Pulmonary Coccidioidomycosis Research Articles

Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis.

In Arizona, USA, primary pulmonary coccidioidomycosis accounts for 15%-29% of community-acquired pneumonia. To determine the evolution of symptoms and changes in laboratory values for patients with mild to moderate coccidioidomycosis during 2010-2012, we conducted a prospective 24-week study of patients with primary pulmonary coccidioidomycosis. Of the 36 patients, 16 (44%) were men and 33 (92%) were White. Median age was 53 years, and 20 (56%) had received antifungal treatment at baseline. Symptom scores were higher for patients who received treatment than for those who did not. Median times from symptom onset to 50% reduction and to complete resolution for patients in treatment and nontreatment groups were 9.9 and 9.1 weeks, and 18.7 and 17.8 weeks, respectively. Median times to full return to work were 8.4 and 5.7 weeks, respectively. One patient who received treatment experienced disseminated infection. For otherwise healthy adults with acute coccidioidomycosis, convalescence was prolonged, regardless of whether they received antifungal treatment.

Video-assisted thoracoscopic surgery for patients with pulmonary coccidioidomycosis

The study objective was to evaluate the use of video-assisted thoracoscopic surgery for removal of pulmonary sequelae of the fungal infection coccidioidomycosis. Retrospective chart review of all patients with pulmonary coccidioidomycosis treated surgically at our tertiary care center between January 1, 2009, and August 31, 2012. Of 2166 patients treated for pulmonary coccidioidomycosis, 58 (2.7%) (median age, 52 years [range, 18-84 years]) required surgical treatment. Surgical resection was performed for diagnosis (n=28 [48%]); 17 with positive positron emission tomography findings); persistent or progressive symptoms despite antifungal therapy (n=23 [40%]); or complications (n=7 [12%] of cavity rupture/infection). Of 33 patients (57%) who had serology performed, 23 (70%) had positive results. Video-assisted thoracoscopic surgery was used for most (95%; n=55) procedures, including 38 (67%) wedge resections, 14 (24%) segmentectomies, and 6 (11%) lobectomies; 4 patients also required additional decortication. Major (8%), including 1 death, and minor (12%) complications occurred in 12 patients postoperatively. Median hospitalization was 3 days (range, 1-8 days). Postoperative antifungal therapy was administered to 50% of patients for a median duration of 2 months. No patient had recurrent coccidioidomycosis at a median follow-up of 19 months. Although rarely necessary for pulmonary coccidioidomycosis, surgical intervention may be indicated. Specific indications include refractory symptomatic disease and complications of the infection, such as cavity rupture. Excisional biopsies also may be required for diagnostic confirmation of indeterminate pulmonary nodules. With video-assisted thoracoscopic surgery, diagnostic and therapeutic intervention can be undertaken with a low risk of complications and shorter length of hospital stay.

Update on the Diagnosis of Pulmonary Coccidioidomycosis

Coccidioidomycosis is a common cause of community-acquired pneumonia in the southwest United States, Mexico, and South America. The disease has seen a marked increase in incidence in the western United States in the last decade and can be acquired by individuals who travel even briefly through an endemic area, presenting a diagnostic dilemma for clinicians who are not familiar with the disease. The clinical and radiographic manifestations of pulmonary coccidioidomycosis often mimic those of other causes of pneumonia. However, because treatment recommendations and the potential for chronic sequelae of acute infection differ substantially from those for bacterial community-acquired pneumonia, accurate, timely diagnosis of coccidioidomycosis is paramount. A number of diagnostic tests are available with varying sensitivity and specificity, making the approach complex. Radiographic features, although nonspecific, sometimes demonstrate patterns more suggestive of coccidioidomycosis than bacterial community-acquired pneumonias. A routine blood count may reveal eosinophilia. Serologic testing is used most widely but may be negative early in the course of disease, potentially leading to misdiagnosis with subsequent inappropriate treatment and follow-up. The sensitivity of serologic testing is lower in immunocompromised patients, a population at the highest risk for developing severe disease. When clinically appropriate, other biologic specimens, such as sputum, bronchoalveolar lavage fluid, or lung biopsies, may allow for rapid, definitive diagnosis. In light of the significantly increased incidence and complexities in diagnosis of coccidioidomycosis, we examine the diagnostic approach and provide examples of classic clinical and radiographic presentations, discuss the utility of serologic testing, and suggest algorithms that may aid in the diagnosis.

