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We describe the epidemiology of coccidioidomycosis among a national cohort of Veterans. Using electronic health record data from adults tested for coccidioidomycosis between 1 January 2013 and 31 December 2022, we analyzed differences in baseline demographics (age, sex, race/ethnicity, birth country, comorbidities, residence, and Charlson Comorbidity Index score) between 4204 coccidioidomycosis-test-positive and 63,322 test-negative Veterans. Log-binomial regression models with adjusted risk ratios (aRRs) were used to evaluate risk factors associated with coccidioidomycosis including dissemination, hospitalization, and mortality. Case counts and incidence rates were highest in select counties in Arizona and California where Coccidioides is endemic. Coccidioidomycosis-positive Veterans were younger, more likely to be male, and Philippine-born. The risk factors most highly associated with being coccidioidomycosis-positive included Native Hawaiian/Pacific Islander (aRR 1.068 [95%CI: 1.039–1.098]), Asian (aRR 1.060 [95%CI: 1.037–1.083]), Black (aRR 1.029 [95%CI: 1.022–1.036]), American Indian/Alaska Native (aRR 1.026 [95%CI: 1.004–1.048]) race, and Hispanic/Latino ethnicity (aRR 1.021 [95%CI: 1.013–1.028]). Black race (aRR: 1.058 [95%CI: 1.037–1.081]) and Hispanic/Latino ethnicity (aRR 1.018 [95%CI: 1.0003–1.036]) were also associated with disseminated coccidioidomycosis, strengthening the evidence for the association of coccidioidomycosis, including severe infections, with specific racial and ethnic groups. There were no statistically significant differences in hospitalization within 45 days of testing or 30-day all-cause mortality. Improving our understanding of coccidioidomycosis risk factors is important for targeted prevention strategies and to reduce delays in diagnosis and ineffective treatment.

BackgroundCoccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations.Materials and methodsWe identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci.ResultsUsing univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making.ConclusionsCareful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

The Temblor Mountain Special Recreation Area (SRMA) on the western flank of the San Joaquin Valley, CA, is located in the endemic area of Coccidioides, a fungal pathogen responsible for the increasing incidence of coccidioidomycosis (Valley fever). Recreationists in the SRMA, such as off-highway vehicle (OHV) drivers and mountain bikers who disturb the soils, are at risk of being exposed to airborne arthroconidia (asexual spores) of the pathogen. To reduce the risk of pathogen exposure for visitors, the Bureau of Land Management (BLM) plans to limit recreational activities to areas with a reduced pathogen presence. They envision an official OHV park in the future, by also restricting access to areas with ongoing restoration efforts and by limiting soil erosion in sensitive areas. To investigate which soils in the Temblor SRMA are most likely to support the growth of Coccidioides spp., soil samples were collected over a 3-year period from dominant soil types in a northern and a southern sampling area and analyzed for the pathogen using a culture-independent PCR-based method. In addition, soil pH and electrical conductivity were determined. The results of this study revealed slight genetic variance in the Coccidioides sequences obtained from the soils of the Temblor SRMA. An analysis of variance (ANOVA) could not confirm differences in soil pH and electrical conductivity (EC) between the different soil types investigated and between sites where the pathogen was detected compared to sites where it could not be found. However, the year of sampling appeared to have an influence on observed soil pH and EC, and the presence of the pathogen. Of all dominant soil types investigated, those belonging to the Littlesignal–Cochora association were the least likely to contain the pathogen, whereas soils of the Beam–Panoza–Hillbrick association appeared more supportive. In addition to pointing out OHV areas with lower pathogen exposure risk in the Temblor SRMA, recommendations were made to educate visitors and BLM workers about the risk of contracting Valley fever.

Background The nonspecific symptoms of Valley fever, or coccidioidomycosis, hinders its proper diagnosis. This results in unnecessary health care costs and antibiotic usage. Thus, this study seeks to determine the coverage of the Valley fever diagnostic test as provided by Arizona insurance companies to increase early diagnosis rates. Methods Through scripted messaging and telephone communications, we contacted 40 health insurance companies in Arizona about their coverage of CPT 86635 (antibody diagnostic assay for Coccidioides) without prior authorization under all plan types provided in both primary and urgent care settings. If prior authorization was required, we discussed the coverage of ICD-10 codes J18.9 (pneumonia, unspecified organism), J18.1 (lobar pneumonia, unspecified organism), or L52 (erythema nodosum). Results Of the 40 health insurance companies contacted, 25 did not answer our inquiries, most requiring member-specific information to share coverage data. The remaining 15 companies covered Valley fever testing, of which 4 required prior authorization for the ICD-10 codes of interest. Of these 15 companies, 14 provided coverage in primary and urgent care settings, and 13 provided coverage for all available plans. Conclusion All payers that provided information covered Valley Fever testing. Most of the insurance companies that were unable to answer our inquiry likely cover Valley fever testing, but were unable to share information with third party inquiries. Obtaining general coverage information is difficult, which can potentially impact patient care.

Anomalous bronchial arteries originate outside the space bound by the T5 and T6 vertebrae at the major bronchi. Here, we highlight a case of a 37-year-old man with a past medical history of coccidioidomycosis and who presented with massive hemoptysis. A bronchial angiogram showed the patient had a right bronchial artery originating anomalously from the left subclavian artery. The patient ultimately underwent a bronchial artery embolization, after which he achieved symptomatic remission.

Background Knowledge of the clinical and magnetic resonance imaging (MRI) features of intracranial Coccidioides infection in dogs is essential for prompt diagnosis to limit disease‐associated morbidity and death. Objectives To describe the MRI appearance of intracranial coccidioidomycosis in dogs, identify associated clinical and clinicopathologic findings, and report outcomes of medical treatment. Animals Forty‐five client‐owned dogs with presumed intracranial Coccidioides infection. Methods Retrospective case series. Medical records and images were reviewed. Clinical history, examination findings, serology, imaging characteristics, treatment, and outcome were recorded. Included cases had an abnormal brain MRI and positive Coccidioides serology by agar‐gel‐immunodiffusion (AGID). Results Median age was 7‐years. Generalized tonic‐clonic seizures were the most common presenting sign (25/45). Two lesion categories were identified: a granulomatous form with 1 or more distinct, intra‐axial, contrast‐enhancing foci (37/45), and a second variation with diffuse, bilateral, symmetrical lesions of the caudate nuclei and frontal lobes (8/45). Serum IgG titers ranged from 1 : 1 to ≥ 1 : 256; 2 dogs had positive IgM titers at 1 : 2. All dogs with follow‐up serology (34/45) had a reduction in titer. Mean duration of follow‐up was 22.4 ± 20.5 months (median 16 months). Six dogs were lost to follow‐up 1‐year. Of the remaining 34 dogs, 28 (82%) were alive ≥ 1‐year after diagnosis. Thirteen of these dogs had follow‐up times ≥ 2‐years. Conclusions and Clinical Importance The prognosis for intracranial Coccidioides infection is generally more favorable with medical treatment than in earlier reports.

