Statement of Work There is an urgent need for improved diagnostic tests for the evaluation of the etiology of febrile states, particularly in immunocompromised hosts. This project will develop host-based biomarker signatures capable of identifying the presence and pathogen class of infections in vulnerable immunocompromised human subjects, thus potentially allowing for earlier, more directed (and thus more effective) therapy as well as reducing the need for potentially harmful empiric anti-infective therapy. In this study we will a) perform high dimensional gene expression analysis on existing samples of at-risk hosts with proven candidemia, viral infection, bacterial infection, or noninfectious illness, b) develop peripheral blood-based gene expression signatures of candidemia and c) generate a combined multinomial classifier capable of differentiating four clinical states: viral infection, bacterial infection, fungal infection (candidemia) and noninfectious illness. The enclosed work offers a true paradigm shift in the way febrile illnesses in this high-risk population are diagnosed and managed.
Statement Timely and accurate differentiation of viral, bacterial, and fungal illness has important implications for both the individual patient and society as earlier/more accurate diagnosis may improve patient treatment and clinical outcomes as well as curb anti-microbial overusage and subsequent proliferation of resistant organisms.
