Presentation description

Antibiotic resistance often evolves during treatment and is shaped by within-host pathogen diversity. While this phenomenon is well documented in bacteria, the dynamics of antifungal resistance remain poorly understood. Fungal pathogens such as Coccidioides immitis and C. posadasii, the causative agents of Valley fever, are understudied despite increasing clinical concern. Acquired by inhaling fungal spores and misdiagnosed in up to 30% of pneumonia cases, understanding within-host genetic diversity in Coccidioides is crucial for improving treatment strategies and anticipating resistance evolution. In this study, we sought to quantify the in-host diversity of Coccidioides within patient infections. We conducted prospective genomic surveillance at a national diagnostic laboratory, ARUP, collecting one or more Coccidioides-positive isolates per patient. Samples were processed through ARUP and sequenced on an Illumina platform at the University of Utah. Sequencing reads were then analyzed using our custom cocci-call pipeline to identify single nucleotide polymorphisms (SNPs), and pairwise comparisons were performed in R to assess isolate similarity. We found significance in the mean SNP difference between isolates from the same patient (mean = 1,447 SNPs), compared to isolates from different patients (mean = 15,303 SNPs). Within-host comparisons revealed lower diversity in C. immitis (mean = 543 SNPs) than in C. posadasii (mean = 757 SNPs). Across-patient comparisons showed the same trend, with C. immitis averaging 9,455 SNPs and C. posadasii 18,583 SNPs. These results reveal unexpectedly high within-host diversity in both species and underscore the need to better understand how such diversity impacts clinical outcomes, pathogen evolution, and antifungal resistance.