Challenges in the Long-term Management of Patients With Coccidioidal Meningitis: A Retrospective Analysis of Treatment and Outcomes.

Background: Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy. Methods: We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed. Results: Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death. Conclusions: Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.

Spinal Arachnoiditis in Patients with Coccidioidomycosis Meningitis-Analysis of Clinical and Imaging Features.

Background: Coccidioidomycosis meningitis (CM) is the most aggressive form of coccidioidomycosis, requiring lifelong antifungal treatment and often cerebrospinal fluid (CSF) diversion. Long-standing CM can be associated with spinal complications such as arachnoiditis. However, studies describing the frequency, clinical, and imaging characteristics of arachnoiditis in patients with CM are limited. Methods: We identified 133 patients with CM based on CSF culture, PCR, or serology between January 2010 and December 2020. Of these, 37 patients underwent spinal imaging. Data on demographics, risk factors, symptoms, antifungal therapy, surgical management, follow-up visits, adherence, serological trends, and imaging findings were reviewed. Results: Abnormal findings were observed in 30 of the 37 patients with CM who underwent spinal imaging. The imaging abnormalities noted in our study included leptomeningeal enhancement (53%), arachnoiditis (53%), syringomyelia (23%), cord signal abnormalities (10%), and osteomyelitis (7%). Of the 30 patients, 90% had symptoms, such as weakness, numbness, or urinary retention. The incidence of arachnoiditis in the present study was 12%. Higher initial CSF protein levels and intra cranial pressure were associated with a higher risk of developing arachnoiditis/syringomyelia. Management of CM was challenging, as evidenced by shunt failure (46%), medication non-compliance (57%), and lack of adequate follow-up (60%). Persistent disabilities were noted in 62% of the patients. Conclusions: Patients with CM develop spinal complications such as arachnoiditis, or syringomyelia. Many cases may go undetected due to lack of symptoms in early stages. CM management challenges such as shunt failure, lack of follow-up care, and medication noncompliance, were frequent.

COVID-19-Associated Pulmonary Aspergillosis: A Single-Center Experience in Central Valley, California, January 2020-March 2021.

Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center's intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%).

Miliary pattern pulmonary infiltrates in a diabetic patient: Coccidioidomycosis.

This is a case of miliary coccidioidomycosis. This case illustrates the importance of early suspicion for coccidioidomycosis in patients from an endemic area. Early identification and recognition of the disease are important to attain early therapy and disease control.

The Rise of Valley Fever: Prevalence and Cost Burden of Coccidioidomycosis Infection in California.

Coccidioidomycosis (CM) is a fungal infection endemic in the southwestern United States (US). In California, CM incidence increased more than 213% (from 6.0/100,000 (2014) to 18.8/100,000 (2017)) and continues to increase as rates in the first half of 2018 are double that of 2017 during the same period. This cost-of-illness study provides essential information to be used in health planning and funding as CM infections continue to surge. We used a "bottom-up" approach to determine lifetime costs of 2017 reported incident CM cases in California. We defined CM natural history and used a societal approach to determine direct and discounted indirect costs using literature, national datasets, and expert interviews. The total lifetime cost burden of CM cases reported in 2017 in California is just under $700 million US dollars, with $429 million in direct costs and $271 million in indirect costs. Per person direct costs were highest for disseminated disease ($1,023,730), while per person direct costs were lowest for uncomplicated CM pneumonia ($22,039). Cost burden varied by county. This is the first study to estimate total costs of CM, demonstrating its huge cost burden for California.

The utility of real-time polymerase chain reaction in detecting Coccidioides immitis among clinical specimens in the Central California San Joaquin Valley.

Coccidioidomycosis, the fungal infection caused by dimorphic Coccidioides species, is typically diagnosed by histopathologic identification of spherules, by culture, or by serology. These tests are reliable but time-intensive, delaying diagnosis and treatment. Rapid real-time polymerase chain reaction (RT-PCR) can be performed and was validated to identify Coccidioides immitis using an in-house developed assay for the Becton Dickinson molecular instrument (BD MAXTM). These studies were performed using patient samples that had been shown to be positive on previously set up fungal cultures. To evaluate this new RT-PCR test in the clinical setting, we conducted a retrospective chart review of patients (N = 1160) who underwent Coccidioides PCR (Cocci PCR) on clinical samples between March 1, 2014, and Dec 31, 2016. We abstracted clinical, microbiologic, serologic, radiographic, treatment, and follow-up data. Specimens of cerebrospinal fluid (CSF), bronchioalveolar lavage fluid (BAL), lung tissue biopsy (LTB), sputum, and pleural fluid were evaluated to determine sensitivity and specificity. Of the 113 specimens that tested positive for Cocci PCR, all had clinical disease defined by traditional clinical criteria, yielding 100% specificity. Overall sensitivity was 74% versus 46% for fungal culture and was available in 4 hours rather than 1-2 weeks. Sensitivities varied by source material and clinical setting. CSF had a sensitivity of 59%, BAL for acute pneumonia 91%, sputum for acute pneumonia 94%, pleural fluid 86%, but LTB for lung nodules only 44%. Overall positive predictive value (PPV) was 100%, while negative predictive value (NPV) was 96%, but again this varied by specimen and clinical setting. Our experience with clinical testing of >1160 specimens over 2-3 years shows we can utilize this technology to improve our ability to diagnose disease but that the sensitivity varies by specimen source and clinical setting.

Development of a real-time PCR Assay for identification of Coccidioides immitis by use of the BD Max system.

