Prevalence and severity of disease varies geographically in a wide array of mammals and birds that protozoan pathogens infect. To reduce the burden of emerging parasitic disease among prevalent zoonoses, a primary goal of our work is to discover the transmission dynamics and the phylogenetic relationships among circulating protozoan parasites that possess complex life cycles and multiple routes of transmission in nature. We seek discoveries in these areas to support the development of new diagnostic tools, identify fundamental paradigms governing virulence shifts in parasitic protozoa and develop efficacious anti-protozoal strategies that mitigate the spread of disease. Periodic shifts in the population genetics and transmission dynamics of pathogenic clones of coccidian parasites such as Toxoplasma gondii and Sarcocystis neurona have been of substantial interest to the parasitology community because both of these heterogamous pathogens possess surprisingly clonal population genetic structures that are punctuated by the dominance of only a few highly successful clones. The genetic basis for how these clones emerge and then rapidly come to dominate has been a matter of intensive study, and great debate. We previously showed that protozoan parasites functionally clone themselves via self-mating during their sexual cycle in nature and this exists as an important factor governing the emergence and/or expansion of clones that can sweep to dominance, or cause virulent epidemics. These data served as the first extensive from-the-field evidence that self-mating is a key adaptation allowing expansion of parasite clones capable of causing disease epidemics. We recently reported a new Toxoplasma gondii outbreak genotype, referred to as Type X, infecting marine mammals in California. The Type X lineage has since been shown to infect >50% of US wildlife and is thought to exist as a clonal lineage. To determine the true genetic ancestry of the Type X lineage, we performed multi-locus genotyping on >52 strains isolated from southern sea otters over a 10 year period. Our genotyping results established that, contrary to recently published data (Dubey et al., 2011;Khan et al., 2011), Type X is not a clonal lineage, but rather exists as a sexual clade of T. gondii recombinants that resulted from a cross between a native North American strain(s) and an ancestral Type II strain. We are currently producing comparative genealogies among different Type X strains to determine the genetic origins of this Type X clade of recombinant strains. We also hypothesize that Toxoplasma genotype is a critical risk factor among patients who develop congenital and ocular toxoplasmosis. To address whether Type X strains infect people, we developed an ELISA-based blood test to detect the presence of strain-specific antibodies that distinguish individuals infected with Type X from those infected with common Type I, II and III strains. Using this test, we showed that 15% of infections among 183 mother-child pairs in a national congenital toxoplasmosis study possessed the II=I/III serotype, consistent with infection by a Type X strain. Furthermore, contrary to what is observed in France, non Type II parasites (NE-II) caused the majority of US congenital infections (61%) and these were associated with premature birth, and more severe forms of eye and brain disease. This work demonstrated, for the first time, that Toxoplasma parasite strain type is a significant factor influencing human disease.

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Wilson, Devon J; Orsel, Karin; Waddington, Josh et al. (2016) Neospora caninum is the leading cause of bovine fetal loss in British Columbia, Canada. Vet Parasitol 218:46-51
Lorenzi, Hernan; Khan, Asis; Behnke, Michael S et al. (2016) Local admixture of amplified and diversified secreted pathogenesis determinants shapes mosaic Toxoplasma gondii genomes. Nat Commun 7:10147
Barbosa, Lorraine; Johnson, Christine K; Lambourn, Dyanna M et al. (2015) A novel Sarcocystis neurona genotype XIII is associated with severe encephalitis in an unexpectedly broad range of marine mammals from the northeastern Pacific Ocean. Int J Parasitol 45:595-603
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Dubey, Jitender P; Sykes, Jane E; Shelton, G Diane et al. (2015) Sarcocystis caninum and Sarcocystis svanai n. spp. (Apicomplexa: Sarcocystidae) Associated with Severe Myositis and Hepatitis in the Domestic Dog (Canis familiaris). J Eukaryot Microbiol 62:307-17
Dubey, J P; Howe, D K; Furr, M et al. (2015) An update on Sarcocystis neurona infections in animals and equine protozoal myeloencephalitis (EPM). Vet Parasitol 209:1-42
Novais, Eduardo A; Commodaro, Alessandra G; Santos, Fábio et al. (2014) Patients with diffuse uveitis and inactive toxoplasmic retinitis lesions test PCR positive for Toxoplasma gondii in their vitreous and blood. Br J Ophthalmol 98:937-40
Romano, Audrey; Inbar, Ehud; Debrabant, Alain et al. (2014) Cross-species genetic exchange between visceral and cutaneous strains of Leishmania in the sand fly vector. Proc Natl Acad Sci U S A 111:16808-13
VanWormer, Elizabeth; Miller, Melissa A; Conrad, Patricia A et al. (2014) Using molecular epidemiology to track Toxoplasma gondii from terrestrial carnivores to marine hosts: implications for public health and conservation. PLoS Negl Trop Dis 8:e2852

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