, delay the onset of drug resistance in the resident parasite population. Such ancillary practices might include closer monitoring of horse movement onto or off the premises, confinement and treatment of new arrivals; closer monitoring of younger horses, adjusting stocking densities on pastures; employing pasture rotations; practicing basic hygiene considerations such as composting manure before spreading onto pastures.
Prior to the advent of the avermectins, Strongylus vulgaris had been, without question, the most pathogenic nematode parasite of horses due to the inflammation and architectural changes that developed in the cranial mesenteric artery (CMA) secondary to larval migration (Fig. 1 and Fig. 2). These arterial changes predisposed the distal vascular beds of the cecum and ventral colon to blockage by thromboemboli, a condition appropriately named "thromboembolic colic", precipitated by this state of "verminous arteritis". A colic could develop from these events and the outcome would be dependent on the size of the blocked vascular bed and its ability to establish collateral circulation. Without collateral circulation, the condition could progress from a painful ischemic event to necrosis with development of endotoxemia and death (Fig. 3 and Fig. 4).
Figure 1. Normal appearance of an uninfected cranial mesenteric artery (CMA) at dissection. To the far right is the opened caudal aorta, with the CMA and associated branches to the left. Note that the endothelium is smooth and glistening, and there is no evidence of clot formation.
Figure 2. Lower magnification of an infected CMA opened at dissection. To the right lower corner is the caudal aorta with the CMA and associated branches opening to the left. Note the loss of smooth endothelium and the abundance of intraluminal clot formation resulting from migration of Strongylus vulgaris larvae. These clots can be carried to distal vascular beds where occlusion of arteries or capillary beds can result in ischemia of the cecum or colon.
Figure 3. Necropsy examination of a horse afflicted with ischemia affecting large areas of the cecum and ventral colon. This condition is known as thromboembolic colic secondary to Strongylus vulgaris-induced lesions of the arterial intima, known as verminous arteritis.
Figure 4. Large areas of the intestine of this horse were occluded by clotting and thrombus formation secondary to the larval migration. The size of the occluded artery dictates the size of the dependent vascular bed that will be deprived of blood flow. If the area is small, collateral circulation can develop, probably resulting in an episode of colic that resolves. If the vascular bed is too large for collateral circulation to develop, ischemia leads to necrosis and death of the horse, as in this case.
Thromboembolic colic does not or did not require an active infection with S. vulgaris larvae within the arteries because the architectural changes induced in the CMA persisted long after the larvae matured and returned to the cecum or colon. These changes included cavitation of the vessel with formation of diverticuli, calcification of the arterial wall and loss of normal arterial elasticity (Fig. 5). Disruption of laminar blood flow through the CMA created an environment favoring clot formation, predisposing the previously infected animals to bouts of colic without the need for a concurrent, active infection.
Figure 5. Dissection of the CMA of a horse previously infected with Strongylus vulgaris. The infection had resolved but architectural changes remain. These changes include the visible cavitation and diverticulae formation apparent grossly, also a loss of elasticity accompanied by calcification of the arterial wall. These changes contribute to clot formation and can result in bouts of thromboembolic colic well past the clearance of infective larvae.
Due to the long prepatent period of all the large strongyles, typically between 6-11 months, regular use of IVM at shorter intervals than this extended prepatent period has greatly reduced the prevalence of any large strongyle on horse pastures. Control of the large strongyles has brought to light the pathogenicity of the small strongyles. Christine Uhlinger followed the incidence of colic over a 5 year period on farms with different anthelmintic control programs using non-IVM products . During this study, no large strongyle infective larva was found in fecal cultures performed for identification of 3rd stage larvae, only cyathostome larvae were recovered. On farms where control programs effectively reduced the strongyle eggs per gram of feces (EPG) passed by the horses, the incidence of colic was also reduced dramatically. Additionally, the findings from this study highlight that the benefits of a control program can be manifest not only during the present grazing season, but during the subsequent grazing season as well.
Cyathostome Life Cycle
The adage "Know thy enemy" is advice that should be heeded by equine practitioners with regards to the cyathostome life cycle [4,5]. The important features of the life cycle do have relevance for the practitioner, particularly pertaining to design of control programs as well as understanding the relative efficacies of different anthelmintics against specific life cycle stages.
Adult cyathostomes produce typical strongyle-type eggs indistinguishable from those of large strongyles (Fig. 6), and are passed in the feces. Under favorable environmental conditions, eggs develop into first-stage larvae (L1) that hatch from the egg. Continued development on pasture is required, also contingent on favorable environmental factors, to second-stage larvae (L2), then to infective third-stage larvae (L3). These L3 retain the sheath of the L2, which provides considerable protection from harsh environmental conditions such as desiccation (Fig. 7). Infective larvae ingested by grazing horses will next develop through a sequence of essential stages that are punctuated by periods of hypobiosis or dormancy. Much or most of this developmental sequence occurs within the tissues of the large intestine, but cyathostomes do not penetrate or migrate through deeper tissues or organs. The signals that orchestrate developmental steps or hypobiosis have been observed but the underlying mechanisms are poorly understood.
