Identification of Biomarkers for the diagnosis of rickettsial diseases.

Rickettsioses are re-emerging throughout the world. The extent of the problem is larger than reported because these tick-transmitted bacterial infections are severely underreported as a consequence of the initial non-specific clinical presentation and the lack of laboratory diagnostic methods. Inappropriate or delayed treatment is the rule. Severe complications or death cannot be prevented under these circumstances because these bacteria target the vascular endothelium in every organ resulting in inflammation, leakage of intravascular fluid, and activation of coagulation. Development of a diagnostic method based on specific serum markers present during the early symptomatic period would prevent the considerable morbidity and potential mortality that accompany rickettsial infections. We hypothesize that early during the clinical course of infections by Rickettsia, there are signature biomarkers in the serum or plasma that derive from the endothelium. Our specific aims are to: 1) identify discriminating protein-biomarkers produced by human endothelial cells; and 2) validate the diagnostic accuracy of biomarkers for rickettsioses in sera from patients with rickettsial spotted fevers. We expect to generate the knowledge necessary to develop accurate and economic diagnostic methods for rickettsial diseases