Diagnosis Of Coccidioidomycosis Research Articles

Overview of the Current Challenges in Pulmonary Coccidioidomycosis.

Coccidioidomycosis is a disease caused by soil fungi of the genus Coccidioides, divided genetically into Coccidioides immitis (California isolates) and Coccidioides posadasii (isolates outside California). Coccidioidomycosis is transmitted through the inhalation of fungal spores, arthroconidia, which can cause disease in susceptible mammalian hosts, including humans. Coccidioidomycosis is endemic to the western part of the United States of America, including the central valley of California, Arizona, New Mexico, and parts of western Texas. Cases have been reported in other regions in different states, and endemic pockets are present in these states. The incidence of reported cases of coccidioidomycosis has notably increased since it became reportable in 1995. Clinically, the infection ranges from asymptomatic to fatal disease due to pneumonia or disseminated states. The recognition of coccidioidomycosis can be challenging, as it frequently mimics bacterial community-acquired pneumonia. The diagnosis of coccidioidomycosis is frequently dependent on serologic testing, the results of which can take several days or longer to obtain. Coccidioidomycosis continues to present challenges for clinicians, and suspected cases can be easily missed. The challenges of coccidioidomycosis disease, from presentation to diagnosis to treatment, remain a hurdle for clinicians, and further research is needed to address these challenges.

Diagnosis of Coccidioidomycosis with the Second-Generation Miravista IgG and IgM Enzyme Immunoassay and the Role of Adding Miravista Coccidioides Antigen Detection to Immunodiagnostic Assays.

In the present study, we validate and compare the second-generation Miravista Coccidioides IgG and IgM enzyme immunoassays (EIA) (MiraVista Diagnostics [MVD] Ab EIA) to Meridian Diagnostics Coccidioides IgG and IgM EIA (Meridian Ab EIA), immunodiffusion (ID) and complement fixation (CF). We also evaluated whether the addition of Coccidioides antigen testing to anti-Coccidioides antibody testing increased the sensitivity for the diagnosis of currently active coccidioidomycosis. We retrospectively studied 555 patients evaluated at Valleywise Health Medical Center between January 2013 and May 2017 for whom coccidioidomycosis was suspected and samples were submitted to MVD for testing. Specimens were tested for antigen in the MVD antigen enzyme immunoassay (MVD Ag EIA) and for IgG and IgM antibodies with MVD and Meridian Diagnostics EIAs. ID and CF were obtained from medical records. Sensitivity and specificity were 83.0% and 91.1% or MVD Ab EIA, 69.3% and 99.7% for Meridian Ab EIA, 85.4% and 100% for ID and 65.5% and 100% for CF. Combined MVD antigen and antibody detection by EIA and ID resulted in increased sensitivity in disseminated and pulmonary disease (MVD Ag/MVD Ab: 100%, 88.3%; MVD Ag/Meridian Ab: 98.2%, 78.6%; and MVD Ag/ID: 100%, 91.7%). The detection of antibodies by MVD EIA was more sensitive than Meridian EIA or CF but similar to ID. This study supports the use of antigen testing in immunocompromised patients and those with suspected disseminated disease. Furthermore, the addition of antigen detection by EIA to antibody detection resulted in higher sensitivity of all serological tests.

Surveillance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis During the COVID-19 Pandemic - United States, 2019-2021.

Coccidioidomycosis, histoplasmosis, and blastomycosis are lower respiratory tract fungal infections whose signs and symptoms can resemble those of other respiratory illnesses, including pneumonia caused by bacterial or viral etiologies; this overlap in clinical presentation might lead to missed or delayed diagnoses. The causative fungi live in the environment, often in soil or plant matter. To describe the epidemiologic characteristics of cases of coccidioidomycosis, histoplasmosis, and blastomycosis during the COVID-19 pandemic, CDC analyzed case surveillance data for 2019-2021. During this period, a total of 59,655 coccidioidomycosis cases, 3,595 histoplasmosis cases, and 719 blastomycosis cases were reported to CDC. In 2020, fewer cases of each disease occurred in spring compared with other seasons, and most cases occurred in fall; national seasonality is not typically observed, and cases were seasonally distributed more evenly in 2019 and 2021. Fewer cases coinciding with the start of the COVID-19 pandemic, along with an unusually high blastomycosis case fatality rate in 2021 (17% compared with more typical rates of 8%-10%), suggest that the pandemic might have affected patients' health care-seeking behavior, public health reporting practices, or clinical management of these diseases. Increased awareness and education are needed to encourage health care providers to consider fungal diseases and to identify pneumonia of fungal etiology. Standardized diagnostic guidance and informational resources for fungal testing could be incorporated into broader respiratory disease awareness and preparedness efforts to improve early diagnosis of coccidioidomycosis, histoplasmosis, and blastomycosis.

