How I Do It: Managing Cavitary Coccidioidomycosis Expert Opinions for Improving Patient Outcomes.

Coccidioidomycosis (CM), caused by the dimorphic fungi Coccidioides immitis (C. immitis) and C. posadasii, is recognized as an increasing threat both nationally and worldwide.

Inferring the composition of a mixed culture of natural microbial isolates by deep sequencing.

Next generation sequencing has unlocked a wealth of genotype information for microbial populations, but phenotyping remains a bottleneck for exploiting this information, particularly for pathogens that are difficult to manipulate. Here, we establish a method for high-throughput phenotyping of mixed cultures, in which the pattern of naturally occurring single-nucleotide polymorphisms in each isolate is used as intrinsic barcodes which can be read out by sequencing. We demonstrate that our method can correctly deconvolute strain proportions in simulated mixed-strain pools.

Musculoskeletal and CNS coccidiomycosis in an individual with multiple sclerosis on fingolimod - A case report.

We report the case of a 56-year-old female with a past medical history of multiple sclerosis on disease-modifying therapy of fingolimod who presented with disseminated infection, initially of the ankles bilaterally before progressing to the central nervous system. CNS coccidiomycosis has thus far not been associated with any pharmacological therapy for multiple sclerosis. Clinicians should have a high degree of suspicion for infection in immunosuppressed patients living in endemic areas.

Discovery of a Unique Set of Dog-Seroreactive Proteins Using Nucleic Acid Programmable Protein Array.

Valley Fever (VF), caused by fungi in the genus , is a prevalent disease in southwestern and western parts of the United States that affects both humans and animals, such as dogs. Although the immune responses to infection with spp. are not fully characterized, antibody-detection assays are used in conjunction with clinical presentation and radiologic findings to aid in the diagnosis of VF.

Access to Urgent Care Practices Improves Understanding and Management of Endemic Coccidioidomycosis: Maricopa County, Arizona, 2018-2023.

Background: Coccidioidomycosis within endemic regions is often undiagnosed because appropriate testing is not performed. A dashboard was developed to provide information about the prevalence of coccidioidomycosis throughout the year.

Methods: Banner Urgent Care Service has many clinics within Maricopa County, Arizona, a highly endemic region for coccidioidomycosis.

Antigenic Relatedness between Mannans from and Spherules and Mycelia.

Immunoassays for cell wall mannans that are excreted into serum and urine have been used as an aid in the diagnosis of many disseminated fungal infections, including coccidioidomycosis. Antigen-detection immunoassays are critically dependent on the detection of an analyte, such as mannan, by antibodies that are specific to the analyte. The goal of this study was to evaluate the extent of cross-reactivity of polyclonal antibodies raised against spp.

Genetic and Other Determinants for the Severity of Coccidioidomycosis: A Clinician's Perspective.

The endemic fungal infection, coccidioidomycosis, occurs after inhalation of one or very few spp. spores. Infections produce diverse clinical manifestations, ranging from insignificant to extremely destructive, even fatal.

Improving Early Recognition of Coccidioidomycosis in Urgent Care Clinics: Analysis of an Implemented Education Program.

Background: Only 0.2% of coccidioidomycosis (CM) diagnoses were made in patients (pts) with pneumonia (PNA) in urgent care (UC), because they were not being tested for CM. Our objective in this study was to improve CM testing rates.

Reactivation of Coccidioidomycosis in a Mouse Model of Asymptomatic Controlled Disease.

The majority of human coccidioidomycosis infections are asymptomatic or self-limited but may have sequestered spherules in highly structured granulomas. Under immunosuppression, reactivation of fungal growth can result in severe disease. B6D2F1 mice asymptomatically infected with C.

Natural history of pulmonary coccidioidomycosis: Further examination of the VA-Armed Forces Database.

