Chronic Pulmonary Coccidioidomycosis Research Articles

Surgical treatment for chronic pulmonary coccidioidomycosis: a retrospective study from a single institution.

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. 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. 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. Pulmonary coccidioidomycosis should be suspected based on travel history and radiological findings. Meticulous care should be taken during specimen processing to prevent cross infection.

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Answer: Chronic pulmonary coccidioidomycosis. An IgG antibody to Aspergillus fumigatus was not present in the patient’s serum, and Aspergillus fumigatus was not detected in either BAL sample by PCR. However, a serum Coccidioides IgG complement fixation titer was positive at 1:32. Coccidioides immitis/Coccidioides posadasii was isolated from culture of the BAL fluid and was also detected by a specific PCR assay. Treatment with fluconazole was initiated (1). The patient’s lengthy history of pulmonary illness suggests that she had acquired her infection in Mexico or Arizona, but autochthonous coccidioidomycosis has also been reported in Washington State (2). Most coccidioidal pneumonia is self-limited, and fewer than 1% of patients develop chronic progressive pulmonary infections, which may be indistinguishable from other chronic fungal or mycobacterial infections (3). Diabetes mellitus is a risk factor for chronic infection. Radiologic manifestations of chronic disease include residual nodules, chronic cavities, persistent pneumonia with or without lymphadenopathy, pleural effusion, and regressive changes such as localized fibrosis, bronchiectasis, and calcification (4). The pulmonary imaging in this patient was not specific for Coccidioides infection; however, the presence of the air crescent sign in the dependent area of the cavitating lesion was not felt to be typical for an aspergilloma, and sparing of the lung apex reduced the likelihood of tuberculosis.

1718. The Natural History of Chronic Pulmonary Coccidioidomycosis in the Pre-Antifungal Era

BackgroundPrior studies to characterize pulmonary coccidioidomycosis (CM) have been limited by small samples. The historical VA-Armed forces CM patient group provides a unique cohort of patients not treated with conventional antifungals to better characterize and describe chronic pulmonary CM with an emphasis on chronic nodules and cavities.MethodsA retrospective study of 374 VA-Armed forces non-disseminated CM patients diagnosed between 1955 and 1958 and followed to 1966. Patients had a pulmonary nodule or a pulmonary cavity secondary to CM. Basic demographic information, complement fixation serology, and details regarding the nodules and cavities were investigated.ResultsThe studied population had a median age of 34 with 97% men and 84% white. Eighty percent had no underlying pulmonary disease and concurrent tuberculosis was the most common comorbid pulmonary condition (11%). Patients with cavities had a median complement fixation (CF) serology of 1:2 (interquartile range (IQR) negative 1:8). Patients with nodules had a median CF serology of negative (IQR negative 1:2). The median number of pulmonary nodules was 1 with a median size of 1–1.9 cm. Sixty-nine percent of the nodules had a sharp, well-defined border, while 10% had a calcified border. The median number of cavities was 1 with a median size of 3–3.9 cm. Forty-five percent of the cavity walls were thin, 31% were thick, and 19% were variable in size. Twenty-six percent of the cavities developed during acute infection with 46% developing without a prior history of primary infection. Twenty-nine percent of the cavities were stable in size, 20% increased in size, 5% disappeared, 4% ruptured, and 2% decreased in size.ConclusionThis study helps further characterize chronic pulmonary nodules and cavities caused by CM. To the best of our knowledge, this is the largest study of the natural history of chronic CM pulmonary cavities and nodules providing valuable descriptive features.Disclosures All authors: No reported disclosures.

