EXAMINATION OF THE ACTIVITIES OF 43 CHEMOTHERAPEUTIC-AGENTS AGAINST NEOSPORA-CANINUM TACHYZOITES IN CULTURED-CELLS

Neospora caninum causes serious disease in dogs, and it, or a similar parasite, is a major cause of abortion in cattle. Little is known abou t the susceptibility of this protozoan to antimicrobial agents. We stu died several antimicrobial agents to determine which classes might hav e activity against this parasite. We also determined whether activity of such agents was coccidiocidal or coccidiostatic. A 2-day of treatme nt, monoclonal antibody-based enzyme immunoassay and a 5-day of treatm ent, cell culture flask (CCF), lesion-based assay were developed to ex amine the ability of test gents to inhibit tachyzoite multiplication. Seven sulfonamides were examined, with the following activities observ ed: sulfathiazole greater than or equal to sulfamethoxazole > sulfadia zine > sulfaquinoxaline > sulfamethazine > sulfadimethoxine > sulfamer azine. Dapsone, a sulfone, had little activity. Six dihydrofolate redu ctase/thymidylate synthase inhibitors were examined, with the followin g activities observed: piritrexim > pyrimethamine > ormetoprim > trime thoprim = diaveridine > methotrexate. Six ionophorous antibiotics were examined; lasalocid, maduramicin, monensin, narasin, and salinomycin had equivalent activities, but alborixin was toxic for host cells at t he lowest concentration examined. Three macrolide antibiotics-azithrom ycin, clarithromycin, and erythromycin-were examined and had equivalen t activities. Two tetracycline antibiotics, doxycycline and minocyclin e, were examined and had equivalent activities. Three lincosamide anti biotics were examined, with the following activities observed: clindam ycin hydrochloride > clindamycin phosphate > lincomycin hydrochloride. Pentamidine and 6 of its analogs were examined, and only hexamidine a nd 1,4-Di[4-(2-imidazolinyl)-2-methoxyphenoxy]butane had activity. Eig ht miscellaneous antiprotozoal agents were examined for activity. Ampr olium, metronidazole, paromomycin, and roxarsone had little activity. Arprinocid, diclazuril, nitrofurazone, and robenidine had good activit y. Eleven agents were examined in both assays, whereas 32 agents were examined in the CCF assay only. The enzyme immunoassay and CCF assay p rovided similar results for agents that rapidly killed tachyzoites. Ho wever, agents that inhibited development, but were not rapidly fatal f or tachyzoites, had better activity in the CCF assay. Of the classes o f agents examined, the dihydrofolate reductase/thymidylate synthase in hibitors, 2 of the 6 pentamidine analogs, and the ionophores were cocc idiocidal and the sulfonamides, macrolides, tetracyclines, and lincosa mides were coccidiostatic. Of the miscellaneous agents examined, arpri nocid, nitrofurazone, and robenidine were coccidiocidal and diclazuril was coccidiostatic.