Small Strongyles

The small strongyles consist of more than 40 species of nematode parasites primarily of the genus Cyathostoma. Small strongyles have a direct and completely enteral life-cycle in which adults produce strongyle type eggs that are indistinguishable from those of large strongyles.^2,3 Eggs passed in the feces develop at a critical temperature range of 7.2° to 29.4° C (45° F to 85° F) to first-stage larvae (L₁), which hatch and undergo continued development on pasture, becoming second-stage larvae (L₂) then infective third-stage larvae (L₃). Transmission is almost totally limited to pasture, with little infection thought to originate from stalls or dry lots. The rate of development is directly proportional to the environmental temperature; development takes as little as 3 days to several weeks at lower temperatures. L₁ die quickly at higher temperatures, and freezing generally kills strongyle eggs. Resilience of the infective L₃ is dramatically different owing to retention of the L₂ cuticle, which protects from desiccation but also prevents continued feeding. Warm weather leads to rapid death of L₃ as energy stores are depleted by activity in the absence of intake. In contrast, at very low temperatures energy depletion does not occur, and L₃ remain viable in freezing conditions. Accordingly, L₃ disappear quickly in hot, dry climates but remain viable in the winter.

L₃ are ingested with herbage and exsheath in the small intestine, cecum, and ventral colon, where the majority enter a period of dormancy as early L₃ (EL₃) in the crypts and epithelial cells of the cecum and colon. Continued development through late L₃ to fourth-stage larvae (L₄) occurs within the cyst. Development to fifth-stage larvae (L₅), the sexually mature, egg-producing stage, occurs in the gastrointestinal (GI) lumen. At any given time EL₃ constitute the greatest proportion of cyathostomes.^4,5 Cyst formation within the wall of the large intestine conveys some degree of protection from the immune response and from anthelmintic therapy.⁶ Practically speaking, limitations to drug diffusion may also be a factor in the generation of anthelmintic resistance for drugs with larvicidal activity. In contrast, anthelmintics that lack larvicidal activity should not be expected to exert resistance pressure in encysted forms. Therefore encysted stages remain effectively in refugia when nonlarvicidal anthelmintic therapies are used.

Encysted L₃ are an important clinical entity for several reasons. There is evidence that seasonal signals as well as signals from lumen-dwelling mature forms delay development of encysted larvae, creating an important reserve for reinfection of the lumen. When environmental conditions are not favorable to larval development, large numbers of EL₃ can remain dormant.^4,5 As seasonal conditions become favorable, large numbers of hypobiotic larvae are signaled to exit and complete their life-cycle.⁷ In addition, lumen-dwelling adult small strongyles remain in balance with encysted forms such that anthelmintic killing of luminal parasites triggers a reemergence and repopulation of the lumen from the intramural reserve.⁸ Studies of small strongyle—parasitized ponies moved to a parasite-free environment indicate that the encysted stages can serve to reseed the lumen for at least 30 months of confinement under parasite-free conditions. Therefore it is obvious that under practical conditions of access to contaminated pastures, viable encysted larvae are present in the colon for years after ingestion, even in the absence of continued exposure. This would indicate that it is relatively difficult to “empty” horses of small strongyles.

Clinical syndromes associated with cyathostome infections have been extensively reviewed.¹ The larval challenge dose, age, prior cyathostome exposure, and immunity of the host interact to determine the clinical picture. Most infections are asymptomatic with little response to encysted larvae. Clinical signs result from larval penetration into or emergence from the large intestinal mucosa.⁹ Despite an emphasis on diarrhea in most reports, weight loss is the primary clinical finding in horses with clinical cyathostomiasis. During an initial high-exposure infection, local irritation can result in decreased feed efficiency, anorexia, anemia, weight loss, and diarrhea as a result of local inflammatory reactions in the large intestine. Blood biochemistry and hematology may demonstrate neutrophilia, hypoalbuminemia, and hyperglobulinemia from 2 to 9 weeks after infection.^9-11 Prior exposure tends to hasten the onset of laboratory abnormalities.

Larval cyathostomiasis is a potentially fatal disease syndrome that results from a synchronous emergence of encysted larvae that disrupt the mucosal barrier of the cecum and ventral colon.^2,12 Fluid and protein transudation into the GI lumen and leakage of bacterial toxins into the vasculature are facilitated. All animals experience some degree of larval reemergence during winter or spring, but larval cyathostomiasis generally affects animals less than 6 years of age, when they have not yet acquired significant resistance to infection.^12-14 Classic clinical signs include colic, which may be severe, impaired GI motility, sudden-onset diarrhea, and weight loss. Weight loss, fever, and dependent edema have also been reported in the absence of diarrhea.¹⁵ Some affected individuals may die acutely with few signs, whereas others may become emaciated and die over a period of 2 to 3 weeks.^2,12

Signs consistent with larval cyathostomiasis have also been observed 7 to 10 days after administration of anthelmintics.¹⁶ This is presumed to result from a synchronous reactivation of hypobiotic larvae that is triggered by removing adult parasites from the GI lumen.⁸ It is conceivable that anthelmintic therapy during the period of seasonal cyathostome emergence superimposes signals for emergence on seasonal signals such that clinical disease is worse than either signal alone.

Cyathostome infection may also cause recurrent diarrhea in adult animals,¹⁷ a severe weight loss syndrome with associated edema and pyrexia in young horses,¹⁵ chronic weight loss leading to diarrhea,^18,19 cecocolic intussusception,^20,21 nonstrangulating infarction,^19,22 cecal tympany.¹⁹

Controlling small strongyle infection is the primary goal of anthelmintic therapy in adult horses. Anthelmintic resistance in small strongyles is a growing problem, and parasite control strategies must be tailored to minimize anthelmintic use and maximize the generation of natural immunity.

Large Strongyles

Three species of large strongyles—Strongylus vulgaris, Strongylus edentatus, and Strongylus equinus—parasitize the horse. All three species have similar preparasitic phases. However, the migratory route of S. vulgaris makes it, on a per-worm basis, the most pathogenic of the enteric parasites of the adult horse. Both the life-cycle of and pathology caused by S. vulgaris have been comprehensively reviewed.⁷⁰ Infective L₃ are ingested from pasture. S. vulgaris L₃ penetrate the mucosa of the small intestine, molt to L₄ over 7 days, and then begin their arterial migration by penetrating the submucosal arteries. L₄ travel via the cecal and colic arteries (by 14 days postinfection), reaching the root of the cranial mesenteric artery and its main branches by day 21 after infection. Larvae mature over a period of 3 to 4 months, then return primarily to the cecum and colon via the arteries. After a short period of maturation within the wall of the cecum and colon, the young adult parasites are released into the lumen of the intestine, where they mature in another 6 to 8 weeks. The prepatent period is 6 to 7 months.

Pathology and accordingly clinical signs of S. vulgaris infection result from the extensive larval migrations through the mesenteric arterial system.^23-25 Larval migrations result in marked cellular infiltration and damage the endothelium of the arteries, leading to thrombus formation. The walls of all branches of the ileocecal colic artery are affected, and with chronicity the vessels become thickened and dilated with aneurysm formation. Disease results from thrombus showering of the bowel, leading to multifocal avascular necrosis in areas of the intestine that are supplied by the occluded arteries. Clinically affected horses show varying degrees of pain depending on the nature of the infarcts. Fever and serosanguineous peritoneal fluid with elevated protein and red and white blood cell counts are common.

The life-cycle of S. equinus was characterized by Slocombe.²⁶S. equinus also invades the wall of the small intestine, cecum, and colon, causing formation of small cystic and hemorrhagic nodules where the organisms molt to L₄. Twelve to 14 days after infection larvae exit the nodules, traversing the peritoneal cavity to the liver by 19 to 20 days after infection. Larvae remain in the liver for at least 12 weeks and then return to the large intestine by traversing the abdominal cavity directly or passing through the pancreas and then the abdominal cavity. By 15 weeks postinfection mature L₅penetrate the lumen of the large intestine to complete the sexual phase of their life-cycle. The prepatent period of S. equinus is approximately 9 months.

S. edentatus L₃ invade the walls of the terminal small intestine, cecum, and right ventral colon, where they penetrate the vasculature and then migrate to the liver via the hepatic portal vein.^27-30 Larvae remain in the liver for approximately 40 days, during which time they molt to L₄.²⁸ Larvae then migrate via the hepatic ligament to the parietal peritoneum of the right flank and molt to immature adults between 13 and 15 weeks after infection.²⁷S. edentatus organisms then return to the large intestine via the mesentery between 3 and 5 months after infection, migrating through the walls of the cecum and colon and causing the formation of parasitic nodules. Adults emerge into the large intestine to complete the sexual phase of their life-cycle. The prepatent period is generally acknowledged to be approximately 11 months, although some authors suggest it may be as short as 6 months.²⁹

The pathology of S. edentatus and S. equinus is fairly restricted to hemorrhagic nodules and parasitic cysts of the large intestine.^26-28 Such lesions are generally regarded as not severe enough to account for recognizable signs of colic. However, these lesions are evidence of poor deworming and a reasonable indicator that other large and small strongyle burdens are likely. Larval migrations through the liver may produce nodules and formation of fibrous tissue but are not considered clinically significant.

Although large strongyle infections are sporadically identified, they have been virtually eliminated in most areas through the widespread use of macrocyclic lactones and larvicidal fenbendazole regimens (10 mg/kg sid × five treatments) that kill both adults and migrating larvae.³¹ This reflects the protracted prepatent period (>5 months) of the large strongyles, coupled with limited survival of larvae in the environment. Simultaneous treatment of all horses on a premises with larvicidal anthelmintic regimens eradicates the parasite because despite continued ingestion of infective larvae from the pasture, the larvae never reach sexual maturity to produce eggs that can recontaminate the pasture. Therefore, given a maximal survival of large strongyle larvae of 12 months on pasture, larvicidal anthelmintics administered at 5-month intervals will effectively eliminate large strongyles from a premises within 18 months.

