Neospora caninum is a protozoan parasite predominantly known for causing abortion in cattle and
neuromuscular disease in dogs. So far, no efficient metaphylactic
chemotherapy has been developed. In preliminary studies,
toltrazuril had been successfully used against experimental neosporosis in mice and calves. In the present study, we used immunocompetent and immunodeficient mouse strains to address the role of immunity in supporting the
chemotherapy of experimental N. caninum
infection. WT, microMT and athymic nude mice were intraperitoneally inoculated with 1x10(6) Nc-1 tachyzoites. The
drug was administered in the
drinking water for 6 consecutive days so as to obtain a daily dose of approximately 20 mg
toltrazuril/kg
body weight. The course of
infection was monitored by clinical, histological and immunohistochemical means, as well as by the search for parasite
DNA using PCR-analyses of various organs. In immunocompetent WT mice, treatment proved to be of high efficacy by abrogation of any lesion formation or PCR-positivity in medicated C57BL/6 mice and a significant reduction of lesion formation or PCR-positivity in BALB/c animals. Similarly, treated microMT mice exhibited a significant reduction in cerebral lesion formation as well as in parasite
DNA detectability by PCR when compared to untreated animals. Athymic nude mice, however, did not respond to treatment in that only a delay of the parasite dissemination was achieved, and nude mice still showed the neosporosis disease symptoms, although later than untreated animals. We conclude that treatment with
toltrazuril appears to act parasitostatically rather than parasitocidically. This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of
toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment. Therefore,
chemotherapy with
toltrazuril against experimental
infections with N. caninum requires the support of T-cell immunity in order to be successful.