Coccidioidomycosis in Northern Arizona: an Investigation of the Host, Pathogen, and Environment Using a Disease Triangle Approach

Abstract

Coccidioides immitis and Coccidioides posadasii are the etiological agents of coccidioidomycosis (Valley fever [VF]). Disease manifestation ranges from mild pneumonia to chronic or extrapulmonary infection. If diagnosis is delayed, the risk of severe disease increases. In this report, we investigated the intersection of pathogen, host, and environment for VF cases in Northern Arizona (NAZ), where the risk of acquiring the disease is much lower than in Southern Arizona. We investigated reported cases and assessed pathogen origin by comparing genomes of NAZ clinical isolates to isolates from other regions. Lastly, we surveyed regional soils for presence of Coccidioides. We found that cases of VF increased in NAZ in 2019, and Coccidioides NAZ isolates are assigned to Arizona populations using phylogenetic inference. Importantly, we detected Coccidioides DNA in NAZ soil. Given recent climate modeling of the disease that predicts that cases will continue to increase throughout the region, and the evidence presented in this report, we propose that disease awareness outreach to clinicians throughout the western United States is crucial for improving patient outcomes, and further environmental sampling across the western U.S. is warranted. IMPORTANCE 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. We present the first evidence of Coccidioides spp. in Northern Arizona soils, suggesting that the pathogen is maintained in the local environment. Until disease prevention is an achievable option via vaccination, we predict that incidence of Valley fever will rise in the area. Therefore, enhanced awareness of and surveillance for coccidioidomycosis is vital to community health in Northern Arizona.

Keywords: Northern Arizona; Southwestern United States; Valley fever; coccidioides; disease triangle; endemic mycoses; environmental microbiology; phylogenetic analysis.

FIG 1

Northern Arizona county location and Valley fever cases. Yearly, the number of cases per 100,000 population increased compared to previous averages in all Northern Arizona counties. Geographic location of northern Arizona counties. Left to right: Mohave, Yavapai, Coconino (largest), Navajo, and Apache. Tribal land located in Northern Arizona counties are shaded. The southern counties that experience the highest yearly case counts per 100,000 are noted with asterisks.

FIG 2

Northern Arizona Valley fever data demographics. (A) Age of patients diagnosed with Valley fever in Arizona during 2018, Northern Arizona counties during 2018, and regional hospital (NAH) between 13 July 2017 and 31 December 2018. (B) Among hospitalized Valley fever patients at NAH, 23% of patients had no documented pre-existing conditions. The other 77% had existing comorbidities such as diabetes (16%), HIV (9%), cancer (10%), and several multiple immunocompromising conditions. (C) The total population treated at NAH is displayed next to inpatient Valley fever cases for reference. Out of the 38 patients diagnosed with Valley fever from 13 July 2017 to 31 December2018, pulmonary infection occurred in 31 (82%) cases, and dissemination to extrapulmonary locations occurred in 7 (12%) of the cases. There were 14 white (36.8%), 2 Hispanic (5.2%), and 22 American Indian/Alaskan Native (57.8%) individuals.

FIG 3

Relationship of Northern Arizona clinical isolates within the C. posadasii population suggests traveled related infection. The seven new clinical isolates (highlighted) group with previously published isolates recovered from patients in Maricopa or Pima county populations. C. posadasii comprises geographically distinct populations designated as Caribbean (top, red), Texas/Mexico and South America (bottom, yellow) and Arizona (middle, blues). Subpopulation structure in Arizona suggests genetically distinct groups within Arizona (Maricopa County; Phoenix and Pima County; Tucson). Midpoint rooted maximum likelihood tree built using 61 previously published and 7 new isolates.

FIG 4

Northern Arizona soils are positive for Coccidioides DNA. (A) Percent positivity for soil in Mohave, Yavapai, Coconino, Navajo, and Apache counties. (B) Approximate location of soil collection sites designated with asterisk. Tribal land located in Northern Arizona counties are shaded. CDx and CocciENV are Coccidioides-specific PCR assays.