Tapeworms

During the last two decades the equine tapeworm, Anoplocephala perfoliata, has risen from clinical obscurity to be recognized as a significant potentiating factor in certain types of abdominal pain. The tapeworm life-cycle is indirect, cycling through oribatid mites, which horses swallow while grazing. Oribatid mites feed on organic material in feces on pasture, ingesting tapeworm eggs. Eggs develop into infective cysticercoids within the mite over a 2- to 4-month period. Tapeworms are hermaphrodites in that each infective form, the cysticercoid, contains the sexual organs of the male and female. After ingestion of cysticercoids by the horse, eggs develop in saclike body segments, termed proglottids, within 6 to 10 weeks.³² Proglottids then break away and pass in the manure. Detection of tapeworm eggs in manure is extremely insensitive for identification of tapeworm infestation, and this is thought to reflect an uneven distribution of the eggs within equine feces, associated with patchy distribution of the disintegrating proglottids.^33-35 Accordingly, serologic diagnostic methods have proven advantages for detection of tapeworm infection.³⁵

Three species of tapeworms have been identified in North America.^36,37A. perfoliata, the most commonly identified, inhabits the region of the ileocecal valve. Anoplocephala mamilliana is the smallest and Anoplocephala magna the largest of the tapeworms that inhabit the small intestine and stomach. Postmortem investigations in Kentucky have indicated that the prevalence of tapeworm infections exceeds 50% of the population.^38,39 Serologic evaluation of horses from 19 U.S. states representing 10 geographic regions chosen to encompass the entire United States indicated an overall prevalence of 54%, with a geographic distribution that was lower in the western United States, ranging from 1.3% in California to near 100% in Minnesota.⁴⁰ Lower prevalence of tapeworm seropositive status in young animals and stallions was attributed to reduced access to pasture in these individuals.

Tapeworms infect horses of all ages, although a peak in worm burden has been identified in animals between 6 months and 2 years of age and in animals over the age of 15 years.⁴¹ Susceptibility to tapeworms appears to mimic susceptibility to small strongyles in that some horses develop immunity, others maintain small burdens, and a small percentage (10%) of horses maintain large tapeworm loads regardless of deworming.^36,39,42-47Anoplocephala organisms cause severe inflammation, ulceration of the mucosa, edema, and scarring at their attachment sites, which can in some cases partially obstruct the lumen.^48-50 This inflammation, in coordination with large quantities of acetylcholine found within A. perfoliata, is believed to interfere with normal peristalsis. Tapeworm burden increases the risk of spasmodic colic eightfold, and the risk of ileocecal impaction twenty-eight-fold.^51-54 Tapeworms also increase the risk of ileocecal intussusception and cecal rupture.^55-58

Effective recommendations for the control of equine tapeworms in the United States are compromised because epidemiologic studies have been confined to Kentucky and investigations of oribatid mites are lacking. Tapeworm infections occur year-round throughout the world.^39,47,59-62 However, investigations in Spain, Switzerland, Sweden, and Kentucky have identified significant seasonal increases in A. perfoliata infection from late summer through early spring.^{30,59-61,63-65} Comprehensive examination of 372 horses from Spanish abattoirs also demonstrated that A. magna infections peaked in fall.⁶⁰ Of importance, gravid A. perfoliata organisms were not evident in summer and displayed an increasing seasonal prevalence peaking in spring, suggesting that strategic use of cestodicidal drugs before spring may be especially effective in interrupting the life-cycle.

Praziquantel (1 mg/kg) and double to triple doses of pyrantel pamoate (13.2 to 19.8 mg/kg) are efficacious in eliminating tapeworms.^66,67 Limited evidence suggests that pyrantel tartrate (2.64 mg/kg) for 30 consecutive days is also efficacious.^68,69 In the United States praziquantel is available only in combination with moxidectin or ivermectin. Annual treatment with an efficacious product is recommended for horses beginning at weaning. Available epidemiologic findings suggest that annual treatments might be of greatest benefit in late fall to minimize burdens and prevent the development of gravid forms. However, on farms with a confirmed tapeworm burden, based on fecal counts, serologic evaluation of the herd, or a history of tapeworm-related colics, treatments two to three times per year may be justified, especially during the late summer through early spring.

Bots

Two primary species of bot larvae infect horses in North America.^39,66,70,71Gasterophilus nasalis lays eggs in the intermandibular region, whereas Gasterophilus intestinalis eggs are found attached to the forelegs. By day 5, larvae hatch and migrate to the mouth in the case of G. nasalis or enter the mouth as the horse rubs and scratches the eggs with its muzzle and teeth in the case of G. intestinalis. First-stage G. intestinalis larvae embed deeply in the tongue and migrate to the interdental spaces of the upper molars, where they molt to L₂, whereas G. nasalis larvae reside in the interdental spaces. L₂ are swallowed and come to reside in species-dependent predilection sites, where they molt to L₃. G. intestinalis organisms attach to the nonglandular lining of stomach in the region of the margo plicatus, and G. nasalis organisms attach to the most proximal portions of the duodenum, where they remain for up to 12 months. In late spring, larvae pass in the feces, pupate to adult flies over 3 to 9 weeks, and begin laying eggs again until fall. Fly activity ceases with the onset of cold weather.

Moderate Gasterophilus species infestations are asymptomatic.⁷¹ Large larval burdens in the tongue can cause inflammation and perhaps difficulty swallowing.^63-65 However, this association is not well recognized. Heavy loads in the stomach may be associated with gastric ulceration, abscessation, and rarely stomach rupture and peritonitis.^75,76

Gasterophilus infection is easily controlled through once-yearly administration of boticidal drugs, ivermectin, or moxidectin.^77,78 Highest numbers of larvae are found in the stomach from winter through early spring.⁷¹ Accordingly, timing of treatment should be in late autumn or early winter. Daily grooming to remove bot eggs, which are yellow and easily visible, minimizes infection.

Pinworms

The parasitic phase of O. equi, the equine pinworm, begins with ingestion of an embryonated egg containing infective L₃. Larvae hatch in the small intestine and come to inhabit the mucosal crypts of the cecum and colon. Maturation to gravid adults includes a lengthy maturation phase that ranges from 139 to 156 days, creating a prepatent period that approximates 5 months. Gravid females lay their eggs in clumps in a yellowish-grey gelatinous material around the anus. After completing their egg laying, the females pass out of the anus and die.

The primary clinical sign of O. equi infection is intense pruritus of the tail head that is referable to drying and cracking of the egg masses in the region of the anus. Tail rubbing facilitates deposition of the eggs in the environment. In severe infections, mild colic can result from inflammation of the cecum and colonic mucosa.

Benzimidazoles (BZDs), pyrantel pamoate, pyrantel tartrate, and the macrocyclic lactones are all efficacious against pinworms. Owing to the prolonged prepatent period, treatment regimens tailored to control ascarid or small strongyle infections will control O. equi infections. Frequent cleansing of the perineum will also limit spread.

Roundworms

Infection with the equine roundworm, P. equorum, is limited to young horses owing to the development of acquired lifelong immunity by 18 to 24 months of age.⁷⁹ The high prevalence, size, fecundity, and persistence in the environment make P. equorum the most pathogenic parasite of the young horse. The life-cycle of P. equorum is direct, with a hepatotracheal migration and a prepatent period of 10 to 12 weeks.^80,81 Mature ascarids range in length from 1 to 14 inches, and the females are extremely prolific, producing hundreds of thousands of eggs per day.⁸⁰ These eggs are very sticky, enabling them to adhere to pasture and surfaces in the environment from which they are ingested. Ascarid eggs are also extremely resistant to chemicals and the environment, remaining viable for over 10 years and being capable of withstanding bleach, iodine, cresol, quaternary ammonium compounds, and steam cleaning.⁸² Over a period of weeks eggs mature to an infective stage in the environment characterized by the presence of L₃, which is visible within the egg. After ingestion, larvae emerge from the eggs in the small intestine, penetrate the intestinal wall, and travel via blood or lymphatics to the liver. Larvae migrate within the liver for approximately a week; they molt to L₄ before being carried, via the vasculature, to the lungs. Larvae break into the alveoli, ascend the bronchial tree, are swallowed and then mature to L₅ and reproduce.

Clinical signs referable to adult ascarid infection include weight loss, stunted growth, rough hair coat, a pendulous pot-bellied appearance, lethargy, depression, and abdominal pain.^83-85 Migratory stages of the parasite are commonly associated with respiratory signs including fever, coughing, and nasal discharge, which may be partially responsive to antimicrobial therapy but recur when therapy is discontinued.^81,84 The most immediately life-threatening effect of ascarid infection is the ascarid impaction which is an obstructive mass of dead worms occurring shortly after deworming in the face of high ascarid burdens.⁸⁶ Affected animals display signs of severe abdominal pain referable to small intestinal obstruction.

High fecundity and egg resistance make elimination of Parascaris from an infected premises virtually impossible. Ascarid burdens in weanlings often reach several hundred, yielding fecal egg counts (FECs) in the millions of eggs per gram feces (epg).⁸⁰ Pasture is the primary route of exposure to ascarids, and accordingly clean pastures (see the discussion under Clean Pasture) should be prioritized for young animals and mares with foals. Young animals are also commonly exposed when they lick the infected stall environment. Despite the chemical and environmental resistance of ascarid eggs, efforts should be made to decrease the environmental load by frequently removing manure from stalls and pasture (before development of infective stages); feeding horses off the ground in feeders that can be cleaned; washing stall surfaces with detergent and phenol-based disinfectant (especially in stalls that have held foals and weanlings); and bathing the mare, including her udder, before foaling. Anthelmintic protocols tailored to the control of Parascaris will also adequately control most other intestinal parasites of the young horse with the exception of tapeworms.

Threadworms

S. westeri is a sporadic cause of diarrhea in foals before weaning. S. westeri is acquired primarily through lactogenic transmission, with infections being acquired during nursing in the first few days postpartum.⁸⁷ Less commonly infection can be acquired from a wet environment.⁸⁸ The life-cycle is completely enteral, with the parasite infecting the small intestine and producing eggs within 6 to 14 days of infection.^87-89 Sources have reported acquired immunity to be complete by 6 to 12 months of age.^88-90S. westeri transmission is significantly reduced, although not eliminated, by treating the mare with ivermectin at foaling.⁹⁰ Foals can be treated empirically with either ivermectin or oxibendazole (15 mg/kg) within the first 2 weeks of life or based on positive fecal examination results.^90-92

A New Paradigm for Equine Parasite Control

For at least two decades administration of anthelmintics has focused on the practice of “rotation” or deworming of all horses with drugs from different anthelmintic classes, each separated by a predictable interval. These regimens are not in the patients’ best interest for several reasons. First, rotation does not slow the progression of resistance and in fact actually selects for resistance to all drugs in the rotation.^93-97 Rotational regimens also provide no venue to detect anthelmintic resistance, and, because an alternate class of dewormer is used sequentially, resistance may be masked by the regular substitution of efficacious products in the deworming schedule. Equally, the concept of “slow rotation,” in which a single anthelmintic is applied for an entire year, is not prudent because of the high prevalence of resistance among small strongyles.⁶ Slow rotation, without monitoring the effectiveness of the anthelmintic by assessing for a reduction in FECs, allows resistant parasites to propagate unchecked for a prolonged period. During this time, parasites that are sensitive to the anthelmintic are selectively killed, allowing the resistant parasites to dominate the population. Computer modeling has demonstrated that the most effective method of delaying resistance is the simultaneous use of two effective and chemically distinct anthelmintics.

