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PubMed1992

Epidemiology of blastomycosis in a region of high endemicity in north central Wisconsin.

The clinical and epidemiologic features of 73 patients with laboratory-confirmed blastomycosis who were identified over an 11-year period in North Central Wisconsin are presented. Pulmonary disease was the sole manifestation in 77% of patients. More than one-half of all patients had symptoms that included fever, cough, weight loss, night sweats, and pleuritic chest pain. Virtually all were previously healthy, and most did not have an outdoor occupation. However, 82% of these patients lived or had visited within 500 m of rivers or associated waterways. The majority experienced the onset of symptoms between December and April. The estimated mean annual incidence rate of infection for Vilas County was 40.4 cases per 100,000 persons, and that for the largest city in the county was 101.3 cases per 100,000 persons. Several areas with an exceptionally high incidence of the infection were observed. We suggest that, in regions where blastomycosis is hyperendemic, clinical disease is most often pulmonary and occurs in immunocompetent individuals and that residence near an ecological focus may be a greater risk factor for acquisition of blastomycosis than is occupation.

Adolescent↗
PubMedDate not supplied

Blastomycosis in Africa: clinical features, diagnosis, and treatment.

Four cases of blastomycosis seen in two acute care hospitals in Harare, Zimbabwe, are described. All patients had symptoms of at least 2 months' duration before presentation, and all had radiographic evidence of pulmonary consolidation. Three patients had confirmed bone involvement, and two had chronic discharging sinuses. The features of blastomycosis in Africa are reviewed, and problems of diagnosis and treatment are discussed. It is concluded that blastomycosis in Africa may often be misdiagnosed as tuberculosis or pyogenic infection in the absence of adequate facilities for mycologic investigation.

Adult↗
PubMed1992

Otitis media due to blastomycosis: report of two cases.

Blastomycosis as a causative agent in cases of otitis media has not previously been reported. Two patients recently presented with otitis media and head and neck masses due to Blastomyces dermatitidis. Initial evaluation suggested neoplastic disease, but biopsy confirmed a fungal etiology for the masses in both patients. Relapse after administration of ketoconazole was noted in one patient, who was an adult; the other patient was a child. Otitis media and masses of the head and neck are unusual features of blastomycosis. Blastomycosis should be considered in the differential diagnosis for patients with such mass lesions and for patients with otitis media.

Adult↗
PubMed1995

Treatment of blastomycosis with fluconazole: a pilot study. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

There are few clinical data concerning the use of fluconazole, a triazole antifungal agent with in vitro activity against Blastomyces dermatitidis, in the treatment of human blastomycosis. We conducted a multicenter, randomized, open-label pilot trial comparing two daily doses of fluconazole (200 mg and 400 mg) in the treatment of non-life-threatening, non-CNS blastomycosis. Twenty-four patients were enrolled in the study, and 23 patients were evaluable for efficacy analysis. Overall, treatment of 15 (65%) of 23 patients was successful, including eight (62%) of 13 who received 200 mg daily and seven (70%) of 10 who received 400 mg daily. The mean duration of therapy for successfully treated patients was 6.7 months. Of the six patients whose prior antifungal therapy had failed, all six eventually responded to fluconazole treatment. We conclude that fluconazole (200 mg to 400 mg daily) given for at least 6 months is moderately effective treatment for blastomycosis.

Adolescent↗
PubMed1996

Blastomycosis in children.

Infections due to Blastomyces dermatitidis are not commonly encountered in children and adolescents. Knowledge of the diagnosis and treatment of this disease is largely based upon experience with adult patients. We recently reviewed our experience with blastomycosis to evaluate the difficulties in diagnosis and treatment of this disease in the pediatric population. Ten patients with blastomycosis were identified during our review, and five had pulmonary disease alone. Of these five patients, four required open-lung biopsy for diagnosis, even though three had previously undergone bronchoalveolar lavage. The response to treatment with the oral azole antifungal agents (ketoconazole, fluconazole, and itraconazole) was limited, and the agent with the greatest success remains amphotericin B. Until more data are available, amphotericin B should be used for complicated and life-threatening cases of blastomycosis. If oral azole agents are used for non-life-threatening cases, patients should be followed closely, and if clinical deterioration occurs or serum levels of medications are not adequate, then amphotericin B should be substituted for the oral azole agent.

Adolescent↗
PubMedDate not supplied

CT findings of intracranial blastomycosis in a dog.

Computed tomography (CT) findings in a dog with intracranial blastomycosis were marked periventricular contrast enhancement of the lateral ventricles, the 3rd ventricle, and the mesencephalic aqueduct. The CT appearance correlated with the histopathologic findings, where severe ependymitis was present throughout the ventricular system and there was stenosis of the mesencephalic aqueduct due to an inflammatory infiltrate. CT is therefore recommended as a screening test for intracranial blastomycosis in dogs and also as an imaging modality for follow-up evaluation after treatment. This is particularly true in dogs with systemic or ocular blastomycosis, which appear to be at higher risk of developing CNS involvement.