Figure 6. Typical strongyle-type eggs viewed with a 101 objective lens. The eggs of large and small strongyles cannot be differentiated visually. The characteristic morphology can be described as thin-shelled, elliptical, embryonated and measuring between 60 - 90 μm in length. Eggs will become larvated quickly at warm temperatures, but practitioners should not be confused by this finding as the strongyle-type eggs are much larger than are the larvated eggs of Strongyloides westeri, which would be expected only in fecal samples of foals.
Figure 7. A typical cyathostome third-stage larvae (L3) viewed with a 401 objective lens. This micrograph demonstrates the L3 retained within the sheath of the L2 stage. This retained sheath protects the larva from dessication, but prevents the larva from continued feeding. The retraction of the L3 within the retained cuticle of the L2 is most easily visualized at the anterior or posterior ends.
Infective L3 ingested by grazing animals will exsheath in the lumen of the small intestine, cecum or ventral colon and the majority arrest development as early L3 (EL3), so described because no physical difference can be seen between the EL3 and the infective L3 ingested on pasture . Many of the ingested EL3 will be found in crypts of the cecum or colon, or encysted within the epithelial cells. Subsequent developmental stages that can be identified are the late L3 (LL3), identifiable by the elongation of the pharynx, which differentiates it from the EL3. The LL3 will develop into the fourth larval stage (L4), identifiable by development of the buccal capsule. The L4 will be the most advanced stage found in mucosal or submucosal tissues (Fig. 8,Fig. 9,Fig. 10). Further development requires that the L4 emerge from encystment and return to the lumen of the cecum or colon where they mature into the fifth larval stage, then fertile adults producing eggs, completing the life cycle. These stages, although arcane to the veterinary practitioner, are relevant when examining the anthelmintic literature claiming efficacy against encysted cyathostomes at different developmental time points.
Figure 8. Low magnification of a section of the cecal wall stretched over a light source for visualization of the encysted mucosal cyathostomes. Based on this visualization, only the more developed later stages of the L3 (LL3) and the L4 can be seen.
Figure 9. Higher magnification of the larvae seen in Figure 8. The coiled larvae can be seen, but one cannot identify a genus or species, and determining if the hypobiotic larva is alive or dead is problematic until sufficient time has passed for the larva to decay and an inflammatory reaction develop around such larvae.
Figure 10. Larvae removed from a scraping of the colonic mucosa. The mucosal tissue must be digested with a pepsin solution to liberate the larvae from the fibrous capsule that envelops each while they are encysted. These larvae were removed and a small quantity of Lugol's iodine was added to the solution to aid in visualization. Note the pronounced difference in sizes between the small LL3 or early L4, and the large L4.
The internal and/or external signals received by cyathostome larvae that orchestrate arrested development or hypobiosis, then trigger the sequence of developmental changes that lead to the final emergence of encysted larvae have not been identified definitively and may remain a mystery. Observational and experimental evidence exists that suggests a role for both seasonal and biological mechanisms. Nonetheless, the major subset of the cyathostome population infecting a horse are in the EL3 stage [7-9]. The relative percentages of EL3, LL3 and L4 may shift seasonally, but the EL3 represent the largest proportion of the total cyathostome population in horses at any time of the year. This point that has relevance to the development or avoidance of drug resistance: if the anthelmintic in question has excellent activity only against the lumen-dwelling stages and little or no activity against the mucosal stages, then very little selection pressure for drug resistance is exerted by that compound. The mucosal larvae that continue to develop and occupy the lumen should be as sensitive to the drug as their predecessors. If an anthelmintic does exert selection pressure on the mucosal larvae, then those that survive and emerge into the lumen to complete the life cycle should be less sensitive to the drug than their predecessors.
The evidence for seasonal signals received by mucosal larvae suggests an evolutionarily conserved function to delays larval development into fertile adults until times when external conditions would favor the development of eggs into infective larvae on pasture. This is manifest during the autumn and winter as a relative increase in the percentage of hypobiotic and encysted stages coupled with a decrease in the percentage of luminal stages. During late winter and early spring, the percentage of luminal stages increases, but never reaches a majority of the total cyathostome population; there is always a more significant population of cyathostomes awaiting development in the mucosa than adults present in the lumen.
