Endemic Fungal Infective Endocarditis Caused by Coccidioides, Blastomyces and Histoplasma Species in the United States.

We describe a recent case of Coccidioides bioprosthetic aortic valve infective endocarditis successfully managed at our institution. This led us to perform a literature review of endemic fungal infective endocarditis in the United States caused by Coccidioides, Blastomyces, and Histoplasma. Symptoms preceded infective endocarditis diagnosis by several months. Patients with Coccidioides and Blastomyces infective endocarditis were younger with fewer comorbid conditions. Valvular involvement was relatively uncommon in Blastomyces infective endocarditis (27%). Fungemia was noted in patients with infective endocarditis due to Histoplasma (30%) and Coccidioides (18%). Mortality rates for infective endocarditis were high (Histoplasma, 46%; Coccidioides, 58%; Blastomyces, 80%); infective endocarditis was commonly diagnosed post-mortem (Coccidioides, 58%; Blastomyces, 89%). Most surviving patients with infective endocarditis (Histoplasma, 79%; Coccidioides, 80%) underwent valve surgery along with prolonged antifungal therapy. The two surviving patients with Blastomyces infective endocarditis received antifungal therapy without surgery.

Coccidioidomycosis in Oklahoma: A retrospective case series.

BACKGROUND: Coccidioidomycosis is a systemic fungal disease endemic to arid regions of the Western Hemisphere. In the south-western US, Coccidioides spp. may account for up to 20%-25% of all cases of community acquired pneumonia. Clinical manifestations vary widely, from asymptomatic infection to life-threatening disease, especially in immunocompromised hosts. OBJECTIVES: The primary objective of the study was to characterise cases of coccidioidomycosis in an area of the United States not considered traditionally endemic for the disease. METHODS: We performed a single-centre retrospective study of all cases of coccidioidomycosis from 1 January 2000 to 31 December 2020, in the University of Oklahoma Health Sciences Medical Center. RESULTS: A total of 26 patients were included for analysis. The central nervous system (CNS) and the lungs were the sites most frequently involved. Twenty (77%) had travelled to a coccidioidomycosis endemic region. Most were male (81%) with a median age of 42 years (range: 3-78 years). The majority (46%) were Caucasians, 19% were African American, 19% Hispanic, and 12% Native American. The most common comorbidities were diabetes mellitus and acquired immunodeficiency syndrome, identified in 27% and 23% of patients, respectively. Patients on immunosuppressive therapy accounted for 12% of all cases. CONCLUSION: Our study is one of the largest single-centre case series of coccidioidomycosis from a non-endemic area. Diabetes mellitus was the most frequent comorbidity. Compared to other case series of coccidioidomycosis, our patient population had higher rates of immunosuppression and had both a higher rate of disseminated disease and overall mortality.

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

Valley Fever (VF), caused by fungi in the genus Coccidioides, 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 Coccidioides 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. These assays often use Complement Fixation (CF) and Tube Precipitin (TP) antigens as the main targets of IgG and IgM reactivity, respectively. Our group previously reported evidence of over 800 genes expressed at the protein level in C. posadasii. However, antibody reactivity to the majority of these proteins has never been explored. Using a new, high-throughput screening technology, the Nucleic Acid Programmable Protein Array (NAPPA), we screened serum specimens from dogs against 708 of these previously identified proteins for IgG reactivity. Serum from three separate groups of dogs was analyzed and revealed a small panel of proteins to be further characterized for immuno-reactivity. In addition to CF/CTS1 antigen, sera from most infected dogs showed antibody reactivity to endo-1,3-betaglucanase, peroxisomal matrix protein, and another novel reactive protein, CPSG_05795. These antigens may provide additional targets to aid in antibody-based diagnostics.

Evaluation of the Analytical Performance of a Lateral Flow Assay for the Detection of Anti-Coccidioides Antibodies in Human Sera-Argentina.