Differential diagnosis of coccidioidomycosis manifested by peripheral pulmonary lesion

We present this clinical case as a demonstration of difficulties in differential diagnosis of pulmonary coccidioidomycosis. Differential diagnostics of peripheral pulmonary lesion performed using bronchoscopy with BAL and TBCB and video-assisted thoracic surgery (VATS) biopsy. Diagnostic specimens were tested using microbiological (luminescent microscopy, culture for M. tuberculosis (BACTEC MGIT960 and Lowenstein-Jensen Medium), RT-PCR, cytological and morphological (hematoxylin-eosin, Ziehl-Neelsen, PAS, Grocott methenamine silver (GMS) stainings) examinations. A diagnosis was verified correctly In Russia the country is not endemic for coccidioidomycosis and patient was treated accordingly. Diagnostics of peripheral pulmonary lesions requires of multidisciplinary approaches. Morphological examination, based on detection of only granulomatous inflammation in lung biopsy cannot be used for finally DS and requires microbiological confirmation for TB or other infections, and dynamic monitoring of the patient with concordance their anamnesis vitae and morbi.

S1081 Incidental Diagnosis of Coccidioidomycosis in Inflammatory Bowel Disease Is Less Likely Associated With Adverse Clinic Outcomes

S1081 Incidental Diagnosis of Coccidioidomycosis in Inflammatory Bowel Disease Is Less Likely Associated With Adverse Clinic Outcomes

Diagnostic Approach to Coccidioidomycosis in Solid Organ Transplant Recipients

Coccidioidomycosis is a fungal infection endemic in the southwestern United States, Mexico, and parts of Central and South America. While coccidioidomycosis is associated with mostly mild infections in the general population, it can lead to devastating infections in immunocompromised patients, including solid organ transplant (SOT) recipients. Early and accurate diagnosis is important in achieving better clinical outcomes in immunocompromised patients. However, the diagnosis of coccidioidomycosis in SOT recipients can be challenging due to the limitations of diagnostic methods including cultures, serology, and other tests in providing a timely and accurate diagnosis. In this review, we will discuss the available diagnostic modalities and approaches when evaluating SOT recipients with coccidioidomycosis, from the use of conventional culture methods to serologic and molecular testing. Additionally, we will discuss the role of early diagnosis in assisting with the administration of effective antifungal therapy to reduce infectious complications. Finally, we will discuss ways to improve the performance of coccidioidomycosis diagnostic methods in SOT recipients with an option for a combined testing approach.

Coccidioidomycosis with Laryngeal Nodule and Cavitary Lung Disease: A Case Report

Coccidioidomycosis is the infection caused by the dimorphic fungi of the genus Coccidioides. Primary pulmonary infection is caused by inhalation of airborne mycelial arthroconidia located in soil. While most infections are asymptomatic, clinical illness ranges from acute pneumonia (Valley Fever) to extra-thoracic disseminated infection. Most cases of coccidioidomycosis in the United States are endemic in the southwestern part of the country, particularly in Arizona, the San Joaquin Valley of California; parts of Mexico and Central and South America. Here we describe the case of a 13- year-old boy with an unusual history of hoarseness of voice, in whom laryngoscopy and biopsy were performed, and subsequent histologic diagnosis of coccidioidomycosis was established.

Clinical Laboratory Utility of a Humanized Antibody in Commercially Available Enzyme Immunoassays for Coccidioidomycosis.

