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Blastomycosis.

Blastomycosis is the least understood of the major endemic mycoses in North America. The fungus exists in the soil in its mycelial form, and when the proper growth conditions exist growth and spore formation will occur. When microfici containing the growing mycelium of blastomyces are disturbed, an infecting aerosol is formed. The spores are inhaled and eventually settle in the alveoli where multiplication by binary fission occurs. Following development of cell-mediated immunity the infection is localized in the lung. During the pre-immune phase of the infection spread to extrapulmonary sites may occur. Most common sites of involvement include the skin, bones, prostate and central nervous system. Pulmonary disease may resolve spontaneously or progress. Treatment is required for progressive pulmonary illness and all episodes of extrapulmonary disease. For life-threatening blastomycosis or blastomycosis of the central nervous system amphotericin B is the treatment of choice, while ketoconazole is an excellent alternative for patients who are not critically ill or have no central nervous system involvement.

Amphotericin B↗

Blastomycosis of the lumbar spine: case report and review of the literature, with emphasis on diagnostic laboratory tools and management.

We report on the conservative and surgical management of a patient with blastomycosis of the lumbar spine, causing severe and crippling deformity. The diagnosis was made through biopsy. Curative removal, reconstruction and realignment of the spine were achieved. Imaging modalities were highlighted, with a detailed discussion of the histology and conservative and surgical management. We emphasize the importance of early, aggressive treatment of blastomycosis to prevent deformity and disability, and to enable identification of the best management of a destructive lesion with deformity. This case demonstrates that empirical treatment should not be used in cases of unusual sinus and abscess locations. Specific diagnosis and early treatment are indicated to prevent dreadful complications and spinal deformity resulting from blastomycosis. Aggressive antifungal therapy can cure the disease but does not control complications related to deformity. The latter can only be addressed by surgical reconstruction. We review the literature of surgical treatment, focusing on abscess drainage, bone fusion and posterior instrumentation in the absence of addressing the deformity component.

Adult↗

Geographic distribution of human blastomycosis cases in Milwaukee, Wisconsin, USA: association with urban watersheds.

Most studies of endemic blastomycosis and outbreaks have involved rural areas. Case homesites in rural Northern Wisconsin have been associated with waterways and sand soils. ARC-GIS was used to geocode addresses and to observe geographic features of homesites from 45 State-mandated reports of human blastomycosis in urban Milwaukee County, Southeastern Wisconsin 2000-2004. Each case property was directly observed, and houses and duplexes (N = 38) were compared with 151 same-street control homesites. Categorical data was analyzed using a chi-square or Fisher's exact test; continuous variables by Kruskal-Wallis test. One case cluster was seen on Milwaukee's North side where the estimated annual incidence was 2.8/100,000 compared to 0.96/100,000 for the entire county. Cases were less common in the most urbanized watersheds (0.49/100,000/yr) versus Lake Michigan shores (0.85) versus remaining three open watersheds (1.4) [P<0.01]. Case homesites averaged 1067 m to waterways and none were on sand soils. (Comparison is made to a Northern Wisconsin community where case homesites averaged 354 m to waterways, 24/25 were on sand soils and annual incidence was 74/100,000.) No unique features of case homesites were identified in Milwaukee County. In this urban area of Wisconsin, relatively low incidence rates may be explained, in part, by lower density of inland waterways and lack of sand soils, however, blastomycosis cases appear to be associated with open watersheds.

Blastomyces↗

Blastomycosis with oral lesions. Report of two cases.

The recent literature suggests that blastomycosis (previously known as North American blastomycosis) with oral lesions may be more common than is generally realized. This report discusses two cases of blastomycosis in which oral lesions played a critical role in the ultimate diagnosis of the disease. The potential importance or oral lesions in early diagnosis and the necessity of culturing the organisms for definitive diagnosis are emphasized.

Adult↗

Indications for the surgical management of central nervous system blastomycosis.