Purpose of Review Coccidioidomycosis is an infectious disease that gained clinical significance in the early 20th century. Many of the foundational contributions to coccidioidomycosis research, including the discovery of the fungal disease agent, Coccidioides spp., were made by women. We review recent progress in Coccidioides research and big questions remaining in the field, while highlighting some of the contributions from women. Recent Findings New molecular-based techniques provide a promising method for detecting Coccidioides, which can help determine the dominate reservoir host and ideal environmental conditions for growth. Genetic and genomic analyses have allowed an understanding of population structure, species level diversity, and evolutionary histories. We present a current, comprehensive genome list, where women contributed many of these entries. Several efforts to develop a coccidioidomycosis vaccine are underway. Summary Women continue to pioneer research on Coccidioides, including the relationships between the fungi and the environment, genetics, and clinical observations. Significant questions remain in the field of Coccidioides, including the main host reservoir, the relationships between genotypic and phenotypic variation, and the underlying cause for chronic clinical coccidioidomycosis cases.

Coccidioides immitis and posadasii are closely related fungal species that cause coccidioidomycosis. These dimorphic organisms cause disease in immunocompetent as well as immunocompromised individuals and as much as 40% of the population is infected in the endemic area. Although most infections resolve spontaneously, the infection can be prolonged and, in some instances, fatal. Coccidioides has been studied for more than 100 years and many aspects of the organism and the disease it causes have been investigated. There are over 500 manuscripts concerning Coccidioides (excluding clinical articles) referenced in PubMed over the past 50 years, so there is a large body of evidence to review. We reviewed the most accurate and informative basic research studies of these fungi including some seminal older studies as well as an extensive review of current research. This is an attempt to gather the most important basic research studies about this fungus into one publication. To focus this review, we will discuss the mycology of the organism exclusively rather than the studies of the host response or clinical studies. We hope that this review will be a useful resource to those interested in Coccidioides and coccidioidomycosis.

Coccidioidomycosis is a typically respiratory fungal disease that, in the United States, occurs primarily in Arizona and California. In California, most coccidioidomycosis cases occur in the San Joaquin Valley, a primarily agricultural region where the disease poses a risk for outdoor workers. We collected 710 soil samples and 265 settled dust samples from nine sites in the San Joaquin Valley and examined how Coccidioides detection varied by month, site, and the presence and abundance of other fungal species. We detected Coccidioides in 89 of 238 (37.4%) rodent burrow soil samples at five undeveloped sites and were unable to detect Coccidioides in any of 472 surface and subsurface soil samples at four agricultural sites. In what is the largest sampling effort undertaken on agricultural land, our results provide no evidence that agricultural soils in the San Joaquin Valley harbor Coccidioides. We found no clear association between Coccidioides and the greater soil fungal community, but we identified 19 fungal indicator species that were significantly associated with Coccidioides detection in burrows. We also did not find a seasonal pattern in Coccidioides detection in the rodent burrow soils we sampled. These findings suggest both the presence of a spore bank and that coccidioidomycosis incidence may be more strongly associated with Coccidioides dispersal than Coccidioides growth. Finally, we were able to detect Coccidioides in only five of our 265 near-surface settled dust samples, one from agricultural land, where Coccidioides was undetected in soils, and four from undeveloped land, where Coccidioides was common in the rodent burrow soils we sampled. Our ability to detect Coccidioides in few settled dust samples indicates that improved methods are likely needed moving forward, though raises questions regarding aerial dispersal in Coccidioides, whose key transmission event likely occurs over short distances in rodent burrows from soil to naïve rodent lungs.

In Kazakhstan natural foci of Crimea-Congo hemorrhagic fever is located on the territory of Turkestan, Kyzylorda and Zhambyl regions. Whereas preventive measures are taken, this disease is diagnosed annually among people, but there is a group of viruses such as Karshi, Tamdy, the Issyk-Kul fever virus and Syr Darya valley fever which are less known. In this regard the goal was set to identify the prevalence of viruses of Karshi, Tamdy, Issyk-Kul fever and fever of the Syr Darya valley in hemorrhagic fever endemic in the Crimea-Congo hemorrhagic fever to determine the main hosts and vectors of infection. Ticks captured in areas natural foci of the Crimean-Congo hemorrhagic fever virus. The species composition of captured ticks was represented by 9 species: Hyalomma scupense, Hyalomma asiaticum, Hyalomma turanicum, Hyalomma anatolicum, Haemaphysalis sucata, Haemaphysalis punctata, Dermacentor niveus, Rhipicephalus pumilio, Rhipicephalus schulzei. Preliminary work was carried out on the selection and design of oligonucleotide primers for the identification of viruses by molecular genetic analysis. As a result of the studies, positive samples were found for viruses of Tamdy and Syr Darya valley fever in ticks H. asiaticum, H. scupense from the Turkestan region. The Crimean-Congo hemorrhagic fever virus was detected in H. asiaticum and H. scupense ticks from Zhambyl and Turkestan regions.

The soil-borne fungal disease coccidioidomycosis (Valley fever) is prevalent across the southwestern United States (US). Previous studies have suggested that the occurrence of this infection is associated with anomalously wet or dry soil moisture states described by the “grow and blow” hypothesis. The growth of coccidioidomycosis is favored by moist conditions both at the surface and in the root zone. A statistical analysis identified two areas in Arizona and central California, with a moderate-to-high number of coccidioidomycosis cases. A Wavelet Transform Coherence (WTC) analysis between El Nino Southern Oscillation (ENSO), coccidioidomycosis cases, surface soil moisture (SSM; 0 to 5 cm) from European Space Agency-Climate Change Initiative (ESA-CCI), and shallow root zone soil moisture (RZSM; 0 to 40 cm depth) from Soil MERGE (SMERGE) was executed for twenty-four CA and AZ counties. In AZ, only SSM was modulated by ENSO. When case values were adjusted for overreporting between 2009 to 2012, a moderate but significant connection between ENSO and cases was observed at a short periodicity (2.1 years). In central CA, SSM, RZSM, and cases all had a significant link to ENSO at longer periodicities (5-to-7 years). This study provides an example of how oceanic-atmospheric teleconnections can impact human health.