Investigations focused on anthelmintic resistance have identified a phenomenon of individual variability in parasite susceptibility in many species including the horse. Certain individuals that are “more susceptible” or permissive to strongyle infection maintain higher quantitative FECs then their herdmates, despite identical exposures, and account for the majority of pasture contamination.^98,99 Other individuals can be identified that limit the infection and pass few to no eggs in their feces. Calendar-driven deworming ultimately translates to anthelmintic overuse in animals whose immune response can limit the infection, whereas suboptimal parasite control may result when the same treatment regimen is applied to susceptible individuals. Anthelmintic overuse hastens development of anthelmintic resistance.^100,101 Therefore the time-honored principle of simultaneous anthelmintic treatment of all herdmates is being rewritten to be simultaneous reevaluation of all herdmates and treatment of horses with moderate and high strongyle susceptibility as documented by elevated FEC.

The last two decades of anthelmintic research have determined that preserving a population of parasites termed refugia or said to be in refugia is critical to controlling anthelmintic resistance. The most basic biologic meaning of refugia is an isolated population of once widespread species. Refugia should be viewed as “wild-type” parasites that have not been selected for anthelmintic resistance. Accordingly, the genetics of parasites in refugia are critical to preventing dominance of anthelmintic-resistant strains. Refugia are protected during anthelmintic treatment of the host only when they are on pasture and, in the case of nonlarvicidal anthelmintics, when they are encysted. Because refugia are anthelmintic sensitive, a central tenant to their preservation is decreasing the frequency of anthelmintic use, especially when parasite numbers are low in the environment. Balancing a desire for decreased anthelmintic treatments with maintaining the health of the horse can be achieved only through the rational application of routine FECs to differentiate horses that need treatment from those that do not.⁶

Factors Influencing Parasite Control Strategies for Adult Horses

The primary goal of parasite control in adult horses is to minimize infective small strongyle larvae on pasture. A thorough understanding of three factors is critical to the proper timing and selection of anthelmintics. These factors are the load of infective larvae in the environment, the residual capacity of the anthelmintic agent, and the horse’s ability to limit egg excretion via an effective immune response.

Climactic conditions of a geographic region directly affect the lifespan of infective larvae and accordingly the load of infective larvae in the environment. This is exploited when developing a parasite control strategy by timing anthelmintic administration for the times of peak fecal egg production.¹⁰² Ultimately such strategic timing will minimize the number of anthelmintic treatments, which limits resistance by decreasing selection pressure. In contrast, anthelmintic treatment should be avoided when pasture refugia are diminished, because such treatments place the greatest selection pressure on the population.¹⁰³ Pasture refugia are at their lowest numbers when climactic conditions limit the survival of infective larvae on pasture.

In warm temperate and subtropical or tropical climates such as the southern United States, refugia are at their lowest during the summer because larvae cannot survive the extreme heat of the southern climate, providing a period of grazing in the summer that is relatively free of exposure to small strongyles.^103,104 In this region, peak fecal egg production occurs from autumn (September) through spring (April). It is important to recognize that infective larvae are present on pastures in the warm temperate, subtropical, and tropical regions of the southern United States throughout the winter months. In the northern cool temperate regions, refugia are at their lowest during the winter, whereas larval development is favored during spring, summer, and fall.^103,105 Northern winters (November through March) do not support hatching of eggs nor larval development, although L₃ that have already developed sufficiently to be competent for infection do persist during these months.¹⁰⁵ This is important to recognize because rested pastures in northern climates remain infective until early summer, when rising temperatures cause the demise of L₃. Despite the fact that infective larvae are present on pasture in northern climates during winter, management practices, in which the horses are stabled and their manure is removed, limit winter exposure to infective larvae. This reflects the requirement for a moist environment in order for strongyle larvae to develop to infective L₃, conditions that are not achieved in the stall. Furthermore, ammonia from a dirty, wet stall environment is toxic to nematode larvae.¹⁰⁶ Together these factors create a winter period in northern climates that is relatively free from exposure to infective strongyle larvae.

In addition to climactic factors, the residual ability of a given class of anthelmintics to suppress egg excretion must be considered. This characteristic of each anthelmintic is reflected in the egg reappearance period (ERP), which is the time after treatment that a horse’s feces will remain negative for strongyle eggs. The ERP has generally been reported to be on the order of 8 weeks for ivermectin^107-110 versus 12 weeks for moxidectin.¹⁰⁹ However, shortening of the ERP for ivermectin to 6 weeks has been demonstrated on some farms, raising concerns regarding reduction in efficacy and emerging resistance to macrocyclic lactones.^97,110,112 For pyrantel the ERP is on the order of 4 to 6 weeks.^108,110,112 ERP after BZD administration is on the order of 4 weeks, but periods as short as 2 weeks have been reported.^112,113 Longer ERPs reflect the residual ability of an anthelmintic to prevent emergence and sexual reproduction of encysted small strongyle larvae. The clinician must recognize that BZD resistance is widespread in small strongyle populations, making monitoring of FEC reduction with these products especially important.^6,114 From the standpoint of formulating an anthelmintic treatment regimen, the ERP is a useful interval for reevaluating FECs after anthelmintic therapy in order to determine if an individual horse requires subsequent anthelmintic therapy. Shortening of the ERP may also be an early indicator of reduction in anthelmintic efficiency.

The ability of a horse’s immune response to limit strongyle infections and egg production directly influences the intervals between anthelmintic administration. Strongyle resistance is reflected in an index termed the Strongyle Contamination Potential (SCP), which is defined as the FEC 4 weeks after the ERP of the previous anthelmintic. At this time residual anthelmintic effects are exhausted, and the ability to limit fecal egg production is reflective of the immunity of the host. SCP has been categorized as low (<150 epg), medium (150 to 500 epg), and high (>500 epg), corresponding to approximately 40%, 25%, and 35% of the population, respectively.¹¹² FECs at the beginning of the parasite season (September in the south, April in the north) are also reflective of the relative immunity of the individual to small strongyles, because infective larvae are in low numbers on pasture at these times. Accordingly, FECs at these times are proportional to the individual’s tendency to “permit” the development and sexual reproduction of the few larvae that are ingested, or more significantly, hypobiotic strongyle larvae that are emerging to complete their life-cycle.

Parasite Control Strategy for Adult Horses

To be effective, parasite control strategies must be multifactorial and take into consideration the husbandry and dynamics of the premises or owner, ages of the patients, and epidemiology of the parasites. Anthelmintic resistance issues have highlighted the need to employ all measures that minimize pasture contamination. Strongyles develop from eggs to infective L₃ outside the host, and simply removing feces from the environment before eggs become infective has been shown to provide parasite control that is superior to that of anthelmintic administration.¹¹⁵ Horses maintained in environments with fecal removal had lower FECs and grazing area was increased by 50% when compared with cohorts that were given anthelmintics. Pasture vacuuming and manual removal of feces from pasture may not always be feasible, and such measures have been dismissed in deworming schemes of the past. However, with anthelmintic resistance rising and with the need to minimize reliance on anthelmintics in order to protect refugia, the ability of manure removal to virtually eliminate anthelmintic use should cause responsible veterinarians to strongly encourage some degree of environmental management.

When targeted deworming is applied, the deworming season begins in September in warm temperate, subtropical, and tropical climates of the southern United States and in April in the cool temperate climates found in the northern regions of North America. Quantitative FECs are performed and reflect the small strongyle susceptibility of the individual horses because environmental loads are minimal at these times. Anthelmintic treatments are administered according to treatment thresholds, which range from 100 to 500 strongyle type epg (generally 150 to 200 epg). Evidence-based medicine indicates that these thresholds are efficacious in decreasing anthelmintic administration while preserving health.^{97,99,111,116} Lowering the treatment threshold imposes greater selection pressure for resistance and serves to limit immunity to small strongyles. After the initial evaluation and treatment at the beginning of the parasite season, FECs are repeated at intervals according to the ERP, with subsequent anthelmintic treatments being administered to only those individuals whose FECs exceed the treatment threshold. Within this program, the fall deworming should be with a macrocyclic lactone and praziquantel combination to target Gasterophilus species and Anoplocephala species. The cost of repeated fecal examinations may be concerning initially to owners employing targeted deworming. However, such regimens have been shown to be economically viable because they decrease anthelmintic use as much as 78%.⁹⁷ Repeated evaluations of FECs indicate that individuals exceeding the treatment threshold at the beginning of the parasite season (or 4 weeks after the ERP of the previous anthelmintic) are likely to maintain elevated FEC and require repeated deworming at intervals consistent with the ERP. Animals with FEC below the treatment threshold should have FECs monitored according to the appropriate ERP and be dewormed when the treatment threshold is reached.

It is proposed that horses whose FEC exceeds 500 after the ERP or in the beginning of the parasite season (i.e., those with high SCP) should be singled out for larvicidal anthelmintic therapy.¹¹² See Table 49-1. This reflects the fact that these animals are permissive to the infection, allowing both pasture-derived larvae and emerging encysted larvae to complete their life-cycle and produce eggs that contaminate the pasture. These horses are a reservoir for contaminating the environment, harboring large numbers of hypobiotic larvae that repopulate the GI lumen when adults are removed by deworming. Both moxidectin and “larvicidal dose” fenbendazole (10 mg/kg for 5 days) have larvicidal activity against encysted small strongyles, making these agents especially useful in managing individuals that are highly permissive to strongyle infections.^117-119 However, it is important to recognize that neither moxidectin nor larvicidal dose regimens of fenbendazole are 100% efficacious. A report of small strongyle resistance to larvicidal fenbendazole doses in Kentucky yearlings should prompt caution in the use of such protocols because they exert extreme resistance pressure.¹²⁰

Table 49-1 Efficacy of Various Anthelmintics Against Strongyles in Horses

A cornerstone of every deworming program is to identify anthelmintic resistance. Anthelmintic resistance is of tremendous concern in small strongyles, in which resistance to all commonly used anthelmintics, with the exception of the macrocyclic lactones, has been identified.⁶ Shortening of the ERP is an important indicator of anthelmintic resistance in the horse.¹²¹ However, the gold standard for detecting resistance has been the FEC reduction test (FECRT). FEC reduction (FECR) is determined by comparing FEC before and 10 to 14 days after anthelmintic administration. The percentage of reduction is calculated using the following formula:

The FECRT has several problems. First, the action levels to identify anthelmintic resistance have not been determined for equine parasites, so values are extrapolated from other species. Second, the FECRT is relatively insensitive, meaning that when anthelmintic resistance is identifiable by FECRT, resistance genes are widely disseminated within the parasite population. At this time egg reductions in excess of 90% are considered evidence of BZD and tetrahydropyrimidine efficacy. Values of 80% to 90% raise suspicion of resistance, and FECRs less than 80% indicate that resistance is present. In the case of the macrocyclic lactones ivermectin and moxidectin, egg reductions less than 98% are cause for concern.^6,122

The primary concern with new additions to the herd is their ability to introduce resistant strongyles to a previously sensitive population.⁶ In this respect it is especially important that farms without anthelmintic resistance take precautions to prevent the introduction of resistant strongyles. FECRT should be performed in conjunction with the initial dewormings, and larvicidal treatment regimens should be selected to kill encysted parasites, which might bear resistance genes. Both moxidectin and larvicidal regimens of fenbendazole may be used. However, the widespread prevalence of BZD resistance in small strongyles must be considered because larvicidal doses of fenbendazole may be inferior to moxidectin to prevent the introduction of resistant worms in new additions. Accordingly, single-dose administration of a macrocyclic lactone has been advocated for new arrivals after fenbendazole larvicidal regimens to remove remaining luminal worms. New additions should be quarantined until appropriate response to anthelmintic therapy, as supported by a reduction in FECs, is available to substantiate that resistant parasites will not be introduced to the herd. On the other hand, horses staying less than 6 weeks may be efficaciously treated with ivermectin because ivermectin resistance is extremely uncommon and the ERP for ivermectin is 6 to 8 weeks.