Evidence also exists for physical or biological signals received by the mucosal larvae, and can be demonstrated following removal of the luminal stages by anthelmintic treatments. Gibson  performed a study with ponies that had grazed pasture then placed into a parasite-free facility where reinfection could not occur. These ponies were naturally infected with cyathostomes during grazing, then treated with phenothiazine, an anthelmintics capable of removing the lumen-dwelling stages but having no effect on the mucosal larvae. Removal of the adults signaled to a portion of the mucosal stages to resume development and occupy the vacated lumen niche. Gibson treated repeatedly and found that the mucosal population was sufficient to replenish the lumen in this manner for at least 30 months of confinement under parasite-free conditions. This study is relevant to the practitioner today for 2 reasons: 1) viable mucosal larvae will be present for years after ingestion, and 2) because the onset of classical larval cyathostomosis has been associated with recent anthelmintic treatments effective for removal of the lumen-dwelling stages . Such treatments given to young horses in late winter or early spring could trigger the onset of the disease by inadvertently signaling for resumed development by the encysted population of cyathostomes. One could speculate in such a situation that the seasonal signal for emergence couples with the biological signal of niche vacancy to exacerbate an already precarious position. A horse could not be in jeopardy without having accumulated a substantial population of mucosal larvae through exposure on pasture. Nonetheless, a veterinary practitioner should be aware of this potential for inducing emergence of the mucosal stages.
Larval Cyathostomosis: Two Clinical Forms
Larval cyathostomosis, the classical form described in the literature [11-14], is characterized by an acute onset diarrhea of horses secondary to the synchronous emergence of encysted larvae that disrupt the mucosal lining of the cecum and ventral colon (Fig. 11,Fig. 12). This form of larval cyathostomosis has analogies to type II ostertagiasis in young cattle. Both can be life-threatening diseases due to synchronous emergence of hypobiotic larvae, both are diseases primarily of young animals that received significant exposure to infective larvae while grazing on pasture, young animals are susceptible before they establish acquired resistance to reinfection, and both are clinical diseases afflicting a small number of animals in a herd despite the fact that most animals in the herd will experience some degree of larval emergence. Both type II ostertagiasis and larval cyathostomosis have a seasonal component in temperate regions. The risk factors described for horses  include an onset during late winter or early spring, affecting animals 6 years of age or younger, and an association with recent anthelmintic treatment removing the lumen-dwelling larvae and adults.
Figure 11. Gross examination of the mucosal lining of a horse suffering from acute larval cyathostomosis. The cecum and colon have been washed of ingesta in order to demonstrate the swollen and edematous mucosal surface disrupted by the synchronous emergence of encysted larvae.
Figure 12. Higher magnification of the mucosa of the cecum of the horse in Figure 11, showing the numerous cyathostome larvae that have emerged into the lumen.
A second form that we have observed occurs into the grazing season but without the acute onset of diarrhea. characteristic of the classical larval cyathostomosis. Instead, the presenting complaint is one of progressive ill-thrift and weight loss in spite of good pasture or feed supplementation. The clinical findings with these animals are equally nonspecific as with the classical form: low plasma proteins, low albumin, variable fibrinogen levels, possibly elevated neutrophil counts with some eosinophils present. This form is not secondary to the emergence of larvae, instead, the disease is secondary to the progressive accumulation of encysted and hypobiotic larvae leading to thickening of the mucosa resulting in poor absorption of nutrients and poor feed efficiency.
A definitive diagnosis of the summer form is equally complicated as with the classical form because these animals are often on an anthelmintic schedule that controls their egg shedding such that the EPG is low or even zero, thus a practitioner is likely to discount parasitism as a cause for ill thrift. The epidemiological picture of affected horses is similar to the classical form, typically horses 6 years or younger, exposed to pasture grazed by other horses on a variety of anthelmintic treatments. A significant difference is that the signs did not develop acutely but progressively over the course of a grazing season. Based on the histories that we have encountered, the anthelmintic treatments that were used routinely would not have removed encysted larvae from these young animals. As the horses continued to graze an infected pasture, their mucosal burdens increased, which progressively lowered their feed efficiency and body condition scores. The common denominator for both the classical larval cyathostomosis or the summer form is the requirement for exposure to infective cyathostome larvae by grazing contaminated pastures.
Controlled and limited exposure of horses to infective larvae on pasture is manageable and achievable with a parasite control program. An effective, comprehensive control program is needed to prevent heavy pasture contamination through strategic anthelmintic treatments of all age groups, not merely targeting the youngest and susceptible animals for these treatments. Many horse owners are unaware that an older animal in excellent condition may be a significant source of egg shedding that leads to pasture contamination, thus owners or farm managers unwisely reduce their perceived anthelmintic expenses by excluding some horses from the program based on external body condition. The equine practitioner must educate these clients to view the program in a more global perspective of pasture management for the benefit of herd health rather than individual treatments. Treatments directed only towards the youngest animals may control levels of their own lumen-dwelling adults, but may not adequately protect from accumulating large numbers of encysted larvae. This accumulated burden can affect nutrient absorption during the present grazing season, could result in poor growth or performance, or could result in acute larval cyathostomosis prior to the next grazing season.
