Analysis of schistosomicidal component(s) within mouse serum and its implications for novel drug development

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Schistosomiasis, a parasitic disease caused by a blood-dwelling fluke, remains the most important neglected tropical disease (NTD) despite large elimination programs that currently depend on the effectiveness of a single drug (Praziquantel). With more than 250 million people infected primarily in tropical and subtropical areas, high reinfection rates and emerging drug resistance urgently require new treatment approaches. The well-established murine infection model has beensuccessfully used in different research groups for the investigation of the immunobiology of the disease. Interestingly, however, a large proportion of penetrating cercariae (>80%) does not develop into adult worms in mice, although the cause is still unclear. Therefore, the use of this model for testing new vaccines or anthelminthics is currently being questioned. Preliminary investigations in our newly developed, cell-free in vitro culture system for generation of Schistosoma mansoni developmental stages up to juvenile worms have shown that fractionated mouse serum rapidly and efficiently kills almost all life cycle stages of the parasite that occur in humans. Thus, the present project aims at identifying these soluble, host-specific molecules and their mode of action. Research platforms such as proteomics, biochemistry and biotechnology will be implemented to develop new therapeutic interventions against this debilitating vascular parasitic infection.