Towards a mechanism of action of an antischistosomal drug: measuring granulocytic activity

Schistosomiasis is a neglected tropical disease caused by a family of schistosome parasites which leads to vital organ damage. Praziquantel (PZ) is the only available treatment, but it is effective only against the adult worm. Partner labs have tested an antischistosomal drug which has been shown to have a higher efficacy against both juvenile and mature parasites in mice and monkeys compared to PZ. This effectiveness does not transfer to in vitro experiments; it kills the parasite outside of its host only at extremely high concentrations. This indicates that its efficacy is host-dependent, but the mechanism by which it functions in vivo remains unknown. The aim of this study is to investigate a possible mechanism of this treatment as a drug which facilitates the activation of the host innate immune system. It is hypothesized that an increased number of eosinophils will undergo degranulation in the mice treated with the drug in vivo, measurable by an increase in the granulocytic proteins eosinophil derived neurotoxin (EDN) and superoxide anions. Male BALB/c mice were orally administered the experimental drug while untreated mice served as controls. Sixteen hours post-treatment, eosinophils were isolated from mouse spleens by magnetic separation. EDN levels were determined by enzyme-linked immunosorbent assay, and superoxide anion concentrations were measured by calculating the reduction of cytochrome c. Preliminary results show that the experimental drug increased superoxide anion levels six fold. This work and future studies on this drug may progress the release of this treatment for schistosomiasis if resistance of PZ grows