Larval Development on Pasture
To achieve simultaneously the first and second objectives of our control strategy, practitioners must understand the dynamics of larval development from the egg to the infective L3 stage, and how these stages survive on pasture. Equine practitioners can effectively reduce the number of treatments and the overall costs of an anthelmintic program by timing the treatments to periods of highest return. With this in mind, practitioners can consider how their local climate and weather will affect the progress of egg development or larval survival on pasture. This will dictate the most beneficial seasons or periods for intensive anthelmintic control measures.
For any horse on pasture, there are 2 sources for infective cyathostome larvae: those L3 that survived on pasture from the previous season, and those that develop de novo from eggs passed in the feces of the horses on that pasture. These eggs are produced by recently maturing adults in the lumen derived from mucosal larvae. Practitioners should assume that all horses will shed some eggs in their feces each spring and anticipate that younger horses (<6 years) may develop high EPG at this time. Older horses, by virtue of their acquired resistance, will have much lower burdens, consequently lower EPG, but are a source of pasture contamination. By the same token, practitioners can assume that some degree of reinfection from larvae overwintering on pasture will occur, and that younger horses will have less resistance to this source of reinfection. These overwintering larvae will not be plentiful until temperatures have warmed sufficiently for their metabolic activity.
As stated earlier, cyathostome larvae develop from typical strongyle-type eggs passed in the feces (Fig. 6), through the L1 to the infective L3 stage. The egg, L1 and L2 stages are more susceptible to harsh environmental conditions than the L3. Eggs passed during cooler weather develop very slowly but a high percentage will survive and develop, whereas eggs passed during hot, dry weather are less likely to develop into the infective L3 stage. Both the L1 and L2 stages are more susceptible to desiccation than the L3, which is protected by the retained sheath of the L2 (Fig. 7). Cooler temperatures of winter and spring are usually accompanied by greater moisture, thus more favorable to survival and development of the L1 and L2 stages. The relevance is that EPG reduction from anthelmintic treatment is most critical during times that favor egg development to infective L3, less critical during times when heat and dryness will desiccate or exhaust the eggs or larvae. Anthelmintic treatments early in the grazing season are essential to prevent heavy pasture contamination.
The relevance of these facts for the practitioner lies in the timing of anthelmintic treatments combined with pasture management practices. Treatments aimed at reduction of egg shedding during the spring and early summer (in northern temperate climates as an example) are essential because environmental conditions favor larval development to the L3. Treatments during hot, dry conditions allow relatively more leeway, in terms of anthelmintic efficacy or egg shedding, because: 1) a lower percentage of any eggs passed would achieve the protected L3 stage, and, 2) infective L3 that would develop will have a shorter life-span during hot weather through exhaustion of their limited energy stores. The retained sheath of the L2 stage does protect the L3 from desiccation but also prevents additional feeding by the infective L3. Infective L3 already on pasture during the winter and colder temperatures of the early spring survive for relatively longer periods due to their lower, temperature-dependent metabolic rate. Allowing a spring pasture to remain vacant during the autumn is one method to extend this time and reduce the number of surviving L3.
The second objective of strategic control programs will be to reduce the overall number of anthelmintic treatments used during a grazing season. Practitioners can orchestrate their anthelmintic treatments to seasons of greatest need or benefit if a practitioner considers local weather conditions or pasture management practices, such as irrigation, harrowing or manure spreading, which could have a bearing on the development or survival of infective larvae. Clearly, fewer larvae can develop if fewer eggs are passed in the feces, but the practitioner can trade low level egg shedding by a few members of the herd during periods that are not conducive for larvae in order to reduce the overall number of anthelmintic treatments. Practitioners are advised to determine when the most inclement conditions for larval development occur in their region so that this will mark the time for such a trade-off.
Egg Reappearance Period (ERP)
If an effective anthelmintic treatment reduces the EPG to zero, this will be only a temporary condition and a resumption of egg shedding will eventually occur when new adult cyathostomes repopulate the lumen. No anthelmintic is totally effective against the mucosal stages, and some infective L3 already on pasture will survive through harsh environmental conditions. This combination virtually guaranteeing reinfection. The period of zero EPG followed by resumption of egg shedding is termed the egg reappearance period (ERP). The length of the ERP will be influenced by the age of the horse, by the anthelmintic employed, and by the intensity of reinfection by pasture larvae . When treated with the same anthelmintic, younger horses will have shorter ERP than older horses on the same pasture, under identical management practices [15,16]. Different anthelmintic classes provide different lengths of ERP, with the pyrantels providing the shortest ERP (4 - 6 weeks), benzimidazoles an intermediate ERP (up to 8 weeks), and the AM the longest ERP (8 - 12 weeks). These dynamic factors require consideration by the practitioner and it is essential that an effective, comprehensive control program be monitored adequately during the grazing season so that the timing of the next treatment is determined by the ERP. Treatment intervals longer than the ERP lead to egg shedding and pasture contamination; treatment intervals shorter than the ERP lead to more treatments than necessary, thus enhance the risk of drug resistance developing. For purposes of costs to the client or efficiency for the veterinary staff, a subset of the horse population rather than the entire herd will be monitored for ERP. Usually a random sample of 10% of the herd will be sampled, but the practitioner could monitor the youngest animals in the herd because they will have the shortest ERP and the highest EPG. Ideally, the practitioner will schedule retreatment of the entire herd before some individuals contaminate the pasture excessively. More flexibility in this retreatment schedule occurs during hot, dry periods because environmental factors favor the practitioner and control program. A return to egg shedding during cool, moist periods, such as spring and autumn in northern temperate regions, gives the advantage to the worms.
