Diagnostics to Detect Host Immunity to Coccidioidomycosis (Valley fever) or Histoplasmosis

Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of anticipated awards: 2-3 Budget (total costs): Phase I: Up to $300,000 for up to one year Phase II: Up to $1,500,000 for up to 3 years. Background Coccidioides spp. and Histoplasma spp. cause serious and often difficult to treat invasive infections. The associated direct medical costs caused by these pathogens in the United States in 2019 were >$400M, according to the Centers for Disease Control and Prevention. Diagnosis of these select endemic mycoses is challenging for many reasons, including crossreactivity of antigen testing, false-negative results in immunocompromised individuals or those with chronic and/or latent infection, and the invasive nature of direct biopsies. These factors contribute to delays in treatment and poor outcomes for patients. Cytokine release assays offer a direct measure of the host adaptive immunity to a particular pathogen and provide distinct advantages over traditional skin tests of delayed type hypersensitivity, which are rarely used for these fungal infections. Diagnostic assays that detect active infection and past exposure to Coccidioides spp. will be critical for the development and deployment of a Valley fever vaccine and are recommended in the NIAID Strategic Plan for research todevelop a Valley fever Vaccine. Additionally, a diagnostic assay to detect subclinical and latent histoplasmosis would improve risk stratification and patient outcomes.