The San Joaquin Valley in Central California is a semiarid region that is known to be highly endemic for coccidioidomycosis infections in high-risk groups. Coccidioidomycosis, also known as valley fever, is caused by the fungal spore Coccidioides, which can be found in the soil in arid and semiarid regions in the Southwest United States and parts of Central and South America. When soil is disturbed through excavation, agricultural activities, or with any other soil movement, these activities can release the fungal spores into air; people who are in close proximity can potentially inhale them. The purpose of this clinical case study is to address the need for coccidioidomycosis infection awareness and educate primary care providers to determine the diagnostic reasoning and process. A simple algorithm and template will aid them to accurately diagnose and treat patients with valley fever earlier in the disease process., Highlights • This article includes education for primary care providers on the pathophysiology, clinical symptoms, diagnostics, and treatments of valley fever. • Evidenced-based research is presented on occupational exposure to dust from soil disturbing activities. • Primary care providers are educated about valley fever and dust exposure using the acronym COCCI (Consider the diagnosis, Order the right tests, Check for risk factors, Check for complications, and Initiate management).

Acute Febrile Neutrophilic Dermatosis, also known as Sweet Syndrome, is an uncommon inflammatory disorder. Though the exact etiology is unclear, it has been presented in association with various entities. The majority of cases present following upper respiratory infections or viral gastroenteritis. Other causes include drug-induced reactions, pregnancy-related manifestations, or in association with specific hematologic or solid tumors. Rarely, it has been associated with Coccidioidomycosis, a prevalent fungus endemic to the Southwestern regions of the United States with a literature review revealing only three previous cases of Coccidioidomycosis-associated Sweet Syndrome. Here we report two new cases in individuals residing in Arizona.

No abstract available. Article truncated after 150 words. A 31-year-old male fire fighter with a history of recurrent “atypical pneumonia,” environmental and drug allergies, nasal polyps, asthma, and Crohn's disease (not on immunosuppressants) was transferred from an outside hospital for management of acute hypoxic respiratory failure with peripheral eosinophilia. Prior to admission he reported a 2-week history of worsening dyspnea, productive cough and wheezing, prompting an urgent care visit where he was prescribed amoxicillin-clavulanate for suspected community acquired pneumonia. Despite multiple days on this medication, his symptoms significantly worsened until he was unable to lie flat without coughing or wheezing. He was ultimately admitted to an outside hospital where his labs were notable for a leukocytosis to 22,000 and peripheral eosinophilia with an absolute eosinophil count of 9700 cells/microL. His blood cultures and urine cultures were negative, and a radiograph of the chest demonstrated bilateral nodular infiltrates. With these imaging findings combined with the peripheral eosinophilia there was …

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.

Coccidioidomycosis (Valley fever) is an infection caused by the soil-dwelling fungus Coccidioides spp., which usually manifests as a mild self-limited respiratory illness or pneumonia but can result in severe disseminated disease and, rarely, death (1,2). In California, coccidioidomycosis incidence increased nearly 800% from 2000 (2.4 cases per 100,000 population) to 2018 (18.8) (2-4). The California Department of Public Health (CDPH) reports statewide and county-level coccidioidomycosis incidence annually; however, a comprehensive regional analysis has not been conducted. Using California coccidioidomycosis surveillance data during 2000-2018, age-adjusted incidence rates were calculated, and coccidioidomycosis epidemiology was described in six regions. During 2000-2018, a total of 65,438 coccidioidomycosis cases were reported in California; median statewide annual incidence was 7.9 per 100,000 population and varied by region from 1.1 in Northern and Eastern California to 90.6 in the Southern San Joaquin Valley, with the largest increase (15-fold) occurring in the Northern San Joaquin Valley. When analyzing demographic data, which was available for >99% of cases for sex and age and 59% of cases for race/ethnicity, median annual incidence was high among males (10.2) and Black persons (9.0) consistently across all regions; however, incidence varied among Hispanics and adults aged 40-59 years by region. Tracking these surveillance data at the regional level reinforced understanding of where and among what demographic groups coccidioidomycosis rates have been highest and revealed where rates are increasing most dramatically. The results of this analysis influenced the planning of a statewide coccidioidomycosis awareness campaign so that the messaging, including social media and TV and radio segments, focused not only on the general population in the areas with the highest rates, but also in areas where coccidioidomycosis is increasing at the fastest rates and with messaging targeted to groups at highest risk in those areas.

No abstract available. Article truncated after the first page. History of Present Illness An 88-year-old man who has been short of breath and febrile up to 101.5° F for the past day presented on October 20, 2020. He has no known sick contacts or exposure to COVID-19. PMH, SH, and FH • No reported pulmonary history although he had a Xopenex MDI which he rarely used. • Coronary artery disease with prior coronary artery bypass grafting (1978); multiple subsequent stents; chronic atrial fibrillation; pacemaker (Micra) • Stage 3-4 CKD (creatinine 1.95) • Chronically on warfarin Physical Examination • Temp 37.3, Sat 92% on RA, 95% on 2 lpm, • Lungs: Few crackles in right upper chest • CV: regular, no murmur • Ext: 1 to 2+ edema (chronic, uses TED hose) Which of the following is/are the most likely diagnosis? 1. Community-acquired pneumonia 2. Congestive heart failure 3. COVID-19 4. 1 and 3 5. Any of the above …

Infection of the thyroid gland with Coccidioides immitis is rare. We report a case with disseminated coccidiomycosis involving thyroid gland as a thyroid nodule. Although historical autopsy studies have indicated that coccidioidal involvement of the thyroid gland can infrequently occur as part of disseminated infection, to our knowledge, only less than 10 other cases have been reported. Optimal treatment duration and dosage of medication are uncertain in literature of this rare involvement of thyroid gland with coccidioidomycosis.

Coccidioidomycosis is a disease found in the southwestern United States and caused by inhalation of arthroconidia of Coccidioides immitis and posadasii. Although the disease is most commonly asymptomatic or respiratory, it has a propensity to disseminate to any tissue in the body with the most common being skin, bone, joints, and central nervous system. This case demonstrates the dissemination of coccidioidomycosis to several foci along with a rare form of parenchymal dissemination with an unusual neuroradiological finding.