BACKGROUND: Blastomycotic infections of the central nervous system (CNS) occur infrequently. The medical literature concerning blastomycosis of the CNS contains little information regarding indications for surgery. METHODS: We report five cases of CNS blastomycosis that required surgery: four intracranial and one intraspinal. One patient had a prior diagnosis of sarcoidosis, whereas none of the others had been diagnosed with any other systemic illness. The patients were evaluated with plain x rays as well as with computed tomography or magnetic resonance imaging. RESULTS: Four of these patients had extradural abscesses that required surgical drainage as well as debridement of granulomatous tissue and infected bone. The remaining patient had an intracerebellar abscess. Postoperatively, three patients were treated with amphotericin B, one with amphotericin B and ketoconazole, and one with an experimental protocol of fluconazole alone. All of the patients recovered without sequelae of seizures, recurrence of disease, or reaction to pharmacotherapy, although one patient had transient renal insufficiency due to amphotericin B. CONCLUSIONS: Our experience with CNS blastomycosis managed surgically is reported. We propose three general surgical indications for these patients: mass lesions, diagnostic biopsy, and osteomyelitis refractory to pharmacotherapy.

Adolescent↗

Immunological basis for susceptibility and resistance to pulmonary blastomycosis in mouse strains.

The immunological basis for a >10-fold resistance of outbred CD-1 mice compared to inbred BALB/c mice to pulmonary blastomycosis was investigated. Bronchoalveolar macrophages (BAM) from CD-1 mice killed yeast cells of Blastomyces dermatitidis (Bd) by 25% and this increased to 59% when activated by IFN-gamma. In contrast, BAM from BALB/c mice lacked significant killing (5%) of Bd but could be activated by IFN-gamma for enhanced killing (19%). Peritoneal macrophages (PM) from CD-1 mice had significant fungicidal activity for Bd (43%) and this increased to 63% with IFN-gamma treatment. By contrast, PM from BALB/c mice did not significantly kill Bd (14%) but were activated by IFN-gamma for significant killing (24%). Fungicidal activity of peripheral blood polymorphonuclear neutrophils (PMN) from CD-1 (87%) was greater than that of BALB/c (75%) (P<0.05). Macrophage inflammatory protein-1alpha (MIP-1alpha) production by BAM from BALB/c was significantly less than that from CD-1 in response to co-culture with Bd. IFN-gamma production by CD-1 spleen cells in response to concanavalin A (Con A, 1microg/ml) was 8-fold greater than that by BALB/c spleen cells. In contrast, BAM and PM from BALB/c mice in co-culture with Bd secreted several-fold more TNFalpha than BAM or PM from CD-1 mice. IL-2 production by BALB/c spleen cells in response to Con A was 3- to 4-fold greater than that by CD-1 spleen cells. Depressed IL-2 production by Con A stimulated CD-1 spleen cells correlated with depressed proliferative responses. Resistance of CD-1 mice to pulmonary blastomycosis correlates with enhanced fungicidal activity of BAM, PM, PMN, and IFN-gamma production by Con A stimulated spleen cells, compared to BALB/c mice. Consistent with the in vitro enhancement of effector cell function by IFN-gamma, in vivo therapy with IFN-gamma significantly (P<0.0001) improved survival of BALB/c mice with pulmonary blastomycosis.

Animals↗

Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay.

Antigen detection is a useful adjunct for the diagnosis of histoplasmosis. The purpose of this study was to evaluate antigen detection in bronchoalveolar lavage (BAL) fluid using an improved second-generation Histoplasma antigen assay. Antigen was detected in 16 of 19 (84%) cases of histoplasmosis and 5 of 6 (83.3%) blastomycosis cases using the second-generation assay vs. 13 of 19 (68%) and 4 of 6 (66.7%), respectively, in the original assay. Ten-fold concentration permitted detection of antigen in an additional case of histoplasmosis and another with blastomycosis, for an overall sensitivity of 23 of 25 (92.0%). Specificity was 98.2% in both assays in controls with other pulmonary infections. These findings support the diagnostic utility of the second-generation assay in patients with pulmonary histoplasmosis and blastomycosis.

Antigens, Fungal↗

The use of ketoconazole to treat systemic blastomycosis presenting as acute epididymitis.

We report on a patient with systemic blastomycosis who presented with acute epididymitis that was followed by the appearance of typical skin and pulmonary lesions. An excellent clinical response was obtained with ketoconazole, a new oral antifungal agent. Only 2 cases of systemic blastomycosis that were treated with ketoconazole have been reported and neither patient had genitourinary involvement. The diagnosis and treatment of systemic blastomycosis with genitourinary involvement, and ketoconazole as the treatment of fungal infections are discussed.

