Coccidioides genomes from low-incidence states reveal complex migration history across the Western United States

The evolutionary history of Coccidioides immitis and C. posadasii, the fungal agents of coccidioidomycosis or Valley fever, can provide insights into historic and ongoing patterns of dispersal. However, in regions with low Valley fever incidence, genomic data are limited. To better characterize Coccidioides diversity and evolutionary history in low incidence states, we prospectively collected Coccidioides-positive isolates submitted to a national diagnostic laboratory between January 2023 and November 2024. We conducted whole-genome sequencing for 27 isolates from Utah, Colorado, and Nevada-- states with limited genomic characterization. Additionally, we sequenced 22 isolates from California. We assessed geographic structure with maximum likelihood phylogenies, including newly sequenced and previously sequenced Coccidioides isolates, and inferred historic patterns of dispersal with ancestral area reconstruction. For patients within the University of Utah Health system, we conducted medical chart reviews to collect information about potential travel, occupational, and recreational exposure history. Among the newly sequenced isolates, 3/27 were C. immitis and 24/27 C. posadasii. We identified both C. immitis (3 isolates from 1 individual patient) and C. posadasii (16 isolates from 10 individual patients) in Utah. The individual infected with C. immitis reported a history of travel to southern California, consistent with a travel-associated infection. Only C. posadasii was detected in Colorado and Nevada. Newly sequenced isolates from Utah, Nevada, and Colorado did not fall into state-specific monophyletic clades, but were instead distributed across the C. posadasii phylogeny. Our collection of C. immitis likely originated in California (likelihood = 0.96), while C. posadasii traces its ancestral area to Arizona (likelihood = 0.99). We inferred at least seven independent introductions of C. posadasii into Utah, two into Nevada, and seven into Colorado. Our findings suggest a complex dispersal history of Coccidioides across the western U.S., with evidence of ongoing and repeated dispersal rather than a single historical emergence event. These findings highlight the importance of continued genomic surveillance to better understand the evolutionary history of Coccidioides in regions outside highly endemic areas.