New or emerging infectious diseases are commonly caused by pathogens that cannot be readily manipulated or studied under common laboratory conditions. These limitations hinder standard experimental approaches and our abilities to define the fundamental molecular mechanisms underlying pathogenesis. The advance of capped small RNA sequencing (csRNA-seq) now enables genome-wide mapping of actively initiated transcripts from genes and other regulatory transcribed start regions (TSRs) such as enhancers at a precise moment from total RNA. As RNA is nonpathogenic and can be readily isolated from inactivated infectious samples, csRNA-seq can detect acute changes in gene regulation within or in response to a pathogen with remarkable sensitivity under common laboratory conditions. Studying valley fever (coccidioidomycosis), an emerging endemic fungal infection that increasingly impacts livestock, pet, and human health, we show how csRNA-seq can unravel transcriptional programs driving pathogenesis. Performing csRNA-seq on RNA isolated from different stages of the valley fever pathogen Coccidioides immitis revealed alternative promoter usage, connected cis-regulatory domains, and a WOPR family transcription factor, which are known regulators of virulence in other fungi, as being critical for pathogenic growth. We further demonstrate that a C. immitis WOPR homologue, CIMG_02671, activates transcription in a WOPR motif-dependent manner. Collectively, these findings provide novel insights into valley fever pathogenesis and provide a proof of principle for csRNA-seq as a powerful means to determine the genes, regulatory mechanisms, and transcription factors that control the pathogenesis of highly infectious agents. IMPORTANCE Infectious pathogens like airborne viruses or fungal spores are difficult to study; they require high-containment facilities, special equipment, and expertise. As such, establishing approaches such as genome editing or other means to identify the factors and mechanisms underlying caused diseases, and, thus, promising drug targets, is costly and time-intensive. These obstacles particularly hinder the analysis of new, emerging, or rare infectious diseases. We recently developed a method termed capped small RNA sequencing (csRNA-seq) that enables capturing acute changes in active gene expression from total RNA. Prior to csRNA-seq, such an analysis was possible only by using living cells or nuclei, in which pathogens are highly infectious. The process of RNA purification, however, inactivates pathogens and thus enables the analysis of gene expression during disease progression under standard laboratory conditions. As a proof of principle, here, we use csRNA-seq to unravel the gene regulatory programs and factors likely critical for the pathogenesis of valley fever, an emerging endemic fungal infection that increasingly impacts livestock, pet, and human health.

Valley fever (coccidioidomycosis) is endemic in the southwestern United States and caused by inhalation of Coccidioides spp. fungal spores from soil or dust; 97% of U.S. Valley fever cases are reported from Arizona and California (1). In California, Valley fever incidence increased 213% from 2014 to 2018 (2). In 2016, the California Department of Public Health (CDPH) added three questions to the adult California Behavioral Risk Factor Surveillance System (BRFSS) survey to better understand whether Californians had heard of Valley fever, knew the environmental risk where they live, and knew who is at risk for severe disease. A total of 2,893 BRFSS respondents aged ≥18 years answered at least one Valley fever question. Using the weighted California population, 42.4% of respondents reported general awareness of Valley fever; awareness was lowest among adults aged 18-44 years (32.9%) and Hispanic persons (26.4%). In addition, despite higher percentages reporting awareness of Valley fever, only 25.0% of persons living in a high-incidence region and 3.0% of persons living in a moderate-incidence region were aware that they lived in areas where Coccidioides spp. exist. Among persons with one or more risk factors for severe disease, 50.8% reported having heard about Valley fever, but only 3.5% knew they were at increased risk for severe disease. The findings from this survey helped to inform a statewide Valley fever awareness campaign implemented during 2019-2020 and to guide outreach to persons living in high- and moderate-incidence regions in California and potentially other southwestern states or who are at risk for severe disease.

This is a case of coccidioidomycosis in a dog, examined for vomiting and labored breathing. Physical examination and thoracic and abdominal imaging revealed pleural and peritoneal effusions, both of which exhibited neutrophilic inflammation with a substantial eosinophilic component. The dog had positive IgM and IgG coccidioidomycosis titers at initial evaluation. The eosinophilic component of the inflammation was attributed to coccidioidomycosis. The dog underwent approximately 6 months of fluconazole treatment, with both effusions and clinical signs improving after 6 weeks. Three months after cessation of antifungal treatment, the dog developed a mid‐diaphyseal lytic and proliferative lesion in the left radius caused by Coccidioides spp. This case illustrates the importance of consideration of coccidioidomycosis when an eosinophilic cavitary effusion is present in dogs that live in or have traveled to endemic regions.

Background Coccidioides spp. are dimorphic fungi endemic to parts of the United States, Mexico, Central and South America. Infection can cause a range of disease from self-limited acute pneumonia to severe disseminated disease. Methods We performed a retrospective chart review of medical records of cases of culture-proven acute coccidioidomycosis at the University of California San Diego between 1 April 2015 and 31 December 2019 and described the demographics, risk factors and outcomes of these cases. Results Over the study period, fifteen evaluable cases of culture-proven acute coccidioidomycosis were identified. Of these, 87% (13/15) had traditional risk factors for coccidioidomycosis infection while two lacked known risk factors, including one patient with cirrhosis and one with chronic hepatitis C infection. Seven of fifteen (47%) had primary coccidioidomycosis of the lungs without dissemination and 7/15 (47%) disseminated disease. Of those with disseminated disease, 6/7 (86%) had either high-risk ethnicity or blood type as their only risk factor. At 90 days, 11/15 (73%) were alive, 3/15 (20%) deceased and 1/15 (7%) lost to follow-up. Of those not alive at 90 days, 1/3 (33%) had disseminated disease and 2/3 (67%) primary coccidioidomycosis, both on immunosuppressive therapy. Discussion Coccidioides spp. infection occurs in a variety of hosts with varying underlying risk factors, with the majority in our cohort overall and 86% with disseminated disease lacking traditional risk factors for invasive fungal infection other than ethnicity and/or blood phenotype. Clinicians should be aware of these non-traditional risk factors in patients with coccidioidomycosis infection.