Pulmonary Coccidioidomycosis After a Renal Transplant in a Nonendemic Region

Coccidioidomycosis is a fungal infection caused by the Coccidioides species, endemic to the southwestern United States. In healthy people, manifestations range mainly from asymptomatic to mild influenza-like signs, whereas in immunosuppressed patients (eg, transplant recipients) this infection is often a severe disseminated disease. We report a case of primary pulmonary coccidioidomycosis in a 61-year-old man with a renal transplant 7 months earlier. The patient had nonspecific symptoms of pulmonary infection, including weakness, anorexia, and weight loss. Both spherules and endospores of Coccidioides immitis were seen histologically after a transbronchial biopsy of a cavitary lesion. The patient was treated with amphotericin B. At the time of this writing (8 months), he remains disease free.

Neither Dectin-2 nor the Mannose Receptor Is Required for Resistance to Coccidioides immitis in Mice

We investigated the roles of the mannose receptor (MR) and Dectin-2 in resistance to pulmonary coccidioidomycosis in C57BL/6 (B6) mice and in the interaction of myeloid cells with spherules, using B6 mice with targeted mutations in Mrc1 and Clec4n. Spherules are the tissue form of Coccidioides, and we determined that the MR on bone marrow-derived dendritic cells (BMDC) was important for recognition of spherules (formalin-killed spherules [FKS]) and for secretion of interleukin 10 (IL-10) and proinflammatory cytokines in response to FKS by both elicited macrophages and BMDC. Infected MR knockout (KO) mice produced more IL-10 in their lungs than did B6 mice, and MR KO mice also made more protective Th-17 cytokines. In contrast to the MR, Dectin-2 was not required for recognition of FKS by BMDC or for the production of cytokines by BMDC in response to FKS. However, Dectin-2 KO was required for stimulation of elicited peritoneal macrophages. Despite that, lung cytokine levels were not significantly different in Dectin-2 KO mice and B6 mice 14 days after infection, except for IL-1β, which was higher in Dectin-2 KO lungs. Although both Dectin-2(-/-) and MR(-/-) myeloid cells had reduced proinflammatory cytokine responses to FKS in vitro, neither MR nor Dectin-2 deficiency reduced the resistance of B6 mice to pulmonary coccidioidomycosis.

Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease

Cavitary pulmonary coccidioidomycosis is a difficult diagnosis to establish due to the poor sensitivity of serological tests and rarity of culture from sputum. A pathologic and clinical analysis was performed of 21 consecutive patients with surgically resected cavities that proved to be coccidioidomycosis. Ten patients (48%) had serological evidence of Coccidioides infection, and 1 patient cultured Coccidioides spp. from sputum. The definitive diagnosis of coccidioidomycosis was made in the remaining 10 patients (48%) upon microscopic examination of tissue. The pleura showed fibrous pleuritis in 7 patients (33%) and eosinophilic pleuritis in 4 cases (19%); granulomas without microorganisms were demonstrated in 4 cases (19%). The cavity wall showed chronic inflammation and occasional giant cells but no granulomas and no microorganisms. The cavity contents included a mycetoma in 6 cases (28%); the cavity lining showed neutrophils and caseous necrosis; Coccidioides hyphae were present in 13 (62%) and spherules in 16 (76%) cases but often were rare. Adjacent lung showed lymphoid hyperplasia with chronic bronchiolitis in all cases; satellite granulomas with diagnostic spherules were variably present. The histopathology of cavitary coccidioidomycosis is strikingly variable depending on what area is sampled by biopsy, and microorganisms may be rare. This may explain the high rate of failure of diagnosis by fine needle aspiration and bronchoalveolar lavage. Pathologists in nonendemic areas must be aware of these findings, as this disease is now diagnosed worldwide.