ABSTRACTCoccidioidomycosis, also called valley fever (VF), is a fungal infection with endemicity in desert regions of the western United States as well as certain arid regions of Central and South America. Laboratory-based diagnosis of VF often relies on the composite results from three serologic-based diagnostics, complement fixation, immunodiffusion, and enzyme immunoassay (EIA). EIA is commonly performed in clinical laboratories because results can be obtained in a few hours. Two commercially available EIAs, IMMY clarus Coccidioides antibody and Meridian Premier Coccidioides, look for the presence of anticoccidioidal IgG and IgM in patient sera that are diluted 1:441. Per regulatory requirements, this dilution step must be verified with a dilution step control despite not being provided as a reagent in either FDA-approved EIA kit. Therefore, clinical laboratories collect and reuse patient sera in subsequent tests that had a positive result in a previous test. This is a nonstandard process, reinforcing the need for a consistent and reliable dilution control. Here, we evaluate the performance of a humanized IgG and IgM antibody as a dilution control in both EIA kits. Both humanized IgG and IgM work well in each EIA and meet the appropriate threshold for positivity.IMPORTANCE In southwestern and western regions of the United States, at least half a million diagnostic tests for coccidioidomycosis (valley fever) are run annually. Enzyme immunoassays (EIAs) are blood tests which require precise dilution of patient serum prior to testing. To ensure patient serum is properly diluted, there is a regulatory requirement to ensure the dilution step is accurate. Two FDA-approved EIAs used to aid in the diagnosis of coccidioidomycosis do not contain controls for this dilution step, leaving clinical laboratories with the only option of using previously positive patient sera, which may not react in a reliable or predictable manner. Here, we evaluate a humanized monoclonal antibody against a coccidioidal antigen and its utility as a dilution control in both available commercial EIAs. The use of a humanized monoclonal antibody provides a standardized and well-characterized dilution control for use in serological assays that aid in diagnosis of coccidioidomycosis.

The Utility of (1→3)-β-D-Glucan Testing in the Diagnosis of Coccidioidomycosis in Hospitalized Immunocompromised Patients.

Coccidioidomycosis is a fungal infection endemic to the Southwestern United States which is associated with high morbidity and mortality in immunocompromised hosts. Serology is the main diagnostic tool, although less sensitive among immunocompromised hosts. (1→3)-β-D-glucan (BDG) is a non-specific fungal diagnostic test that may identify suspected coccidioidomycosis and other invasive fungal infections. We retrospectively investigated the utility of BDG between 2017 and 2021 in immunocompromised hosts with positive Coccidioides spp. cultures at our institutions. During the study period, there were 368 patients with positive cultures for Coccidioides spp.; among those, 28 patients were immunocompromised hosts, had both Coccidioides serology and BDG results available, and met other inclusion and exclusion criteria. Half of the patients had positive Coccidioides serology, and 57% had a positive BDG ≥ 80 pg/mL. Twenty-three (82%) had at least one positive test during their hospitalization. Among immunocompromised hosts with suspicion for coccidioidomycosis, the combination of Coccidioides serology and BDG can be useful in the initial work up and the timely administration of appropriate antifungal therapy. However, both tests failed to diagnose many cases, underscoring the need for better diagnostic techniques for identifying coccidioidomycosis in this population.

Comparison of Immunodiagnostic Assays for the Rapid Diagnosis of Coccidioidomycosis in Dogs.

Coccidioidomycosis is a disease caused by the dimorphic fungi Coccidioides spp., which affects humans and a variety of animal species, including domestic dogs. In dogs, accurate diagnosis could provide a substantial improvement on the quality of canine life, as well as an advancement in the mapping of regions endemic for coccidioidomycosis. The purpose of this study was to compare immunodiagnostic assays for anti-Coccidioides antibody (Ab) detection in dogs’ serum. Three commercially available immunodiagnostic assays (IMMY®; Norman, OK, USA) were evaluated, including the sōna Coccidioides Ab Lateral Flow Assay (LFA), Coccidioides IDCF immunodiffusion assay (IDCF), and the Clarus Coccidioides Ab Enzyme Immunoassay (EIA). Assays were evaluated using 98 dog serum samples: 29 from dogs with coccidioidomycosis, 15 from dogs diagnosed with histoplasmosis, 10 from dogs diagnosed with blastomycosis, and 44 from dogs without a fungal disease. Using specimens from dogs with coccidioidomycosis, the IDCF had an accuracy of 92% (95% confidence interval [95% CI] = 85–96%), the EIA had an accuracy of 91% (95% CI = 83–96%), and the LFA displayed an accuracy of 82% (95% CI = 73–89%). Using Kappa analysis, the agreement between LFA and EIA was 0.59 (95% CI = 0.42–0.75), that between LFA and IDCF was 0.64 (95% CI = 0.48–0.79), and that between EIA and IDCF was 0.79 (95% CI = 0.64–0.90). Most cross-reactions were observed in dogs with histoplasmosis. Compared with EIA and IDCF, the LFA requires substantially less laboratory equipment and infrastructure and rapidly produces results, offering a substantial improvement for the initial screening of coccidioidomycosis in dogs.