Antifungal Agents↗

Blastomycosis in Missouri: epidemiology and risk factors for endemic disease.

Between 1992 and 1999, 93 cases of blastomycosis, including 25 laboratory confirmed cases, were identified in Missouri (annual incidence, 0.2/100,000 population). Mississippi County in southeastern Missouri had the highest incidence (12/100,000) with a much higher rate among blacks than whites in this county (43.21/100,000). The mortality rate, 44% was also higher among blacks. To determine risk factors for endemic blastomycosis, a case-control study was conducted among southeastern Missouri residents. Independent risk factors for blastomycosis were black race and a prior history of pneumonia. No environmental exposures or socioeconomic factors were significantly associated with increased risk. The increased risk among blacks may possibly be related to genetic factors, but further studies are needed to clarify this. However, heightened awareness of the disease and a better understanding of the risk factors are important and may lead to earlier diagnosis and start of treatment, possibly improving outcome.

Adolescent↗

Blastomycosis: organ involvement and etiologic diagnosis. A review of 123 patients from Mississippi.

Blastomycosis can only be diagnosed through the identification of the yeasts of Blastomyces dermatitidis in body fluids, tissues, or cultured material. The charts from 123 patients treated for blastomycosis at the University of Mississippi Medical Center from January 1980 through May 2000 were reviewed to determine the role of wet preparation, cytology, histology, and culture in diagnosing this fungal disease. Cytology uncovered the etiologic agent in 56.1% of all cases and in 71.8% of pulmonary cases. Cytology also was the first method to disclose the fungus in 57.7% of pulmonary cases. Sputum was the cytology specimen examined in 51% of the patients. In 69 patients with lung involvement, pulmonary cytology was positive in 97% of cases. Wet preparation was the second method to most commonly uncover the fungus in 37.4% of all cases. Histology was the third method with 32.5% of positive cases. Cultures were positive in 64.2% of all cases but they were the first to detect the fungus in only 3.2% of all patients. There was pulmonary involvement in 87% of patients, cutaneous involvement in 20%, osseous involvement in 15%, and central nervous involvement in 3%. In the medical literature the relative proportion of pulmonary versus disseminated disease clearly increased in series reported after 1959. Proportionally to the pattern of patients admitted to the University of Mississippi Medical Center, there is a clear predominance of black males among patients with blastomycosis followed by black females. White females constitute the sex/ethnic group least affected by this fungal disease.

Adolescent↗

Acute respiratory distress syndrome and blastomycosis: presentation of nine cases and review of the literature.

Mississippi has the highest prevalence of blastomycosis in the country. In 20 years and 5 months there were 123 patients treated for blastomycosis at the University of Mississippi Medical Center. Among these, 107 patients had lung involvement and nine patients (8.4%) developed acute respiratory distress syndrome. Seven of the nine patients (78%) died of respiratory failure. In six patients, the lungs were the only organs involved. The three other patients had involvement of other organs as well. Average survival after the onset of acute respiratory distress syndrome was 6.9 days (range, 2 to 17 days). Acute respiratory distress syndrome can be triggered by pulmonary infections caused by bacterial diseases and other fungi. Massive proliferation of yeasts in the pulmonary parenchyma is the typical finding of patients with blastomycosis and acute respiratory distress syndrome. Underlying diseases that lead to immunodepression were present in only one patient and probable partial immunodepression was present in two other patients. Data from 19 other cases reported in the literature are discussed. Ann Diagn Pathol 5:1-9, 2001.

Adult↗

Isolation of Blastomyces dermatitidis in soil associated with a large outbreak of blastomycosis in Wisconsin.

In investigating six cases of blastomycosis in two school groups that had separately visited an environmental camp in northern Wisconsin in June 1984, we identified a large outbreak of the disease and isolated Blastomyces dermatitidis from soil at a beaver pond near the camp. Of 89 elementary-school children and 10 adults from the two groups, 48 (51 percent) of the 95 evaluated in September had blastomycosis. Of the cases, 26 (54 percent) were symptomatic (the median incubation period was 45 days; range, 21 to 106 days). No cases were identified in 10 groups that visited the camp two weeks before or after these two groups. A review of camp itineraries, a questionnaire survey, and environmental investigation showed that blastomycosis occurred in two of four groups that visited a beaver pond and in none of eight groups that did not. Walking on the beaver lodge (P = 0.008) and picking up items from its soil (P = 0.05) were associated with illness. Cultures of soil from the beaver lodge and decomposed wood near the beaver dam yielded B. dermatitidis. We conclude that B. dermatitidis in the soil can be a reservoir for human infection.