Falla de tratamiento en neumonía adquirida en la comunidad: coccidioidomicosis en un viajero

Treatment failure in community-acquired pneumonia is defined as a clinical condition with inadequate response to antimicrobial therapy. Resistant and unusual microorganisms and noninfectious causes are responsible for treatment failure. Coccidioides immitis is a fungus that causes pneumonia in the northern hemisphere, especially in the United States and northern Mexico. We report a case of pulmonary coccidioidomycosis imported from Mexico to Chile. After a comprehensive study, histopathology was able to establish Coccidiodes immitis as the causative agent, achieving clinical and radiological improvement with antifungal therapy.

Immunological Characterization of Bronchoalveolar Lavage Fluid in Patients With Acute Pulmonary Coccidioidomycosis

The specific cellular immunological characteristics of bronchoalveolar lavage (BAL) fluid in acute pulmonary coccidioidomycosis have not been defined. BAL fluid from patients living in a coccidioidomycosis-endemic region of Arizona who were undergoing bronchoscopy because of pulmonary infiltrates was analyzed. Mononuclear cells from BAL fluid and peripheral blood mononuclear cells (PBMCs) were incubated with the coccidioidal antigen T27K in vitro, and cellular immunological assays were performed. Forty-six patients were studied. Twelve received a diagnosis of acute pulmonary coccidioidomycosis, 17 received other diagnoses, and 17 had no diagnosis established. There was an increased proportion of polyfunctional CD8(+) T cells after antigen stimulation from subjects with coccidioidomycosis as compared to those with another diagnosis (P = .025). In cells collected from BAL fluid and in PBMCs, the concentrations of interferon γ, tumor necrosis factor α, and interleukin 17 (IL-17) were all significantly increased in samples from those with acute pulmonary coccidioidomycosis, compared with the other 2 groups (for all, P<.05). When incubated in vitro with a coccidioidal antigen preparation, cells from both BAL fluid and peripheral blood obtained from patients with pulmonary coccidioidomycosis demonstrated specific cellular immune responses, including expression of IL-17.

The impact of early and brief corticosteroids on the clinical course of primary pulmonary coccidioidomycosis

Primary pulmonary coccidioidomycosis can often be associated with hypersensitivity symptoms treatable with a short course of palliative corticosteroids. Long-term use of corticosteroids is a known risk factor for severe or disseminated infection but the effects of short-term use are not known. A retrospective review was conducted of immunocompetent patients with acute pulmonary coccidioidomycosis who received systemic corticosteroids for relief of coccidioidal-related symptoms. Age- and sex-matched controls were also reviewed. Predetermined end-points were assessed. Seventy-four patients met inclusion criteria for the corticosteroid-treated group, and 74 controls were identified. Cumulative corticosteroid (prednisone-equivalent) doses were 10 mg → 3,600 mg (mean = 206 mg; median = 120 mg). Corticosteroids were prescribed most commonly for rash 43/74 [58%] or asthma/wheezing/cough 30/74 [41%]. Coccidioidal-related hospitalization occurred in 19 patients in the corticosteroid group vs. 22 in the control group (P = .58). Coccidioidal-related symptoms resolved within a mean of 19 weeks (median = 8 weeks [range = 2-208 weeks]) vs. 32.3 weeks (median = 8 weeks [range = 1-1040 weeks]) in the corticosteroid and control groups (P = .38). Relapse of symptoms occurred in 12% of both groups (P > .99). Extrapulmonary dissemination occurred in 3% vs. 4.0% (P > .99) in the corticosteroid and control groups, respectively. This study found no adverse effects of short-term corticosteroid therapy for early symptomatic treatment in acute pulmonary coccidioidomycosis.