Monitoring the control program means checking the feces for the presence of strongyle eggs and is the indispensable contribution of the equine practitioner. Fecal exams should not be viewed as independent events but a sequence of necessary events, as with paired serum antibody titers. Paired samples provide more information. Equine practitioners can establish a set monthly fee for a farm or stable as bovine practitioners have done successfully for large clients. Reasons for monitoring the EPG include:
- Evaluation of the level of parasitism in a herd prior to treatment;
- Verification of the post-treatment response to an anthelmintic at 10-14 days;
- Determination of the ERP, which will dictate the timing of the next treatment;
- Comparison of the cost-effectiveness of different anthelmintics.
For successful reduction in the incidence of colic, Uhlinger  scheduled anthelmintic treatments for an entire herd when 25% of that herd had reached 200 EPG. Using this measure, Uhlinger was able to reduce the incidence of colic, reduce the number of anthelmintic treatments used overall, as well as reduce the level of pasture contamination that had been prevalent when these farms employed a program of 8 week intervals. Uhlinger monitored all animals in each of 4 herds. Monitoring is labor intensive and cost prohibitive, thus raises the question of what segment of the horse population to sample for efficiency if the herd numbers are large and the veterinary technical staff is overworked. Sampling at least 10% of any population is a commonly cited rule-of-thumb based on the uneven distribution of parasite burdens within a population. Ewert et al. , recommend monitoring 20% of the herd following anthelmintic treatments to verify efficacy of the drug employed. The most important single recommendation for any equine practitioner is to monitor the same animals pre- and post-treatment for evaluation of a 90% reduction of the EPG after treatment. The actual percentage of the herd monitored will be determined by the realities of the financial arrangements between clients and veterinarians. If the cost or complexity of a program dictates that fewer animals can be followed pre- and post-treatment, and for determination of the ERP, then concentrating the sample population on younger animals would be the most logical approach for reasons outlined above.
The fecal exam used in such a monitoring program is absolutely critical, as it must have sufficient sensitivity to measure accurately a wide range of EPG. A 90% reduction of EPG following anthelmintic treatment is the minimum desired for an effective anthelmintic compound. Less than 90% reduction is highly suggestive of a treatment failure or the onset of drug resistance. The fecal exam employed must be sufficiently sensitive to measure accurately the lower post-treatment EPG, or the practitioner will miss this indication of problems. As an example, if a pretreatment EPG is 400, a 90% reduction would mean an acceptable post-treatment EPG of only 40 EPG. A technique capable of accuracy at 40 EPG is essential for this determination. The McMasters fecal test is not sufficiently sensitive for this purpose. The McMasters exam quantifies strongyle-type eggs in 1/100th of the original fecal sample. Mathematically this requires at the least 100 EPG for a single egg to be counted with repeatability, thus limiting the sensitivity to 100 EPG. Many practitioners and parasitologists alike are under the mistaken impression that the McMasters test is accurate to 50 EPG by virtue of counting the 2 chambers of a McMasters slide. This misconception overlooks the necessity of counting both chambers as a means of verifying the accuracy of a count from either individual chamber. Practitioners must be aware that the fecal sample is diluted in a hypertonic flotation medium that will affect the distribution of eggs in the flask, or in the pipette used to load the individual chambers. Due to this inescapable source of error, 2 chambers must be counted to establish some confidence interval that both counts are repeatable and representative of the true EPG. The mathematical limitation of each chamber is 100 EPG and adding the counts of 2 chambers cannot lower this accuracy to 50 EPG, although this mistake is regularly reported in the literature. Please bear in mind that the average count of 2 chambers could be 50 +/- 100 EPG, and it is the wide confidence interval that should exclude the McMasters test from use when accuracy at low EPG is essential for interpretation of the response to treatment.
Compounding this mathematical source of error is the frequent commission of technical error. A common mistake made in the interest of saving time by veterinary technicians using the McMasters exam is to load both chambers of the slide with a single draw of the pipette, instead of loading 1 chamber, expelling the contents of the pipette back into the dilution flask, remixing the diluted sample, drawing a second pipette to load the remaining chamber. Such a failure enhances the disparity of counts between chambers because the eggs must be rising within the float solution inside the pipette. Each chamber should be loaded after a thorough remixing of the fecal dilution. No time can be saved without reducing the accuracy or repeatability of the exam.