PARASITE CONTROL STRATEGIES FOR YOUNG HORSES

S. westeri is the earliest maturing nematode of foals, passing eggs by 10 to 14 days, followed by small strongyle eggs which can be detected at 6 weeks.^3,87-89 However, by virtue of its prevalence, size, fecundity, and pathogenicity in young horses, management of P. equorum is the primary focus of deworming strategies for horses under 18 months of age. Unfortunately, studies to identify treatment thresholds based on FEC, expected ERPs, and FECRT thresholds to identify resistance are not available. Anthelmintic strategies for controlling P. equorum should be expected to change as such data become available. In the absence of these data, current recommendations focus on interval administration designed to prevent egg production, which is known to exert significant anthelmintic resistance pressure in nematodes. Accordingly, it is prudent to document the presence of P. equorum on a premises by examining the feces for characteristic eggs. Four- to 6-month-old foals have been shown to have the highest P. equorum FECs, making them excellent sentinels.¹²³ Parasite control programs in young horses on farms that lack P. equorum should focus on small strongyles.

Several published reports show poor reductions in ascarid FEC after both ivermectin and moxidectin, indicating macrocyclic lactone resistance.^110,123,124 Daily exposure to low doses of pyrantel tartrate and monthly deworming with ivermectin are being scrutinized for their role in perpetuating anthelmintic resistance in equine parasites.^6,122 Daily administration of pyrantel tartrate has been shown to interfere with the development of acquired immunity to small strongyles.¹²⁵ Although the effect of daily pyrantel administration on immunity to ascarids is not known, inhibition of invasion and migration that are characteristic of this therapy could also limit immunity to ascarids. This is especially concerning in horses that have been maintained on daily dewormer and then introduced to heavily contaminated premises. In such horses the lower innate immunity to the parasite could increase morbidity associated with infection.

Monthly deworming with ivermectin has been advocated to decrease lung pathology in young horses caused by ascarid migration. However, ascarid resistance to ivermectin raises concern regarding the selection pressures imposed by monthly ivermectin administration. Accordingly, practitioners should monitor vigilantly for evidence of anthelmintic resistance in young horses where repeated ineffective deworming could yield burdens capable of causing an ascarid impaction on subsequent deworming with an efficacious product. A link between emerging ivermectin resistance in P. equorum populations and surgical ascarid impactions has been postulated.¹²⁶Resistance should be considered a possibility with any anthelmintic agent, particularly when a single drug is used repeatedly. Guidelines for FECRT identification of P. equorum resistance are not available. However, FECR for both BZDs and pyrantel have been shown to reach 100% in ivermectin-resistant P. equorum populations, suggesting that values previously described for small strongyles are reasonable choices.¹²⁴

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BZDs, tetrahydropyrimidines (pyrantel pamoate and pyrantel tartrate), and the macrocyclic lactones (ivermectin and moxidectin) are generally considered efficacious against ascarids. Moxidectin products are not approved for use in foals under 6 months of age. Recognize that doses of BZDs required to effectively kill ascarids are double the doses recommended to kill parasites of adult horses. This highlights the need for accurate weights to ensure proper administration, which is a problem in young horses, in which body weight is often estimated. This problem can be alleviated by use of weight tapes.

Although the timing of the initial anthelmintic treatment is influenced by the environmental load of P. equorum, treatment on endemic farms should begin at 8 to 10 weeks of age, which is the minimal prepatent period after initial exposure.^80,81,127 Recognize that in addition to ascarid control, ivermectin administration should be incorporated at 5-month intervals if large strongyles are present on the farm. One of these treatments should be an ivermectin and praziquantel combination in the fall to kill Gasterophilus and Anoplocephala species. Both BZDs and pyrantel pamoate have a slightly shorter duration of ascarid egg suppression than the macrocyclic lactones because they do not kill migrating ascarids. The treatment interval with these compounds is 56 days, which is the minimum time required for migrating larvae not killed by BZD or pyrantel treatment to reach the intestine and produce eggs. More frequent administration of BZD or pyrantel maximizes resistance pressure without altering egg production unless shortening of the ERP occurs.

Macrocyclic lactones (restricted to ivermectin administration in foals) and larvicidal fenbendazole regimens (10 mg/kg × 5 days) have the advantage of killing all ascarids in the intestine as well as migrating larvae outside of the intestine.^128-129 See Table 49-2. Therefore treatment intervals shorter than 56 days with larvicidal drugs are still efficacious in the control of ascarid infections but maximize resistance pressure. On farms with a high P. equorum burden, ivermectin may be administered as early as 45 days of age. Treatment intervals as short as 30 to 45 days with larvicidal drugs have been recommended by some practitioners on farms with high ascarid loads to minimize lung pathology. These recommendations should be critically evaluated in light of the resistance pressure imposed by the practice. Treatment intervals after administration of larvicidal agents should approximate 70 days because the foal is essentially cleared of all ascarids and begins the cycle of infection anew after treatment. Commonly the recommended ivermectin interval is shortened to 60 days for brevity in communication. Regardless, larvicidal drugs should be followed by retreatment before 70 days, and nonlarvicidal agents require retreatment in 56 days. Treatments are repeated until the horse develops solid acquired immunity as supported by negative ascarid fecal examinations, which generally occurs by 18 months of age. Failure to remain within these intervals risks egg contamination of the pasture that persists for years.

Table 49-2 Anthelmintics Effective Against Ascarids in Horses

Ascarid eggs are extremely resilient, and infection occurs from both pasture and fomites in the stall environment. Emerging anthelmintic resistance in P. equorum highlights the need to institute management practices that prevent ingestion of parasite eggs. Clean pastures (see below) should be provided for young animals and mares with foals. Manure should be removed at least twice weekly from stalls and pasture, before infective larvae can develop. Horses should be fed off of the ground in feeders that can be cleaned. Although ascarid eggs already in the environment cannot be eliminated, washing stall surfaces, especially those that have held foals and weanlings, and bathing the mare including her udder before foaling help to minimize egg contamination.

A word of caution: if high ascarid burdens are suspected based on a prior poor deworming history or high FECs, deworming with highly efficacious anthelmintics is contraindicated because of the risk of ascarid impaction. In such cases young horses should be initially dewormed with an anthelmintic of lower efficacy, such as fenbendazole at a dose of 5 mg/kg, followed in 1 to 2 weeks with proper doses of an anthelmintic known to be efficacious on the premises.

Less Common Equine Parasites

Life-Cycle

Adult female nematodes produce eggs that are passed out of the host with the feces. Under optimal conditions in the external environment, first-stage larvae (L₁) can develop and hatch from eggs within 24 hours. L₁ grow and develop to second-stage larvae (L₂), which in turn grow and develop into third-stage larvae (L₃). In general, the third stage is the infective larval stage. After ingestion, L₃ develop into fourth-stage larvae (L₄), which then develop into immature adults. Sexually mature adult nematodes develop within 2 to 4 weeks after ingestion of the L₃ unless arrested development occurs. The life-cycle of Nematodirus is the same except that development to infective L₃ occurs within the egg before hatching. For Trichuris, development to the infective L₁ occurs in the egg. However, rather than hatching in the external environment, L₁ hatch after ingestion of the eggs by the animal, and approximately 8 weeks are required before sexually mature adults are present.^147,148

Climate and management of pastures and animals are among the numerous factors that influence the level and extent of parasitism. Although temperature is considered to be the driving force behind larval development, larval development can proceed only in the presence of adequate moisture. Larvae of all stages can be killed by extremely low temperatures, desiccation, and/or exposure to direct sunlight. Larval development and transmission tends to occur in predictable seasonal patterns based in part on regional climatic differences.^146,147,149 In the southern United States, infective L₃ persist longest when conditions are cool and wet (October to May) but die off quickly during the summer after rain-induced liberation from the fecal pat.^150,151 Nematodes acquired by grazing cattle during the summer months came from eggs recently deposited on pasture. In the northern United States, infective L₃ may be on pasture year-round. Significant numbers of Cooperia and Nematodirus may be acquired for at least 12 months after deposition of eggs on pasture, with acquisition of fewer numbers for up to 24 months. Acquisition of low levels of Ostertagia can occur for at least 14 months after deposition of eggs. In subtropical climates, seasonality may be much less marked, and pasture infectivity may follow the rainfall pattern. In arid climates, large numbers of larvae may be present on the pasture whenever local conditions permit lush grass growth.^147,152-154

Not only can larvae survive on pasture, but some species can arrest development within the host. This usually occurs during the season when adverse environmental conditions would decrease larval survival in the external environment. Best known for this phenomenon is Ostertagia ostertagi. In northern temperate climates, pasture larval populations peak in the summer and early fall, and L₄ tend to overwinter in the host, resuming development in the spring. In warmer climates with hot, dry summers, the highest numbers of infective larvae may be found in the late spring to early summer, and L₄ tend to oversummer in the host, resuming development in the fall.^147,155,156

Pathophysiology

Of all the cattle nematodes, O. ostertagi has long been considered to be the most pathogenic nematode in temperate regions. The pathophysiology of ostertagiasis centers around the development of larvae in the gastric glands of the abomasum. As the larvae develop within the glands, they cause gland hyperplasia and intense eosinophilic infiltration. Mucosal glandular cells lose their differentiation, and cell junctions are weakened. Albumin is lost into the lumen. Parietal cells cease to function, causing a decrease in HCl production. The change in pH stimulates overproduction of gastrin, which initiates cell proliferation and hyperplasia. Alkalinity also decreases the bactericidal activity of the abomasum, resulting in bacterial overflow from the rumen into the intestine. In addition a pH greater than 5 prevents the conversion of pepsinogen to pepsin. As a result, pepsinogen is released into the blood through permeable cell junctions. Hyperplasia and loss of cell differentiation become widespread and create the typical “Moroccan leather” appearance of the abomasum. In experimental models, Ostertagia infection in calves is associated with elevated peripheral eosinophil counts and decreased lymphocyte counts. Emergence of the larvae may complete the destruction of the glands. If the infection is severe, the proliferated cells and abomasal mucosa may slough, producing a diphtheritic membrane.^149,157

Populations at Risk

Although exposure to some GI nematodes (GINs) readily induces immune responses that limit future populations of nematodes within the gut, cattle remain susceptible to O. ostertagi for many months. Protective immunity is usually not evident without prolonged exposure and may not occur until the animals are 2 years of age or older.¹⁴⁹ Consequently, clinical type I ostertagiasis occurs primarily in young cattle (up to approximately 18 months of age) during their first grazing season, with type II disease present in older animals (2 to 4 years of age). After their initial exposure and induction of immunity, adult cattle rarely show signs of nematode infection or require anthelmintic treatment. Although mature cattle ingest infective larvae, fewer larvae establish infections, so parasite burdens and the magnitude of fecal egg shedding generally are decreased. Most preventive and treatment strategies therefore are directed at young grazing stock, primarily beef calves and dairy replacement heifers.