Dectin-1 Is Required for Resistance to Coccidioidomycosis in Mice

ABSTRACTWe assessed the role of Dectin-1 in the immune response to the pathogenic fungus Coccidioides, both in vitro and in vivo, using mice with a targeted mutation in Clec7a. Elicited peritoneal macrophages responded to formalin-killed spherules (FKS) and alkali-treated FKS by secreting proinflammatory cytokines in a Dectin-1- and β-glucan-dependent manner. The responses of bone marrow-derived dendritic cells (BMDC) to the same stimulants were more complex; interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) secretion was independent of Dectin-1, while IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were largely but not entirely dependent on Dectin-1. After intranasal infection, Dectin-1−/− mice had lower concentrations of IL-12p70, gamma interferon (IFN-γ), IL-1β, and the Th17 cytokines IL-22, IL-23, and 17A in the lung lavage fluid, which may explain why they were significantly more susceptible to pulmonary coccidioidomycosis two weeks after infection. The Dectin-1 mutation was even more deleterious in (B6 × DBA/2)F2 mice, which are more resistant to coccidioidomycosis than B6 mice by virtue of protective genes from DBA/2, a genetically resistant strain. We also found that two susceptible strains of mice (B6 and BALB/c) expressed much less Dectin-1 in their lungs than did resistant DBA/2 mice. We conclude that Dectin-1 is necessary for resistance to Coccidioides immitis, that Dectin-1 promotes both Th1 and Th17 protective immune responses to this infection, and that there is a correlation between expression of Dectin-1 by the inflammatory infiltrate and resistance to coccidioidomycosis.

Problemas clínicos en micología médica: problema número 45

A 43 year-old diabetic woman, who suffered chronic cough and brown expectoration, is presented in this clinical problem. X-ray exam and CT thorax scan showed a cavitary lung lesion, located at the upper field of the left lung. This lesion had 5 cm in diameter, with a thick wall and a spherical shadow inside. The diagnosis of chronic cavitary pulmonary coccidioidomycosis was based on the isolation of Coccidioides sp. from cultures of expectoration and bronchoalveolar lavage, and the detection of specific antibodies in immunodiffusion test and counterimmunoelectrophoresis with coccidiodin. Her diabetes was not well controlled. She was treated with intravenous amphotericin B and oral itraconazole, with good clinical response; after four months of treatment the patient abandoned clinical controls.We suppose that the patient presented a coccidioidal fungus ball, inside a chronic cavitary lesion due to pulmonary coccidiodomycosis. She came from an endemic zone of coccidioidomycosis in the Northwest of the Argentine Republic (Catamarca Province).

Pulmonary coccidiomycosis in New Delhi, India

Coccidioidomycosis is an endemic disease of the western hemisphere. In cases occurring in non-endemic areas, eliciting a history of exposure as well as a high index of suspicion is imperative for timely and accurate diagnosis. In this case, a 65-year-old male presented to our hospital with fever, dry cough and malaise, and on X-ray chest, was found to have a lower lobe consolidation left lung with nodular lesions in both lungs and necrotic mediastinal lymphadenopathy. He lived in Arizona, USA, for 6 months before admission. Pulmonary coccidioidomycosis was confirmed by the isolation of Coccidioides spp. in pure culture from both broncho-alveolar lavage and lung biopsy specimens. The identity of the isolate was confirmed as C. posadasii by gene sequencing. The patient improved after being treated with fluconazole.

Does the presence of mediastinal adenopathy confer a risk for disseminated infection in immunocompetent persons with pulmonary coccidioidomycosis?

Pulmonary coccidioidomycosis is caused by inhaling airborne arthroconidia of Coccidioides, a soil-dwelling fungus endemic to the desert southwestern United States. Although uncommon, disseminated coccidioidal infection can be associated with well-defined risk factors, such as cell-mediated immunodeficiency, certain racial heritages (e.g. African or Filipino), male sex, or pregnancy. Before widespread use of computed tomography (CT), the presence or persistence of mediastinal lymphadenopathy was postulated to be a risk factor for disseminated coccidioidal infection. To investigate the use of CT scanning to identify the presence of mediastinal lymphadenopathy in patients with pulmonary coccidioidomycosis, and to correlate such lymphadenopathy with disseminated coccidioidal infection, we performed a retrospective review of patients with pulmonary coccidioidomycosis who were evaluated by chest CT. Two radiologists independently interpreted 150 CT scans from patients with pulmonary coccidioidomycosis. Forty-nine patients met CT criteria for mediastinal lymphadenopathy, whereas 101 patients did not. Disseminated coccidioidal infection was observed in 5 (10%) of the 49 patients with mediastinal lymphadenopathy and in 6 of the 101 (6%; P = .34) without such adenopathy. Among patients with coccidioidomycosis, patients with mediastinal lymphadenopathy, as assessed by CT, had a higher rate of disseminated infection, but the difference was not statistically significant.