Update on the Epidemiology, Diagnosis, and Treatment of Coccidioidomycosis.

Coccidioidomycosis is a fungal infection caused by Coccidioides immitis and Coccidioides posadasii. The dimorphic fungi live in the soils of arid and semi-arid regions of the western United States, as well as parts of Mexico, Central America, and South America. Incidence of disease has risen consistently in recent years, and the geographic distribution of Coccidioides spp. appears to be expanding beyond previously known areas of endemicity. Climate factors are predicted to further extend the range of environments suitable for the growth and dispersal of Coccidioides species. Most infections are asymptomatic, though a small proportion result in severe or life-threatening forms of disease. Primary pulmonary coccidioidomycosis is commonly mistaken for community-acquired pneumonia, often leading to inappropriate antibacterial treatment and unnecessary healthcare costs. Diagnosis of coccidioidomycosis is challenging and often relies on clinician suspicion to pursue laboratory testing. Advancements in diagnostic tools and antifungal therapy developments seek to improve the early detection and effective management of infection. This review will highlight recent updates and summarize the current understanding of the epidemiology, diagnosis, and treatment of coccidioidomycosis.

Intestinal and tracheal microbiomes inhibit in vitro growth of Coccidioides immitis

Abstract Valley fever is a disease caused by Coccidioides, a fungal pathogen, and is frequently misdiagnosed as community acquired bacterial pneumonia and treated with several rounds of antibiotics prior to accurate diagnosis. Antibiotic treatment changes the microbiome repertoire and host immunity; the impact of these microenvironmental changes on Coccidioides invasiveness is unknown. A soil microbial antagonist related to Bacillus subtilis inhibits in vitro growth of Coccidioides immitis through a clear zone of inhibition between fungi and bacteria. Whether host microbiota also could inhibit Coccidioides is unknown. To assess host microbiota inhibition capabilities against Coccidioides, we performed two types of inhibition assays. A 50/50 inhibition assay was performed in which the host microbiota and Coccidioides were placed in direct competition simultaneously on agar plates. A spike in inhibition assay was also performed in which the host microbiota was allowed to reach ~80% confluency, to mimic an established in vivo microbiome, before spiking in Coccidioides. The area of growth was observed and measured at day 4, 7, and 11. Our in vitro data indicate that specific intestinal and tracheal host microbiome species inhibit Coccidioides growth. To assess if partial in vitro depletion of host microbiota allows greater Coccidioides growth, antibiotic disc diffusion assays were performed. Our data suggests that depleting commensal microbiomes, allows a niche for Coccidioides growth. These in vitro findings could have clinical relevance and shape the way physicians assess prescription of antibiotics and coccidioidomycosis diagnosis. Experiments to identify the inhibitory microbiota and proteomic interactions are ongoing.

Coccidioidomycosis Cases at a Regional Referral Center, West Texas, USA, 2013–2019

We describe 73 patients with coccidioidomycosis diagnosed or treated at a regional referral center in West Texas, USA. Patients most at risk worked in oil production or agriculture; the most-associated health factors were smoking and diabetes. Patient demographics suggest that access to care may affect coccidioidomycosis diagnosis in this region.

Coccidioidomycosis: A Contemporary Review.

