Histopathologic features of canine heartworm microfilarial infection after treatment with ivermectin.

Tissues of dogs treated with ivermectin were examined microscopically to learn the fate of microfilariae of canine heartworm that disappear from the peripheral circulation within a few days of treatment. Medicated dogs were killed 18 hours, 3 days, and 6 days after treatment with 0.5 mg of ivermectin/kg of body weight subcutaneously. Ivermectin was dissolved in 60% propylene glycol and 40% glycerol formal. In dogs killed at posttreatment hour 18, the peripheral microfilaremia had decreased by an average of 89%. At this time, a dense mass of RBC, WBC, and macrophages plus many microfilariae was found in pulmonary alveolar septae. Similar reactions were seen in liver, kidney, and spleen. Phagocytosis of microfilarial fragments was evident. In dogs killed at posttreatment day 3, many microfilariae were fragmented and phagocytosis of the fragments was common. In dogs killed at posttreatment day 6, microgranulomas were common, particularly in such vascular organs as lungs, kidney, and liver. Microgranulomas containing microfilariae were also seen in spleen, skeletal and cardiac muscles, diaphragm, lymph nodes, gastrointestinal tract, and pancreas. Small glial nodules were seen in the CNS. Denudation of the atrial epicardium was associated with fragments of microfilariae and granulomatous inflammatory cells. Renal epithelial crescents were observed in treated and nontreated dogs. Plasma cells were conspicuous in treated and nontreated dogs, especially in some livers and kidneys. Before treatment, all dogs were severely microfilaremic. At the end of the experiment, the peripheral microfilaremia was reduced by 98%.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of arprinocid on the reproductive potential of a field isolate of Eimeria tenella.

Oocyst production by an isolate of Eimeria tenella propagated from birds medicated with 50 ppm arprinocid was compared with that of the same isolate propagated from unmedicated birds. Statistically significant (P less than 0.05) reductions in oocyst production were found for the drug-exposed isolate for inocula levels of 64 and 250 sporulated oocysts per bird. Numerical reductions were observed for inocula levels of 1,000 oocysts per bird, but with higher levels of inocula, no differences were seen. Inhibitory drug effects for the inocula levels of 64 and 250 oocysts per bird appear to be meaningful because they coincide with the maximum reproductive potential (oocysts produced per oocyst inoculated). The results indicated that significant information can be masked by excessive inoculum with consequent crowding and reduction in reproductive potential.

Effects of arprinocid on developmental stages of Eimeria tenella.

Restricted medication experiments were done to correlate time of arprinocid medication with developmental stages of the life cycle of Eimeria tenella. By the criterion of histopathology and using a massive inoculum (10(6) sporulated oocysts), 50 ppm was partially active and 70 ppm was fully active against the first asexual generation when medication was delayed until day 1. When medication was delayed until day 2, full activity was demonstrated against the late, first asexual generation. When medication was delayed until day 3, definite but less complete activity was shown against the late, second asexual generation. Using the conventional efficacy parameters and with an inoculum of 5 X 10(4), full activity occurred with 50 ppm when medication was started up to day 2. Essentially full activity was observed with 60 ppm started at day 3. The combined results of the two tests are interpreted to indicate high activity against both the first and second asexual generations. Medication with 70 ppm changed the wall-forming bodies of the macrogamete. They were indistinct and less intensely eosinophilic than controls.

Battery efficacy studies with arprinocid against field strains of Coccidia.

Graded levels of 9-[2-chloro-6-fluorophenyl)methyl]-9H-purin-6-amine (arprinocid) ranging from 30 ppm to 90 ppm in the diet have been tested for anticoccidial efficacy in controlled battery experiments against 20 field isolates of coccidia. These isolates, representing five major species of Eimeria, were collected from various geographic locations and all but one were found to be resistant to one or more of the currently marketed products. Arprinocid prevented mortality, increased weight gains, and reduced or eliminated intestinal lesions and oocyst production. A level of 60 ppm arprinocid provided adequate control of all isolates and no evidence of cross resistance was observed between arprinocid and the marketed products tested. On the basis of these studies, it is concluded that arprinocid at levels of 60 ppm to 70 ppm is effective in controlling coccidiosis in broilers, even that caused by isolates refractory to many of the marketed products.

Anticoccidial and tolerance studies in the chicken with two 6-amino-9-(substituted benzyl)purines.

Initial assays of 6-amino-9-(2-chloro-6-fluorobenzyl) purine (MK-302) and 6-amino-9-(2,6-dichlorobenzyl)purine (coded L-628,914) showed potential as anticoccidial agents on the basis of broad-spectrum activity and safety. In battery efficacy studies, dietary levels of 60 to 70 p.p.m. and above MK-302 and 45 to 60 p.p.m. L-628,914 proved to have excellent broad-spectrum anticoccidial activity in chickens given heavy exposure to virulent field isolates of coccidia. Eight-week floor-pen tolerance trials showed that the maximum tolerated diet concentration (MTC) of MK-302 was approximately 95 p.p.m. while the MTC of L-628,914 was approximately 60 p.p.m. Dietary relationships (p.p.m. MK-302:p.p.m. L-628,914 for equivalent effects) derived from the efficacy and tolerance results were 1.2:1 and 1.6:1 respectively and clearly demonstrated a higher therapeutic ratio for MK-302.