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Summary

The capability of diclazuril, a benzeneacetonitrile anticoccidial agent, to inhibit development of tachyzoites of Toxoplasma gondii was examined in cultured human foreskin fibroblast cells and in Hsd:ICR mice. Treatment of infected cell cultures with 10.0, 1.0, 0.1 or 0.01 μg of diclazuril/ml for 3 days resulted in > 99% reduction in tachyzoite counts, compared with controls. Treatment with 0.005 μg of diclazuril/ml resulted in > 97% reduction in tachyzoite counts, compared with controls. Treatment of host cells with 10.0, 1.0, 0.1, and 0.01 μg of diclazuril/ml for 24 hours prior to tachyzoite inoculation resulted in 97, 31, 0, and 0% reduction in tachyzoite counts, compared with controls, respectively, 3 days after inoculation. All mice that were treated orally with 10.0 mg of diclazuril/kg of body weight and 80% of mice treated orally with 1.0 mg of diclazuril/kg 1 day prior to and for 10 days after tachyzoite inoculation were protected against acute toxoplasmosis. Mice treated with 10.0 mg of diclazuril/kg did not develop protective immunity, whereas mice treated with 1.0 mg of diclazuril/kg survived challenge exposure.

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association

SUMMARY

The ultrastructure of Isospora suis sporozoites, type-1 meronts, and type-1 merozoites was examined, using transmission electron microscopy of infected cultured cells. The ultrastructure of sporozoites and type-1 merozoites was similar. Each possessed trimembranous pellicles, subpellicular microtubules, a conoid, anterior and posterior polar rings, rhoptries, micronemes, a single vesicular nucleus, tubular mitochondria, Golgi complexes, ribo-somes, endoplasmic reticula, inactive micropores, amylopectin bodies, lipid bodies, dense bodies, and crystalloid bodies. Merozoites were produced by endodyogeny. Ultrastructural events associated with merozoite production by type-1 meronts are described.

Free access
in American Journal of Veterinary Research

Summary

Thirty-two mixed-breed male and female cats were blocked by sex, arranged by body weight from greatest to least, and allocated to 4 groups of 8 (4 male, 4 female) cats, using random numbers. Cats in each of 3 groups were treated orally with a 7% suspension formulation of lufenuron at dosage of 15, 30, or 45 mg/kg of body weight. Cats in the fourth group were treated orally with an excipient suspension without lufenuron. Cats were infested with newly emerged, unfed cat fleas (Ctenocephalides felis felis) on days - 7 and — 3 before treatment and at approximately weekly intervals after treatment. Flea eggs were collected from beneath each cat on selected days before and after treatment and placed in an artificial rearing medium. Flea eggs and medium were kept for 35 days in an insectary to determine effects of lufenuron or excipient suspension on emergence of adults of the F1 generation. Lufenuron was 100% effective in inhibiting development of C felis at all dosages for 11 days after treatment. Thereafter, efficacy exceeded 92% in all dosages groups. On day 32, when the study was terminated, efficacy for each of the dosage groups was: 15 mg/kg, 95.2%; 30 mg/ kg, 98.2%; and 45 mg/kg, 99.6%. Adverse reactions or side effects were not observed in cats, regardless of treatment dosage.

Free access
in American Journal of Veterinary Research

Abstract

Objective

To examine the efficacies of combinations of 7 sulfonamides and 5 dihydrofolate reductase/thymidylate synthase (DHFR/TS) inhibitors against tachyzoites of Neospora caninum in cultured cells. Mutant tachyzoites that were resistant to pyrimethamine were produced and examined for resistance to other DHFR/TS inhibitors.

Design and Procedures

After 5 days of treatment, a cell culture flask lesion-based assay was used to determine efficacies of combinations of sulfonamides and DHFR/TS inhibitors against N caninum tachyzoites and to evaluate the sensitivity of pyrimethamine-resistant mutants of N caninum to test agents. Cultured cells that were infected with the appropriate strains of N caninum and treated or not treated (controls) with test agents were examined. Mutations were induced by chemical mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidme or by selection for growth in permissive concentration of pyrimethamine.

Results

Synergism was detected for combinations of pyrimethamine, ormetoprim, trimethoprim, or diaveridine with the sulfonamides. Methotrexate did not have improved efficacy when combined with sulfonamides. Two mutants were produced that were resistant to pyrimethamine. Both mutants were resistant to other DHFR/TS inhibitors. Both mutants remained resistant to pyrimethamine in the absence of continuous exposure to the agent, indicating that the induced resistance was stable. Synergism was detected for combinations of DHFR/TS inhibitors and sulfonamides against these pyrimethamine-resistant mutants.

Conclusions

Combinations of suboptimal concentrations of sulfonamides with suboptimal concentrations of DHFR/TS inhibitors results in improved efficacy of the agents in a cell culture assay. Stable resistance to pyrimethamine can be induced in N caninum tachyzoites by use of chemical mutagenesis or by selection.

