The impact of parasite genetics on transplacental infection by coccidian parasites
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Abstract
Apicomplexan species, a phylum of single-called, obligate intracellular parasites, are of important public health concern because these parasites contribute significantly to morbidity and mortality in humans, wildlife, and domesticated animals. These parasites include Plasmodium spp., Cryptosporidium spp., and the coccidian parasites Toxoplasma gondii, Neospora caninum, Sarcocystis spp., and Eimeria spp. All coccidian species can cross the placenta, resulting in congenital infections, prematurity, fetal loss, and other perinatal complications. Numerous factors influence the progression and severity of transplacental infections, including parasite genetics. The objective of the thesis is to understand the impact of parasite genetics on transplacental infections in multiple host species, including hominids, ungulates, pinnipeds, and cetaceans. An ELISA protocol for serotyping T. gondii with an extended set of peptides was validated using previously typed sera. Using the expanded set of peptides, mother-baby paired serum samples from the National Collaborative Chicago-Based Congenital Toxoplasmosis Study were tested to determine the serotype associated with specific congenital toxoplasmosis outcomes. Cattle sera were analyzed using ELISA to determine the seroprevalence of T. gondii and N. caninum. DNA was extracted from bovine and marine mammal abortion cases to screen for coccidian species using PCR primers that amplify across the trans-ITS. Positive amplicons were analyzed by Sanger sequencing to identify the coccidian species present. In humans, T. gondii serotype has previously been associated with both severity and type of congenital toxoplasmosis implicating parasite genetics is an important variable in the progression and outcome of congenital disease. Specifically, Type II serotype was associated with an increased risk of non-aqueductal hydrocephalus, and non-Type II serotypes (NE-II) was linked to prematurity and severe disease at birth. N. caninum represented the most significant agent associated with bovine abortion in cattle, however, work herein has identified other coccidian species, including T. gondii, S. caninum, and S. cruzi as important pathogens capable of causing fetal abortion. Coccidian parasites including T. gondii, N. caninium, S. neurona, S. lutrae, and several new species of Sarcocystis parasites were also identified infecting marine mammal placenta tissue, pups in utero, and aborted fetuses, indicating that these parasites also cause fetal loss, prematurity, and neonatal death in threatened pinniped and cetacean species, which is impacting their recovery in the wild. Thus, coccidian parasites have a major impact in perinatal outcomes and fecundity in a wide range of host species. Severity and outcome of congenital toxoplasmosis in people is highly dependent on parasite genotype. Our molecular and immunologic results support both T. gondii and N. caninum as major causal agents contributing to fetal loss in cows. Our work also identified a range of coccidian parasite species capable of affecting the fertility and pregnancy of vulnerable marine mammals. Addressing coccidian parasites in different host species highlights how this class of pathogens impact congenital disease beyond humans.