The efficacy of a beef-based, chewable formulation of ivermectin against a mixed infection of Ancylostoma braziliense and A tubaeforme was determined in cats. Ivermectin administered orally at approximately 24 microgram/kg of body weight was 92.8% effective against adult A braziliense and 90.7% effective against adult A tubaeforme. The number of eggs per gram of feces had decreased 98.1% by 7 days after treatment. Clinical signs of hookworm disease also decreased after treatment. Location of adult parasites within the small intestine, percentage of infecting larvae that developed to the adult stage, and egg size in cats with infections of A braziliense and A tubaeforme were similar to those reported for cats with separate infections of either species.

The anthelmintic efficacy of ivermectin (IVM) delivered from a sustained-release (SR) bolus was evaluated against natural infections with gastrointestinal tract nematodes in 12 crossbred beef heifers in spring. The 12 calves were randomly allotted to 2 groups of 6 calves each. Group-1 calves were treated with an SR bolus designed to deliver 8 mg of ivermectin/d. Group-2 calves were nontreated controls. Cattle groups were kept in separate concrete-floored pens (grass hay nutrition) and slaughter was performed at 35 days after treatment. Fecal egg counts for group-1 calves remained zero after treatment, except for detection of < 1 egg/g of feces in 1 calf at the time of slaughter; counts in nontreated calves increased. Mean and range of Ostertagia ostertagi inhibited larvae in nontreated calves were 27,093 and 10,622 to 56,368, respectively. Efficacy of the IVM SR bolus was 100% against O ostertagi developing fourth-stage larvae (L4) and inhibited early L4, Haemonchus placei adults, Cooperia punctata and C spatulata adult males, Cooperia spp adult females, Cooperia spp L4, Trichostrongylus colubriformis adults, Bunostomum phlebotomum adults, and Oesophagostomum radiatum adults. Efficacy for O ostertagi and T axei adults was 99.9%. Numbers of nontreated calves infected with C pectinata adult males and Oes radiatum L4 were too low to evaluate efficacy. Calves treated with the IVM bolus gained 10.2 kg, whereas nontreated calves lost 1.8 kg. Abomasal lesions were dearly greater in nontreated calves on the basis of index comparisons of abomasal weight and total live weight and gross pathologic features.

We examined the efficacy of ivermectin in the control of ear mites (Psoroptes cuniculi) in rabbits. The study involved 40 female and 35 male rabbits that were known to be naturally infested with ear mites. After a period of acclimation to the animal care facilities, the rabbits were ranked on the visual appearance of any ear lesion and the number of mites on glycerin-dipped ear swabs. The rabbits were then randomly assigned to 1 of 4 treatment groups; vehicle only (group 1), 50 micrograms of ivermectin/kg of body weight (group 2), 100 micrograms of ivermectin/kg (group 3) and 200 micrograms of ivermectin/kg (group 4). The rabbits were treated by SC injections on day 0 and day 14 of the trial; thus, the total dose of ivermectin given to groups 1 through 4, was 0, 100, 200, or 400 micrograms/kg, respectively. The study ended 2 weeks after the last treatment. Ear lesions of the treated rabbits improved significantly (P < 0.001). By 28 days after the first treatment, the mean number of mites on the ear swabs (both ears) was 57.5 for untreated rabbits and 9.1, 0.5, and 2.5, respectively, for rabbits in groups 2, 3, and 4. The mean number of mites recovered from the ears of the untreated rabbits at necropsy was 24,297. For groups 2, 3, and 4, the mean number of mites recovered from the ears was 5,352, 96, and 96, respectively. The efficacy of treatment with a total dose of 100 micrograms/kg was 77.96%, with 200 micrograms/kg was 99.61%, and for 400 micrograms/kg was 99.61%.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxacaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 X that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

In 2 trials, the efficacy of an in-feed preparation of ivermectin was evaluated in 40 pigs naturally infected with endoparasites and Sarcoptes scabiei var suis. Treated pigs (n = 10 in each trial) were fed a ration containing 2 ppm ivermectin for 7 days, followed by consumption of a nonmedicated ration for the remainder of the trial. Control pigs (n = 10 in each trial) were fed a complete, nonmedicated ration for the duration of the trial. Pigs in trial A were monitored for 14 days after treatment; those in trial B were monitored for 35 days after treatment. In trial A, treatment efficacy of ivermectin was 100% against Ascaris suum, Physocephalus sexalatus, Oesophagostomum dentatum, O brevicaudum, Metastrongylus spp; 99.8% against Ascarops strongylina; 90.9% against Trichuris suis; and 13.1% against Macracanthorhynchus hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were observed between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Oesophagostomum spp. On posttreatment day 14, S scabiei were not found in any scrapings taken from treated pigs, but were found in scrapings from 3 of 10 control pigs. The number of infested pigs in the treatment group was not statistically different from the number of infested pigs in the control group. In trial B, treatment efficacy was 100% for A suum and Metastrongylus spp; 96.9% for Ascarops strongylina; and 76.9% for M hirudinaceus. At the terminus of the trial, statistically significant (P < 0.05) differences were evident between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Metastrongylus spp. On posttreatment days 7, 2 1, and 35, S scabiei were not found in scrapings taken from treated pigs. On posttreatment days 7, 2 1, and 35, S scabiei were found in scrapings from 8, 6, and 1 pig, respectively, whereas live mites were not found on scrapings taken from treated pigs on these days. Statistically significant (P < 0.05) differences were evident between the numbers of infested pigs in the treated and control groups on days 7 and 21. Ivermectin fed to swine ad libitum in a complete ration at 2 ppm was shown to be highly effective as an anthelmintic and acaricide.