Coccidiomycosis is a potentially life-threatening fungal infection endemic to certain regions of Argentina. The infection is caused by Coccidioides spp. and is primarily diagnosed by Coccidioides antibody (Ab) detection. Access to rapid, highly accurate diagnostic testing is critical to ensure prompt antifungal therapy. The sona Coccidioides Ab Lateral Flow Assay (LFA) performs faster and requires less laboratory infrastructure and equipment compared with other Ab detection assays, potentially providing a substantial improvement for rapid case screening in coccidioidomycosis-endemic regions; however, validation of this test is needed. Thus, we aimed to evaluate the analytical performance of the sona Coccidioides Ab (LFA) and compare agreement with anti-Coccidioides Ab detection assays. A total of 103 human sera specimens were tested, including 25 specimens from patients with coccidioidomycosis and 78 from patients without coccidioidomycosis. The sona Coccidioides Ab Lateral Flow Assay (LFA) was performed with a sensitivity of 88%, and specificity and accuracy of 87%. Furthermore, the Coccidioides Ab LFA had good agreement with other anti-Coccidioides Ab detection assays. Our findings suggest the sona Coccidioides Ab LFA has satisfactory performance and may be useful for diagnosing coccidioidomycosis in endemic regions.

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. All clinic visits and subset analyses for patients with International Classification of Diseases, Tenth Revision codes for pneumonia (J18.*) or erythema nodosum (L52) during 2018-2024 were included. Tabulated were daily frequencies of visits, pneumonia and erythema nodosum coding, coccidioidal testing, and test results. Banner Urgent Care Services' counts of monthly coccidioidomycosis diagnoses were compared with those of confirmed coccidioidomycosis cases reported to Maricopa County Department of Public Health. RESULTS: Monthly frequencies of urgent care coccidioidomycosis diagnoses strongly correlated with public health coccidioidomycosis case counts (r = 0.86). Testing frequency for coccidioidomycosis correlated with overall pneumonia frequency (r = 0.52). The proportion of pneumonia due to coccidioidomycosis varied between <5% and >45% within and between years. Coccidioidomycosis was a common cause of erythema nodosum (65%; 95% confidence interval, 45%-67%) and independent of pneumonia. Over half of Banner Urgent Care Services' coccidioidomycosis diagnoses were coded for neither pneumonia nor erythema nodosum. CONCLUSION: Data provided by the coccidioidomycosis dashboard can assist urgent care practitioners in knowing when coccidioidomycosis is prevalent in the community. Patients with exposure to endemic coccidioidomycosis who develop erythema nodosum or pneumonia should routinely be tested for coccidioidomycosis. Data from private health care organizations can augment surveillance of diseases important to public health.

Fulminant Disseminated Coccidioidomycosis With Histoplasma Antigen Cross-Reactivity.

A 79-year-old man with type II diabetes mellitus and recently diagnosed idiopathic thrombocytopenic purpura presented to the Emergency Department with progressive dyspnea over the course of two weeks. He was found to have diffuse miliary nodules, dense cavitary consolidation, and widespread cystic changes on chest imaging and died within 48 hours of admission to the hospital. His serum Coccidioides antibody and urine Histoplasma antigen were both positive. He later grew Coccidioides immitis from the blood, supporting the theory that Histoplasma positivity was likely the result of antigen test cross-reactivity. Coccidioidomycosis typically presents with mild, self-limited symptoms, but may also disseminate rapidly, causing fulminant, life-threatening disease. Prompt recognition of risk factors for fulminant coccidioidomycosis and understanding flaws in serologic testing are essential to the appropriate diagnosis and management of this disease.

Atypical Pleural Effusion in an Immunocompetent Patient With Valley Fever: A Case Study and Review of the Literature.

