Schistosome infections, caused by a family of helminth parasites, are major neglected tropical diseases (NTDs) that have serious implications for socio-economic development in many tropical countries. These debilitating and chronic diseases are endemic in more than 70 countries but diagnostic tools are limited and new tests are necessary to limit morbidity and mortality. The development of such tests may be facilitated by the identification of disease-specific biomarkers that are positive early in infection, that can distinguish between acute and chronic infection and that can serve as validation of cure. This thesis work has two major goals: (a) to identify stage-specific proteomic patterns during early (3 week), acute (6 week) and chronic (12 week) Schistosoma mansoni infection in a mouse model; (b) to profile the sera of humans infected by S. mansoni, or S. haematobium and compare these patterns with the protein profile of healthy human serum. To achieve these goals, proteomic analyses were performed on mouse and human sera using several different mass spectrometry (MS) methodologies. These investigations not only identified large numbers of host proteins/protein peaks that are up- or down-regulated in infected sera (mouse and human) but also found large numbers of schistosome-origin proteins in the serum of infected mice. The presence of host proteins, such as transferrin and alpha 1- antitrypsin, as well as one of the schistosome proteins, glutathione S-transferase (GST), were confirmed by Western blot. In addition to these disease- and stage-specific protein profiles, we also identified a number of host proteins that may individually have potential as novel diagnostic tests for schistosome infections in humans, including apolipoprotein A-I (Apo A-I: up-regulated in chronic S. haematobium infected patients) and carbonic anhydrase 1 (CA1: down-regulated in chronic S. mansoni infected patients). If confirmed in larger field studies, these novel
2
biomarkers, and others yet to be identified from our large MS databases, have the potential to contribute significantly to schistosomiasis detection and subsequent eradication efforts. |