Clinical Relevance

In vitro evidence indicated that combination treatment, using sulfonamides and DHFR/TS inhibitors, may be effective in treating neosporosis. (Am J Vet Res 1996;57:68-72)

Free access
in American Journal of Veterinary Research
in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Twenty-four, adult, female Beagles were arranged by body weight from greatest to least and allocated to 2 groups of 12 dogs, using random numbers. Dogs were housed collectively in 2 adjacent metal buildings, each divided into 4 rooms measuring 2.1 × 3.7 m. Each room was paneled and carpeted and had an access door to the outside with a connecting run that measured 2.1 × 9.1 m. Each run had a surface consisting of 5 cm of pea gravel overlaying 5 cm of sand, and was partially covered by an awning that provided shade at its proximal end. For placement in room/run units, dogs in each of the treated and control groups were allotted to 4 subgroups of 3 dogs each. Each subgroup of dogs was placed in a separate room/run unit. Units containing treatment or control subgroups were alternated to avoid placing identically treated subgroups adjacent to each other. Dogs of subgroups A, C, E, and G were treated with lufenuron monthly at a minimal target dosage of 10 mg/kg of body weight; those of subgroups B, D, F, and H were treated with excipient tablets. Dogs were treated on study days 7, 37, 68, and 98. Each dog was infested with 100 newly emerged, unfed, insectary-reared, adult Ctenocephalides felts on each of study days 0 and 2. Thereafter, infestations on all dogs were dependent on continued development of fleas either in the indoor or outdoor environment. Numbers of fleas on each of the treated and control dogs were determined, using a nondestructive counting technique on days 6, 14, 21, 28, 35, 56, 70, 84, 98, 112, and 119. On study day 21 and on each collection day thereafter, numbers of adult fleas recovered from treated dogs were significantly (P < 0.05) fewer than those recovered from control dogs. Proportion reduction of fleas on treated vs control dogs exceeded 90% by study day 35 and 95% by study day 56. Efficacies exceeded 95% on all remaining study days except days 98 (94.4%) and 119 (90%). Results of this study indicate that control of flea populations can be achieved in treated dogs approximately 4 to 5 weeks after initial treatment with lufenuron, and that continued monthly treatments will maintain effective control of flea infestations. Adverse reactions or side effects to treatment with lufenuron were not observed in dogs after treatment at any time throughout the study.

Free access
in American Journal of Veterinary Research

Summary

Neospora caninum causes serious disease in dogs, and it, or a similar parasite, is a major cause of abortion in cattle. Little is known about the susceptibility of this protozoan to antimicrobial agents. We studied several antimicrobial agents to determine which classes might have activity against this parasite. We also determined whether activity of such agents was coccidiocidal or coccidiostatic. A 2-day of treatment, monoclonal antibody-based enzyme immunoassay and a 5-day of treatment, cell culture flask (ccf), lesion-based assay were developed to examine the ability of test agents to inhibit tachyzoite multiplication. Seven sulfonamides were examined, with the following activities observed: sulfathiazole ≥ sulfamethoxazole > sulfadiazine > sulfaquinoxaline ≥ sulfamethazine > sulfadimethoxine > sulfamerazine. Dapsone, a sulfone, had little activity. Six dihydrofolate reductase/thymidylate synthase inhibitors were examined, with the following activities observed: piritrexim > pyrimethamine > ormetoprim > trimethoprim = diaveridine > methotrexate. Six ionophorous antibiotics were examined; lasalocid, maduramicin, monensin, narasin, and salinomycin had equivalent activities, but alborixin was toxic for host cells at the lowest concentration examined. Three macrolide antibiotics—azithromycin, clarithromycin, and erythromycin—were examined and had equivalent activities. Two tetracycline antibiotics, doxycycline and minocycline, were examined and had equivalent activities. Three lincosamide antibiotics were examined, with the following activities observed: clindamycin hydrochloride > clindamycin phosphate > lincomycin hydrochloride. Pentamidine and 6 of its analogs were examined, and only hexamidine and 1,4-Di[4-(2-imidazolinyl)-2-methoxy-phenoxy]butane had activity. Eight miscellaneous antiprotozoal agents were examined for activity. Amprolium, metronidazole, paromomycin, and roxarsone had little activity. Arprinocid, diclazuril, nitrofurazone, and robenidine had good activity. Eleven agents were examined in both assays, whereas 32 agents were examined in the ccf assay only. The enzyme immunoassay and ccf assay provided similar results for agents that rapidly killed tachyzoites. However, agents that inhibited development, but were not rapidly fatal for tachyzoites, had better activity in the ccf assay. Of the classes of agents examined, the dihydrofolate reductase/thymidylate synthase inhibitors, 2 of the 6 pentamidine analogs, and the ionophores were coccidiocidal and the sulfonamides, macrolides, tetracyclines, and lincosamides were coccidiostatic. Of the miscellaneous agents examined, arprinocid, nitrofurazone, and robenidine were coccidiocidal and diclazuril was coccidiostatic.

Free access
in American Journal of Veterinary Research