Tumor necrosis factor alpha (TNFα) is a pluripotent cytokine that is important in many infections, though its role in Coccidioides infection remains poorly understood. The need to understand TNFα in Coccidioides infection has increased recently with the widespread use of TNFα inhibitors for a wide variety of autoimmune conditions. Here, we couple the newly developed Coccidioides infection model using strain Cp1038 and C57BL/6 × DBA/2J F1 (B6D2F1) mice. B6D2F1 mice develop long-lasting control of Cp1038. Treatment of B6D2F1 mice with anti-TNFα antibodies permits significant fungal proliferation and death. Additionally, we show that antibody treatment limited to the first 2 weeks of infection was sufficient to induce this same loss of fungal control. Importantly, anti-TNFα antibody treatment initiated after fungal control leads to a loss of host control. These results highlight the importance of TNFα in both the initial control of murine Coccidioides and ongoing suppression of the fungal disease.

Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi of arid regions in North and South America that are responsible for Valley fever (coccidioidomycosis). Forty percent of patients with Valley fever exhibit symptoms ranging from mild, self-limiting respiratory infections to severe, life-threatening pneumonia that requires treatment. Misdiagnosis as bacterial pneumonia commonly occurs in symptomatic Valley fever cases, resulting in inappropriate treatment with antibiotics, increased medical costs, and delay in diagnosis. In this proof-of-concept study, we explored the feasibility of developing breath-based diagnostics for Valley fever using a murine lung infection model. To investigate potential volatile biomarkers of Valley fever that arise from host–pathogen interactions, we infected C57BL/6J mice with C. immitis RS (n = 6), C. posadasii Silveira (n = 6), or phosphate-buffered saline (n = 4) via intranasal inoculation. We measured fungal dissemination and collected bronchoalveolar lavage fluid (BALF) for cytokine profiling and for untargeted volatile metabolomics via solid-phase microextraction (SPME) and two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS). We identified 36 volatile organic compounds (VOCs) that were significantly correlated (p < 0.05) with cytokine abundance. These 36 VOCs clustered mice by their cytokine production and were also able to separate mice with moderate-to-high cytokine production by infection strain. The data presented here show that Coccidioides and/or the host produce volatile metabolites that may yield biomarkers for a Valley fever breath test that can detect coccidioidal infection and provide clinically relevant information on primary pulmonary disease severity.

The literature on pediatric extrapulmonary coccidioidomycosis is limited. We reviewed the clinical course, diagnostic studies, treatment and outcomes of children with extrapulmonary coccidioidomycosis followed at a tertiary care center in central California.Retrospective study of 78 patients ≤21 years old with extrapulmonary coccidioidomycosis diagnosed over 10 years (1/1/07-12/31/16).The median age was 9.7 years (interquartile range, 4.5-14.8). The majority of patients were males (55%), Hispanic (65%) and without comorbid conditions (85%). Over two-thirds (68%) had concurrent pulmonary disease. Organ involvements included bones and joints (33%), mediastinum (19%), central nervous system (19%), cervical lymph nodes (15%), larynx (6%) and skin (5%). Most cases (84%) resolved and/or became stable on maintenance therapy, 14% experienced relapse and/or progressive disease, and 2% were fatal. Children ≥10 years of age tended to have1 site of involvement (47% vs. 25%, P = 0.06), and more relapsed/progressive/fatal disease (21% vs. 5%, P = 0.06) compared with those10 years. They also required longer durations of treatment (median, 611 vs. 349 days, P = 0.02). Non-Hispanics were more likely to require1 drug therapy (85% vs. 70%, P = 0.04) and tended to have Coccidioides complement fixation titers ≥1:32 (89% vs. 72%, P = 0.04) compared with Hispanics.Extrapulmonary coccidioidomycosis in children can be severe and spread to multiple sites and requires prolonged treatment. Non-Hispanics and those ≥10 years of age are more likely to experience severe disease, suggesting a need for early recognition and intervention in these populations.

Coccidioidomycosis is an emerging infection in Washington State. The epidemiology of the disease in Washington is poorly understood at present; underrecognition and underreporting of coccidioidomycosis is suspected based on reports of only severe disease. We sought to characterize healthcare provider knowledge, attitudes, and practices regarding coccidioidomycosis awareness, diagnosis, and treatment in south-central Washington. We conducted a cross-sectional survey of actively practicing healthcare providers in four counties in south-central Washington, an area recently described as endemic for Coccidioides. Survey results were used to assess awareness of reporting requirements, confidence in ability to diagnose and treat, confidence that knowledge is current, calculated knowledge score, and consideration of risk in patient population. The majority of respondents were unaware of the reporting requirement for coccidioidomycosis in Washington and further unaware that the disease had been reported in the state. Less than a third of survey respondents reported confidence in their ability to diagnose coccidioidomycosis and confidence that their knowledge is current. The majority of respondents never or rarely consider a diagnosis of coccidioidomycosis, and

Dust storms, such as those associated with haboobs and strong regional winds, are frequently assumed to cause increases in cases of Valley fever (coccidioidomycosis). The disease is caused by inhaling arthroconidia of Coccidioides fungi that, after being disturbed from semi‐desert subsoil, have become airborne. Fungal arthroconidia can be transported in low‐wind conditions as well as in individual dust events, but there is no reliable evidence that all or most dust storms consistently lead to subsequent increases in coccidioidomycosis cases. Following a review of the relevant literature, this study examines the relationship between dust storms and coccidioidomycosis cases to determine if there is a consistent and general association between them. All recorded dust storms from 2006 to 2020 in and near the Phoenix area of Maricopa County, Arizona and the Bakersfield area of Kern County, California were used in a compositing analysis (superposed epoch analysis) of subsequent coccidioidomycosis cases in each area. Analyses of monthly and weekly disease case data showed no statistical differences in the patterns of coccidioidomycosis cases following dust storms versus non‐dust storm conditions, for the entire data set as well as for seasonal subsets of the data. This study thoroughly analyzes post‐dust storm coccidioidomycosis cases for a large set of dust storms, and it confirms and expands upon previous literature, including a recent study that measured airborne arthroconidia and found no consistent links connecting wind and dust conditions to increases in coccidioidomycosis., Key Points It is often asserted that large dust storms like haboobs generally lead to increases in cases of Valley fever (coccidioidomycosis)This study thoroughly tests that assertion using dust storm and coccidioidomycosis case data over many yearsConsistent with literature, results show no statistical difference in cases of the disease after dust storm and non‐dust‐storm conditions

