naphthoquinones and halofuginone

The horse-parasitizing species Babesia equi Laveran, 1901 was redescribed as Theileria equi Mehlhorn, Schein 1998 and, thus, transferred from one valid genus to another. This transfer was needed since it turned out that this horse parasite showed the relevant characteristics of theilerians with regard to biological data, morphological features, biochemical properties, and molecular biological relationships.

Topics: Animals; Antiprotozoal Agents; Arachnid Vectors; Babesia; Erythrocytes; Horse Diseases; Horses; Life Cycle Stages; Lymphocytes; Naphthoquinones; Piperidines; Quinazolines; Quinazolinones; Theileria; Theileriasis; Ticks

Groups of calves were infected by the injection of ground-up-tick supernatant from ticks infected with ODE-Anand stock of Theileria annulata, the causative agent of tropical theileriosis. Treatment with long-acting oxytetracycline, at 20 mg kg-1, injected intramuscularly, had no effect against severe Theileria annulata infection when administered either as a single injection on the day of infection or as three injections given on days 8, 10 and 12 after infection. Halofuginone lactate, given orally at 1.2 mg kg-1 was effective but caused anorexia, diarrhoea and debility. Parvaquone at 20 mg kg-1 intramuscularly given on day 11 after infection, had a marked suppressive effect, while buparvaquone was highly effective. A single treatment with buparvaquone, either at 5 mg kg-1 or 2.5 mg kg-1 intramuscularly, rapidly eliminated schizonts and piroplasms of T annulata. At 5 mg kg-1 it resulted in rapid recovery of all the treated calves.

Topics: Animals; Antiprotozoal Agents; Cattle; Male; Naphthoquinones; Oxytetracycline; Quinazolines; Quinazolinones; Theileria annulata; Theileriasis

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Lymphocytes; Naphthoquinones; Quinazolines; Quinazolinones; Theileriasis; Triazines

The efficacy of halofuginone (DL-trans-7-bromo-6-chloro-3,3-(3-hydroxy-2-piperidyl) acetonyl-4-(3H) quinazolinone), Wellcome 993 C (2-hydroxy-3-cyclohexyl-1,4-naphthoquinone), and oxytetracycline, all of which have been shown to have a schizonticidal effect in the treatment of bovine theileriosis, and the babesicidal drug diminazene diaceturate, were tested against the schizont stages of Babesia equi in cell culture. The in vitro test system measured DNA synthesis in treated and untreated cell lines. Halofuginone (0.02 microgram/ml) and Wellcome 993 C (5 micrograms/ml) suppressed the incorporation of tritiated thymidine by more than 80%. Oxytetracycline was less effective, while diminazene diaceturate showed no notable effect. The insufficient schizonticidal activity may explain the failure of diminazene diaceturate to cure B. equi infections. Schizonticidal drugs either alone, or in combination with known babesicidal drugs, should be tested in the chemotherapy of B. equi infections.

Topics: Amidines; Animals; Antiprotozoal Agents; Babesia; Cell Line; Diminazene; DNA; Lymphocytes; Naphthoquinones; Oxytetracycline; Piperidines; Quinazolines; Quinazolinones; Thymidine

The efficacy of Wellcome compound 993C and halofuginone was compared using cattle artificially infected with Theileria parva and using in vitro cultures of T parva. At a total dose of 20 mg/kg administered by the intramuscular route, 993C cured all nine cattle of advanced theileriosis and no major recrudescences of the infection occurred. Halofuginone was given by mouth at 1.2 mg/kg and cured five cattle of early clinical theileriosis, but significant recrudescences of infection occurred. Halofuginone at 1.2 mg/kg cured a further five out of six cattle with advanced theileriosis, but four of the five survivors developed moderate to severe resurgences of infection. The dose of 20 mg/kg of 993C was known to be close to its effective level, but 1.2 mg/kg halofuginone, the dose used by earlier workers, may not have been adequate. All 10 untreated control cattle died of acute theileriosis. The in vitro EC50 of both compounds was 0.003 mg per litre but, whereas the dose response curve of 993C was sigmoid, that of halofuginone was bellshaped. This may reflect toxicity to the host lymphoblastoid cells with higher concentrations of halofuginone.

Topics: Animals; Antiprotozoal Agents; Apicomplexa; Cattle; Coccidiostats; Lymph Nodes; Male; Naphthoquinones; Piperidines; Quinazolines; Quinazolinones; Theileriasis