Activity of closantel in the prevention of Gasterophilus and Strongylus vulgaris larval infections in equine foals and yearlings

Two controlled tests were conducted in equine foals and yearlings to determine the optimal oral dosage and the duration of activity of closantel for the prevention of Gasterophilus spp larval infections. Additional data were collected on the activity of closantel against Strongylus vulgaris larval infections. In experiment 1, 12 foals and 12 yearlings were equally allocated to 4 experimental groups, and were given oral treatments with closantel at dosages of 0 (nontreated controls), 2, 5, or 8 mg/kg of body weight every 2 months during bot season. The foals and yearlings were allowed to graze on open pasture throughout the experiment to provide a natural source for bot and helminth infections. All animals were euthanatized and necropsied 6 weeks after the final treatment. Closantel was highly effective (98.6% to 100%) at all doses in preventing Gasterophilus spp larval infections in the foals, but only the 8 mg/kg dose had significant (P less than 0.05) activity (99.7%) in the yearlings. This dose also significantly reduced the numbers of 4th-stage and immature adult S vulgaris (86.0%) in the mesenteric arteries as compared with nontreated controls. In experiment 2, 9 foals and 9 yearlings received a single oral treatment of 8 mg of closantel/kg of body weight; 3 foals and 3 yearlings were kept as nontreated controls. Groups of 6 treated (3 foals, 3 yearlings) and 2 control (1 foal, 1 yearling) animals were euthanatized and necropsied 1, 2, and 3 months after treatment. Closantel remained effective for 2 months in preventing infections of G intestinalis larvae in these foals and yearlings. Clinical signs of toxicosis were not observed in the treated animals of either study.     

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.     

Effects of repeated Strongylus vulgaris inoculations and concurrent ivermectin treatments on mesenteric arterial lesions in pony foals

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures greater than 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of antibodies against Sarcocystis neurona in cerebrospinal fluid from clinically normal neonatal foals

OBJECTIVE: To determine whether antibodies against Sarcocystis neurona could be detected in CSF from clinically normal neonatal (2 to 7 days old) and young (2 to 3 months old) foals. DESIGN: Prospective study. ANIMALS: 15 clinically normal neonatal Thoroughbred foals. PROCEDURE: Serum and CSF samples were obtained from foals at 2 to 7 days of age and tested for antibodies against S. neurona by means of western blotting. Serum samples from the mares were also tested for antibodies against S. neurona. Additional CSF and blood samples were obtained from 5 foals between 13 and 41 days after birth and between 62 and 90 days after birth. RESULTS: Antibodies against S. neurona were detected in serum from 13 mares and their foals; antibodies against S. neurona were detected in CSF from 12 of these 13 foals. Degree of immunoreactivity in serum and CSF decreased over time, and antibodies against S. neurona were no longer detected in CSF from 2 foals 83 and 84 days after birth. However, antibodies could still be detected in CSF from the other 3 foals between 62 and 90 days after birth. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that antibodies against S. neurona can be detected in CSF from clinically normal neonatal (2 to 7 days old) foals born to seropositive mares. This suggests that western blotting of CSF cannot be reliably used to diagnose equine protozoal myeloencephalitis in foals < 3 months of age born to seropositive mares.     

Immune responses of pony foals during repeated infections of Strongylus vulgaris and regular ivermectin treatments.