Coccidioides immitis and Coccidioides posadasii are causative agents of Valley fever, a serious fungal disease endemic to regions with hot, arid climate in the United States, Mexico, and Central and South America. The environmental niche of Coccidioides spp. is not well defined, and it remains unknown whether these fungi are primarily associated with rodents or grow as saprotrophs in soil. To better understand the environmental reservoir of these pathogens, we used a systematic soil sampling approach, quantitative PCR (qPCR), culture, whole-genome sequencing, and soil chemical analysis to identify factors associated with the presence of C. immitis at a known colonization site in Washington State linked to a human case in 2010. We found that the same strain colonized an area of over 46,000 m2 and persisted in soil for over 6 years. No association with rodent burrows was observed, as C. immitis DNA was as likely to be detected inside rodent holes as it was in the surrounding soil. In addition, the presence of C. immitis DNA in soil was correlated with elevated levels of boron, calcium, magnesium, sodium, and silicon in soil leachates. We also observed differences in the microbial communities between C. immitis-positive and -negative soils. Our artificial soil inoculation experiments demonstrated that C. immitis can use soil as a sole source of nutrients. Taken together, these results suggest that soil parameters need to be considered when modeling the distribution of this fungus in the environment. IMPORTANCE Coccidioidomycosis is considered a highly endemic disease for which geographic range is likely to expand from climate change. A better understanding of the ecological niche of Coccidioides spp. is essential for generating accurate distribution maps and predicting future changes in response to the changing environment. Our study used a systematic sampling strategy, advanced molecular detection methods, and soil chemical analysis to identify environmental factors associated with the presence of C. immitis in soil. Our results demonstrate the fungus can colonize the same areas for years and is associated with chemical and microbiological soil characteristics. Our results suggest that in addition to climate parameters, soil characteristics need to be considered when building habitat distribution models for this pathogen.

Transition metals are necessary cofactors and structural elements in living systems. Exposure to high concentrations of biologically important transition metals, such as zinc and copper, results in cell toxicity. At the infection site, the immune system deploys metal sorbent proteins (e.g., lactoferrin and calprotectin) to starve pathogens of necessary metals (such as iron), while phagocytes expose engulfed pathogens to high levels of other metals, such as copper and zinc. The opportunistic pathogen Streptococcus pneumoniae (the pneumococcus) encounters macrophages during initial and protracted infections. The pneumococcus employs a copper export pathway, which improves colonization and persistent infection of the nasopharynx and the upper respiratory tract. Because copper is tightly regulated in the host, we instead sought to leverage the localized power of nutritional immunity by identifying small molecules with copper-dependent toxicity (CDT) through a targeted screen of compounds for antibiotic efficacy. We chose to include dithiocarbamates, based on the copper synergy observed in other organisms with 1-(diethylthiocarbamoyldisulfanyl)-N,N-diethyl-methanethioamide (tetraethylthiuram disulfide, disulfiram). We observed CDT of some dithiocarbamates in S. pneumoniae. Only N,N-dimethyldithiocarbamate (DMDC) was consistently toxic across a range of concentrations with copper both in vitro and in vivo against the pneumococcus. We also observed various degrees of CDT in vitro using DMDC in Staphylococcus aureus, Coccidioides posadasii, and Schistosoma mansoni. Collectively, we demonstrate that the compound DMDC is a potent bactericidal compound against S. pneumoniae with antimicrobial efficacy against bacterial and fungal pathogens. IMPORTANCE With the rise of antibiotic resistance, approaches that add new antimicrobials to the current repertoire are vital. Here, we investigate putative and known copper ionophores in an attempt to intoxicate bacteria and use ionophore/copper synergy, and we ultimately find success with N,N-dimethyldithiocarbamate (DMDC). We show that DMDC has in vitro efficacy in a copper-dependent manner and kills pathogens across three different kingdoms, Streptococcus pneumoniae, Coccidioides posadasii, and Schistosoma mansoni, and in vivo efficacy against S. pneumoniae. As such, dithiocarbamates represent a new potential class of antimicrobials and thus warrant further mechanistic investigation.

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. Methods Phase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. Objectives The primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. Discussion This trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed., Highlights • Clinical impact of early antifungal therapy for pneumonia in Coccidioides endemic regions is unknown. • We designed a phase IV trial in adults with community-acquired pneumonia in regions endemic for Coccidioides. • Trial was halted early due to slow enrollment and low prevalence of coccidioidomycosis in the enrollment population. • Lost to follow-up and treatment discontinuation were common in this trial.

The Southwestern USA has been identified as one of the most persistent dust-producing regions of North America, where exposure to inhalable particulate matter (PM10) originating from desertic landscape during dust events/dust exposures (DEs) can reach hazardous levels. El Paso, Texas’s ambient air has reached hazardous levels of PM10 from dust with near zero visibility due to these natural events originating in the surrounding Chihuahuan Desert. The aim of this study was to investigate whether dust exposures in El Paso (generally acute, short-term exposures from nearby source areas) are associated with significant increases in hospitalizations on the day of the exposure and up to seven days afterwards. Using a Poisson regression, it was found that the relative risks of hospitalizations due to a variety of conditions were associated with dust exposures (through increases of 100 μg/m3 maximum hourly PM10 and/or increases of 4.5 m/s maximum hourly wind speed) in El Paso County, Texas between 2010 and 2014. Valley fever, coronary atherosclerosis, genitourinary diseases, neurodegenerative diseases, injury and poisoning, circulatory system conditions, respiratory system diseases, births, septicemia, Associated Diseases (the aggregation of hospital admissions for all causes, each associated with at least 5% of hospitalizations), and all ICD-9 admissions were significantly positively associated with dust exposures, indicated from higher to lower significant risk, at different lag periods after exposure. These findings, showing that an association does exist between dust exposures and hospitalizations, have important implications for residents of the world’s dryland cities.

Coccidioidomycosis is a fungal, respiratory disease caused by Coccidioides immitis and Coccidioides posadasii. The host immune responses that define disease outcome during infection are largely unknown, although T helper responses are required. Adaptive immunity is influenced by innate immunity as antigen-presenting cells activate and educate adaptive responses. Macrophage and dendritic cell (DC) recognition of pathogen surface molecules are critical for Coccidioides clearance. We characterize the broad innate immune responses to Coccidioides by analyzing macrophage and dendritic cell responses to Coccidioides arthroconidia using avirulent, vaccine Coccidioides strain NR-166 (Δcts2/Δard1/Δcts3), developed from parental virulent strain C735. We developed a novel flow cytometry-based method to analyze macrophage phagocytosis to complement traditional image-scoring methods. Our study found that macrophage polarization is blocked at M0 phase and activation reduced, while DCs polarize into proinflammatory DC1s, but not anti-inflammatory DC2, following interaction with Coccidioides. However, DCs exhibit a contact-dependent reduced activation to Coccidioides as defined by co-expression of MHC-II and CD86. In vivo, only modest DC1/DC2 recruitment and activation was observed with avirulent Coccidioides infection. In conclusion, the vaccine Coccidioides strain recruited a mixed DC population in vivo, while in vitro data suggest active innate immune cell inhibition by Coccidioides.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption of small, nonfollicular, sterile pustules on an edematous and erythematous background. This cutaneous eruption is frequently accompanied by systemic findings, including fever and leukocytosis. Although the vast majority of AGEP cases are associated with medications, infectious causes have been implicated.1, 2, 3 Once the underlying cause is addressed, symptoms typically resolve spontaneously within 2 weeks. Given the potential for serious comorbidities, identifying the underlying cause is imperative for successful outcome. This case report describes AGEP associated with an acute coccidioidomycosis infection.