Clinical Manifestations

In young animals, GINs may simply cause poor growth and ill thrift, or they may cause serious clinical illness and even death. Inappetence, a common feature of parasitic gastroenteritis, can result in reduced weight gain, growth, and onset of puberty.

The synchronous development and maturation of inhibited larval O. ostertagi can result in severe clinical disease, called type II ostertagiasis. Usually seen in cattle 2 to 4 years of age, it occurs months after ingestion of infective larvae. Anorexia, ill thrift, and hypoproteinemia are consistent signs. The animals may also show fever, diarrhea, anemia, and submandibular edema. The prognosis for recovery is guarded owing to the widespread destruction of abomasal glands. Conversely, type I ostertagiasis results from the rapid acquisition of large numbers of larvae that complete development to the adult stage within the usual 3-week time frame. The primary physiologic change is appetite suppression, which accounts for the reduction in weight gains in calves during their first grazing season. Although the underlying mechanism for the two types is the same, the seasonal occurrence of each type varies in accordance with the epidemiologic patterns of the area.^145,146,158

Compounding the effects of O. ostertagi is the presence of other GINs. Larval and adult Haemonchus organisms are blood feeders, producing anemia. T. axei produces local and systemic changes similar to those produced by O. ostertagi, resulting in similar clinical signs. Infection with Oesophagostomum radiatum produces structural and functional changes including anemia, hypoproteinemia, diarrhea, anorexia, and weight loss.^146,159

Control of Gastrointestinal Nematodes

ANTHELMINTICS

Adult Ostertagia and other GINs are susceptible to most of the commonly used anthelmintics. Drugs and doses are listed in Table 49-3. Drug withdrawal times must be considered when selecting anthelmintics for beef cattle and lactating dairy cows, and the manufacturers’ recommendations followed. Eprinomectin and moxidectin, in topical formulations, have no withdrawal period for either meat or milk.

Table 49-3 Efficacy of Various Anthelmintics Against Gastrointestinal Nematodes in Ruminants

The newer macrocyclic lactones are particularly effective against both adult and larval stages of the various GINs in cattle, including inhibited L₄.^160-162 In addition, their residual effect helps minimize pasture infectivity during the grazing season (see later).^163-166 Intraruminal sustained-release devices (SRDs) containing a BZD, levamisole, morantel, or ivermectin can also be highly effective at limiting both clinical disease and pasture infectivity.^167-171 Use of highly efficacious drugs or SRDs can attenuate the immune response to GINs during the first grazing season in calves. However, in most cases immunity is sufficient to prevent clinical disease during the following grazing season, and weight gains by the end of the second season are similar to those of immune animals.^168,169,171

Although the macrocyclic lactones are all highly effective, some differences between products in both efficacy and duration of effect are apparent. Doramectin, eprinomectin, and moxidectin are more effective and/or have a longer residual effect than ivermectin against Ostertagia and Cooperia.^172-178 Doramectin, eprinomectin, and moxidectin have a residual effect against Ostertagia for approximately 5 weeks, whereas ivermectin is effective for only 2 to 3 weeks.^165,178 As the prepatent period for Ostertagia is approximately 3 weeks, the treatment intervals in most management situations are 8 weeks for doramectin, eprinomectin, and moxidectin and 5 to 6 weeks for ivermectin. Duration of effect also varies somewhat with the parasite and the level of infection. Persistence of effect against Cooperia appears to be 1 to 2 weeks shorter than for Ostertagia, regardless of the product used.^{164,165,178-180} The residual effect may be shortened by a week or so at high infection levels.^178,179

Historically, anthelmintic resistance by GINs has been far less of a problem in cattle than in sheep or goats. However, this situation appears to be changing. Reports of anthelmintic-resistant nematodes of cattle are on the increase in the United States and elsewhere around the world.^149,181-187 Resistance has been reported in the most frequently used anthelmintic classes including the BZDs, macrocyclic lactones, and imidazothiazoles. Species of Cooperia are most commonly associated with these reports, although resistant species of Ostertagia and Haemonchus have also been documented.

Treatment Intervals

The choice of drug and treatment interval should be made on the basis of an individual herd or farm, as part of an overall control program. Factors to consider include the geographic location, time of year, and grazing management. Grazing management is discussed elsewhere.¹⁸⁸ There are several options for preventing clinical disease and maximizing gains in first-season grazing calves using strategic anthelmintic treatments:

Two treatments with an avermectin or moxidectin early in the grazing season. The first treatment can be given either at turnout or weaning or 3 weeks into the grazing period. Depending on the product used, the second dose is given 6 weeks (ivermectin) or 8 weeks (doramectin, eprinomectin, moxidectin) later. This strategy can prevent clinical disease, keep FECs low, and increase weight gains during the first grazing season.^189,190 An alternative when using ivermectin in situations in which pasture infectivity is high is to treat calves at 3, 8, and 13 weeks after turnout or weaning.¹⁹¹

Use of an intraruminal SRD, where available, at turnout or weaning. This strategy may be most cost-effective on farms where pasture infectivity is high.

Treatment during peak pasture infectivity (e.g., summer and early autumn in temperate climates). Treatment interval depends on the product being used: every 3 weeks for nonivermectin drugs, every 5 weeks for ivermectin. For example, ivermectin can be given at 10, 15, and 20 weeks after turnout or weaning. This strategy prevents clinical disease in the majority of calves while allowing some level of infection, which stimulates an immune response in first-season calves. However, treatment at the start of the grazing season has been shown to result in better weight gains than tactical treatments given during the grazing season.¹⁶⁷

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“Dose and move” strategy. This strategy consists of treating calves with a single dose of anthelmintic, then moving them to a clean pasture just before the anticipated peak in pasture infectivity (e.g., early to mid summer in temperate climates). This strategy minimizes the number of anthelmintic treatments during the grazing season. However, it is effective only on farms where a clean pasture is available. Furthermore, any residual nematodes left behind will likely possess resistant genes; therefore contamination of the clean pasture will be with resistant nematodes. This must be taken into account when planning for the future use of the pasture (see later).

Integrating effective pasture management can reduce the number of anthelmintic treatments necessary¹⁹²; however, there currently is no realistic alternative to the continued use of available compounds. Therefore it is imperative that the efficacy of these compounds be maintained for as long as possible. Recommendations designed to promote this in cattle include the following: (1) do not treat second-year and adult cattle to maintain a population of unexposed nematodes (refugia) on the farm; (2) do not graze first-year calves on the same pasture each year (avoids exposure to larvae produced from resistant nematodes); and (3) do not use the same family of anthelmintic year after year in calves.¹⁸⁴

The use of complimentary classes of drugs may be necessary in the situation where a producer is not satisfied with the response to treatment. The combination of a macrocyclic lactone with a BZD or levamisole has been shown to be effective against all important nematodes, including anthelmintic-resistant forms. Similar combinations may also be used in feedlots to help provide maximal productivity and enhance response to vaccination programs. However, care must be exercised when using this recommendation because heavy, indiscriminate use of anthelmintics is a strong selector for resistant genotypes and will hasten the development and spread of drug-resistant parasite populations.¹⁴⁹

Adult Cattle

The cattle most at risk for clinical disease and production losses are beef calves and dairy replacement heifers in their first season at pasture. Strategic treatment early in the grazing season is effective in most management situations. Development of immunity should protect the animals during their second and subsequent grazing seasons. Treatment of adult cattle generally is unnecessary, unless immunity is inadequate or pasture infectivity is high. Anthelmintic treatment is most likely to be warranted in first-calf heifers and newly acquired cows that may not have been pastured as heifers. In some situations it may be beneficial to treat beef cows after spring calving.

Clinical Management

Life-Cycle^201,202

The life-cycle of GINs is direct and consists of a host phase and a free-living phase. Worms mate in the host, and females lay eggs that pass in the feces. Eggs hatch and develop to infective larvae while remaining in the fecal mass. Infective larvae then move from the fecal mass onto the surrounding forage, where they can be consumed during grazing, thus completing the cycle. The time from ingestion of infective larvae to egg-laying adults, the prepatent period, is approximately 3 weeks. The time for development from egg to infective larvae can be as short as 4 to 10 days (especially during the summer months); therefore transmission (reinfection) and continual pasture contamination can be rapid. During the colder months, however, development is delayed, and organisms may take up to a month or two to reach the infective larvae stage; therefore pasture contamination and reinfection are minimized. The infective larvae have a protective sheath that makes them relatively resistant to adverse environmental conditions; they can therefore survive for months, thus extending transmission potential. As long as the temperature and moisture conditions remain favorable, development and survival continue; conditions that are too hot, too cold, and/or too dry threaten parasite survival.

Epizootiology^201,202

The life-cycle of GINs has four phases.

Pathophysiology of Gastrointestinal Nematode Parasites

The damage done by H. contortus is the result of the blood sucking by L₄ and adult parasites. The pathogenesis of ostertagiasis in sheep is similar to that described in cattle and is a result of destruction of abomasal mucosa. T. axei causes abomasitis, whereas Trichostrongylus colubriformis penetrates beneath the intestinal mucosa and causes blood loss and enteritis.