Our laboratory employs the modified Stoll's technique exclusively for quantitative fecal exams of horses . This technique is merely a sugar centrifugation technique that employs a known quantity of the diluted fecal sample. Several advantages of this technique present themselves in contrast to the McMasters technique, but it does require centrifugation. We have found that a swinging bucket centrifuge will provide the most accurate and repeatable results over a fixed-head centrifuge using a sugar solution of 1.20 specific gravity, or over the McMasters technique (Monahan, unpublished data). With the Stoll's technique, there is no fixed-chamber slide as for the McMasters technique, thus some leeway in the dilution factor is possible that allows for sensitivity as low as 2 - 5 EPG. Briefly, a measured quantity of feces (either 2 or 5 grams, depending on desired sensitivity) is diluted with a measured quantity of regular tap water to a final quantity of 100 grams: 2 grams feces plus 98 ml water, or, 5 grams feces plus 95 ml water. The fecal sample is dispersed evenly in the water, then 10 ml of the fecal slurry is decanted into a graduated centrifuge tube. This represents 10% of the original fecal sample (either 0.2 or 0.5 grams). This sample is pelleted by centrifugation, the supernatant discarded, then the flotation solution is added to the centrifuge tube and mixed thoroughly. The tube is placed into the centrifuge, a slightly bulging meniscus is formed by adding several drops of additional flotation solution to the tube, and a coverslip is secured onto the meniscus and centrifuge tube. We centrifuge for 10 minutes at approximately 200 x g, remove the coverslip after centrifugation and count all strongyle-type eggs that are recovered. We count only the strongyle-type eggs and make a notation if other parasitic structures are present. Based on this count of all strongyle-type eggs present in 10% of the original fecal sample, we establish the EPG by a simple multiplication constant (5 if beginning with 2 grams of feces; 2 if beginning with 5 grams of feces).
To achieve the second objective of the control strategy (reduction of the number of anthelmintic treatments used during a year or grazing season), the practitioner should consider the time of year, the distinct benefits of the anthelmintic classes available, and couple this with an understanding of the relative susceptibilities of the different age groups to be treated. There is no single protocol effective for all circumstances, and, contrary to the publications by pharmaceutical firms, no single product so effective that its use precludes consideration of the other compounds or classes. The risks of most parasitic diseases are seasonal, thus there are seasonal benefits to the use of different antiparasitic compounds. By the same token, the risks of parasitism change between different age groups of horses, thus there is a rationale for using more powerful anthelmintics in younger horses but different products in older, more resistant horses.
A distinct advantage of rotating anthelmintics lies in the ability to target other parasites within the spectrum of activity of the drug employed. No single product has efficacy against the entire spectrum of equine parasites. At some time point, a practitioner must select different antiparasitic compounds to control tapeworms or botfly larvae, as examples. A theoretical advantage of rotating between drug classes is the belief that a nematode subpopulation that begins to develop resistance to 1 drug class could be controlled by use of a second drug class, thereby reducing the potential of establishing resistance genes within the genome [1,19,20]. Anthelmintic control strategies are usually described as either "fast" or "slow" rotations based on whether the anthelmintic classes are rotated between treatments or between calendar years.
Although multiple drug classes exist for use with horses , the most commonly employed anthelmintics for use in all age groups of horses fall into 1 of 3 major drug classes: avermectins/milbemycins (AM), benzimidazoles (BZD), or pyrantel salts (PYR). Comprehensive control programs can be based on use of these 3 classes alone, and use of each class is warranted to control some aspect of the parasite spectrum. As an example, IVM could be used for control of the nematodes and bots, reserving the occasional use of an elevated dosage of a benzimidazole for removal of encysted cyathostome larvae from young horses , and treatments using pyrantel pamoate to target tapeworms such as Anoplocephala perfoliata .
Several terms are used commonly to describe the rotation strategies for equine anthelmintic control programs: fast rotation, slow rotation, no rotation, selective treatments and targeted treatments [21,24]. Fast rotation of anthelmintics implies that drug classes are changed between sequential treatments during a grazing season. To target the entire spectrum of horse parasites, a fast rotation of compounds is essential. Slow rotation of anthelmintics means that a single drug class is utilized for an entire grazing season, then a different drug class employed for the duration of the following year. The entire spectrum of equine parasites cannot be treated effectively during a grazing season using this strategy. No rotation, as the name implies, means that a single drug class is employed until it no longer works, and has been used on farms where IVM has been the only anthelmintic employed for many years. Again, no single antiparasitic compound is effective for the entire spectrum of equine parasites. Targeted treatments are those directed only to of those horses with high EPG or clinical disease, while allowing other horses to go untreated. This strategy can be dangerous because significant pasture contamination may be present by the time the first clinical case is discovered. Daily deworming with a pyrantel tartrate feed additive has been utilized by some horse owners, and can be a useful adjunct to a rotational program, but should not substitute for a comprehensive program. Inherent in these rotational programs is the need to rotate between drug classes, not merely a rotation between products. A simple change from fenbendazole to oxibendazole, or febantel, is not a change between drug classes or the underlying mechanisms of action because all are related benzimidazoles. A change between IVM or MO1 likewise would not constitute a change in drug class.