No abstract available. Article truncated after 150 words. There are a number of books and articles written by doctors that relate their own experience as patients. Count this as another although I promise it will not be nearly as entertaining as “The House of God”. Over a month ago I became short of breath and a chest x-ray revealed left lower lobe consolidation. Despite lack of fever, it seemed that an infectious process was most likely, and when multiple tests for COVID-19 were negative, it was felt by my pulmonary physician to be most likely coccidioidomycosis despite a negative cocci serology. After beginning on empirical therapy with fluconazole for nearly a month, I am feeling better. Most of us know that there is considerable laboratory to laboratory variation in serologic tests for Valley Fever (1). However, when my initial cocci serology was negative, efforts to send it a good reference lab such as Pappagianis’ Lab at UC Davis …

Coccidioidomycosis, or valley fever, is an infectious fungal disease currently endemic to the southwestern United States. Symptoms of valley fever range in severity from flu-like illness to severe morbidity and mortality. Warming temperatures and changes in precipitation patterns may cause the area of endemicity to expand northward throughout the western United States, putting more people at risk for contracting valley fever. This may increase the health and economic burdens from this disease. We developed an approach to describe the relationship between climate conditions and valley fever incidence using historical data and generated projections of future incidence in response to both climate change and population trends using the Climate Change Impacts and Risk Analysis (CIRA) framework developed by the U.S. Environmental Protection Agency. We also developed a method to estimate economic impacts of valley fever that is based on case counts. For our 2000–15 baseline time period, we estimated annual medical costs, lost income, and economic welfare losses for valley fever in the United States were $400,000 per case, and the annual average total cost was $3.9 billion per year. For a high greenhouse gas emission scenario and accounting for population growth, we found that total annual costs for valley fever may increase up to 164% by year 2050 and up to 380% by 2090. By the end of the twenty-first century, valley fever may cost $620,000 per case and the annual average total cost may reach $18.5 billion per year. This work contributes to the broader effort to monetize climate change–attributable damages in the United States.

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. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development.

Coccidioidomycosis is an infection caused by inhalation of arthroconidia of Coccidioides. Forty percent of patients will develop mild and self-limited respiratory infection, and a small fraction of these individuals will develop extrapulmonary disseminated disease. This is the case of a patient with a known history of disseminated coccidioidomycosis, who initially presented for symptoms of persistent pneumonia. On evaluation, the patient was found to have a hepatic abscess for which he underwent percutaneous drainage. Culture grew Coccidioides immitis, and the patient was treated with systemic antifungal. This is a rare case of disseminated coccidioidomycosis in the liver.

Pulmonary coccidioidomycosis and pulmonary actinomycosis are unheard of as co-pathogens. Infection with these organisms on their own can mimic lung cancer, thus presenting a diagnostic challenge. We present the case of a 75-year-old woman presenting with haemoptysis with a chest CT chest finding of a lung mass suggestive of lung cancer. A diagnosis of concomitant infection by Coccidioides posadasii/immitis and Actinomyces odontolyticus was made based on culture and histopathology results. The patient was successfully treated with a combination of antifungal and antibacterial therapy. This is the first reported case of co-infection by these two microorganisms. LEARNING POINTS: Pulmonary coccidioidomycosis and pulmonary actinomycosis can mimic lung cancer. The diagnosis of infection by Coccidioides posadasii/immitis and Actinomyces odontolyticus is best obtained by histopathology and tissue culture. Treatment comprises a combination of oral azoles and a beta-lactam antibiotic for a total of 12 months.

Coccidioides species are the etiological agent of Valley fever (Vf). Disease ranges from pneumonia to extrapulmonary infection. If diagnosis is delayed or missed, the risk of severe disease increases. We investigate the disease triangle (intersection of pathogen, host, and environment) of Vf in Northern Arizona, where the risk of acquiring the disease is lower but prevalent and rising. We inspect reported and hospitalized cases of VF hosts. Then assess pathogen origin by comparing Northern Arizona clinical isolates to isolates from other regions. Lastly, we survey Northern Arizona soils for evidence of Coccidioides. We found that cases of Vf are increasing some requiring hospitalization. The Northern Arizona Coccidioidies isolates were genetically related to Southern Arizona populations. However, we detected Coccidioides DNA in Northern Arizona soils. We expect that cases will continue to increase and suggest increased awareness and screening for the disease is crucial to limit severe illness in Northern Arizona.Article Summary LineOur work is the first description of the Valley fever disease triangle in Northern Arizona, which considers the complex interaction between host, pathogen and environment in the region. Our data suggests that the prevalence of diagnosed cases is rising in the region, some of which are extreme enough to 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 anticipate that incidence of Valley fever will rise in the area. Therefore, enhanced disease awareness and screening for the coccidioidomycosis is vital to the communities of Northern Arizona.

Coccidioides immitis (and Coccidioides posadasii) are endemic fungi of the southwestern United States and northern Mexico. Uncomplicated, symptomatic Coccidioides infection most commonly causes a self-limited pneumonia; however, immunocompromised patients can manifest severe pneumonia with an additional risk of dissemination to bone, joints, soft tissues, and in the most severe cases, the central nervous system. In 2020, clinicians were challenged with a previously unseen volume of acute respiratory complaints as a result of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We present a patient with respiratory failure secondary to SARS-CoV-2 who experienced prolonged hypoxia and neurologic deterioration, eventually leading to a diagnosis of occult disseminated coccidiomycosis involving meningitis, miliary-pattern pneumonia, and cutaneous lesions.

