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The investigation of two Trypanosoma cruzi isolates for their ability to complicate disease progression in the host

Perez, Catherine (2017) The investigation of two Trypanosoma cruzi isolates for their ability to complicate disease progression in the host. PhD thesis, Murdoch University.

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Chagas disease (CD) is caused by infection with the zoonotic protozoan Trypanosoma cruzi. CD is endemic to Latin America, where a range of its insect vectors reside, however economic instability and increased global migration have led to the movement of infected individuals outside of endemic areas. Recent reports estimate that 10 million people are infected worldwide, and the potential implications within non-endemic health systems unfamiliar with this disease, must be considered.

CD is highly heterogeneous in symptoms, disease progression and host outcome, which is thought to be due, at least in part, to T. cruzi genetic variation. The species has been classified into six genetically different discrete typing units (DTUs) TcI-TcVI, with a recently proposed seventh branch, Tcbat. Although DTUs appear to differ in some clinically and epidemiologically important characteristics, very few strains have been characterised phenotypically and the extent to which parasite genetic variation explains variation in drug susceptibility, virulence, tissue tropism and disease progression is unknown.

In this study, two phenotypically uncharacterised isolates, C8 clone 1 (TcI) and 10R26 (TcIV), were investigated and compared to the Tulahuen (TcVI) isolate for their in vitro growth kinetics across three mammalian cell lines; their capacity to induce disease within a mouse host; and the propensity for inoculant size, the route of transmission, reinfection and immune-suppression to complicate infection.

Isolate in vitro growth was significantly affected by cell line, with differences among isolates in the cell line providing the best growth response. Infection studies in mice found no effect of inoculant size or inoculation route on host morbidity or mortality for either isolate. For both isolates whether single and mixed infections, reinfection was associated with an acute and fatal outcome. Immune suppression of C8 clone infected hosts significantly reduced morbidity and mortality, with positive associations between immune suppression, mean pathology scores and mean number of organs showing pathology.

Item Type: Thesis (PhD)
Murdoch Affiliation(s): School of Veterinary and Life Sciences
United Nations SDGs: Goal 3: Good Health and Well-Being
Supervisor(s): Thompson, Andrew and Lymbery, Alan
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