Clinical Signs of Gastrointestinal Nematode Parasites

Most animals acquire mixed infections of nematodes. Clinical signs may therefore reflect the effects of more than one species of parasite. There appears to be some synergism between O. circumcincta and T. colubriformis, which makes the effect of the combined infection more severe than that of either alone. Although mixed infections with GINs are assumed, the actual population of parasites in small ruminants will vary depending on the geographic location. In general, the majority of clinical illnesses result from H. contortus infections. Most parasitic infections in small ruminants are associated with altered gut function, anorexia, ill thrift, weight loss, and hypoproteinemia. Diarrhea is a variable sign. Animals may die suddenly without overt clinical signs or may exhibit chronic wasting. Clinical signs of H. contortus infection can vary from peracute to chronic and result from decreased nutrient use and anemia or hypoproteinemia. The most common signs are failure to thrive, weight loss, and decreased appetite. Weakness, bottle jaw, pale mucous membranes, poor capillary refill time, and possibly diarrhea develop with more severe or long-term infections. After sudden exposure to large numbers of infective larvae, animals can die acutely, even before the infection is patent. Other diseases such as pneumonia and heat stress may result secondarily.

Anemic Crisis and Patient Management

The anemia created by H. contortus is due to blood consumed by the parasite and usually is chronic. Parasitized patients presented with lethargy and weight loss often have hematocrits <10%, yet many are still capable of rising and walking. Addressing the anemia by blood transfusion must be weighed carefully against stress to the patient caused by restraint, jugular catheterization, and blood administration as well as by the hemolysis of these same cells several days later. Obviously, in life-threatening circumstances (the patient that is unable to stand), administration of whole blood can be critical. In the noncrisis situation (patient rising and/or eating) treatment with an effective anthelmintic should eliminate the parasite and halt blood loss. Because H. contortus consumes blood, the affected animal actually loses substrates essential to erythrocyte production (iron, cobalt, copper). Providing supplemental iron and B-complex vitamins should speed reversal of the anemia. Assuming blood loss has been halted, a 1- to 1.5-point rise in the hematocrit per day is expected when the bone marrow is maximally stimulated. In most parasitized patients a rise of one half this value is a more realistic expectation.²⁰³

If blood is to be given, it is essential to be certain that the donor has a normal packed cell volume. An animal in the same environment may be as anemic as the patient, but the individual may be more capable of dealing with the anemia. In lambs weighing less than 45 kg, 1 unit of whole blood (approximately 450 mL) is often sufficient to survive a crisis, provided H. contortus has been controlled.

Populations at Risk

Young animals are most susceptible to infection and clinical manifestations of disease. Lambs and kids may become heavily infected with parasites and shed large numbers of nematode eggs. In sheep, some degree of immunity develops as the animal approaches 1 year of age. Adult animals typically have complete immunity against Nematodirus and variable resistance to Trichostrongylus species. Some immunity to Haemonchus and Ostertagia species develops with age; compared with lambs or kids, adults are more resistant to infection with these species. However, even mature animals may succumb to parasitic infection when malnourished or challenged with heavily contaminated pasture. A PPR in fecal egg production is seen in ewes and does.

Goats are more susceptible to GIN infections than are sheep. The difference lies in part in the host’s immunologic responses to nematode antigens. Goats prefer to browse on brush and trees, and they graze grass only when forced to by management. Under natural conditions, goats would have a low level of exposure to infective larvae, and this might explain their lower level of natural immunity compared with sheep.^204,205

Refugia

Biologically, refugia refers to isolated populations of once widespread animal or plant, or in this case parasite, species. Most parasitologists now consider levels of refugia as the single most important factor contributing to selection for anthelmintic-resistant parasites.^206,207 Worms in refugia provide a pool of genes susceptible to anthelmintics, thus diluting the frequency of resistant genes. For many years parasitologists and veterinarians have recommended that all animals should be treated with an anthelmintic at the same time. However, this strategy has proven problematic, and a selective approach is now recommended. Only those animals in danger of severe parasitism should actually receive medication. This selective approach is highly compatible with host-parasite dynamics, as 20% to 30% of animals harbor approximately 80% of the parasites.²⁰⁸ Animals with low worm burdens are an important source of refugia, are not in danger of the negative effects of parasitism, and should not be treated.

Management of Gastrointestinal Nematodes in Small Ruminants

The traditional approaches of deworming often, rotating classes of anthelmintics, and moving to clean pastures have allowed anthelmintic resistance to all classes of drugs to develop and the resistant parasites to disseminate over a wide area. It is obvious that drastic changes in the management of GINs in sheep and goats are long overdue.

Life-Cycle

The life-cycle of D. viviparus is direct, with no intermediate host involved. Adults produce embryonated eggs that hatch shortly after oviposition. L₁ are passed in the feces, where they develop to L₂ and L₃ within a week under optimal environmental conditions. After the infective L₃ are ingested, they migrate through the wall of the intestine to the mesenteric lymph nodes and through lymphatics into the bloodstream and finally arrive, as L₄, in the lung as early as 7 days after ingestion. Larvae may then develop to sexually mature adult worms or they may arrest development as late L₄ or immature adults. Arrested development can prolong the normal prepatent period from 3 to 4 weeks to approximately 5 months.²³⁹

Most problems with cattle lungworms in North America occur in areas of moist climates where larvae on pasture are protected from desiccation and larval migration away from the fecal pat onto herbage is facilitated. Under favorable conditions, infective L₃ can survive on pasture for approximately 11 months.^240,241 These larvae plus the larvae produced from carrier animals harboring small numbers of adults or adults developing from arrested larvae can result in high levels of contamination on spring pastures. In subtropical climates, larvae are virtually absent during the hot summers; larval contamination of the pasture peaks in the autumn as a result of carrier animals.²⁴²

The life-cycle of D. filaria is similar to that of D. viviparus including the ability of the larvae to arrest development. The prepatent period is approximately 26 days, with peak larval output occurring 39 to 57 days postinfection. As with D. viviparus, D. filaria is more prevalent in moist climates and larvae can survive on pasture throughout the winter. Spring pastures contaminated with overwintering larvae and larvae produced from adults developing from arrested larvae in carrier animals are sources of infection for susceptible lambs or kids.^239,243-245

The life-cycle of D. arnfieldi is similar to that of other species of Dictyocaulus except that, in addition to L₁, larvated eggs may be passed with the feces. The prepatent period is 2 months.²⁴⁶

Unlike species of Dictyocaulus, M. capillaris and P. rufescens have indirect life-cycles that involve intermediate molluscan hosts. Adults, occurring in the parenchyma (M. capillaris) or small bronchioles (P. rufescens), produce eggs that develop and hatch. L₁ are passed with the feces; once on pasture, larvae invade the foot of a susceptible species of snail or slug and develop to infective L₃. Sheep and goats become infected when inadvertently ingesting the mollusk while grazing. The larvae penetrate the intestine and migrate to the lung in much the same manner as Dictyocaulus. Early L₄, developing L₄, and adult M. capillaris become embedded within a fibrous nodule within the parenchyma. Protostrongylus larvae mature in the alveoli and enter the bronchioles as adults. The prepatent period is 5 to 6 weeks, although arrested development may prolong the prepatent period of M. capillaris.^239,243-247

Pathophysiology

Although infections with few worms may be inapparent, D. viviparus often results in parasitic pneumonia and bronchitis. The disease process is divided into four phases: penetration, prepatent, patent, and postpatent. In the penetration phase (days 1 to 7), no clinical sign or significant respiratory pathology occurs as the larvae migrate to the lungs. During the prepatent phase (days 7 to 25), clinical signs and lesions become evident. An eosinophilic infiltrate blocks bronchioles; excess mucous production and alveolar collapse occurs. The patent phase (days 25 to 55) is associated with egg-laying adults in the bronchi and trachea. Bronchial and tracheal epithelial damage occurs, air passages are blocked by exudate, and consolidation of lobules results from aspiration of eggs and L₁ into bronchioles and alveoli. Bronchitis, tracheitis and pneumonia follow. During the postpatent phase (after day approximately day 50), surviving animals recover and adult worms die off. Peribronchial fibrosis and epithelialization of alveoli may remain. Secondary bacterial infections resulting from weakened pulmonary defenses may also occur.²³⁹

Goats tend to be more susceptible to infection with D. filaria and more severely affected than sheep, although individual susceptibility to infections does occur. Heavy infections in both species produce bronchitis, pulmonary edema, atelectasis, and emphysema, although death is uncommon.^239,243,244 As with D. viviparus, secondary bacterial infections can occur.

In donkeys, whether D. arnfieldi causes pathologic lesions on its own is controversial because of the presence of other pathologic agents; however, in healthy infected individuals, pathologic changes include discrete circular areas of overinflation surrounding affected bronchi. Histologically these areas contain a small bronchus packed with nematodes. The small airways are often occluded with exudate. Small amounts of mucus surround adult worms in the main bronchi with little cellular reaction. L₁ are surrounded by an intense mucopurulent reaction. In addition to these types of lesions in horses, many immature nematodes are present in smaller bronchi, accompanied by bronchial epithelial hyperplasia with large amounts of mucus and pus. Many areas of alveolar hemorrhage and edema are also present.²⁴⁶

Although morbidity with M. capillaris may be high in most flocks, massive infections with M. capillaris or P. rufescens are not common. Pathologic changes caused by P. rufescens are similar to chronic, low-grade Dictyocaulus infection. Heavy infections with M. capillaris infection in goats can result in interstitial pneumonia, bronchopneumonia, or fibrinous pleuritis. In sheep and goats, distinct subpleural nodules containing adults and L₁ are common. Secondary bacterial infections can also occur.^239,248-251

Populations at Risk

Clinical disease occurs most frequently in pastured calves, lambs, and kids in the first year of life. The disease is also reported in housed cattle, related either to heavily contaminated bedding material or to synchronous maturation of large numbers of hypobiotic larvae. Clinical lungworm infestation is more of a problem in cattle than in sheep, possibly because lambs are treated for GINs more frequently than are calves under most management systems.

Immunity to lungworm infection occurs after first exposure and can develop before the end of the first grazing season. However, it is variable in both degree and duration. In cattle, exposed animals may be immune for 7 to 12 months after infection. In subsequent infections most larvae are either killed before reaching the lung or are inhibited from maturing into adults. Usually the immunity developed during the first grazing season is boosted by exposure in subsequent years and prevents manifestations of disease. However, without reexposure to infective larvae, immunity wanes and disease can occur in adult cattle.²³⁹

Occasionally, outbreaks of acute lungworm disease are seen in adult cattle on pasture whose immunity is overwhelmed by exposure to very large numbers of larvae. This condition is called the reinfection syndrome. Although most ingested larvae are killed or fail to mature, some reach the lung and incite an acute, immune-mediated reaction.

