| Description |
- Caused by the parasite Trypanosoma cruzi, Chagas disease is one of the most neglected tropical diseases in the world and poses a significant burden to the estimated eight million people living with disease. As primary infection is largely asymptomatic, the majority of T. cruzi infections go undiagnosed with only about 1% of cases being identified and treated. As disease progresses to the chronic phase, parasitic loads fall to undetectable levels while indolent destruction of cardiac and gastrointestinal tissue persists. An estimated 30% of individuals develop life-limiting cardiac complications. Current methods of detection include peripheral blood smears, PCR tests, and serological assays; however, all methods have limited sensitivity in identifying disease and are generally unavailable in regions where disease is most prevalent. No antigen detection assay for Chagas disease currently exists. By using a non-directed strategy in which mice were immunized with the serum of infected mice and screened against a microarray of known T. cruzi proteins, we identified circulating T. cruzi antigens with promising diagnostic potential. Spleens from the immunized mice were used to construct a single chain antibody phage display library, from which we selected three high affinity antibodies specific for one target antigen. In sandwich ELISAs, these antibodies could detect T. cruzi in acutely and chronically infected mice at serum dilutions of 1:2,000 and 1:128 respectively. We anticipate these antibodies can be used for a point-of-care antigen detection assay for T. cruzi infection, thus addressing the need for earlier detection, intervention, and monitoring of Chagas disease.
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