Ten helminth-free pony foals divided into three groups were used in this study. Eight foals were each experimentally infected per os with 50 Strongylus vulgaris infective larvae weekly for 4 weeks, at which time one foal died of acute verminous arteritis. The remaining seven foals subsequently received 50 S. vulgaris infective larvae every 2 weeks for an additional 20 weeks. Four of the infected foals remained untreated (Group 1) and three of the infected foals were given ivermectin at 8, 16 and 24 weeks post initial infection (Group 2). Two foals served as controls (Group 3). Foals in Group 1 developed eosinophilia, which was sustained throughout the course of infection. A mild eosinophilia also developed in Group 2 foals; however, the eosinophil numbers were markedly reduced for 3 weeks after each ivermectin treatment. Only foals in Group 1 developed significant (P less than 0.05) hyperproteinemia, hyperbetaglobulinemia and a reversal of the albumin/globulin (A/G) ratio 4 weeks after initial infection. Significant (P less than 0.05) IgG anti-S. vulgaris ELISA titers developed in foals in Groups 1 and 2 3 weeks after infection and were sustained for the duration of the experiment. Western blot analysis of soluble somatic antigens of S. vulgaris adult female and male worms probed with sera from foals in Groups 1 and 2 revealed only subtle differences between these animals. The blastogenic reactivity of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin and concanavalin A was not significantly different between groups. Peripheral blood mononuclear cells from foals in Groups 1 and 2 developed significant (P less than 0.05) blastogenic reactivity to S. vulgaris soluble adult somatic antigen when examined at 25 weeks after infection. Mesenteric lymph node cells from foals in Group 2, although not statistically significant, were more reactive to antigen than were the mesenteric lymph node cells from foals in Group 1 when examined at 27 weeks after infection. These results suggest that significant alterations in the immune response of ponies to S. vulgaris does not occur after intravascular killing of larvae by ivermectin treatments.     

Microcytosis, hypoferremia, hypoferritemia, and hypertransferrinemia in standardbred foals from birth to 4 months of age

At birth, 24 Standardbred foals were assigned at random to 1 of 2 groups and were given a placebo supplement (group 1) or an iron supplement (248 mg of iron/treatment; group 2). Foals were given iron supplement or placebo 4 times during the second and third weeks after birth. Hematologic variables and general health were monitored until foals were 4 months old. Mean PCV in foals of both groups decreased during the first 2 weeks after birth, but values remained within adult horse reference ranges. During the first 6 weeks after birth, foal erythrocytes were smaller than adult horse erythrocytes, but foal erythrocyte glucose-6-phosphate dehydrogenase activity was greater than that in adult horses. At every measurement, indices of anisocytosis were lower in foals, compared with adult horse reference values, suggesting that foals have a homogeneous population of microcytic erythrocytes during early foalhood. In 2-week-old foals of both groups and in 4-week-old placebo-treated foals, mean serum iron concentration was lower than that in adult horses. In foals at birth and during the first 4 months, total iron-binding capacity values were above the adult reference range. In newborn foals, transferrin saturation percentage values decreased to below the reference range in foals from 2 weeks to 4 months after birth. When foals were born, serum ferritin concentration values were above the adult horse reference range, but decreased to within the reference range by the time foals were 1 day old. From 2 through 6 weeks after birth, foal ferritin concentration values were below the adult reference range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of liver copper status of mare and newborn foal on the development of osteochondrotic lesions

REASON FOR PERFORMING STUDY: To elucidate the highly contentious role of copper in the pathogenesis of osteochondrosis. HYPOTHESIS: There would be no relationship between liver copper concentration of mares and foals and incidence of radiographically detectable osteochondrotic lesions in foals and yearlings was tested. METHODS: Liver copper concentration was assessed in biopsies taken within 4 days after birth from both mares and foals and from the same foals at age 5 months. Biopsies were taken in the standing, sedated animal under ultrasonographic guidance. Radiographs were taken of both hocks (lateromedial, dorsoplantar and dorsomedial-plantarolateral oblique views) and stifles (lateromedial and caudolateral-craniomedial oblique views) at ages 5 and 11 months and scored for the presence and severity of osteochondrotic lesions. RESULTS: Copper concentrations in newborn foals were high with a large variation (351 +/- 201 mg/kg DM). They declined until reaching values comparable to those in mature animals at 5 months (20 +/- 8 mg/kg DM; mares: 19 +/- 20 mg/kg DM). Radiographic osteochondrotic lesions decreased in number and severity from 5 to 11 months. This pattern was more predominant in the stifle than in the hock, as has been described previously. CONCLUSIONS: There was no relationship between foal or mare liver copper concentration and osteochondrosis status at either 5 or 11 months. However, osteochondrotic lesions in foals with low-level copper status at birth decreased significantly less in number and severity than those in foals with high-level copper status at birth. POTENTIAL RELEVANCE: It is concluded that copper is not likely to be an important factor in the aetiopathogenesis of osteochondrosis, but this study indicates that there may be a significant effect of high copper status on the natural process of repair of early lesions.     

