Background: A miliary pattern on chest imaging is often attributed to tuberculosis (TB) infection. However, a myriad of conditions can cause a miliary pattern, many of which are imminently life-threatening. Research Question: The primary aim of our study is to elucidate the potential causes of miliary chest imaging patterns to improve workup and empiric therapy selection. The secondary aims are to discern the predictors of miliary disease etiology and to determine whether appropriate empiric antimicrobial therapies were given. Study Design and Methods: In this retrospective cohort study, we searched a radiology database for patients with chest imaging studies described by the word \"miliary\". Subjects were excluded if they were under 18 years of age and if there were insufficient objective data to support a miliary disease etiology. A radiologist independently reviewed all imaging studies, and studies that did not appear to have a true miliary pattern were excluded. The collected data include patient demographics, immunocompromising risk factors, conditions associated with miliary disease, β-D-glucan levels, serum eosinophil count, and empiric therapies received. Results: From our 41-patient cohort, 22 patients (53.7%) were clinically diagnosed with coccidioidomycosis, 8 (19.5%) with TB, 7 (17.1%) with metastatic solid cancer, 1 (2.4%) with lymphoma, 1 (2.4%) with other (Mycobacterium simiae), and 3 (7.3%) with unknown diseases (the sum equals 42 patients because one individual was diagnosed with both coccidioidomycosis and TB). All six patients with greater than 500 eosinophils/μL were diagnosed with coccidioidomycosis. Of the 22 patients diagnosed with coccidioidomycosis, 20 (90.91%) were empirically treated with an antifungal regimen. Of the eight patients with TB, six were empirically treated for TB. Interpretation: Based on our data from a Coccidioides-endemic region with close proximity to tuberculosis-endemic areas, the leading cause of miliary disease is coccidioidomycosis, although TB and cancer are also common etiologies. Serum eosinophilia and elevated β-D-glucan levels were strongly predictive of coccidioidomycosis in our patient cohort with a miliary chest imaging pattern.

Valley Fever is a respiratory disease caused by inhalation of arthroconidia, a type of spore produced by fungi within the genus Coccidioides spp. which are found in dry, hot ecosystems of the Western Hemisphere. A quantitative microbial risk assessment (QMRA) for the disease has not yet been performed due to a lack of dose-response models and a scarcity of quantitative occurrence data from environmental samples. A literature review was performed to gather data on experimental animal dosing studies, environmental occurrence, human disease outbreaks, and meteorological associations. As a result, a risk framework is presented with information for parameterizing QMRA models for Coccidioides spp., with eight new dose-response models proposed. A probabilistic QMRA was conducted for a Southwestern US agricultural case study, evaluating eight scenarios related to farming occupational exposures. Median daily workday risks for developing severe Valley Fever ranged from 2.53 × 10-7 (planting by hand while wearing an N95 facemask) to 1.33 × 10-3 (machine harvesting while not wearing a facemask). The literature review and QMRA synthesis confirmed that exposure to aerosolized arthroconidia has the potential to result in high attack rates but highlighted that the mechanistic relationships between environmental conditions and disease remain poorly understood. Recommendations for Valley Fever risk assessment research needs in order to reduce disease risks are discussed, including interventions for farmers.

OBJECTIVE: Coccidioidomycosis, caused by the Coccidioides species, is a well-known disease in the Southwestern United States and North Mexico, with scattered reports in Latin America countries. While this disease is still rare in Japan and other Asian countries, its incidence has been increasing over the last two decades. Coccidioides species are highly infectious and require caution when encountered. This study presents a case series of chronic pulmonary coccidioidomycosis surgically treated at a single institution.
METHODS: We conducted a retrospective chart review of six patients who underwent lung resection for pulmonary coccidioidomycosis at Chiba University Hospital between January 2007 and December 2021.
RESULTS: All six patients had travelled to the Southwestern United States. Preoperative serology was negative for the anti-Coccidioides antibody in four patients and positive in two. Chest computed tomography revealed a single, well-defined round nodule in all patients. Preoperative biopsy taken from three patients failed to obtain a definitive diagnosis. Histopathological examination of the resected pulmonary nodules revealed granulomas that contained numerous spherules with many endospores, thereby confirming the diagnosis of pulmonary coccidioidomycosis.
CONCLUSIONS: Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.