Rapid real-time PCR (RT-PCR) can be performed in a community hospital setting to identify Coccidioides species using the new Becton Dickinson molecular instrument BD Max. Following sample preparation, DNA extraction and PCR were performed on the BD Max using the BD Max extraction kit ExK-DNA-1 test strip and a master mix prepared by BioGX (Birmingham, AL). Sample preparation took 2 h, and testing on the BD Max took an additional 2 h. Method sensitivity and specificity were evaluated along with the limits of detection to confirm that this convenient method would provide medically useful information. Using serial dilutions, the lower limit of detection was determined to be 1 CFU/µl. Testing with this method was validated using samples from various body sites, including bronchial alveolar lavage (BAL) fluid; sputum and lung tissue samples; and pleural and spinal fluids. Safety protocols were established, and specimen preparation processes were developed for the various types of specimens. The range for the cycle threshold (CT) indicating adequate fluorescent signal to signify a positive result was established along with the acceptable range for the internal standard. Positive controls run with each batch were prepared by spiking a pooled BAL fluid specimen with a known dilution of Coccidioides immitis organism. Our experience with testing >330 patient samples shows that clinically relevant information can be available within 4 h using an RT-PCR method on the BD Max to identify Coccidioides spp., with sensitivity equivalent to culture.

Coccidioidomycosis: adenosine deaminase levels, serologic parameters, culture results, and polymerase chain reaction testing in pleural fluid.

BACKGROUND: In a patient with positive serum serology for coccidioidomycosis, the differential diagnosis of concurrent pleural effusions can be challenging. We, therefore, sought to clarify the performance characteristics of biochemical, serologic, and nucleic-acid-based testing in an attempt to avoid invasive procedures. The utility of adenosine deaminase (ADA), coccidioidal serology, and polymerase chain reaction (PCR) in the evaluation of pleuropulmonary coccidioidomycosis has not been previously reported. METHODS: Forty consecutive patients evaluated for pleuropulmonary coccidioidomycosis were included. Demographic data, pleural fluid values, culture results, and clinical diagnoses were obtained from patient chart review. ADA testing was performed by ARUP Laboratories, coccidioidal serologic testing was performed by the University of California-Davis coccidioidomycosis serology laboratory, and PCR testing was performed by the Translational Genomics Research Institute using a previously published methodology. RESULTS: Fifteen patients were diagnosed with pleuropulmonary coccidioidomycosis by European Organization for the Research and Treatment of Cancer/Mycoses Study Group criteria. Pleural fluid ADA concentrations were < 40 IU/L in all patients (range, < 1.0-28.6 IU/L; median, 4.7). The sensitivity and specificity of coccidioidal serologic testing was 100% in this study. The specificity of PCR testing was high (100%), although the overall sensitivity remained low, and was comparable to the experience of others in the clinical use of PCR for coccidioidal diagnostics. CONCLUSION: Contrary to prior speculation, ADA levels in pleuropulmonary coccidioidomycosis were not elevated in this study. The sensitivity and specificity of coccidioidal serologic testing in nonserum samples remained high, but the clinical usefulness of PCR testing in pleural fluid was disappointing and was comparable to pleural fluid culture.

Disseminated Coccidioidomycosis with Clinically Evident Splenomegaly in an Immunocompetent Host, First Case Reported in the literature.

Coccidioidomycosis is a dimorphic fungus endemic to the southwestern United States, Central and South America. We report a case of a previously healthy person who presented with respiratory failure and disseminated Coccidioidomycosis who eventually had a fatal outcome. Coccidioidomycosis, or "Valley Fever" has been called the "great imitator" (1) as it can have a wide variety of clinical presentations. This case is unique as it represents the first described case of an immunocompetent host with rapidly progressing, disseminated coccidioidomycosis with clinically apparent splenomegaly and hepatomegaly.

Immune reconstitution inflammatory syndrome presenting as superior vena cava syndrome secondary to Coccidioides lymphadenopathy in an HIV-infected patient.

A 39-year-old man living with AIDS presented with a swollen face. He was found to be HIV infected after presenting with Coccidioides pneumonia 2 years previously and was placed on daily fluconazole and then on highly active antiretroviral therapy. Computed tomography confirmed superior vena cava obstruction secondary to lymphadenopathy. Biopsy confirmed coccidioidomycosis with no evidence of malignancy. To our knowledge, this is the first description of superior vena cave syndrome secondary to coccidioidomycosis and the first description of immune reconstitution inflammatory syndrome involving Coccidioides.

Pleural effusion in hospitalized patients with Coccidioidomycosis.

INTRODUCTION: Coccidioidomycosis is a common fungal infection primarily affecting the lungs. The prevalence and the characteristics of pleural effusion in Coccidioidomycosis are not well described. Therefore, a retrospective analysis of data from patients admitted to a teaching hospital with a diagnosis of Coccidioidomycosis and pleural effusion was done. METHODS: All patients admitted with a diagnosis of Coccidioidomycosis were identified using ICD 9 from 114 to 114.9 from computerized medical records. Epidemiological, clinical and laboratory data were transcribed from medical records of all inpatients. Pleural effusion was identified using reports of chest radiography, ultrasound and CT scan of chest. RESULTS: Pleural effusion occurred in 22 of 146 (15%) patients hospitalized for Coccidioidomycosis. The proportion of patients with pleuritic chest pain, cough and dyspnea were significantly higher in patients with effusion than without effusion (p<0.01). There was a tendency for pleural effusions to occur more often on the left side (p=0.064). Empyema occurred in 22.7% of pleural effusions. Pleural fluid chemistry showed that all effusions were exudates with a mean (+/-S.E.M.) pleural fluid eosinophil count of 10.3+/-4.65. CONCLUSION: Pleural effusions are common in hospitalized patients with Coccidioidomycosis. Pleural fluid eosinophilia should alert clinician to Coccidioides immitis as a possible etiological agent especially in an endemic area. Empyema occurred in a quarter of pleural effusions and resolution required thoracotomy.