Young horses are more susceptible to heavy burdens of all parasites, including cyathostomes, until an age-related or acquired resistance to infection is established around 6 years of age [24,25]. Older horses could become heavily parasitized, but younger horses represent the greatest concern for a practitioner. As discussed earlier, younger horses are likely to establish significant burdens of mucosal cyathostome larvae that impede nutrient absorption and can result in clinical disease. At or towards the end of the grazing season, practitioners should consider giving horses in this age group 1 treatment to reduce the encysted larval cyathostome burdens. A 5-day protocol of fenbendazole has demonstrated greater activity against mucosal cyathostomes . Oxibendazole used in a similar protocol has also shown efficacy . Theoretically, these larvae will die in situ within the mucosa, and the decaying larvae could serve as a source of cyathostome antigens to provide the immune system with sufficient exposure to speed the development of acquired resistance at an earlier age than if allowed to develop naturally on pasture alone. Due to widespread benzimidazole resistance in adult cyathostomes, this could become the only use of a benzimidazole during a grazing season, and restricted to horses under 6 years of age.
At present within the United States, only pyrantel pamoate among the available, licensed anthelmintics for horses has been reported to be effective for removal of horse tapeworms at elevated dosages . Praziquantel is effective for removal of Anoplocephala perfoliata, but not yet approved for use in horses in the United States. Practitioners must decide when during the year to use pyrantel pamoatefor treatment of tapeworms, cognizant that the ERP for the cyathostome eggs will be of shorter duration following pyrantel use. If this treatment is scheduled early in the season when weather conditions would favor egg to larva development, a pyrantel treatment should be followed by an IVM treatment for a prolonged ERP during this critical portion of the grazing season.
The timing of treatments for control of botfly larvae varies regionally due to temperatures affecting the adult fly. In northern regions, the fly season is more defined or limited than in warmer or semitropical regions where adult flies may persist for many months or be present in some numbers in any month. In northern regions, a single judicious treatment following a killing frost that eliminates the egg-laying adult females is the optimum method for both controlling the bots. A systemic compound, such as IVM or MO1 can have excellent efficacy against the migrating stages in the mouth as well as attached to the stomach lining. Against bots, IVM has shown superiority over MO1[8,28-30]. During such a time of the year, however, the encysted cyathostomes could be of concern, thus the practitioner must weigh the benefits of partial activity against the encysted larvae versus the relatively non-pathogenicity of botfly larvae.
The very real concern has been raised whether regular use of MO1 will lead to cyathostomes with drug resistance to the AM class as a whole . The mechanism of action for both compounds as well as the development of cross resistance to both IVM and MO1 in other species has been reviewed [1,19]. The concern within the equine community is based on the potential selection pressure exerted by MO1on the encysted and hypobiotic larval stages. Since the advent of avermectins in the early 1980s, there has not been a report of IVM-resistant cyathostomes, possibly due to its limited efficacy against the encysted and hypobiotic larval stages. The use of MO1 is desired by equine practitioners by virtue of the perceived activity against encysted larvae, but reports of this activity have been variable, which may be due in some measure to different post-treatment necropsy time-points. Earlier work on encysted cyathostomes used a 2-week post-treatment time-point [8,29,30], but this has been extended to 35 days to allow the dying larvae to be more recognizable as such . Although differences in necropsy time-points may seem insignificant, there are 2 important ramifications on the interpretation of drug trial data. Time-points 2 weeks post-treatment may not allow sufficient time for affected larvae to die and decay, as they are hypobiotic [8,29-31]. Extending the post-treatment necropsy time-point to 5 weeks may also obscure the true activity of a drug because removal of the L4 could then triggers the residual population of EL3 or LL3 to occupy that niche; this may occur during that 5 week period . As stated earlier, the EL3 represent the majority of the mucosal larvae and have sufficient numbers to replace the LL3 or L4 subsets of a population that might be removed by a treatment.
Use of IVM at therapeutic dosages exerts no selection pressure on the encysted cyathostomes because of limited activity against the mucosal stages [8,30], nor at elevated dosages . Since the advent of IVM, there has never been a confirmed report of drug resistant cyathostomes. Eysker has shown that MO1 exerts its principal effect against the L4 and not against the EL3 when examined at 5 week post-treatment intervals . As the EL3 constitute the majority of encysted or hypobiotic larvae, lack of MO1 activity against EL3 may translate into negligible selection pressure; however, comparison of the pharmacokinetics of MO1 and IVM demonstrated that MO1 has an extended mean plasma residence time (18.4 days) over IVM (4.8 days) . Furthermore, MO1 maintained plasma concentrations above 1 ng/ml for over 80 days, whereas IVM fell below 1 ng/ml in less than 20 days.