Demographic and clinical indicators have been described to support identification of coccidioidomycosis; however, the interplay of these conditions has not been explored in a clinical setting. In 2019, we enrolled 392 participants in a cross-sectional study for suspected coccidioidomycosis in emergency departments and inpatient units in Coccidioides-endemic regions. We aimed to develop a predictive model among participants with suspected coccidioidomycosis. We applied a least absolute shrinkage and selection operator to specific coccidioidomycosis predictors and developed univariable and multivariable logistic regression models. Univariable models identified elevated eosinophil count as a statistically significant predictive feature of coccidioidomycosis in both inpatient and outpatient settings. Our multivariable outpatient model also identified rash (adjusted odds ratio 9.74 [95% CI 1.03-92.24]; p = 0.047) as a predictor. Our results suggest preliminary support for developing a coccidioidomycosis prediction model for use in clinical settings.

Meningitis is the most devastating form of coccidioidomycosis. A convenient, rapid diagnostic method could result in early treatment and avoid many meningitis complications. We studied cerebrospinal fluid (CSF) samples in patients with documented coccidioidal meningitis, and controls, with complement fixation (CF), immunodiffusion (ID) (the \"classical\" assays), lateral flow assays (LFA; one-strip and two-strip), and two enzyme immunoassays (EIA). The two-strip LFA and EIAs not only enabled separate testing for IgG and IgM antibodies separately, but also could aggregate results for each method. CF with ID or the aggregate use of IgG and IgM tests were considered optimal test uses. LFAs and EIAs were evaluated at 1:21 and 1:441 dilutions of specimens. All assays were compared to true patient status. With 49 patient specimens and 40 controls, this is the largest comparative study of CSF coccidioidal diagnostics. Sensitivity of these tests ranged from 71-95% and specificity 90-100%. IgM assays were less sensitive. Assays at 1:441 were similarly specific but less sensitive, suggesting that serial dilutions of samples could result in assays yielding titers. Agreement of positive results on cases was 87-100%. When kits are available, hospital laboratories in endemic areas can perform testing. LFA assays do not require a laboratory, are simple to use, and give rapid results, potentially even at the bedside.

Coccidioidomycosis is a predominantly respiratory infection of animals and humans caused by soil-dwelling fungi. Long known to be endemic to North American deserts, locally acquired human cases first emerged in Washington State in 2010. To inform development of an environmental niche map, we conducted an ecological cross-sectional study of the association between soil and climactic variables and canine seroprevalence in Washington State, at the zip code tabulation area level. Soil predictors included soil texture (per cent sand, silt and clay), pH, electrical conductivity and water storage capacity; climactic predictors included mean annual air temperature and liquid precipitation. Clustering was evaluated with Moran\'s I, and four modelling approaches were adopted a priori: two models without any smoothing (logistic regression and quasi-logistic regression) and two smoothing models (non-spatial and spatial smoothing). No evidence was found for clustering, and both smoothing models resulted in marked attenuation of all coefficients. Temperature was found to have a positive effect in the non-smoothing models (prevalence odds ratio, logistic model: 1.70, 95% confidence interval 1.02, 2.84). While no other significant associations were found, there was suggestive evidence of a positive effect for pH. Despite the limitations inherent to the ecological and cross-sectional nature of these data, these findings provide insight for the development of an environmental niche map in Washington State and demonstrate the utility of using data from an animal sentinel to predict human disease risk.