Multiple Lung Abscesses Caused by Actinomyces graevenitzii Mimicking Acute Pulmonary Coccidioidomycosis

Actinomyces graevenitzii is a newly recognized Actinomyces species that is seldom isolated from clinical specimens. A case of multiple pulmonary abscesses mimicking acute pulmonary coccidioidomycosis is described in this study, and the findings indicate that this organism is an opportunistic human pathogen.

Interstial granulomatous dermatitis as initial presentation of juvenile mixed connective disease and its response to tacrolimus

Purpose Interstitial granulomatous dermatitis (IGD) has been reported in association with autoimmune disorders in adults. These associated conditions include rheumatoid arthritis, seronegative arthritis, SLE, autoimmune thyroiditis and others. It has also been described in drug-reaction pulmonary coccidioidomycosis, Lyme’s disease and pulmonary silicosis. IGD has rarely been described in children.

A Reformulated Spherule-Derived Coccidioidin (Spherusol) to Detect Delayed-Type Hypersensitivity in Coccidioidomycosis

The ability of spherule-derived coccidioidin containing 0.4 % phenol and 0.0001 % thimerosal in buffered saline to induce delayed-type hypersensitivity (DTH) was evaluated in four separate studies. The skin test antigen was titrated in 20 adult volunteers with a recent history of pulmonary coccidioidomycosis using intradermal doses of 0.4, 0.8, and 1.6 μg of antigen, based on total dry weight. Based on these data, a dose of 1.27 μg was shown to elicit a mean ± SEM induration response of 23.5 ± 2.3 mm at 48 h, similar to the 23.6-mm response after 48 h of the U. S. Reference coccidioidin last tested approximately 13 years ago. The 1.27 μg dose in 0.1 mL of the spherule-derived antigen (Spherusol) was then examined in three separate groups of adult volunteers to determine the sensitivity and specificity of the product. Fifty-nine of 60 individuals living in a non-endemic area for coccidioidomycosis were skin test negative to Spherusol. Twelve subjects with a recent history of pulmonary histoplasmosis were skin test negative to Spherusol. Finally, 51 of 52 individuals with a recent diagnosis of acute pulmonary coccidioidomycosis were skin test positive to Spherusol. Within this group, prior therapy with fluconazole did not appear to reduce the reactivity to Spherusol. No serious adverse events were observed in the four studies. From these data, Spherusol was found to be safe and has an overall observed sensitivity and specificity of ≥ 98 % in detecting DTH in coccidioidomycosis.

Comprehensive study of pulmonary coccidioidomycosis in patients admitted to a tertiary hospital

Comprehensive study of pulmonary coccidioidomycosis in patients admitted to a tertiary hospital

Coccidioidomycosis: First Imported Case in Italy

We report a case of pulmonary coccidioidomycosis imported from the United States to Italy. This disease should enter in the differential diagnosis of any febrile patient (especially if presenting with pulmonary symptoms, with or without hypereosinophilia) coming from Coccidioides immitis endemic areas.

Occupational Coccidioidomycosis in California

To describe the investigation of a 2007 occupational coccidioidomycosis outbreak in California, recommend prevention measures, and assess statewide disease burden. We evaluated the worksite, observed work practices, interviewed the workers and employer, reviewed medical records, provided prevention recommendations including risk-based respirator selection, and analyzed statewide workers' compensation claims. Ten of 12 workers developed acute pulmonary coccidioidomycosis; none used respiratory protection. We recommended engineering, work practice, and administrative controls, powered air-purifying respirator use, and medical care. Occupational coccidioidomycosis incidence nearly quadrupled in California from 2000 to 2006, with the highest rates in construction and agricultural workers. Construction workers are at risk for occupational coccidioidomycosis. The high attack rate in this outbreak was due to lack of awareness, rainfall patterns, soil disruption, and failure to use appropriate controls. Multiple risk-based measures are needed to control occupational coccidioidomycosis in endemic areas.

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.