The pathogenesis of experimental neosporosis in pregnant sheep.

Three groups of eight pregnant sheep were inoculated with tachyzoites of the NCl isolate of Neospora caninum at 45 (group 1), 65 (group 2) or 90 (group 3) days' gestation. A further six animals (group 4) served as controls. Fourteen of the infected ewes developed a fever, which in two cases was biphasic. In six ewes in group 1, the fetuses died and were resorbed, and in the other two the fetuses were aborted. In group 2, one ewe resorbed her fetus, six aborted dead fetuses and one produced a live lamb. In group 3, six ewes aborted and two produced one live and one stillborn lamb each. Thus, the stage of gestation influenced the outcome of infection. All but one of the ewes "seroconverted", as shown by enzyme-linked immunosorbent assay, and 10 of 13 fetal sera examined by an indirect immunofluorescent antibody test were positive. The polymerase chain reaction was also used to detect DNA of N. caninum in aborted tissues. Immunohistochemical examination showed that the parasite had invaded the placentas of all cases examined, displaying an apparent predilection for fetal chorionic epithelium and fetal placental blood vessels, as well as inducing thrombosis in some maternal caruncular blood vessels. Organisms were associated with fetal vasculitis, focal degeneration and inflammation of the chorioallantois, and widespread, severe focal necrosis in the placentome. Characteristic lesions were seen in the fetal brains, in addition to focal leucomalacia, thought to be due to anoxia resulting from the placental damage. The six control sheep in group 4 remained clinically healthy and produced normal uninfected lambs.