Maternal antibodies against equine influenza virus in foals and their interference with vaccination.

Foals that were born to mares vaccinated twice a year against influenza had moderate to high haemagglutination-inhibition antibody titers at 24 hours after birth. The foals were vaccinated at six and ten weeks of age, and again at three to five months after birth. Four months after the third vaccination no antibodies against A/H7N7 and A/H3N8 influenza viruses were detected in these foals. Thus, maternal antibodies probably prevented the development of antibodies against equine influenza virus after vaccination. Foals born to the same mares one year later were monitored to determine the rate of decline of maternal antibodies against influenza viruses. Antibody titers of the foals shortly after birth were similar to those of the mares at foaling. The antibodies persisted for three to six months, and their biological half-life was estimated to be approximately 38 days. Two vaccinations of foals against influenza after the maternal antibodies had virtually disappeared resulted in an antibody response in most, but still not all, foals. These findings suggest that foals should not be vaccinated against influenza until maternal antibodies have disappeared.     

Strongylus vulgaris in the tunica media of arteries of ponies and treatment with ivermectin

A preliminary investigation was made into the effect of fourth-stage Strongylus vulgaris larvae sequestered in the tunica media of ileocolic arteries of pony foals treated with ivermectin. The foals had been reared parasite-free, inoculated with infective larvae and given orally a placebo or ivermectin paste. Two foals received subsequently one or two further inoculations with larvae and treatment with ivermectin. Arteriography was used to identify the lesions in the ileocolic artery following inoculation and their regression following treatment. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was highly effective against fourth-stage larvae and those present in the media appeared not to unduly affect the integrity of the ileocolic artery. Increased numbers of larvae were not found in the media of foals receiving repeat inoculations and repeat treatments. Larvae were not found in the media of foals treated with a placebo. The major pathological changes in the arterial wall of all foals were attributed to infection with S. vulgaris and there was no strong tendency for the damaged arteries to return to normal after the S. vulgaris were removed.     

Maturation of insulin and glucose responses to normal feeding in foals

SUMMARY Postprandial insulin and glucose concentrations were measured in 3 Arabian and 3 Thoroughbred foals at 1 day, 1 week, 1 month and 3 months of age. Prefeeding serum Insulin concentrations were similar in foals at 1 day (25.9 ± 5.1 pmol/L), 1 week (32.4 ± 5.8 pmol/L), and 1 month (38.2 + 7.9 pmol/L), but had Increased significantly to 131.0 ± 20.2 pmol/L at 3 months of age (P < 0.05). There was significantly increased serum Insulin secretion after a feed In foals at 3 months of age (P < 0.05) when compared with that at younger ages. Prefeeding serum glucose concentrations ranged from 6.0 ± 0.7 mmol/L at 1 day, to 5.9 ± 0.9 mmol/L at 1 week, 4.9 ± 1.7 mmol/L at 1 month, and 4.4 ± 1.5 mmol/L at 3 months of age. There were lower postprandial glucose concentrations with advancing age. It appeared that there was a period of maturation in pancreatic β-cell function after birth in foals, which reached adult levels by 3 months of age.     

The efficacy of fenbendazole in the control of immature strongyle infections in ponies

The efficacy of fenbendazole against immature stages of Trichonema spp., Strongylus vulgaris and Strongylus edentatus was evaluated. Naturally infected 6 to 12 month old ponies were given single, oral doses of 0, 15, 30 and 60 mg/kg of body weight. A dose response relationship was noted between increasing dose levels and efficiency against larval trichonemes and migrating stages of S. vulgaris and S. edentatus. Dose levels of 30 mg/kg and higher removed 93 per cent of mucosal stages of Trichonema spp., while doses of 60 mg/kg removed 83 per cent and 89 per cent of the migrating larvae of S. vulgaris and S. edentatus respectively.     