There are still many limitations related to the understanding of the natural history of differing forms of coccidioidomycosis (CM), including characterizing the spectrum of pulmonary disease. The historical Veterans Administration-Armed Forces database, recorded primarily before the advent of antifungal therapy, presents an opportunity to characterize the natural history of pulmonary CM. We performed a retrospective cohort study of 342 armed forces service members who were diagnosed with pulmonary CM at VA facilities between 1955 to 1958, followed through 1966, who did not receive antifungal therapy.

Vaccines to Prevent Coccidioidomycosis: A Gene-Deletion Mutant of Coccidioides Posadasii as a Viable Candidate for Human Trials.

Coccidioidomycosis is an endemic fungal infection that is reported in up to 20,000 persons per year and has an economic impact close to $1.5 billion. Natural infection virtually always confers protection from future exposure, and this suggests that a preventative vaccine strategy is likely to succeed.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

Cross-Sectional Study of Clinical Predictors of Coccidioidomycosis, Arizona, USA.

Demographic and clinical indicators have been described to support identification of coccidioidomycosis; however, the interplay of these conditions has not been explored in a clinical setting. In 2019, we enrolled 392 participants in a cross-sectional study for suspected coccidioidomycosis in emergency departments and inpatient units in Coccidioides-endemic regions. We aimed to develop a predictive model among participants with suspected coccidioidomycosis.

The WOPR family protein Ryp1 is a key regulator of gene expression, development, and virulence in the thermally dimorphic fungal pathogen Coccidioides posadasii.

Coccidioides spp. are mammalian fungal pathogens endemic to the Southwestern US and other desert regions of Mexico, Central and South America, with the bulk of US infections occurring in California and Arizona. In the soil, Coccidioides grows in a hyphal form that differentiates into 3-5 micron asexual spores (arthroconidia).

TNFα Blockade Inhibits Both Initial and Continued Control of Pulmonary .

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in infection remains poorly understood. The need to understand TNFα in infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice.

Contribution of Biologic Response Modifiers to the Risk of Coccidioidomycosis Severity.

Background: The risk of coccidioidomycosis (CM) as a life-threatening respiratory illness or disseminated CM (DCM) increases as much as 150-fold in immunosuppressed patients. The safety of biologic response modifiers (BRMs) as treatment for patients with autoimmune disease (AI) in CM-endemic regions is not well defined. We sought to determine that risk in the Tucson and Phoenix areas.

Mouse Model of a Human STAT4 Point Mutation That Predisposes to Disseminated Coccidiomycosis.

STAT4 plays a critical role in the generation of both innate and adaptive immune responses. In the absence of STAT4, Th1 responses, critical for resistance to fungal disease, do not occur. Infection with the dimorphic fungus, , is a major cause of community-acquired pneumonia in the endemic regions of Arizona and California.

Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis.

Disseminated coccidioidomycosis (DCM), often a severe and refractory disease leading to poor outcomes, is a risk for people with certain primary immunodeficiencies (PID). Several DCM-associated PID (STAT4, STAT3, IFNγ, and Dectin-1) are modeled in mice. To determine if vaccination could provide these mice protection, mice with mutations in , , , (Dectin-1), and Rag-1 (T- and B-cell deficient) knockout (KO) mice were vaccinated with the live, avirulent, Δ vaccine strain and subsequently challenged intranasally with pathogenic Silveira strain.

A randomized, double-blind, placebo-controlled clinical trial of fluconazole as early empiric treatment of coccidioidomycosis pneumonia (Valley Fever) in adults presenting with community-acquired pneumonia in endemic areas (FLEET-Valley Fever).

Introduction: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown.

FDA Public Workshop Summary-Coccidioidomycosis (Valley Fever): Considerations for Development of Antifungal Drugs.

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common.

Clinical and Economic Burden of Valley Fever in Arizona: An Incidence-Based Cost-of-Illness Analysis.

Background: Coccidioidomycosis, ie, Valley fever, is an important fungal infection in the Southwest, with half to two thirds of all cases occurring in Arizona. This endemic respiratory disease can range from primary uncomplicated pneumonia to disseminated infection such as meningitis with chronic pulmonary complications. Valley fever diagnoses have risen over recent years and cause substantial morbidity and economic burden in Arizona.