Valley fever is a fungal infection, commonly of the lungs, caused by Coccidioides immitis or Coccidioides posadasii. This disease is endemic to the southwestern United States, Central America, and South America. Infected individuals are typically asymptomatic but may develop community-acquired pneumonia. On rare occasions, coccidioidomycosis can present with severe complications in addition to the pulmonary manifestation. In this study, a 58-year-old immunocompetent male presented to the Emergency Department with a cough, night sweats, and pleuritic chest pain. Despite the administration of broad-spectrum antimicrobials, he developed a large right pleural effusion that did not resolve following thoracentesis. Serology was positive for Coccidioides, and the patient was referred to a thoracic surgeon due to persistent effusion. It is rare for patients with coccidiomycosis to develop a large pleural effusion requiring surgical intervention, especially in immunocompetent individuals. This case highlights the importance of monitoring patients with unresolved acute pneumonia in endemic areas and considering Coccidioides as a possible etiology.

Proceedings of the Second International Meeting on Endemic Mycoses of the Americas (IMEMA), and First International Symposium on Implantation Mycoses (ISIM).

The Second International Meeting on Endemic Mycoses of the Americas (IMEMA) and the First International Symposium on Implantation Mycoses (ISIM) took place in Santiago del Estero, Argentina during September 25-27th, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors in the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges.

IMEMA/ISIM, held in Santiago del Estero, Argentina, convened experts to discuss endemic and implantation mycoses, covering topics such as epidemiology, diagnostics, treatment, and advocacy. The event highlighted ongoing efforts in combating these diseases.

Unique presentation of an endemic opportunistic fungal infection: Disseminated coccidioidomycosis mimicking metastatic lung cancer with endotracheal and endobronchial involvement.

Coccidioidomycosis is a fungal infection primarily Endemic in the Southwest United States. Disseminated Coccidioidomycosis is a life-threatening variant that mainly occurs in an immunocompromised host. This report describes an unusual presentation of disseminated Coccidioidomycosis in an immunocompetent individual. The patient was admitted with a subacute cough, progressively worsening shortness of breath, significant weight loss, nodular skin lesions in upper extremities, and acute hypoxemic respiratory failure. Chest imaging revealed extensive nodularity and mass-like lesions. What sets this case apart is the significant endotracheal and endobronchial involvement, which mimicked metastatic lung cancer. The diagnosis was confirmed through serology and bronchoscopy biopsy. This case underscores the critical importance of considering detailed travel history and maintaining a high index of suspicion for fungal infections in patients with endobronchial lesions, particularly in regions where Coccidioidomycosis is endemic.

Coccidioidomycosis-Related Hospital Visits, Texas, USA, 2016-2021.

We analyzed hospital discharge records of patients with coccidioidomycosis-related codes from the International Classification of Diseases, 10th revision, Clinical Modification, to estimate the prevalence of hospital visits associated with the disease in Texas, USA. Using Texas Health Care Information Collection data for 2016-2021, we investigated the demographic characteristics and geographic distribution of the affected population, assessed prevalence of hospital visits for coccidioidomycosis, and examined how prevalence varied by demographic and geographic factors. In Texas, 709 coccidioidomycosis-related inpatient and outpatient hospital visits occurred in 2021; prevalence was 3.17 cases per 100,000 total hospital visits in 2020. Geographic location, patient sex, and race/ethnicity were associated with increases in coccidioidomycosis-related hospital visits; male, non-Hispanic Black, and Hispanic patients had the highest prevalence of coccidioidomycosis compared with other groups. Increased surveillance and healthcare provider education and outreach are needed to ensure timely and accurate diagnosis and treatment of coccidioidomycosis in Texas and elsewhere.

Musculoskeletal Coccidioidomycosis in the Setting of Adalimumab: A Case Report.