Equine verminous arteritis. An arteriographic evaluation of the larvicidal activity of albendazole

Albendazole was an effective larvicidal anthelmintic against the fourth stage Strongylus vulgaris larvae as late as one month post-infection. The drug was administered at a dose rate of 25 mg/kg three times daily for 5 days. Diarrhoea occurred in 3 of 4 foals treated and of these one died during belated intravenous therapy for dehydration. Arteriography allowed for an in vivo assessment of the development and regression of lesions in infected-treated foals compared to the continued development of lesions in infected-untreated foals. The arteriographic findings were confirmed at necropsy.     

Risk of postnatal exposure to Sarcocystis neurona and Neospora hughesi in horses

OBJECTIVE: To estimate risk of exposure and age at first exposure to Sarcocystis neurona and Neospora hughesi and time to maternal antibody decay in foals. ANIMALS: 484 Thoroughbred and Warmblood foals from 4 farms in California. PROCEDURE: Serum was collected before and after colostrum ingestion and at 3-month intervals thereafter. Samples were tested by use of the indirect fluorescent antibody test; cutoff titers were > or = 40 and > or = 160 for S neurona and N hughesi, respectively. RESULTS: Risk of exposure to S neurona and N hughesi during the study were 8.2% and 3.1%, respectively. Annual rate of exposure was 3.1% for S neurona and 1.7% for N hughesi. There was a significant difference in the risk of exposure to S neurona among farms but not in the risk of exposure to N hughesi. Median age at first exposure was 1.2 years for S neurona and 0.8 years for N hughesi. Highest prevalence of antibodies against S neurona and N hughesi was 6% and 2.1 %, respectively, at a mean age of 1.7 and 1.4 years, respectively. Median time to maternal antibody decay was 96 days for S neurona and 91 days for N hughesi. There were no clinical cases of equine protozoal myeloenchaphlitis (EPM). CONCLUSIONS AND CLINICAL RELEVANCE: Exposure to S neurona and N hughesi was low in foals between birth and 2.5 years of age. Maternally acquired antibodies may cause false-positive results for 3 or 4 months after birth, and EPM was a rare clinical disease in horses < or = 2.5 years of age.     

Duration of maternally derived antibodies against equine influenza in newborn foals

Serum antibody concentrations against influenza A-equi-1 virus and A-equi-2 virus were measured in a group of 18 foals from birth to 4 months of age. More than 50% of the foals were seronegative to A-equi-1 virus infection by 4 weeks of age, with titers of less than or equal to 1:16. For A-equi-2 virus, more than 50% of the foals were seronegative by 2 weeks of age, with titers of less than or equal to 1:8. Passively derived antibodies against influenza A-equi-1 virus and A-equi-2 virus in foals obtained from recently vaccinated mares and from mares not vaccinated within 6 months before foaling were low in titer. The duration of passively derived antibodies was also short-lived.     

Changes in liver copper concentration of thoroughbred foals from birth to 160 days of age and the effect of prenatal copper supplementation of their dams

OBJECTIVES: To monitor the change in liver copper concentration of Thoroughbred foals from birth to 160 days of age and to determine the effects of supplementation by two injections of copper edetate given to dams in late gestation on the liver copper concentration of their foals at birth. PROCEDURE: Ten mares pregnant to the same stallion were randomised into two groups on the basis of age, liver copper concentration and expected foaling date. The treatment group mares were given 100 mg and 250 mg copper edetate intramuscularly during the ninth and tenth months of gestation respectively. Foals had liver biopsies taken weekly in the first month of life, then monthly for four months. Foals were euthanased at 160 days of age; liver samples were taken and the copper concentrations were determined. RESULTS: Two distinct patterns of age dependent decline in liver copper concentration were evident. The mean (+/- SD) liver copper concentration of the foals was high at birth (374 +/- 130 mg/kg DM), and for seven it declined to adult values by 160 days of age (21 +/- 6 mg/kg DM). In three foals the decline was at a slower rate than in the other seven and at 160 days of age the mean concentration was 162 +/- 32 mg/kg DM. Repeated measures analysis showed significant differences between each biopsy (P < 0.01) and between 'normal' and 'accumulator' foals (P < 0.002). Copper injections given to mares in late pregnancy had no effect on the liver copper concentration of foals at birth. CONCLUSIONS: The significance of the two patterns of age dependant decline in liver copper concentration is unknown. Parenteral copper supplementation of the dam in late gestation had no effect on the liver copper concentration of the foal at birth.     

