The genus Coccidioides consists of two species: C. immitis and C. posadasii. Prior to 2000, all disease was thought to be caused by a single species, C. immitis. The organism grows in arid to semiarid alkaline soils throughout western North America and into Central and South America. Regions in the United States, with highest prevalence of disease, include California, Arizona, and Texas. The Mexican states of Baja California, Coahuila, Sonora, and Neuvo Leon currently have the highest skin test positive results. Central America contains isolated endemic areas in Guatemala and Honduras. South America has isolated regions of high endemicity including areas of Colombia, Venezuela, Argentina, Paraguay, and Brazil. Although approximately 15,000 cases per year are reported in the United States, actual disease burden is estimated to be in the hundreds of thousands, as only California and Arizona have dedicated public health outreach, and report and track disease reliably. In this review, we survey genomics, epidemiology, ecology, and summarize aspects of disease, diagnosis, prevention, and treatment.

Coccidioidomycosis, listed as a priority mycosis by the WHO, is endemic in the United States but often overlooked in Central and South America. Employing a multi-institutional approach, we investigate how disease characteristics, pathogen genetic variation, and environmental factors impact coccidioidomycosis epidemiology and outcomes in South America. We identified 292 cases (1978–2021) and 42 outbreaks in Piauí and Maranhão states, Brazil, the largest series outside the US/Mexico epidemic zone. The male-to-female ratio was 57.4:1 and the most common activity was armadillo hunting (91.1%) 4 to 30 days before symptom onset. Most patients (92.8%) exhibited typical acute pulmonary disease, with cough (93%), fever (90%), and chest pain (77%) as predominant symptoms. The case fatality rate was 8%. Our negative binomial regression model indicates that reduced precipitation levels in the current (p = 0.015) and preceding year (p = 0.001) predict heightened incidence. Unlike other hotspots, acidic soil characterizes this region. Brazilian strains differ genomically from other C. posadasii lineages. Northeastern Brazil presents a distinctive coccidioidomycosis profile, with armadillo hunters facing elevated risks. Low annual rainfall emerges as a key factor in increasing cases. A unique C. posadasii lineage in Brazil suggests potential differences in environmental, virulence, and/or pathogenesis traits compared to other Coccidioides genotypes.

The fungal disease Valley fever causes a significant medical and financial burden for affected people in the endemic region, and this burden is on the rise. Despite the medical importance of this disease, little is known about ecological factors that influence the geographic point sources of high abundance of the pathogens Coccidioides posadasii and C. immitis, such as competition with co-occurring soil microbes. These “hot spots”, for instance, those in southern Arizona, are areas in which humans are at greater risk of being infected with the fungus due to consistent exposure. The aim of this study was to isolate native microbes from soils collected from Tucson, Arizona (endemic area for C. posadasii) and characterize their relationship (antagonistic, synergistic, or neutral) to the fungal pathogen with in vitro challenge assays. Secreted metabolites from the microbes were extracted and described using analytical techniques including high-performance liquid chromatography (HPLC) and mass spectrometry. Bacteria belonging to the genus Bacillus and fungi in the Fennellomyces and Ovatospora genera were shown to significantly decrease the growth of Coccidioides spp. In vitro. In contrast, other bacteria in the Brevibacillus genus, as well as one species of Bacillus bacteria, were shown to promote growth of Coccidioides when directly challenged. The metabolites secreted from the antagonistic bacteria were described using HPLC and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The microbes identified in this study as antagonists to Coccidioides and/or the metabolites they secrete have the potential to be used as natural biocontrol agents to limit the amount of fungal burden at geographic point sources, and therefore limit the potential for human infection.

Our work is the first description of the Valley fever disease triangle in Northern Arizona, which addresses the host, the pathogen, and the environmental source in the region. Our data suggest that the prevalence of diagnosed cases rose in 2019 in this region, and some severe cases necessitate hospitalization.