Both sheep and goats develop a strong immunity to D. filaria; disease is more common in young animals. As with cattle, continued immunity in sheep depends on reexposure.^239,252

Individual horse susceptibility to infection with D. arnfieldi is evident. Infections can occur during any time in the life of the horse. Donkeys apparently do not develop an immunity to infection, with larval excretion increasing with age.^246,253

Although immunity to M. capillaris appears to be incomplete (adult nematodes can live for up to 4.5 years), responses to subsequent exposures do limit the numbers of adults that develop and the numbers of larvae shed in the feces. However, reexposure may be cumulative, resulting in older animals harboring larger numbers of worms.²³⁹

Clinical Manifestations

Clinical disease (“husk”) caused by lungworm infection in cattle can occur within 1 or 2 weeks of the introduction of susceptible animals to contaminated pasture. However, clinical disease most often occurs 2 to 4 months into the grazing season. Affected animals develop either an acute or a subacute form of the disease, depending on the number of larvae ingested and the animal’s level of immunity. With acute verminous pneumonia in calves, dyspnea and cough are prominent signs. Auscultation of the lungs initially reveals vesicular murmurs and bronchial tones that progress to moist rales as fluid accumulates. The animal may expectorate froth. Occasionally, emphysema occurs and crackling noises are heard on auscultation. Fever may be as high as 40.5° C (105° F). Mortality rates are high, and animals may die before a patent infection has been established.²³⁹ The similarity between this presentation and that of bacterial pneumonia or shipping fever should be noted.

The subacute or chronic manifestation of disease is more common. In all species the primary signs are coughing, dyspnea, and loss of condition. The animals show elevated respiratory rates but initially are afebrile. Bronchial irritation caused by adult worms and fluid accumulations produces paroxysmal coughing. Animals with the subacute form of lungworm disease are susceptible to bacterial pneumonia. In fact, the subacute form is easily confused with enzootic pneumonia in calves. Signs of reinfection syndrome in adult cattle include severe cough, tachypnea, harsh respiratory sounds, and, for dairy cattle, a sudden drop in milk production approximately 2 weeks after exposure to heavily contaminated pastures.²³⁹

In horses, lungworm infection typically causes a syndrome similar to chronic obstructive pulmonary disease, although asymptomatic infections may also occur. Clinical signs include persistent coughing, nasal discharge, and respiratory distress; death is uncommon. Donkeys, the source of infection in most cases of lungworm disease in horses, tend to remain asymptomatic, although harsh lung sounds may be auscultated.^246,253

Infections with M. capillaris are generally asymptomatic; however, impaired pulmonary gas exchange, reduced weights and breeding performance, and increased mortality have been reported.^248,249,254

Control of Lungworm Infection

Management strategies designed to decrease exposure to infective larvae are most effective in preventing dictyocaulosis. Young animals should not be overstocked or allowed to graze in moist, low-lying pastures. It is often helpful to rotate pastures so that successive calf crops do not graze the same area. Young stock should not be grazed with older, clinically immune animals that may serve as a source of infective larvae. Horses should not be grazed with donkeys. If they are, then donkeys should be monitored for L₁ and treated to reduce larval output and pasture contamination. Limiting contact with intermediate hosts and provision of mollusk-free housing will decrease infections with parasites that require these intermediate hosts.

Evaluation of Preventive Programs

The efficacy of preventive programs is best assessed by evaluating the number of susceptible animals that demonstrate signs of infection. Because total eradication of the parasite is difficult and low numbers of parasites produce minimum problems, a useful goal is the control of clinical signs such as cough and loss of condition. Fecal larval counts are an unreliable means of evaluating the severity of lungworm infection in an individual animal.

Clinical Management

FEC and FEC Reduction Testss_body;^274–276 (Box 49-1)

Determining numbers of nematode eggs in feces is the simplest and least invasive way to evaluate a parasite control program. Fecal examination may be of limited value in an individual animal because animals dying of parasitic infection may have no eggs in the feces, whereas animals with high FECs may be clinically normal. Nevertheless, FECs can provide information on the level of infection present in an individual animal, particularly when egg counts are repeated over the course of 2 to 3 weeks. Herd average FECs are more useful and provide an accurate reflection of the degree of environmental contamination and rate of infection. Pretreatment and posttreatment FECs can also be used to establish the efficacy of an anthelmintic in a particular group of animals. A quantitative McMaster or Stolley technique, rather than simple flotation, is crucial for accurate monitoring.

It is suggested that guidelines published by the World Association for the Advancement of Veterinary Parasitology (WAAVP) be used to perform and evaluate data from an FECRT test, applying practical modifications to fit the situation on the farm.²⁷⁶ Briefly, groups of 15 animals that have not been treated within the past 8 weeks are randomly allocated to treatment groups, and FECs are performed using a modified McMaster technique 10 to 14 days after treatment. An untreated control group must be included. If fewer than 12 to 15 animals per group are available, then treatment groups should be balanced by performing a pretreatment FEC. Animals are then stratified by FEC from highest to lowest, blocked by number of treatment groups, and then within each block are randomly assigned to treatment. Alternatively, where Haemonchus is the primary parasite, animals may be scored using the FAMACHA method as they come through the chute, blocked by FAMACHA score, and then randomly assigned to treatment within blocks. This approach is a bit more complicated but will result in -groups that are balanced, which will result in a more accurate test. Calculations are performed using the following formula:

where Xt and Xc are the arithmetic mean number of eggs per gram (epg) in the treated (t) and untreated control (c) groups, respectively. Software is available for free that performs all calculations and gives data interpretation.²⁷⁷ If the RESO calculator is used, the assignment of resistance status is based both on percent reduction and the 95% confidence intervals. If the RESO calculator is not used, the following guidelines can be applied: reductions of greater than 95% indicate sensitivity, reductions of 90% to 95% indicate low or suspected resistance, and reductions of <90% indicates resistance. FECRT yields reliable data only if FECs are sufficiently high to properly measure a reduction from treatment. If the control group’s mean FECs are below 150 epg, then objective assessment of resistance will not be reliable. Group mean FECs of less than 150 epg can be common in adult sheep; therefore when FECRT is performed on a sheep farm it is preferable to use weaned lambs if available. With goats, low FECs are usually not a problem.

Larval Identification

Ideally, if there is <90% egg count reduction, the eggs should be hatched and the larvae species identified. In the majority of cases these will be H. contortus, but other species, especially Trichostrongylus species, readily develop resistance as well. One can sometimes be fooled into an improper interpretation of egg count reduction results if mixed species are present and only one is resistant.

Egg Hatch Assays and Larval Development Tests²⁷⁶

Eggs from feces are incubated with concentrations of the anthelmintic to be tested, and the eggs hatched. A dose-response curve is generated (DrenchRite test from Horizon Technology).²⁷⁵ The advantage of this test is that a single fecal sample can be tested for all available classes of anthelmintics simultaneously. The cost of this test has recently increased and may discourage owners from pursuing this diagnostic. However, when compared with the cost of using anthelmintics that are ineffective, it is easy to justify the use of this test. It is important to read instructions for submitting this test and scheduling a testing date before the samples are collected.

Larval Culture

Larval cultures can be used to distinguish between large and small strongyles in horses and to identify the various nematode species in ruminants. Most parasitology laboratories can perform this examination. It requires submission of 200 to 400 g of fresh feces. Pooled samples from several herd members are often used.

Pasture Larval Counts

Counts of parasitic larvae on herbage are useful to indicate the level of exposure experienced by the grazing animal. This examination is somewhat tedious but can be performed by many university laboratories. A 2-kg sample of forage is gathered for submission to the laboratory. The grass is sampled by walking a V pattern across the acreage and stopping every three paces to sample grass. The samples are subsequently washed and passed through screening to isolate and identify larvae.

Necropsy Evaluation

The nature and magnitude of parasitic infections can be established by necropsy examination. Gross examination and an estimate of adult worm population in the gut lumen are often sufficient. Many worms detach from the mucosa as the carcass cools; however, the damage done by the parasites can be seen on gross or histologic examination. Occasionally it is necessary to use digestion techniques or histologic examination to document the presence of hypobiotic larvae.

Drug Action

To use an anthelmintic properly, it is necessary to consider its mode of action, spectrum of activity, and duration of effect. Efficacy for a given drug may be defined as its ability to kill adult or larval parasites, suppress parasitic egg production, or promote the expulsion of worms from the GI tract.

Because of the emergence of drug-resistant strains of nematodes, it is difficult to predict how a particular drug will perform in a specific animal or herd. Package inserts should be regarded as guidelines rather than gospel. It is prudent to run periodic pretreatment and posttreatment fecal examinations to assess the performance of commonly used drugs on a given farm. Readers should refer to the sections on horses, cattle, and small ruminants for more specific recommendations.

Avermectins and Milbemycins

The avermectins and milbemycins are macrocyclic lactones. They act by increasing the permeability of parasite cell membranes to chloride ions, which results in nonspastic paralysis and death of the parasite. These drugs may also act by potentiating presynaptic release of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, although this theory has been challenged.

These products have a high level and broad spectrum of activity against adult and larval nematodes. They are also effective against various ectoparasites such as mites, lice, ticks, bots, and cattle grubs; however, they are ineffective against flukes and tapeworms. These drugs suppress nematode egg production for longer than other anthelmintics. Because of its long duration of effect, moxidectin suppresses fecal egg counts and protects against reinfection for longer than ivermectin. Concern has been expressed about the environmental impact of these long-acting anthelmintics in grazing animals.

Several products have been developed for use in animals. The avermectins include ivermectin, abamectin, doramectin, and eprinomectin. The milbemycins include nemadectin and moxidectin. Oral (drench, sustained-release intraruminal device), topical (“pour-on”), and injectable formulations are available, depending on the drug. Ivermectin is safe to use during pregnancy, but currently it is not approved for use in lactating dairy animals or females of breeding age. Similarly, doramectin and moxidectin are not approved for use in female dairy cattle of breeding age. Eprinomectin is unique in that it has no withholding period for milk or meat, so there are no restrictions on its use in cattle. At labeled doses, moxidectin is a safe drug; however, accidental overdosage has caused neurologic signs in foals and miniature horses.

Benzimidazoles

BZDs comprise a large class of anthelmintics that interfere with parasitic carbohydrate metabolism by inhibiting the enzyme fumarate reductase. Many BZDs have been developed and marketed. They include albendazole, fenbendazole, mebendazole, oxfendazole, oxibendazole, parbendazole, ricobendazole, thiabendazole, triclabendazole, and the probenzimidazole drugs febantel and netobimin.

BZDs are widely used in horses and ruminants. In general they exhibit a high degree of safety and a broad spectrum of activity against GINs and lungworms. Some members of this class (e.g., albendazole) are also active against liver flukes and certain cestodes in ruminants. Albendazole and netobimin can cause teratogenicity and embryo toxicity in sheep when given during early pregnancy. Fenbendazole, oxfendazole, and oxibendazole are considered to be safe for use in pregnant animals.

