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Coccidioidomycosis is a potentially fatal fungal disease of humans and animals that follows inhalation of Coccidioides spp. arthroconidia in the environment. The disease in dogs resembles that in people, and because dogs may be at increased risk of exposure due to their proximity to the ground and digging behavior, they are valuable models for the disease in humans. Dogs have been sentinels for identification of new regions of endemicity in Washington and Texas. Canine serosurveillance has also been used to predict variables associated with environmental presence of Coccidioides spp. Expansion of the endemic region of coccidioidomycosis with climate change-along with predicted population increases and increased development in the southwest United States-may result in 45.4 million additional people at risk of infection by 2090. Here we provide an overview of the value of dogs as sentinels for the disease and encourage the routine reporting of coccidioidomycosis cases in dogs to public health agencies. We also highlight the value of dogs as naturally occurring models for studying novel treatment options and preventatives, such as a novel live avirulent coccidioidomycosis vaccine., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Coccidioidomycosis is a fungal disease in arid regions of the United States that is predicted to expand with climate change. Cases in military personnel and military working dogs (MWDs) impact personnel readiness and result in healthcare costs. To examine Coccidioides exposure among MWDs, 276 banked serum samples were retrieved from dogs housed in California, Texas, Arizona, New Mexico, Nevada, and Utah. Using gel immunodiffusion, six (2.1%) specimens were IgG-positive and three (1.1%) were equivocally IgM-positive. The IgG-positive samples were from Arizona (2 [prevalence 8.0%]) and California (4 [3.7%]). These data will guide future efforts to study MWDs as sentinels for human coccidioidomycosis., (Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology 2023.)

Given the predisposition of South American camelids to coccidioidomycosis, we sought to describe the disease presentation in alpacas and llamas and identify potential risk factors for these species. The records of 224 llamas and alpacas that were tested for Coccidioides infection using immunodiffusion serology at the Coccidioidomycosis Serology Laboratory of the University of California, Davis, between 1990 and 2016 were examined; of those, 46 alpacas and 42 llamas had positive test results. The remaining 99 alpacas and 37 llamas were used as control groups. We found that male llamas were at increased risk for Coccidioides infection when compared with female llamas and when compared with male alpacas. South American camelids living within California were at higher risk for infection than camelids living in other states. Alpacas were more likely than llamas to have subclinical infections. We documented five cases of abortion or neonatal mortality attributable to coccidioidomycosis in alpacas. Our study demonstrates that South American camelids are susceptible to Coccidioides infection in areas where the disease is endemic, lending support to the importance of vigilance for this disease in alpacas and llamas and suggesting a possible role for these animals as sentinel species., Lay Summary: We examined cases of Valley Fever and described the disease and risk factors for llamas and alpacas. Male llamas were at increased risk for infection as were animals living within California. Five alpacas had miscarriages or neonatal deaths as a result of Valley Fever infections., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Canine coccidioidomycosis, a systemic fungal infection endemic to arid and semiarid regions of North, Central, and South America, is commonly diagnosed in dogs living in or traveling through lower Sonoran life zones in the states of California and Arizona. Canine and human cases have geographic overlap. Similarities between clinical coccidioidomycosis in dogs and humans include asymptomatic infection, primary respiratory disease and disseminated disease. Differences include a high rate of dissemination in dogs, differences in predilection of dissemination sites, and a granulomatous or diffuse meningoencephalopathic form in the canine central nervous system (CNS) without the obstructive component seen in humans. Dogs presenting with CNS coccidioidomycosis most commonly experience seizures. Prior disease history and serology are unreliable indicators of CNS coccidioidomycosis. Magnetic resonance imaging (MRI) is advantageous for diagnosis of CNS coccidioidomycosis in dogs. Long-term administration of antifungal medication is promoted for treatment of both primary and disseminated coccidioidomycosis in dogs. Supportive treatment addressing pain, fever, inappetance, coughing, and other clinical signs improves patient care. Glucocorticoids and or anticonvulsants are also recommended for canine disseminated CNS disease. Protracted treatment times, lack of owner compliance, failure of the disease to respond to the first antifungal drug selected, and high cost are challenges of successfully treating dogs.

Cryptococcosis is an opportunistic fungal infection caused by members of the two sibling species complexes: Cryptococcus neoformans and Cryptococcus gattii. Flucytosine (5FC) is one of the most widely used antifungals against Cryptococcus spp., yet very few studies have looked at the molecular mechanisms responsible for 5FC resistance in this pathogen. In this study, we examined 11 C. gattii clinical isolates of the major molecular type VGIII based on differential 5FC susceptibility and asked whether there were genomic changes in the key genes involved in flucytosine metabolism. Susceptibility assays and sequencing analysis revealed an association between a point mutation in the cytosine deaminase gene (FCY1) and 5FC resistance in two of the studied 5FC resistant C. gattii VGIII clinical isolates, B9322 and JS5. This mutation results in the replacement of arginine for histidine at position 29 and occurs within a variable stretch of amino acids. Heterologous expression of FCY1 and spot sensitivity assays, however, demonstrated that this point mutation did not have any effect on FCY1 activities and was not responsible for 5FC resistance. Comparative sequence analysis further showed that no changes in the amino acid sequence and no genomic alterations were observed within 1 kb of the upstream and downstream sequences of either cytosine permeases (FCY2-4) or uracil phosphoribosyltransferase (FUR1) genes in 5FC resistant and 5FC susceptible C. gattii VGIII isolates. The herein obtained results suggest that the observed 5FC resistance in the isolates B9322 and JS5 is due to changes in unknown protein(s) or pathway(s) that regulate flucytosine metabolism.

Elevated fluconazole minimum inhibitory concentrations (MICs) are more frequently observed in Cryptococcus gattii compared to C. neoformans isolates; however, the development of in vivo resistance and the molecular mechanisms responsible have not been reported for this species. We report a case of Cryptococcus gattii (molecular type VGIII) that developed reduced susceptibility to fluconazole during therapy and delineate the molecular mechanisms responsible. Multilocus sequence typing and quantitative DNA analysis of the pre- and post-treatment isolates was performed using well-characterized methods. Pre- and post-treatment clinical isolates were confirmed isogenic, and no differences in ERG11 or PDR11 sequences were found. qPCR found an overexpression of ERG11 and the efflux pump PDR11 in the resistant isolate compared to the isolate collected prior to initiation of antifungal therapy. Reversion to wild-type susceptibility was observed when maintained in antifungal-free media confirming the in vivo development of heteroresistance. The in vivo development of heteroresistance to fluconazole in our patient with C. gattii is secondary to overexpression of the efflux pump PDR11 and the drug target ERG11. Additional work in other clinical isolates with elevated fluconazole MICs is warranted to evaluate the frequency of heteroresistance versus point mutations as a cause of resistance., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)