Background Coccidioidomycosis is often diagnosed with a collection of tests that rely on the patient’s ability to mount an immune response to the fungus (antibody-based diagnostics), making diagnosis of this infection challenging. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in human serum. Methods An inhibition-based enzyme-linked immunoassay (ELISA) was developed that utilizes a monoclonal antibody specific for coccidioidal CTS1. CTS1 was quantified in commercial antigen preparations using recombinant CTS1 as a standard. Sera from 192 individuals from an endemic area were tested, which included 78 patients (40.6%) with proven or probable coccidioidomycosis. Results The quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. CTS1 antigenemia was detected in 87.2% of patients with proven or probable coccidioidomycosis. Specificity was determined to be 96.94% using serum from individuals who reside in the Phoenix, Arizona area who did not have coccidioidomycosis. Levels of CTS1 correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Conclusions Since the CTS1 inhibition ELISA described in this report does not depend on the host immune response, it is a promising diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis., Diagnosis of coccidioidomycosis often relies on the host’s ability to mount an immune response. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 in human serum to diagnose coccidioidomycosis independent of host immune status.

Coccidioides spp. are important pathogens in regions where they are endemic, and new treatment options are needed. Here, isavuconazonium sulfate (ISAVUSULF) and fluconazole (FLU) were evaluated in experimental disseminated coccidioidomycosis to characterize drug exposures associated with efficacy. Broth macrodilution was performed on Coccidioides isolates to measure minimal effective concentrations (MEC) and minimal fungicidal concentrations (MFC). Mice were inoculated with Coccidioides posadasii (Silveira strain). Treatment started 4 days postinoculation. In model 1, mice were treated for 19 days, followed by 30 days of off-therapy observation, measuring survival through day 49 and residual fungal burden. Treatments included ISAVUSULF (prodrug; 186, 279, or 372 mg/kg twice daily), FLU (20 or 100 mg/kg once daily), and no treatment. Model 2 included 7-day treatment with ISAVUSULF (prodrug; 74.4, 111.6, or 148.8 mg/kg twice daily), FLU (20 or 100 mg/kg once daily), and no treatment. Serial plasma and tissues samples were obtained for pharmacokinetics (PK) and fungal burden measurement, respectively. Fifty percent minimal effective concentration (MEC50) values were 0.39 mg/liter (isavuconazole [ISAV]) and 12.5 mg/liter (FLU). Treatment with ISAVUSULF186 or with either FLU dose resulted in higher survival compared to that in the untreated group. Treatment with ISAVUSULF186 or ISAVUSULF279 twice daily or FLU100 reduced fungal burden in all organs (model 1). In model 2, a >1 log10 CFU/organ reduction was demonstrated, with ISAV area under the concentration-time curve (AUC) values achieved with 111.6 mg/kg twice daily (56.8 mg · h/liter) in the spleen and liver. FLU AUC values of 100 and 500 mg·h/liter for 20 and 100 mg/kg doses, respectively, resulted in a >1 log10 CFU/organ mean reduction in all organs. ISAVUSULF and FLU improved survival and reduced fungal burden. Increasing plasma drug exposures resulted in decreases in fungal burden.

Coccidioides immitis (and C. posadasii) are endemic fungi of the southwestern United States and northern Mexico. Uncomplicated, symptomatic Coccidioides infection most commonly causes a self-limited pneumonia; however, immunocompromised patients can manifest severe pneumonia with an additional risk of dissemination to bone, joints, soft tissues, and in the most severe the cases, the central nervous system. In the year 2020 clinicians are challenged with a previously unseen volume of acute respiratory complaints as a result of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. We present a patient with respiratory failure secondary to SARS-CoV-2 who experienced prolonged hypoxia and neurologic deterioration, eventually leading to a diagnosis of occult disseminated coccidiomycosis involving meningitis, miliary-pattern pneumonia, and cutaneous lesions.

Coccidioidomycosis, otherwise known as Valley Fever, is caused by the dimorphic fungi Coccidioides immitis and C. posadasii. While most clinical cases present with self-limiting pulmonary infection, dissemination of Coccidioides spp. results in prolonged treatment and portends higher mortality rates. While the structure, genome, and niches for Coccidioides have provided some insight into the pathogenesis of disease, the underlying immunological mechanisms of clearance or inability to contain the infection in the lung are poorly understood. This review focuses on the known innate and adaptive immune responses to Coccidioides and highlights three important areas of uncertainty and potential approaches to address them. Closing these gaps in knowledge may enable new preventative and therapeutic strategies to be pursued.

Problem/condition Coccidioidomycosis (Valley fever) is an infection caused by the environmental fungus Coccidioides spp., which typically causes respiratory illness but also can lead to disseminated disease. This fungus typically lives in soils in warm, arid regions, including the southwestern United States. Reporting period 2011-2017. Description of system Coccidioidomycosis has been nationally notifiable since 1995 and is reportable in 26 states and the District of Columbia (DC), where laboratories and physicians notify local and state public health departments about possible coccidioidomycosis cases. Health department staff determine which cases qualify as confirmed cases according to the definition established by Council of State and Territorial Epidemiologists and voluntarily submit basic case information to CDC through the National Notifiable Diseases Surveillance System. Results During 2011-2017, a total of 95,371 coccidioidomycosis cases from 26 states and DC were reported to CDC. The number of cases decreased from 2011 (22,634 cases) to 2014 (8,232 cases) and subsequently increased to 14,364 cases in 2017; >95% of cases were reported from Arizona and California. Reported incidence in Arizona decreased from 261 per 100,000 persons in 2011 to 101 in 2017, whereas California incidence increased from 15.7 to 18.2, and other state incidence rates stayed relatively constant. Patient demographic characteristics were largely consistent with previous years, with an overall predominance among males and among adults aged >60 years in Arizona and adults aged 40-59 years in California. Interpretation Coccidioidomycosis remains an important national public health problem with a well-established geographic focus. The reasons for the changing trends in reported cases are unclear but might include environmental factors (e.g., temperature and precipitation), surveillance artifacts, land use changes, and changes in the population at risk for the infection. Public health action Health care providers should consider a diagnosis of coccidioidomycosis in patients who live or work in or have traveled to areas with known geographic risk for Coccidioides and be aware that those areas might be broader than previously recognized. Coccidioidomycosis surveillance provides important information about the epidemiology of the disease but is incomplete both in terms of geographic coverage and data availability. Expanding surveillance to additional states could help identify emerging areas that pose a risk for locally acquired infections. In Arizona and California, where most cases occur, collecting systematic enhanced data, such as more detailed patient characteristics and disease severity, could help clarify the reasons behind the recent changes in incidence and identify additional opportunities for focused prevention and educational efforts.