388. New Observations in Coccidioidomycosis Serology

BackgroundCoccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Current understanding of serologic kinetics and serologic features are largely based on serologic studies from the 1950s before antifungals were widely available. The effects of antifungal therapy on serologic characteristics has not previously been evaluated.MethodsWe retrospectively analyzed chart history and complement fixation titer trends of 434 patients classified by infectious disease physicians as having either uncomplicated pulmonary coccidioidomycosis (UPC) (n = 248), chronic pulmonary coccidioidomycosis (CPC) (n = 64), disseminated coccidioidomycosis not including meningitis (DC) (n = 86), or coccidioidal meningitis (CM) (n = 36). All patients received azole antifungal therapy. Serologic kinetics and features were analyzed and compared between groups.ResultsRoughly 94% of UPC, 61% of CPC, 29% of DC, and 56% of CM patients developed maximum complement fixation titers ≤1:32. Surprisingly, 25.4% of UPC, 6.3% of CPC, 2.3% of DC, and 8.3% of CM patients did not develop a detectable complement fixation titer during the study period (at least 3 years after diagnosis for each patient). The median maximum titer was 1:4 (range <1:2 – 1:512) for UPC, 1:24 (range <1:2 – 1:2,048) for CPC, 1:128 (range <1:2 – 1:4,096) for DC, and 1:32 (range <1:2 – 1:4,096) for CM patients. Few significant differences were observed in the mean time to maximum titer (overall mean 31 days, 95% CI 13–50) and serologic resolution rates (average 3–4 months/dilution reduction). However, 9% of UPC, 36% of CPC, 50% of DC, 52% of CM patients exhibited serologic reactivations (defined as ≥2 dilution titer increase >90 days from initial positive serology). Meanwhile, 15% of UPC, 25% of CPC, 31% of DC, and 25% of CM patients exhibited a serofast phenotype despite antifungal therapy.ConclusionOur findings provide an update to serologic studies performed prior to long-term triazole therapy. An understanding of the serologic features and kinetics for patients with varying forms of coccidioidomycosis receiving antifungal therapy is key to clinical evaluation and therapeutic decision making.Disclosures All authors: No reported disclosures.

孤立結節陰影を呈し肺癌との鑑別を要した慢性肺コクシジオイデス症の1切除例

孤立結節陰影を呈し肺癌との鑑別を要した慢性肺コクシジオイデス症の1切除例

Chronic Pulmonary Coccidioidomycosis Diagnosed by Transbronchial Lung Biopsy

Chronic Pulmonary Coccidioidomycosis Diagnosed by Transbronchial Lung Biopsy

Coccidioidomycosis: An Update

Coccidioidomycosis is the oldest of the major mycoses. In recent years the incidence of the disease has increased in California and Arizona, which may be partially due to the massive migration to the endemic region. The endemic region for the disease lays exclusively in the Western Hemisphere, between the 40° latitudes north and south. The disease manifests in one of four clinical syndromes: acute pulmonary, chronic pulmonary and acute or chronic disseminated coccidioidomycosis. Serologic tests identifying anticoccidioidal antibodies are the most frequently employed assays for diagnosis. Primary coccidioidomycosis is usually self-limited; therapy of primary disease is recommended when symptoms persist for more than 6 weeks, for severe acute cases and for patients with impaired cellular immunity. Chronic pulmonary coccidioidomycosis and all forms of disseminated coccidioidomycosis require antifungal therapy. The drugs of choice are either fluconazole or itraconazole.

Safety, Tolerance, and Efficacy of Posaconazole Therapy in Patients with Nonmeningeal Disseminated or Chronic Pulmonary Coccidioidomycosis

Coccidioidomycosis can be difficult to treat with available therapies, particularly in patients with progressive or disseminated disease. Posaconazole is a new azole antifungal with potent activity against Coccidioides species, the causative agent of coccidioidomycosis. Twenty patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were enrolled in a multicenter trial to study the safety and tolerability of posaconazole therapy, with efficacy as a secondary end point. Patients received posaconazole (400 mg/day) in capsule formulation for up to 6 months. Safety was evaluated on the basis of the occurrence of adverse events. A satisfactory efficacy response was defined as a >or=50% reduction in the Mycoses Study Group score from baseline. Seventeen (85%) of 20 patients had a satisfactory response to treatment. The median duration of treatment was 173 days. Paired baseline and end-of-treatment culture results for Coccidioides species were available for 4 patients, all of whom converted from being positive to being negative for Coccidioides species. Relapse was experienced by 3 of 9 patients who did not receive antifungal therapy during the follow-up period. In general, posaconazole therapy was well tolerated, with 12 of 20 patients reporting adverse events that were possibly or probably related to treatment. The most common adverse events were dry mouth (in 5 patients [25%]) and headache (in 3 patients [15%]). Courses of posaconazole therapy that were up to 6 months in duration were well tolerated in patients with coccidioidomycosis. Although this study was limited by the number of patients enrolled, it clearly demonstrates that posaconazole shows promise in the treatment of patients with coccidioidomycosis and warrants additional investigation in a full-scale clinical trial.

