Ten controlled tests were done between 1972 and 1989, in lambs on pasture, evaluating activity of fenbendazole (FBZ; 5 mg/kg of body weight), oxfendazole (OFZ; 3.5 and 10 mg/kg), oxibendazole (OBZ; 10 mg/kg), pyrantel pamoate (PRT; 25 mg of base/kg), and thiabendazole (TBZ; 44 and 50 mg/kg) against natural infections of helminths, with emphasis on 2 strains (A and B) of Haemonchus contortus. Strain A was phenothiazine-susceptible and strain B was phenothiazine-resistant when isolated in 1955. For approximately 10 years prior to these tests, sheep infected with both strains had been treated periodically each year with several compounds, including thiabendazole, which was used many more times than the other drugs. For this study, 4 (FBZ, OFZ, OBZ, and PRT) of the 5 compounds were evaluated in either 1 or 2 controlled tests. The fifth compound, TBZ, was used for 5 tests. Strain A H contortus was resistant to TBZ for all years tested, but more susceptible to FBZ, OFZ, OBZ, and PRT. Overall, strain B was susceptible to TBZ (with a few exceptions), and also to FBZ, OFZ, OBZ (activity less on immature forms), and PRT. Other abomasal parasites (2 species of Ostertagia and 3 of Trichostrongylus) were found in low numbers, but removal overall was good for the compounds tested. Trichostrongylus axei, found in higher numbers than species of Ostertagia and other species of Trichostrongylus, were effectively removed by all compounds in most cases. Activities of TBZ and PRT were also evaluated against several species of intestinal helminths, most of which were found in low numbers. Cooperia curticei were inconsistently removed by TBZ, but activity of PRT was effective. Both compounds were active on mature Nematodirus spathiger, but TBZ had variable activity on immature forms. Strongyloides papillosus were effectively removed by TBZ. Other parasites found in lower numbers than the aforementioned 3 species were Capillaria spp, Trichuris spp, and Oesophagostomum columbianum; removal was variable for both drugs.

Although cats are less susceptible to infection with Dirofilaria immitis than are dogs, the possibility of severe consequences from infection or adulticidal treatment renders preventive treatment a desirable alternative in endemic areas. To evaluate the efficacy of milbemycin oxime as a chemoprophylactic agent in cats, 48 cats were inoculated with infective D immitis larvae. Single oral treatment with 2.3 mg of milbemycin oxime (0.5 to 0.9 mg/kg of body weight) at 30 or 60 days after inoculation with infective larvae gave strong but incomplete protection. Treatment at 60, as well as 90, days after inoculation with infective larvae was completely effective in preventing development of infection. A control group of inoculated, but untreated, cats was monitored biweekly for hematologic changes and for changes in parasite-specific serum antigen and antibody concentrations. Pronounced increases in total leukocyte counts and eosinophil numbers were associated with the estimated time of in vivo molting from fourth- to fifth-stage larvae. Antibody reactivity correlated with infection status, but serum antigen concentrations through 161 days after inoculation were undetectable.

Tablets containing praziquantel, pyrantel embonate, and febantel were tested for efficacy against helminths in dogs. A single treatment with this drug combination gave 100% reductions in Toxocara canis and Taenia hydatigena in experimentally induced infections in dogs. In dogs with naturally acquired infections, treatment gave > 97 to 98% reductions in fecal egg counts attributable to Toxascaris leonina, T canis, and Uncinaria stenocephala. Efficacy against Trichuris vulpis was > 92%.

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.