Musculoskeletal coccidioidomycosis is a rare disseminated fungal infection caused by either Coccidioides immitis or Coccidioides posadasii endemic to the southwestern United States and northwestern Mexico, as well as Guatemala, Brazil, and other locations in Central and South America. Symptomatic primary infection of coccidioidomycosis can present as pneumonia with influenza-like symptoms, but the majority of cases remain asymptomatic. When dissemination occurs, the most common extrapulmonary sites include the skin, lymph nodes, musculoskeletal system, and meninges. We present a case of a 53-year-old female with a history of breast cancer and ankylosing spondylitis treated with adalimumab who presented with disseminated coccidioidomycosis. On presentation, she reported subcutaneous nodules on the right forearm and elbow. Radiologic evaluation utilizing magnetic resonance imaging (MRI) and positron emission tomography (PET) scan revealed multiple subcutaneous and bony enhancing lesions in her right forearm, lumbar spine, iliac wing, and axillary lymphadenopathy. Given the patient's history of breast cancer, there was concern for metastatic disease. Axillary lymph node biopsies were negative for malignancy, but immunoreactive for C. immitis with a positive Grocott methenamine silver (GMS) stain and a C. immitis antibody panel confirmed the diagnosis of disseminated coccidioidomycosis. Treatment with fluconazole was initiated along with discontinuation of adalimumab. Fluconazole was transitioned to itraconazole due to adverse effects. Treatment was successful as evidenced by improved PET imaging and downtrending C. immitis antibody titers. This case highlights the concerning potential for dissemination of endemic mycoses with anti-tumor necrosis factor-α (TNF-α) therapies and the unique ways in which they can present. Further investigation is needed to determine the long-term implications of the disease and the role that immunosuppressive medications play in disease susceptibility.

The Known and Unknown "Knowns" of Human Susceptibility to Coccidioidomycosis.

Coccidioidomycosis occurs after inhalation of airborne spores of the endemic, dimorphic fungus, Coccidioides. While the majority of individuals resolve the infection without coming to medical attention, the fungus is a major cause of community-acquired pneumonia in the endemic region, and chronic pulmonary and extrapulmonary disease poses significant personal and economic burdens. This review explores the literature surrounding human susceptibility to coccidioidomycosis, including chronic pulmonary and extrapulmonary dissemination. Over the past century of study, themes have emerged surrounding factors impacting human susceptibility to severe disease or dissemination, including immune suppression, genetic susceptibility, sex, pregnancy, and genetic ancestry. Early studies were observational, frequently with small numbers of cases; several of these early studies are highly cited in review papers, becoming part of the coccidioidomycosis "canon". Specific genetic variants, sex, and immune suppression by TNF inhibitors have been validated in later cohort studies, confirming the original hypotheses. By contrast, some risk factors, such as ABO blood group, Filipino ancestry, or lack of erythema nodosum among black individuals, are repeated in the literature despite the lack of supporting studies or biologic plausibility. Using examination of historical reports coupled with recent cohort and epidemiology studies, evidence for commonly reported risk factors is discussed.

Diagnosis, Treatment, and Outcome of Coccidioidal Osseous Infections: A Systematic Review.

Extrapulmonary infections by Coccidioides spp., though rare, can occur via dissemination, affecting singular or multiple sites, including the skin and musculoskeletal system. Skeletal involvement often manifests as osteomyelitis, particularly in the axial skeleton. The present systematic review evaluates all documented cases of skeletal coccidioidomycosis to assess the diagnostic and treatment strategies alongside the outcomes, drawing insights from an analysis of 163 verified cases. A systematic review following PRISMA guidelines identified all studies reporting skeletal infections by Coccidioides spp. up to 2023 from the PubMed and Scopus databases. Eligible studies evaluated osteoarticular infections from Coccidioides spp. Data extraction included demographics, microbiological data, diagnostic methods, and treatment outcomes. Of the 501 initially identified records, a total of 163 patients from 69 studies met the inclusion criteria. Most cases were from the USA, predominantly males, while the median age of the population was 36 years. Diabetes mellitus was the common comorbidity (14.7%). C. immitis was the most prevalent pathogen. The spine and hand were common sites of infection (17.5% and 15.1%, respectively). Osteomyelitis by Coccidioides spp. was diagnosed, in most cases, by positive cultures (n = 68; 41.7%), while, in 49 (30.9%), both the histological examination and cultures yielded the fungus. Surgical debridement was performed in 80.9% of cases. A total of 118 (72.3%) patients were treated with monotherapy, while combination therapy with two or more antifungal agents was reported in 45 (17.7%). Amphotericin B (either liposomal or deoxycholate) was the most commonly given agent as monotherapy in 51 (31.2%) patients, while 30 (18.4%) patients received itraconazole as monotherapy. The rate of infection's resolution was higher in patients undergoing surgical debridement (79.5%), compared to those treated only with antifungal agents (51.6%, p = 0.003). Treatment outcomes showed complete resolution in 74.2% of patients, with a mortality rate of 9.2%. Coccidioidal osseous infections present diagnostic and therapeutic challenges. Surgical intervention is often necessary, complementing antifungal therapy. Vigilance for Coccidioides spp. infections, especially in regions with endemicity, is crucial, particularly when bacterial cultures yield negative results.