Resistance to BZDs has been documented in certain equine, ovine, and caprine parasites. In general a strain of parasite resistant to one BZD drug quickly develops resistance to other BZDs or pro-BZDs, a phenomenon known as side resistance.

Levamisole

Levamisole acts by causing neuromuscular depolarization and paralysis of the parasite. It has been widely used in ruminants to treat GIN and lungworm infections. However, levamisole resistance has become a problem in many areas.

The dose of levamisole should be calculated carefully because toxic doses are only one to two times therapeutic doses. Signs of toxicity may mimic those of OP toxicity, including muscle fasciculations around the lips and eyelids, hypersalivation, spastic movements, depression, and diarrhea. In ruminants, muzzle foam may develop after oral administration of the drug but usually disappears within a few hours after administration. In horses, transitory excitement has been seen after treatment. Levamisole is not recommended for use as an anthelmintic in horses. Concurrent administration of morantel, pyrantel, diethylcarbamazine, or OPs could enhance the toxic effects of levamisole.

Morantel and Pyrantel

The tetrahydropyrimidines morantel and pyrantel are cholinergic agonists that exert their anthelmintic effect by depolarizing neuromuscular junctions and causing irreversible paralysis of susceptible parasites. Morantel is slower in its onset of action but much more potent than pyrantel. These products are effective against many species of adult nematodes but do not appear to be active against larval stages. Pyrantel is also effective against tapeworms in horses when given at twice the recommended dose. The margin of safety is relatively wide, and there is no contraindication to use with other cholinergic drugs. However, it is recommended that morantel and pyrantel not be used concurrently and that neither be given with levamisole. Piperazine antagonizes the effects of morantel and pyrantel, so it should not be used with either of these drugs. Resistance to morantel and pyrantel has been documented in strains of H. contortus and in some cyathostomes (equine small strongyles).

Organophosphates

OPs block neurotransmission by inhibiting acetylcholinesterase. Various formulations of OP drugs are available for treating GI nematodiasis. Commonly used OPs include haloxon, coumaphos, trichlorfon, and dichlorvos. Toxicity occurs with these products in a dose-related manner, so dosages should be calculated with care. In addition, the potential danger to humans administering these products should not be overlooked. Atropine is recommended in cases of overdose in livestock.

Phenothiazine

The mode of action of phenothiazine (PTH) has not been clarified; it is thought to interfere with anaerobic metabolism of nematodes. The various formulations of PTH differ in purity and particle size. The purified product (99% PTH) with small particle size (2 μm) is the most effective.

Although PTH is effective against a wide spectrum of GINs, resistant strains of parasites have emerged in several species. The drug is synergistic with piperazine; combinations of these drugs have effective activity against PTH-resistant nematodes. PTH used in combination with piperazine can be administered at a much lower dose.

PTH toxicity has been reported. Toxic reactions include corneal inflammation, abortion, ataxia, hemolytic anemia, photosensitization, and nephrotoxicity. The drug should not be administered to debilitated or anemic animals or to animals in the last month of pregnancy.

Piperazine

Piperazine salts block neuromuscular transmission, resulting in paralysis of susceptible GINs. The worms are then passively removed from the GI tract by intestinal peristalsis. Piperazines have low toxicity and are safe in young or pregnant animals. However, their spectrum of activity is limited, in practical terms, to ascarids. Piperazine must be used with caution in horses heavily infested with ascarids because the paralyzed ascarids can cause an impaction that may culminate in bowel rupture. Diethylcarbamazine is a piperazine derivative that has been used to control lungworm infection in sheep and cattle.

Praziquantel

Praziquantel is a cesticidal drug that causes spastic paralysis, decreased glucose uptake, and disruption of the tapeworm’s tegument. Although not approved for this use, praziquantel is effective for treating tapeworm infestation in horses. It has also been used to control various cestodes in small ruminants.

Life-Cycle

Coccidiosis in ruminants is caused by intracellular parasites of the genus Eimeria. Essentially all of the species of Eimeria occurring in ruminants are rigidly host-specific. The life-cycle is complex, involving both sexual and asexual phases within the same host. Single-cell oocysts are passed in the feces and subsequently sporulate in the external environment to become infective. The sporulated oocysts are ingested by the host with contaminated food or water. Digestive enzymes activate the sporozoites within the oocysts, which excyst in the intestine and enter intestinal cells. The asexual phase of development, in which two or more cycles of merogony occurs, is then initiated. Asexual fission results in the production of merozoites. As the meronts mature, they rupture, releasing the merozoites, which enter other cells and repeat the cycle or progress to the sexual phase of development (gamegony). In this phase, merozoites enter new cells and produce macrogametes and microgametes. Microgametes are released by cell rupture and fertilize a macrogamete to form a zygote. A cyst wall then forms around the zygote, resulting in the next generation of oocysts. Once again the host cell ruptures, releasing oocysts into the lumen of the intestine, where they are then passed with the feces. The prepatent period is approximately 2 to 3 weeks and varies with the particular species of Eimeria.^278,279

Pathophysiology

Most intestinal Eimeria organisms develop in the epithelial cells of the lamina propria, although a few exceptions (e.g., Eimeria bovis) do exist. As a result of the developmental cycle, particularly the sexual phase, infected host cells are destroyed. However, the degree of damage depends on the species of Eimeria involved, the number of oocysts ingested, and various host factors including age, physical condition, genetic susceptibility, and immunity from previous exposure.^278,279 If the number of oocysts ingested is low, nonimmune healthy animals may tolerate infection and show no signs of disease. Intestinal cells are destroyed, but because they normally are replaced at a rapid rate the damage done to the gut is minimal. However, if nonimmune animals are exposed to many oocysts, widespread rupture and exfoliation of intestinal cells alters gut function; causes loss of blood, fluid, albumin, and electrolytes into the gut; and allows secondary bacterial invasion. Sections of sloughed intestinal mucosa and fibrin casts may be seen in the feces, and the feces may be blood tinged.

Neurologic signs have been reported during coccidiosis outbreaks caused by Eimeria zuernii in calves and weaned beef cattle.^279,280 The pathophysiology of this manifestation has not been definitively established, and conflicting theories have been proposed, including copper imbalance, plasma electrolyte imbalances, a labile neurotoxin, and a combination of stressors in which coccidia are only one factor.^279,281-283

Populations at Risk

Infections with mixtures of pathogenic and nonpathogenic species of Eimeria occur regularly throughout the life of mature animals; hence they provide the source of oocyst contamination leading to infections in young animals. After an initial period of infection the host acquires species-specific immunity. The degree of immunity acquired depends on the quantity of oocysts ingested and is boosted by continuous exposure to oocysts. It is possible that when exposed to few or moderate numbers of oocysts, a nonprotective immune response may occur; however, initial exposure is generally sufficient and animals are usually protected against clinical disease on reexposure to the same species.^278,279 Clinical coccidiosis is therefore primarily a disease of young, nonimmune animals crowded together in areas such as feedlots, small pastures, shady creek bottoms during hot summer weather, or areas near feed or water tanks or salt licks. Under these conditions the environment is highly contaminated with oocysts from the immune animals, which pose a significant threat to other young, immunologically naive animals in the same areas. Stress, such as from shipping, weaning, dietary changes, and/or adverse weather (e.g., blizzards), appears to facilitate outbreaks.^278,279 Corticosteroid treatment or concurrent illness can also precipitate a peracute form of coccidiosis.

Although outbreaks have been reported in range animals, coccidiosis is chiefly a disease of confinement. Clinical disease usually occurs in cattle less than 1 year of age. In dairy cattle, coccidiosis is most common in calves when they are taken from hutches into group calf pens or mini—free-stall barns. In beef cattle the disease is most prevalent in feedlot calves. In sheep, disease is usually limited to lambs less than 6 months old. Coccidiosis is most common in intensively reared lambs, although suckling lambs on pasture in constant use at high stocking rates are also at risk. Young kids appear particularly susceptible to coccidiosis, with clinical disease especially prevalent 2 to 3 weeks after weaning.²⁸⁴ Previously exposed animals may show clinical signs under conditions of stress and heavy infections. Occasionally, adult animals develop coccidiosis when moved into a new herd and exposed to different species of the parasite to which they are not yet immune.

Clinical Manifestations

The destruction of epithelial cells and subsequent loss of blood, albumin, fluid, and electrolytes typically cause a profuse, sometimes bloody, catarrhalic diarrhea. Dehydration may occur, but most animals continue to drink water and can meet their fluid requirements. Despite the blood loss, anemia is not usually apparent. Typical of infections in dairy cattle, light infections tend to cause watery feces, poor condition, and reduced weight gain. Severe infections cause projectile, bloody diarrhea with mucus, rectal tenesmus, inappetence, dehydration, and weight loss. Clinical signs last approximately 1 week. In lambs, clinical signs are similar to those of cattle except blood and tenesmus do not usually occur. In kids, clinical signs include pasty, watery diarrhea and dehydration.²⁸⁴ Sudden death can occur in both lambs and kids, but the case fatality rate is usually low in most outbreaks. After recovery from the disease the gut does not return to normal function for several weeks, and appetite may be suppressed concurrently, leading to poor growth and/or stunting. Animals that develop “nervous” coccidiosis may exhibit muscle tremors, hyperesthesia, convulsions, nystagmus, and blindness. The mortality rate is high.

Evaluation of Preventive Programs

Oocysts can be found using standard flotation techniques.²⁸⁴ However, the presence or absence of oocysts does not necessarily correlate with the presence of disease. In any given herd or group a baseline level of oocyst shedding is normal. Because immunity is incomplete, many immune animals shed oocysts. On the other hand, nonimmune animals with low-level infections may shed oocysts but have no clinical signs or need for treatment. Furthermore, because intestinal damage occurs during the prepatent period, animals with clinical coccidiosis may not yet be shedding oocysts. This variation complicates both evaluation of preventive measures and the diagnosis of coccidiosis in clinically affected animals. The presence of oocysts in healthy or sick animals does not necessarily indicate the need for anticoccidial treatment.

Nevertheless, microscopic examination of diarrheic or bloody feces from young animals still remains the most direct and cost-effective method of diagnosis.^278,279 Examination of fecal samples from several animals is needed to obtain a true estimate of the presence of coccidia within a group. Because pathogenicity of the various species of Eimeria varies considerably and the clinical picture is not specific, it is imperative that species identifications be determined.²⁷⁷ This information is then combined with a good history and thorough knowledge of the herd management on the farm in question to guide interpretation of clinical observations and diagnostics.

Herds that require preventive strategies have a history of prior disease and a large proportion of herd members shedding high numbers of oocysts. Efficacy is evaluated on the basis of a decreased prevalence of clinically ill animals.

Clinical Management