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

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.

A global to local genomics analysis of Clostridioides difficile ST1/RT027 identifies cryptic transmission events in a northern Arizona healthcare network.

Clostridioides difficile is a ubiquitous, diarrhoeagenic pathogen often associated with healthcare-acquired infections that can cause a range of symptoms from mild, self-limiting disease to toxic megacolon and death. Since the early 2000s, a large proportion of C. difficile cases have been attributed to the ribotype 027 (RT027) lineage, which is associated with sequence type 1 (ST1) in the C. difficile multilocus sequence typing scheme. The spread of ST1 has been attributed, in part, to resistance to fluoroquinolones used to treat unrelated infections, which creates conditions ideal for C. difficile colonization and proliferation. In this study, we analysed 27 isolates from a healthcare network in northern Arizona, USA, and 1352 publicly available ST1 genomes to place locally sampled isolates into a global context. Whole genome, single nucleotide polymorphism analysis demonstrated that at least six separate introductions of ST1 were observed in healthcare facilities in northern Arizona over an 18-month sampling period. A reconstruction of transmission networks identified potential nosocomial transmission of isolates, which were only identified via whole genome sequence analysis. Antibiotic resistance heterogeneity was observed among ST1 genomes, including variability in resistance profiles among locally sampled ST1 isolates. To investigate why ST1 genomes are so common globally and in northern Arizona, we compared all high-quality C. difficile genomes and identified that ST1 genomes have gained and lost a number of genomic regions compared to all other C. difficile genomes; analyses of other toxigenic C. difficile sequence types demonstrate that this loss may be anomalous and could be related to niche specialization. These results suggest that a combination of antimicrobial resistance and gain and loss of specific genes may explain the prominent association of this sequence type with C. difficile infection cases worldwide. The degree of genetic variability in ST1 suggests that classifying all ST1 genomes into a quinolone-resistant hypervirulent clone category may not be appropriate. Whole genome sequencing of clinical C. difficile isolates provides a high-resolution surveillance strategy for monitoring persistence and transmission of C. difficile and for assessing the performance of infection prevention and control strategies.