Removal of lumenal adults by MO1 may result in biological signals to EL3, LL3 and L4 to resume development, become metabolically active, thus susceptible to the residual drug levels in the plasma and killed during a 5 week post-treatment period. Unfortunately, plasma persistence of anthelmintics has been proposed as a major factor contributing to selection for drug resistance . This prolonged plasma residence time of MO1 may exert profound selection pressure on developing larvae, suggesting that the use of MO1 be reserved for age groups that have not developed acquired resistance, and used only at time-points of the grazing season when the advantages outweigh this risk.
By selective use of MO1, a smaller fraction of the total cyathostome genome would be exposed to selection pressure. Because horses under 6 years of age are most susceptible to mucosal burdens, these would receive the greatest benefit from a larvacidal treatment. Restricting the use of MO1 to this age group, and used only towards the end of the grazing season when encysted larvae are at their highest levels, a practitioner could reduce any potential selection pressure. If used wisely, MO1 can be incorporated into a control program without development of resistance; however, the risk is real and alternatives for removal of mucosal larvae do exist. Fenbendazole has been demonstrated to provide superior efficacy against EL3 (91 - 99%), LL3 and L4 (96%) when used at 10 mg/Kg consecutively for 5 days . Given this option, practitioners must decide whether to employ higher and prolonged dosages of fenbendazole with the added expense and inconvenience of 5 sequential daily treatments, versus the convenience and lower cost of a single treatment, but potential risk associated with MO1. As stated earlier, such larvacidal treatments of young animals may speed the acquisition of resistance by exposing the immune system to larval antigens.
Daily Deworming Programs
Three trials have demonstrated interesting results when examining the benefits of daily deworming. Two studies compared daily deworming with an interval anthelmintic treatment [33,34]. Each study reported seemingly contradictory results worthy of analysis. A study of Quarter Horse weanlings under excellent management conditions did not find significant advantage to using the daily dewormer when compared to IVM administered at 8 wk intervals . Both treatment groups had very low EPG. A study of Thoroughbred yearlings also found little difference between groups that received either daily pyrantel tartrate or monthly pyrantel pamoate , but the results of the second study showed both groups to have unacceptably high EPG. The Quarter Horse yearlings followed by Craig et al., , were assigned to individual paddocks and never developed appreciable pasture contamination regardless of treatment, whereas the Thoroughbred yearlings shared pasture and both groups developed high EPG . The difference between the 2 studies could be attributed to management more so than anthelmintic efficacy. Individual paddocks with excellent control reduces the rate of reinfection and daily deworming proved to be inconsequential. The second study demonstrates that susceptible animals on pasture where significant challenge exists will develop higher EPG regardless of the pyrantel salt employed.
A third study of foals raised on pasture with their dams, then moved to a contaminated weaning pasture may answer some questions regarding the potential benefits of daily deworming . In this study, 2 groups of mares and foals were maintained on separate pastures according to treatment. Under this management system, the treated mares and foals did not contaminate their pasture and infection levels did not rise appreciably during the grazing season. Untreated mares and foals did contaminate their pasture and did develop elevated EPG. Under the management system in this study, daily deworming was successful because the entire population of horses on that pasture received the same treatment and passed low numbers of eggs, minimizing pasture infectivity.
At weaning, however, both groups of foals were moved together to a heavily contaminated weaning pasture where daily pyrantel tartrate supplement was given to the treatment foals, and the untreated foals continued to receive only the pelleted supplement. Under conditions of stress and high pasture infectivity, the daily deworming did not adequately protect from infection. This finding is consistent with that of Herd and Majewski  and indicates that the benefit of daily deworming can be negated by significant challenge with infective larvae and that the daily regimen is best used as an adjunct for purposes of pasture management. Taken in conjunction with the results of the Quarter Horse study , a practitioner would conclude that if pasture infectivity is kept low, as seen with individual paddocks , or herd management of all animals occupying the same pasture , the anthelmintic used for this control is less important than the successful effort to control egg shedding. An additional finding from the latter study  was that foals raised on pasture with daily deworming did not develop resistance to infection when challenged experimentally with large and small strongyle larvae. The untreated foals in this experiment did not develop the same clinical response to challenge, suggesting that the brief exposure during the initial grazing season was beneficial. Control of the level of parasitism is the objective, not an unrealistic goal of elimination.
The author gratefully acknowledges the indispensable help of Dr. T.R. Klei, Louisiana State University in Baton Rouge, LA, as well as his permission to use several photomicrographs. The author would also like to thank Dr. Dwight Bowman, Cornell University, Ithaca, NY, for the invitation to participate in this project.
1. Shoop WL. Ivermectin resistance. Parasitol Today 1993; 9:154-159.
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Affiliation of the authors at the time of publication
Department of Veterinary Preventive Medicine, College of Veterinary Medicine, Ohio State University, Columbus, Ohio, USA.