Adult↗

Blastomycosis in a South Indian patient after visiting an endemic area in USA.

We describe a case of blastomycosis in a diabetic patient from South India who had visited Milwaukee, Wisconsin, an endemic area for blastomycosis in the USA. After his return to Bangalore, India, the patient developed intermittent fever of moderate to high grade, cough, loss of weight and appetite, and abscesses in the left cubital fossa and thigh regions. Systemic examination at our hospital revealed that he had dullness to percussion over the chest region and decreased breath sounds. Direct examination of Gram-stained smears of the pus from an abscess showed many broad-based budding yeast cells and culture yielded a dimorphic fungus later identified as Blastomyces dermatitidis. Histologic examination of the curettage tissue slides stained with hematoxylin and eosin, periodic acid Schiff's reagent, and Gomori's methenamine silver stain procedures showed many broad-based budding cells characteristic of B. dermatitidis. The patient was successfully treated, initially with amphotericin B, followed by oral itraconazole for a period of 6 months. Blastomycosis cases in India are reviewed and the likely source of infection in this patient is discussed.

Adult↗

Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado.

On the basis of case reports of blastomycosis, Blastomyces dermatitidis is widely accepted to be endemic in the central United States in and around the Ohio and Mississippi River Valleys. Blastomycosis also occurs in parts of Canada and in the southeastern United States. However, there has been no large-scale skin testing, and the environmental range of B. dermatitidis may have been underestimated. We describe 2 immunocompetent patients with blastomycosis acquired while working in the Front Range region of the Rocky Mountains. The patients were coworkers engaged in a prairie dog relocation project. In the course of this work, they had extensive contact with contaminated soil. Significantly above-average rainfall before the exposure may have contributed to favorable conditions for sporulation of the fungus.

Adult↗

Investigation of anti-WI-1 adhesin antibody-mediated protection in experimental pulmonary blastomycosis.

Infection with Blastomyces dermatitidis elicits strong antibody responses to the surface adhesin WI-1. The antibodies are directed chiefly against the adhesive domain, a 25-amino-acid repeat. Tandem-repeat-specific monoclonal antibodies (mAbs) were studied for their opsonic activity in vitro and their capacity to adoptively transfer protection in murine experimental blastomycosis. mAbs to WI-1 enhanced binding and entry of B. dermatitidis yeasts into J774. 16 cells but did not enhance killing or growth inhibition of the yeast. Passive transfer of 8 mAbs to WI-1 into 3 different inbred strains of mice also did not improve the course of experimental infection and sometimes worsened it. mu-deficient mice were more resistant to experimental blastomycosis than were intact littermates, and passive transfer of the mAbs into these mice did not protect them against experimental infection. Thus, antibody to WI-1 does not appear to improve the outcome of murine blastomycosis and may enhance the infection.

Adoptive Transfer↗

Cutaneous inoculation blastomycosis.

Cutaneous inoculation blastomycosis is a rare illness. We report a case of cutaneous inoculation blastomycosis in a patient who was inoculated after being struck by a projectile while performing yard work. We also review cases of cutaneous inoculation blastomycosis described elsewhere, to improve characterization of the syndrome.

Adult↗

Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Recent clinical data suggest that fluconazole at daily doses of 200 to 400 mg for at least 6 months is moderately effective therapy for non-life-threatening blastomycosis. To examine the usefulness of higher doses of fluconazole therapy for this disorder, we conducted a multicenter, randomized, open-label study to determine the efficacy and safety of two different daily doses of fluconazole (400 and 800 mg) in the treatment of non-life-threatening blastomycosis. Of 39 patients evaluable for efficacy analysis, 34 (87%) were successfully treated, including 89% and 85% of patients who received 400 and 800 mg, respectively. Five (83%) of six patients for whom prior antifungal therapy had failed were successfully treated. The mean duration of therapy was 8.9 months for successfully treated patients. Nineteen patients (48%) reported adverse events, although most were minor. We conclude that fluconazole at daily doses of 400 to 800 mg for at least 6 months is effective therapy for non-life-threatening blastomycosis.

Adolescent↗