Mechanisms mediating adverse birth outcomes in the context of S. Japonicum infect

Rhode Island Hospital, Providence RI

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Abstract

DESCRIPTION (provided by applicant): The broad goals of this K02 are to expand our understanding of basic mechanisms mediating adverse birth outcomes in the context of S. japonicum infection and to extend the areas of scientific expertise of an established investigator. The proposed work will leverage the infrastructure and samples collected by an NIH funded randomized controlled trial (U01AI066050) of praziquantel treatment for S. japonicum during pregnancy. The U01 study just started its second of five years and will begin recruitment in mid June of 2007. The specific goals of this work are to examine how treatment for S. japonicum alters placental iron metabolism, modifies the cytokine micro-environment of the placenta, and how this alters placental health as defined by quantification of trophoblast apoptosis. This work is highly collaborative in nature, allowing examination of basic mechanism of S. japonicum related pregnancy morbidity not addressed by the U01 study. This will allow the principal investigator to explore novel avenues of inquiry, not currently her primary skill set. S. japonicum offers an outstanding model for understanding how systemic inflammation, including anemia of inflammation with attendant alterations in iron metabolism affects pregnancy outcomes. Due to the fact that it is easily treated and systemic inflammation is shown to dissipate within a few weeks of therapy, this disease provides an excellent model in which to study the effects of systemic inflammation during pregnancy. Thus, this work is generalizable to a host of infectious and non-infectious diseases of pregnancy that generate an exuberant pro-inflammatory immune response including HIV, tuberculosis, systemic lupus erythematosus, and many others.