Abstract

Chagas disease, caused by infection with the parasite Trypanosoma cruzi, is the most important parasitic infection in the Western hemisphere. An estimated 6-7 million people are infected and the disease is emerging as a global threat. Infection is lifelong and between 30-40% of those infected go on to develop life-threatening cardiac or digestive pathology. There is no vaccine and only two drugs, both of which are toxic and both are activated by the same parasite enzyme. Hence there is a need for good pre-clinical animal models which recapitulate the human disease and can be used to examine mechanisms of immunity, pathogenesis and drug action. We have developed murine models for both cardiac and digestive forms of the disease using highly sensitive bioluminescent reporter parasites that allow for the dynamics of the infection to be monitored for months in individual animals. The model has been further developed for analysis of host-pathogen interactions at the cellular level by incorporation of dual bioluminescence/fluorescence reporters. We have utilised this model to examine the effects of treatment on cardiac pathology and we have been able to analyse parasite replication within the tissues. We are currently using this system to examine the immunology of the infection and to identify mechanisms of immune evasion.

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