Toxoplasma Population Genetics

Prevalence and severity of disease of the protozoan parasite Toxoplasma gondii varies geographically in the wide array of hosts T. gondii infects. These facts highlight the need to discover the transmission dynamics and the genetic relationship among strains that are causing the wide spectrum of disease states identified in nature. Specifically, our research addresses the emergence and re-emergence of parasitic zoonotic diseases that have complex life-cycles with multiple routes of transmission that impact people and animals who co-exist in the same ecological niche. We seek discoveries in these areas to support the development of new diagnostic tools, discover fundamental paradigms governing virulence shifts in parasitic protozoa and ultimately develop efficacious anti-protozoal strategies to 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. <P>The genetic basis for how these clones emerge and then rapidly come to dominate has been a matter of intensive study, and great debate. For Toxoplasma, the ability of this parasite to effectively bypass its sexual stage and propagate asexually via carnivory has been proposed as one pivotal mechanism for clonal dominance Su et. al., 2003, Science 299:414. However, the potential for these parasitic protozoa to functionally clone themselves via self-mating during their sexual cycle has not so far been assessed as an important factor governing the emergence and/or expansion of clones that can sweep to dominance, or cause virulent epidemics in nature.<P>In our work published this year, we applied high-resolution genotyping to rectify this lack of knowledge and showed, for the first time, that two waterborne outbreaks in Brazil and California originating from oocyst/sporocyst infections were in fact clonal strongly arguing that self-mating in the definitive host was principally responsible for the epidemic expansion of single clones that caused each outbreak. These data serve 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. This offers a new perspective for how virulent clones dominate transiently during an outbreak, or conversely, how highly successful clones can outcompete less fit strains to sweep to pandemic levels, effectively diluting out genetic diversity and provides a fresh rationale to explain the highly clonal nature of parasite population genetic structures among the Apicomplexa. <P>In another epidemiological study published this year, we investigated polyparasitism (infection with multiple parasite species) as a modulator of disease by examining the association of concomitant infection of T. gondii and the related parasite Sarcocystis neurona with disease severity in marine mammals of the Pacific Northwest. These hosts ostensibly serve as sentinels for the detection of terrestrial parasites implicated in water-borne epidemics of humans and wildlife in this endemic region. Marine mammals sampled over 6 years were assessed for protozoal infection using multi-locus PCR-DNA sequencing directly from host tissues. Genetic analyses uncovered a high prevalence and diversity of protozoa, with 147/161 (91%) of our sampled population infected with T. gondii and/or S. neurona. From 2004 to 2009, the relative frequency of S. neurona infections increased dramatically, surpassing that of T. gondii. The majority of T. gondii infections were by strains bearing type I lineage alleles, though strain genotype was not a predictor of virulence. Significantly, polyparasitism with S. neurona and T. gondii was common (42%) and was associated with higher mortality and more severe protozoal encephalitis. <P>Our finding of widespread polyparasitism among marine mammals indicates pervasive contamination of public waterways by fecally-transmitted terrestrial-sourced zoonotic agents. Furthermore, the significant association of polyparasitism with virulent protozoal disease identifies polyparasitism as an important predictor of disease severity. Our study advocates the need to adopt specific policies for disease control, namely surveillance of public waterways, and expands upon two important avenues for infectious disease research, the significance of polyparasitism in disease dynamics and the utility of wildlife sentinel species for investigating real-time transmission of zoonotic parasites.