Coccidioidomycosis Detection Using Targeted Plasma and Urine Metabolic Profiling

Area of Science:

• Medical Mycology
• Metabolomics
• Biomarker Discovery

Background:

• Coccidioidomycosis, or Valley fever (VF), is a life-threatening fungal infection causing over 200 US deaths annually.
• Current diagnostic methods for VF lack robust metabolic markers for effective screening, rapid diagnosis, surveillance, and treatment monitoring.

Purpose of the Study:

• To develop a targeted metabolic profiling approach for identifying novel biomarker candidates for Valley fever.
• To enable rapid, highly sensitive, and specific detection of VF through metabolic analysis.

Main Methods:

• Utilized targeted liquid chromatography-tandem mass spectrometry for metabolic profiling of plasma and urine samples.
• Analyzed 147 samples (48 VF patients, 99 controls) to detect and monitor metabolites.
• Employed univariate and multivariate statistical analyses, including ROC curves and OPLS-DA models.

Main Results:

• Identified potential plasma (3 metabolites) and urinary (9 metabolites) biomarker panels for VF detection.
• Achieved high diagnostic performance with plasma metabolites: 94.4% sensitivity and 97.6% specificity.
• Detected significant disturbances in glycine and serine metabolism in both plasma and urine of VF patients.

Conclusions:

• This study presents the first discovery of novel metabolite markers for VF, potentially enabling diagnosis within 24 hours.
• The findings expand the understanding of VF's metabolome and suggest potential therapeutic targets.
• The results provide a foundation for larger studies to validate these biomarkers and improve clinical care for VF.