Coccidioidomycosis, colloquially known as Valley Fever, is an invasive dimorphic fungal infection caused by Coccidioides immitis and C. posadasii. The fungi are found in the arid desert soils of the southwestern US, as well as in parts of Mexico and Central and South America. Acquisition is typically via inhalation of arthroconidia which become airborne after both natural (e.g., earthquakes, dust storms, and fires) and human-related events (e.g., military maneuvers, recreational activities, agriculture, and construction). The incidence of infection in increasing likely a result of both climatic and populational changes. Further, the recognized geographic distribution of Coccidioides spp. is expanding, as cases are being diagnosed in new areas (e.g., eastern Washington, Oregon, and Utah). Most coccidioidal infections are asymptomatic (60%); however, approximately one-third develop a pulmonary illness which is a leading cause of community-acquired pneumonia in highly endemic areas. Uncommonly (0.5–2% of cases), the infection disseminates to extrapulmonary locations (e.g., skin, bones/joints, and the central nervous system), and is most commonly seen among persons with cellular immunodeficiencies (e.g., transplant recipients, HIV, and pregnancy) and non-Caucasian races (especially African Americans and Filipinos). The diagnosis of coccidioidomycosis requires astute clinical suspicion and laboratory findings, including positive serology, cultures, and/or histopathology results. Treatment is warranted among persons with pneumonia who have risk factors for complicated disease and among those with extrapulmonary disease. Novel antifungals with improved fungicidal activity and rapidity of action with fewer side effects and drug interactions are needed. Preventive strategies (e.g., education regarding the disease, dust avoidance, mask wearing, including among select groups, antifungal prophylaxis, and surveillance laboratory testing) are advised for residents and travelers to endemic areas. Currently, no preventive vaccine is available. Coccidioidomycosis has been recognized for over a century, and an expanding wealth of knowledge has been gained regarding this emerging infectious disease which will be reviewed here.

115. The Utility of (1→3)-β-D-glucan Assay in the Diagnosis of Severe Coccidioidomycosis Infections among Immunocompromised Hosts

BackgroundCoccidioidomycosis is associated with increased morbidity and mortality in immunocompromised (IC) patients. The diagnosis of invasive fungal infections can be challenging in IC hosts. Culture results may take time to identify Coccidioides species, and serologic based tests are less sensitive in IC patients. (1-3)-β-d-glucan (BDG) has been reported to be detected in patients with coccidioidomycosis. We hypothesized that BDG in combination with serology may assist in the early detection of coccidioidomycosis in IC patients.MethodsAfter the institutional review board approved the study, we conducted a retrospective chart review from 10/1/2017 through 09/15/2020, including ≥18 years old IC patients with a confirmed diagnosis of coccidioidomycosis by culture. Information regarding demographics, comorbidities, immunosuppression, medications, BDG, serology, and clinical presentation was collected. Patients with infusions that can result in possible false-positive BDG were excluded. Patients with other fungal infections were also excluded. Chi-square test was used to compare categorical variables, Wilcoxon rank-sum and Kruskal-Wallis tests were used to compare non-parametric variables, accordingly.ResultsOver the study period, 269 encounters with positive Coccidioides spp. cultures were identified, 78/269 of patients were IC patients, 55/78 were excluded, and 23 cases were included in the final analysis. Among the 23 IC patients, the median age was 64, 43% were female, 74% were White. There were 8 post solid organ transplantation, 7 with a hematological malignancy, and 8 with other types of IC conditions. 19/23 had a pulmonary infection. 4/23 patients died within one month of their encounter. There was no statistical significance difference between positive BDG and serology tests, with 12/23 had positive BDG, and another 12/23 had positive serology. Combined serology and BDG detected 18/23 of the Coccidioidomycosis cases. 17% of the cohort died within the one-month follow-up.ConclusionThe combined use of BDG assay and Coccidioides serology increases the sensitivity of coccidioidomycosis diagnosis to 78% in IC patients. Future prospective studies are needed to further evaluate the utility of serum BDG in diagnosing coccidioidomycosis in IC patients.Disclosures Mohanad Al Obaidi, MD, Shionogi Inc. (Advisor or Review Panel member)