Efficacy of ivermectin in injectable and oral paste formulations against eight-week-old Strongylus vulgaris larvae in ponies

A controlled test method was used to evaluate the efficacy of injectable micelle and oral paste formulations of ivermectin (22,23-dihydroavermectin B1) against 8-week-old Strongylus vulgaris larvae in experimentally infected pony foals. The dosage level of the drug in both formulations tested was 0.2 mg/kg. Ponies were euthanatized and necropsied 5 weeks after treatment. Based on the recovery of live vs dead S vulgaris from mesenteric arteries, both formulations were greater than 99% effective. Increased weight gains and marked reductions in the severity of arterial lesions were observed in treated ponies.     

Intravascular plasma disposition and salivary secretion of closantel and rafoxanide in sheep

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(alpha)) of <30 min), long elimination half-life (t1/2(beta)) of 17.0 +/- 4.0 days for closantel and 7.2 +/- 0.6 days for rafoxanide), small apparent volume of distribution (V(SS) of <0.15 l/kg) and a slow rate of total body clearance (Cl of <0.01 ml/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(beta) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(alpha)), whereas the parameters of elimination (k10, t1/2(beta) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04 +/- 0.05 microg/mL) and rafoxanide (mean of 0.07 +/- 0.04 microg/mL) was observed during the 24-h examination period after dosing.     

Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.

Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.     

Studies on Haemonchus contortus. XII. Effect of Trichostrongylus axei in Dorper lambs on natural pasture lightly infested with H. contortus

Weaned Dorper lambs on natural pasture were predosed with 40 000 infective larvae (L3) of Trichostrongylus axei, irradiated (0,3 kGy) L3 of T. axei or closantel at 10 mg/kg either in September or November 1978 and were compared with Merino yearlings predosed with 40 000 L3 of T. axei in November 1977. The following summer (December-March) only 178,6 mm of rain fell and very few H. contortus were present on pastures. Artificial challenge with 20 000 L3 of Haemonchus contortus with the local strain from the University of Pretoria's experimental farm was given 6-7 months after predosing with T. axei. When compared with the controls, significant reductions occurred only in Group 11 (T. axei irradiated at 0,3 kGy on Day +63) (P = 0,025); Group 2 (T. axei on Day 0) (P = 0,003) and Group 4 (T. axei and closantel on Day 0) (P = 0,049). We concluded that predosing with T. axei was unsuccessful in Dorpers and Merinos artificially challenged 6-7 months later with H. contortus.     

Flukicidal action of closantel against immature and mature Fasciola hepatica in experimentally infected rats and sheep

The relative importance of peak level- and residual level-related flukicidal activity of closantel against immature and mature Fasciola hepatica was evaluated in a comparative efficacy trial using two animal species with a different plasma elimination pattern, that is, the rat and the sheep with an elimination half-life of less than one week and of two to three weeks, respectively. The rats were dosed orally with closantel at 20 mg kg-1 at two, four, six, eight and 10 weeks; the sheep at 10 mg kg-1 at eight, 10 and 12 weeks after artificial infection. Necropsy was performed either one week after treatment or 12 weeks after infection. Efficacy rates and the length of the recovered flukes were evaluated. It was demonstrated that the flukicidal effect of closantel is directly related to its peak plasma levels and less to its residual plasma concentrations. In the rat, a high efficacy (P less than 0.001) could be demonstrated against immature stages of four weeks or older. The two-week immature stages were less markedly affected. No significant differences in efficacy and size of the flukes were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection. In the sheep, the efficacy against six-week and eight-week-old immature stages varied between 70.3 and 76.8 per cent and between 92.8 and 96.5 per cent, respectively. As in the rats, no marked differences in efficacy were noted between the animals autopsied one week after treatment and those autopsied 12 weeks after infection.(ABSTRACT TRUNCATED AT 250 WORDS)