Most pulmonary coccidioidal infections are intraparenchymal; the pleurae are rarely involved. Pleuritis is a recognized complication of ruptured cavitary infections and occasionally occurs in other settings but has not been fully characterized. To define the clinical and histopathologic characteristics of pleural coccidioidomycosis as encountered by surgical pathologists, we reviewed the clinical history, imaging, and histology of 36 biopsy-, resection-, or autopsy-confirmed cases (with coccidioidal spherules present in pleural tissue; median age, 39 years; 22 men). These represented 7% of all pulmonary coccidioidal infections and showed 2 modes of presentation, including ruptured cavitary infection (26) and pleural-predominant disease with milder parenchymal involvement (10). Risk factors included immunodeficiency, smoking, and occupational exposure to soil. Common symptoms (median, 5 weeks) included cough (47%), chest pain (44%), and dyspnea (39%). Imaging often showed pleural adhesions (64%) and effusions (61%). Treatment included lobectomy or decortication, with antifungal medications. All cases showed granulomatous pleuritis. Both modes of presentation showed similar histologic features, including the composition of inflammatory infiltrates, degree of fibrosis, and extent of necrosis. Spherules were usually few (mean density, <1/10 high-power field). Three deaths occurred (all with ruptured cavities); the remaining patients recovered. Differential diagnosis of pleural effusions should include coccidioidomycosis, particularly in endemic areas, even without significant intrapulmonary disease. Most cases of coccidioidomycotic pleuritis are encountered by pathologists after resection of ruptured cavities with decortication, but pleural-predominant infections may be biopsied for diagnostic purposes. Spherules are usually rare in pleural tissue, and liberal sampling, cultures, or serologic studies may be required to confirm the diagnosis.

State-reported coccidioidomycosis cases in Arizona have dramatically increased since 1997, raising concerns about a possible epidemic, its cause, and associated risk factors, including spatio-temporal differences in susceptibility and exposure. This stratified, two-stage, cross-sectional study evaluates inherent, socio-economic, and environmental risk factors of coccidioidomycosis from information collected during an address-based telephone survey of 5460 households containing 14,105 individuals in greater Tucson, Arizona. Three geomorphic and two demographic strata controlled for differences in group-level exposures and susceptibility, and assured recruitment of a minority population. Logistic regression of self-reported cases indicates that location of residence by geomorphic and demographic strata was a risk factor that confounded the associations of coccidioidomycosis with age, race-ethnicity, and educational attainment. The risk due to age is more evenly distributed across the population than bivariate results when individual- and group-level exposure and susceptibility factors are controlled. Similarly the association for being Hispanic decreased from strong bivariate 0.28 odds ratio to a weak multivariate 0.75. Location of residence confounded the risk due to race-ethnicity and was an effect modifier of risk due to age. Differential misclassification of exposure to Coccidioides spores and susceptibility to coccidioidomycosis was reduced through landscape stratification by demographics and geomorphic types. Landscape epidemiological studies of diseases with strong environmental and demographic determinants can reduce residual confounding and account for spatial and temporal differences between neighborhoods and at broader scales.

BACKGROUND: Three fungal species causing human disease, namely Paracoccidioides brasiliensis, Histoplasma capsulatum and Coccidioides sp., are endemic in different areas of Argentina. Rates of infection in domestic dogs have been used in other Latin American countries as indicators of the presence of these pathogens in a given area. We used such an approach to investigate the epidemiological relevance of paracoccidiodomycosis, histoplasmosis and coccidioidomycosis in our country.
OBJECTIVE: To investigate the presence of P. brasiliensis, H. capsulatum and Coccidioides sp. in a rural area of Argentina called Interfluvio Teuco-Bermejito, located in Chaco province.
METHODS: We applied Western Blotting to determine the presence of specific antibodies in sera from 89 domestic dogs inhabiting the area. Antibodies against the following extra-cellular fungal antigens were investigated: gP43 of P. brasiliensis, H/M of H. capsulatum and 120, 82 and 48kDa antigen bands of Coccidioides sp.
RESULTS: Specific antibodies against H. capsulatum were found in 9/89 (10%) sera: 8 reacted against both H and M antigens and 1 only reacted against antigen M. Of these 9 sera, one showed additional anti-gp43 activity and another reacted against all the fungal antigens tested.
CONCLUSIONS: This is the first study using dog infection to assess the presence of endemic fungal pathogens in Argentina. Our results suggest that H. capsulatum is the main dimorphic fungal pathogen in the Interfluvio Teuco-Bermejito area. Therefore, the diagnosis of histoplasmosis should be taken into account in patients living in this geographic region who show pulmonary or mucocutaneous symptoms compatible with the disease.

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