Schistosomiasis, caused by three principle species of dioecious trematodes (flatworms), currently infects over 250 million individuals, results in an estimated 2-15% chronic disability, and contributes to poor health and economic stagnation in endemic areas [1]. Although schistosomiasis is effectively treated with praziquantel (PZQ), rapid reinfection with rebound morbidity and fibrosis precludes effective control based on chemotherapy alone. The resubmission of our R03 application seeks to develop a quantitative immunoassay for fibrosin and apply it to epidemiologically well-characterized sera already collected and available from a longitudinal cohort study of Schistosoma japonicum-infected patients (n=616). The principle goal is to determine whether serum fibrosin concentrations are associated with concurrent hepatic fibrosis and whether baseline serum fibrosin levels predict hepatic fibrosis one year post-PZQ treatment. The work serves as the first translation to human research of extensive related studies of S. mansoni-infected mice that led to the discovery of fibrosin and its apparent role in hepatic fibrogenesis. Based on our published observations in infected mice (and in a small preliminary study of S. mansoni-infected patients,) we anticipate that patients infected with S. japonicum will have significantly elevated serum fibrosin concentrations compared to uninfected controls, and that those with ultrsonographically-demonstrable liver fibrosis will have the highest levels. Furthermore, we anticipate that fibrosin levels measured in serum collected from S. japonicum infected individuals 4 weeks post-PZQ will be significantly higher in patients who develop fibrosis at one yr of follow-up compared to levels in patients who do not develop fibrosis at a one-year follow-up assessment. Such a biomarker for patients at risk of developing fibrosis has the potential to profoundly influence disease management. Specifically, a rapid diagnostic test (RDT) for fibrosin could identify those individuals at risk of hepatic fibrosis and prioritize them from more frequent PZQ treatment.
The overall aim of this R03 resubmission is determine the utility of fibrosin as a biomarker for schistosomal hepatic fibrosis. We will leverage serum samples and epidemiologic data already collected from a treatment-reinfection cohort to examine the relationship between baseline serum fibrosin levels and subsequent risk of developing hepatic fibrosis.