Preliminary Evaluation of Whole-Blood Gamma Interferon Release for Clinical Assessment of Cellular Immunity in Patients with Active Coccidioidomycosis

Assessment of the cellular immune response in coccidioidomycosis has epidemiologic and prognostic importance. Measurement of delayed-type hypersensitivity to skin testing has been used in the past to determine cellular immunity in coccidioidomycosis. However, no skin tests are currently available in the United States. Assay of gamma interferon (IFN-gamma) release in whole blood in response to incubation with antigen has been used to assess cellular immunity in tuberculosis. We used a similar assay using the coccidioidal antigen preparation T27K to measure the in vitro cellular immune responses among a cohort of 69 subjects with active coccidioidomycosis. IFN-gamma release was bimodal, with concentrations above and below 5 IU/ml. Using multivariate logistic regression, underlying disease and disseminated or chronic pulmonary coccidioidomycosis was significantly associated with the release of IFN-gamma at a concentration of <5 IU/ml (P = 0.02 or 0.05, respectively). In addition, the release IFN-gamma concentration was <5 IU/ml in all subjects with a clinical severity score of > or =6 (P = 0.02). The release IFN-gamma concentration correlated with expression of CD69 on T lymphocytes in an in vitro assay using T27K as the antigen (Spearman's rho = 0.59; P < 0.01). These results suggest that the IFN-gamma release assay with T27K as the antigen may be a useful clinical test for assessing cellular immunity in patients with active coccidioidomycosis.

A Case of Coccidioidomycosis Manifested as Solitary Pulmonary Nodule

Coccidioidomycosis is a fungal infection acquired by inhalation of the arthrospore of Coccidioides immitis, and endemic disease in specific geographic areas, such as south central California, south Arizona. Nevada, and New Mexico. Approximately 60 percent of infected people is asymptomatic and the remainders mostly exhibit respiratory complaints, from flu-like coughing to overt pneumonia. Usually the infection due to Coccidioides immitis is self-limited. Symptoms resolve within several weeks but radiographic abnormalities could be resolved more slowly. If the radiographic abnormalities persist more than 8 weeks, the term' chronic pulmonary coccidioidomycosis' is designated. They take forms of nodules, cavities or progressive pneumonia. When manifested as nodule(s), lung malignancy is suspected as a possible diagnosis and histologic confirmation is needed. Here, we report a case of chronic pulmonary coccidioidomycosis manifested as solitary pulmonary nodule in a Korean woman who has traveled in Arizona, which is diagnosed finally by lobectomy and histologic examination.

Ketoconazole for treatment of chronic pulmonary coccidioidomycosis.

Twenty-one patients with chronic pulmonary coccidioidomycosis were treated with ketoconazole. In 16 patients with chronic cavitary disease, nine improved, four showed no change, and the condition of three deteriorated; three of nine patients had culture conversion. Roentgenograms showed improvement in two patients, no change in 12, and deterioration in two. Serologic improvement was not noted. In five patients with persistent infiltrative disease, the response was more favorable. Radiographic improvement, culture conversion, and serologic improvement were seen in most patients. Ketoconazole-induced side effects were mild and of short duration, ending in the first days of therapy. Ketoconazole seems to be of significant value in infiltrative pulmonary disease, but seems unable, at the doses used, to change finding in the sputum or to change radiographic findings in chronic cavitary disease. Further long-term observation is necessary to evaluate fully the role of this drug in chronic pulmonary coccidioidomycosis.