692. Coccidioides sp. Infective Endocarditis: A Review of the Literature

BackgroundDespite the endemic nature of Coccidioides sp. to the American Southwest, the incidence Coccidioides sp. infective endocarditis (CIE) is rare. Following successful treatment of a patient with CIE at our institution, we reviewed the literature to identify trends in disease presentation, patient characteristics, and outcomes.MethodsWe reviewed all cases of CIE reported since 1938. Details including patient demographics, underlying immunodeficiency, time to diagnosis, treatment, and outcome were collected for analysis of diagnostic challenges and survival.ResultsIncluding ours, we identified 11 published cases of CIE. The majority (7) occurred in men. 5 patients were of either African American or Hispanic descent. Of the 10 patients with reported ages, the median age was 35.5 years (range 3 weeks – 61 years). 5 patients had a previous diagnosis of coccidioidomycosis and only 3 had an immunocompromising condition. These comprised pregnancy, heart transplant, and juvenile inflammatory arthritis. Three cases had multi-valvular involvement, but the majority affected the mitral (5) and the aortic (4) valves. Only 2 of the 11 cases involved a prosthetic valve. Of the 8 cases with reported blood cultures, only 2 were positive. Ten of the 11 cases had extra-cardiac disease. Complement fixation (CF) titers were heterogenous with a median of 1:32 and a range of 1:1 to 1:2048. There was no obvious correlation between a patient’s CF titer and their survival. Average time to diagnosis was 3.5 months (range 2.5 – 36 months). Diagnosis was made post-mortem in 4 of the 11 cases. 6 patients (54%) did not survive. Notably, 2 of the fatal cases preceded the discovery of amphotericin B (1969) and 4 occurred prior to the discovery of fluconazole (1990). Of the five patients that survived, four required surgical intervention in addition to azole therapy.ConclusionCIE is a diagnostic and therapeutic challenge. The diagnosis itself is rare, culture incubation times are long, and the symptoms are often non-specific thus delaying definitive therapy. The introduction of azole therapy appears to have had significant impact on rates of survival. Despite this, successful management of CIE still requires concurrent surgical intervention with aggressive, indefinite anti-fungal therapy.Disclosures All Authors: No reported disclosures

980. Universal Lifelong Fungal Prophylaxis and Risk of Coccidioidomycosis in Lung Transplant Recipients Living in an Endemic Area

Abstract Background Previous studies suggested that 6-12 months of universal or targeted azole prophylaxis is effective in preventing coccidioidomycosis for various organ transplant recipients. However, limited reports have described outcomes with longer prophylactic durations or using mold-active azoles in lung transplant recipients. Therefore, the purpose of this study was to investigate the incidence of coccidioidomycosis and tolerability of universal lifelong azole therapy in this high-risk patient population. Methods This study was an IRB-approved, retrospective cohort study of lung transplant recipients transplanted from January 2013 through December 2018. Adult recipients who were initiated on azole antifungal prophylaxis were eligible for inclusion. Recipients who died or received pre-emptive or definitive treatment for coccidioidomycosis during the transplant admission, or who received a previous transplant were excluded from the study. Outcomes were assessed through December 2019 or until the time of coccidioidomycosis diagnosis, death, second transplant, or date lost to follow-up. Results Of 544 lung transplants completed between 2013-2018, 493 patients were included with a mean age at transplant of 62 ± 11; 57.3% were male, 88.6% were white, and 77.1% developed post-transplant diabetes. The majority of patients ( > 70%) lived in Arizona or California pre-transplant and at 1-year post-transplant, and most patients had primary transplant indication of COPD and/or pulmonary fibrosis (~75%). One proven coccidioidomycosis infection and one new asymptomatic seropositivity for Coccidioides (incidence 0.2% each) occurred during the study period with median follow-up duration of 31 months. Azole therapy changes were common but permanent discontinuation was rare (1.4%) with reasons for azole switch varying among the different agents as summarized in Table 1. Table 1. Comparison of azole antifungal exposures and reasons for discontinuation Conclusion Lifelong azole antifungal prophylaxis was well-tolerated and effectively protected lung transplant recipients at an Arizona transplant center against coccidioidomycosis. Thus, in the absence of documented intolerance or contraindication, universal lifelong azole antifungal prophylaxis should be considered for all lung transplant recipients residing in a coccidioidomycosis-endemic area. Disclosures Michael D. Nailor, PharmD, BCPS (AQ-ID), AbbVie (Consultant)Merck (Consultant)Shionogi (Consultant) Rajat Walia, MD, Astellas (Consultant, Speaker)

Development of a Quantitative Antigen Assay to Detect Coccidioidal Chitinase-1 (CTS1) in Human Serum.