Epidemiology of coccidioidomycosis in Argentina, an update.

The National Reference Laboratory in Clinical Mycology of Argentina conducted a retrospective review of human coccidioidomycosis cases diagnosed by the National Mycology Laboratory Network of Argentina between 2010 and 2022 to determine the burden of the disease in the country. A total of 100 human coccidioidomycosis cases were documented, with a higher prevalence in male patients (male-to-female ratio of 1.9:1), with a median age of 41 years. Comparing the number of cases between two 10-year periods (2000-2009 and 2010-2019), the increase was 36.51% (from 63 to 86 cases). Among the 100 recorded cases, 79 tested positive using the double immunodiffusion test. Spherules were observed in 19 cases through histopathology or direct microscopic examination and the fungus was isolated in 39 cases. Thirty-six isolates were identified as Coccidioides posadasii through partial sequencing of the Ag2/PRA gene. Catamarca province had the highest number of cases, comprising 64% of the total, with an incidence rate above 1.0-2.5/100,000 inhabitants until 2018. However, there has been a recent downward trend in the region from 2018 to 2022. It is concerning that more than half of diagnosed cases were chronic pulmonary or disseminated forms, indicating a lack of early disease detection. To rectify this issue, it is imperative to conduct targeted training programs for healthcare personnel and enhance public awareness within the endemic area. This will contribute to a better understanding of the true burden of coccidioidomycosis and enable the implementation of appropriate sanitary control measures.

The Host Response to Coccidioidomycosis.

Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very slowly. Furthermore, second infections are very rare and natural immunity after infection is robust. Therefore, the host response to this organism is very effective at resolving the infection in most cases and immunizing to prevent second infections. People who are immunocompromised are much more likely to develop disseminated infection. This is a comprehensive review of the innate and acquired immune responses to Coccidioides spp., the genetics of resistance to severe infection, and the search for an effective vaccine.

Coccidioidomycosis as a Potential Trigger for Sarcoidosis: A Case Study.

This study explores the complex interplay between coccidioidomycosis (valley fever) and sarcoidosis through a detailed case study of a 54-year-old male patient. The patient presented with elevated calcium levels, chronic kidney disease (CKD), and unintended weight loss. Interdisciplinary collaboration between nephrologists and pulmonologists played a crucial role in navigating the intricate medical challenges, including hypercalcemia, renal dysfunction, and pulmonary anomalies. The diagnostic journey involved extensive laboratory findings uncovering the involvement of both infectious agents and granulomatous disorders. The patient exhibited positive cocci IgG antibodies, indicating coccidioidomycosis. Further complications included glomerulonephritis, as revealed by ongoing systemic inflammation. Tailored management strategies were implemented, including corticosteroid therapy for sarcoidosis-related inflammation and antifungal interventions for coccidioidomycosis. Vigilant monitoring of renal function, hypercalcemia, and weight loss was essential for comprehensive patient care. The study underscores the significance of interdisciplinary collaboration, systematic diagnostics, and personalized patient care in managing complex medical presentations and contributes to understanding the interplay between these two conditions.