Novel Circulating RNA-based Markers as Diagnostic Biomarkers of Infectious Diseases

In resource limited settings, rapid and accurate diagnosis of infections is critical for managing potential exposures to highly virulent pathogens, whether occurring from an act of bioterrorism or a natural event. This is especially important for hard to detect intracellular bacterial and alphavirus infections, that overlap symptomatically and often treated empirically due to a lack of reliable and rapid diagnostics. We propose to undertake a systematic in vivo study to identify and validate the circulatory RNAs and exosomal-based biomarkers of Venezuelan equine encephalitis virus, Rickettsia prowazekii, and Brucella abortus infections. Multiple clinical matrices (urine, blood) and infection routes will be studied to analyze the RNA biomarker dynamics in a specified diagnostic window (0-14 days, post infection). Exosome contents (e.g., miRNA) and other host-based biomarkers will also be analyzed and compared for specificity and sensitivity. Finally, we will integrate the animal outcome in computational models to predict pathogen kinetics, translation of findings from animals to humans, and to make predictions of prognostic factors for treatment efficacy and the risk of relapse and progression. Ultimately, we envision to develop a low cost, in vitro diagnostic device for rapid and sensitive detection of pre-symptomatic, symptomatic or convalescent biomarkers of these infectious diseases.