BackgroundCoccidioidomycosis is often diagnosed with a collection of tests that measure a patient’s ability to mount an immune response to the fungus (antibody-based diagnostics) utilizing fungal protein preparations. Here we present an antigen-based assay that detects and quantifies coccidioidal chitinase-1 (CTS1) in diagnostic antigen preparations with potential for use in human serum.MethodsAn 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.ResultsThe quantity of CTS1 in diagnostic commercial antigen preparations from different suppliers varied. Temporal constraints of availability of different lots of commercial antigens does not allow for immediate comparison of lot-to-lot variability. Assay results from patient serum samples correlated with low- and high-titer serology from patients with a coccidioidomycosis diagnosis. Further analysis suggested that patient derived anti-CTS1 antibodies may overlap with the mouse monoclonal antibody used in the assay. This unexpected overlap in CTS1 binding suggests the assay can detect antigen, antibody, or both, which contributes to its high level of clinical sensitivity of 89.74% and specificity of 94.90%.ConclusionsThe CTS1 inhibition ELISA described in this report is a promising tool to aid in quality control of antigens used in the diagnosis of coccidioidomycosis. Further optimization is needed to harness its utility as a diagnostic tool to aid in diagnosis and disease monitoring of coccidioidomycosis.

Lung microbiome influences Coccidioides colonization and invasiveness

Abstract It has long been thought that the lung is a sterile environment; however, recent studies revealed that healthy lungs are colonized by bacteria, fungi, and viruses. Coccidioidomycosis, also known as Valley fever, is a lung infection caused by the fungal species Coccidioides. Because of poor testing strategies 60–80% of patients are treated with antibiotics prior to accurate diagnosis of coccidioidomycosis. This potentially depletes bacteria with symbiotic relationships within the lung microenvironment and promotes susceptibility to invasion by Coccidioides. Coccidioides immitis is a dimorphic fungal pathogens whose fungal life cycle alternates between the saprophytic phase (soil mycelia) and parasitic phase (tissue infecting spherules). Natural microbial antagonists that inhibit soil Coccidioides immitis have been identified; Bacillus subtilis displays antifungal activity against Coccidioides growth through a clear zone of inhibition between fungi and bacteria. Whether these findings hold true in the host phase of the Coccidioides life cycle is unknown but have major implications for patient treatment. Our preliminary data suggest that host microbiome inhibits Coccidioides growth, and antibiotic treatment shifts or depletes the lung microbiome allowing a niche for Coccidioides growth. We are also exploring how this interface between the lung, Coccidioides, and the microbiome influences host innate and adaptive immune responses. Furthermore, these findings could shape the way physicians assess prescription of antibiotics prior to fungal diagnosis.

Using soil survey data to model potential Coccidioides soil habitat and inform Valley fever epidemiology.

Coccidioidomycosis, also known as Valley fever, is a disease that can result in substantial illness and death. It is most common in the southwestern United States and areas of Latin America with arid climates, though reports increasingly suggest its range is wider than previously recognized. The natural habitat of the causative organisms, Coccidioides spp., have been associated with certain soil properties and climatic conditions. Current understanding of its geographic range is primarily defined by skin test studies and outbreak locations. We developed a fuzzy system model to predict suitable soil habitats for Coccidioides across the western United States based on parameters (electrical conductivity, organic matter content, pH, water holding capacity, temperature, and precipitation) from sites where soil sampling has confirmed the presence of Coccidioides. The model identified high coccidioidomycosis incidence areas as having high suitability and identified pockets of elevated suitability corresponding with outbreak locations outside the traditional range. By providing high-resolution estimates of Coccidioides suitability, including areas without public health surveillance for coccidioidomycosis, this model may be able to aid public health and clinical provider decision making. Awareness of possible Coccidioides soil habitats could help mitigate risk during soil-disturbing activities and help providers improve coccidioidomycosis diagnosis and treatment.