A study for about a 30-month period was done to compare strongyle control programs, using per os treatments of ivermectin (IVE) paste exclusively or alternation of 4 antiparasitic paste compounds: IVE, oxfendazole (OFZ), oxibendazole (OBZ), or pyrantel pamoate (PRT). Every 8 weeks, 1 group of horses (barn C; n = 14 to 16) was given IVE paste exclusively, and a second group (barn E; n = 16) was given the 4 antiparasitic pastes on an alternating schedule. Worm eggs and larvae per gram of feces (epg and lpg, respectively) values were determined every 2 weeks during the investigation. This study in grazing horses (mares and fillies), naturally infected with internal parasites, was conducted during the period between Oct 22, 1987 and Feb 8, 1990, with an additional observation on Mar 28, 1990. For barn-C horses, treated exclusively with IVE (200 micrograms/kg of body weight) 14 times, 2-week posttreatment mean strongyle epg and lpg (small strongyle) values were reduced 99 to 100%. Mean strongyle epg and lpg (small strongyle) values for each 2-week sample period remained low (< 20) throughout the study period, except for 1 moderate transient increase in July 1988. For the entire study period, the aggregate mean strongyle epg value was 12 and the lpg value was 6. Two-week posttreatment mean strongyle epg and lpg (small strongyle) values for barn-E horses, treated alternately with therapeutic (approx) dosage of IVE (200 micrograms/kg, 4 times), OFZ (10 mg/kg; 5 times), OBZ (10 mg/kg; 4 times), or PRT (6.6 mg base/kg; 2 times), varied within and between compounds. Posttreatment (2-week) mean epg values were reduced 100% by IVE, 0 to 100% by OFZ, 74 to 100% by OBZ, and 92 to 100% by PRT. Mean small strongyle lpg values at 2 weeks after treatment indicated reduction of: 100% for IVE, 0 to 76% for OFZ, 43 to 100% for OBZ, and 97 to 100% for PRT. For the entire study period, the aggregate mean strongyle epg value was 54 and the lpg value was 64. The epg and lpg reduction values for the 2 benzimidazoles indicated an increase in the benzimidazole-resistant segment of small strongyles. Fecal cultures for horses in both groups contained larvae of large strongyles (Strongylus vulgaris and S edentatus) only at the time of initial treatment. Treatment program evaluations included necropsy of 9 foals (56 to 203 days old), 7 born to barn-C mares and 2 born to barn-E mares. Generally, low numbers of bots (Gasterophilus intestinalis) and Habronema muscae were found in foals of both groups. Intestinal stages of immature and mature ascarids (Parascaris equorum) were also found in foals born to both groups of mares. Mature pinworms (Oxyuris equi) were found in 1 barn-C foal. Only barn-E foals had Strongyloides westeri. Small strongyles were detected in foals of both groups, up to several thousand in some. The latter finding indicates, in particular, that although barn-C mares had low small strongyle epg and lpg values throughout the study, eggs and larvae built up on pasture in sufficiently high numbers for major transmission to foals born there. Small strongyles in foals were composed of 3 genera and 10 species for barn-C foals and of 3 genera and 8 species for barn-E foals. Seasonal transmission of parasites also was observed.

Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and P. charlesii, is a new anthelmintic with potential broad-spectrum use. In initial trials, it had an excellent safety profile in cattle and sheep at doses efficacious against a dozen or more helminths, but recently it produced unexpected and severe toxicosis in dogs at doses far below those that were safe in the ruminants. To provide data on which to build rational safety tests in the future, we tested the acute toxicity of paraherquamide administered PO to male CD-1 mice and compared its profile with the most potent anthelmintic known, ivermectin. The estimated doses lethal to 50% of a group of mice were 14.9 and 29.5 mg/kg of body weight for paraherquamide and ivermectin, respectively. The no-effect doses were 5.6 and 18.0 mg/kg for paraherquamide and ivermectin, respectively. Signs of intoxication in paraherquamide-treated mice, if they developed, emanated within 30 minutes of administration, irrespective of dose, and consisted of either mild depression with complete recovery or a 5- to 10-minute period of breathing difficulty followed by respiratory failure and death by 1 hour after treatment. Gross necropsy findings in paraherquamide-treated mice that died in the high-dose group were normal. Ivermectin-related toxicity was slower and more predictable, taking place over a 3-day period, with dose-dependent signs of intoxication consisting of tremors, ataxia, recumbency, coma, and death. Necropsy of ivermectin-treated mice that died in the high-dose group revealed dehydration, a condition most likely resulting from the coma-induced state. These observations are congruent with clinical data from dog studies and suggest that if broad-spectrum use of ivermectin (expected to be approx 0.2 mg/kg) is unlikely because of idiosyncratic toxic effects in certain dogs, then use of a compound for dogs with an acute safety factor half of ivermectin, such as paraherquamide, would be even more unlikely. These data are also coupled with observations from anthelmintic trials to suggest that ivermectin possesses a substantially greater therapeutic index than does paraherquamide as a broad-spectrum antiparasiticide for ruminants. Although paraherquamide has a lesser therapeutic index, a strategic use for it as an anthelmintic against ruminant parasites that have become resistant to any or all of the other modern broad-spectrum anthelmintics can be suggested.