Animals↗
PubMed1990

Treatment of murine pulmonary blastomycosis with SCH 39304, a new triazole antifungal agent.

SCH 39304, a broad-spectrum azole derivative, was evaluated in an experimental mouse model of blastomycosis pneumonia. Five days after being inoculated with Blastomyces dermatitidis, infected mice were treated with either oral SCH 39304, fluconazole, or intraperitoneal amphotericin B. A dose response protective effect was observed with SCH 39304 at 5 to 100 mg/kg of body weight per day, with 5 mg of SCH 39304 per kg per day providing activity similar to that of 100 mg of fluconazole per kg per day. Colony counts of yeasts in the lungs of mice sacrificed while on therapy with SCH 39304 were consistently below those of controls, and several lungs were sterile. We conclude that SCH 39304 is effective in murine blastomycosis treatment and deserves to be evaluated in the treatment of human blastomycosis.

Amphotericin B↗
PubMed1993

Activities of the triazole D0870 in vitro and against murine blastomycosis.

The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml). In vivo, D0870 was approximately 100-fold more active than fluconazole on the basis of milligrams per kilogram of body weight given once daily (QD) against blastomycosis. D0870 doses of both 1 or 10 mg/kg given QD and 10 or 100 mg/kg given every other day prolonged survival (P < 0.001) over fluconazole (100 mg/kg given QD). A D0870 dosage of 1 mg/kg QD was equivalent to fluconazole given at 100 mg/kg in reduction of lung burdens of B. dermatitidis, and D0870 administered at 10 mg/kg QD and 10 or 100 mg/kg every other day caused greater reduction (P < 0.001). However, D0870 at 100 mg/kg given QD was lethally toxic, whereas fluconazole at 100 mg/kg was not. These results indicate that D0870 is an effective therapy for murine blastomycosis and should be further tested.

Animals↗
PubMed1988

Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis.

Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.

Animals↗
PubMed1987

Two outbreaks of blastomycosis along rivers in Wisconsin. Isolation of Blastomyces dermatitidis from riverbank soil and evidence of its transmission along waterways.

Blastomycosis cannot yet be prevented or controlled, in part because the natural habitat of the causative fungus, Blastomyces dermatitidis, remains ill defined. In investigating 2 outbreaks of blastomycosis that occurred in the summer of 1985 among persons engaged in activities along rivers in contiguous central Wisconsin counties, we isolated B. dermatitidis from soil at one of the riverbanks. Blastomycosis developed in 7 (58%) of 12 residents and guests who had gathered at a pheasant farm on the Tomorrow River in early May, and in 7 (88%) of 8 boys and 1 adult who had visited a site on the Crystal River in early June. Of the 14 patients, 13 (93%) were symptomatic. Two patients visiting the sites only once became ill 23 and 78 days after exposure, respectively. We traced one outbreak to fishing from the bank of the Tomorrow River, and the other to climbing into an underground timber fort along the Crystal River. A culture of soil and organic debris from the fishing site yielded B. dermatitidis. From these and other outbreaks, and studies of endemic disease, we conclude that riverbanks can be a natural habitat of B. dermatitidis, and that the environment around waterways represents the most important site yet identified for transmission of B. dermatitidis.

Adult↗
PubMed1990

A new enzyme immunoassay specific for blastomycosis.

A highly specific enzyme immunoassay (EIA) was developed for the serodiagnosis of blastomycosis. Among the earliest sera available from eight active cases of blastomycosis, seven were reactive by EIA, three by immunodiffusion, and three by complement fixation. The one seronegative case was associated with acquired immunodeficiency syndrome (AIDS). No cross-reaction was observed with sera from 12 patients with active histoplasmosis or from five patients with active coccidioidomycosis or from 23 healthy persons. In contrast, all patients' sera cross-reacted in conventional EIAs based on commercial immunodiffusion antigens. The blastomycosis-specific EIA seems to offer sensitivity without compromising specificity. Rheumatoid factors, which could cause false-positive reactions, were controlled for.

Antigens, Fungal↗
PubMed1981

Radioimmunoassay: a sensitive screening test for histoplasmosis and blastomycosis.

Currently available serologic tests for histoplasmosis and blastomycosis have limited sensitivity. In order to develop a more sensitive screening test, the radioimmunoassay (RIA) technique was adapted to detect circulating antibodies to Histoplasma mycelial, Histoplasma yeast, and Blastomyces yeast antigens. Results were compared with those of complement fixation (CF) using serums from 4 groups of subjects. Group 1 (n = 104) consisted of consecutive healthy blood donors from an endemic area. Group 2 (n = 8) had active histoplasmosis and Group 3 (n = 12) had active blastomycosis. Group 4 (n = 30) had other chronic lung diseases. Among Group 1 subjects, elevated titers to at least 1 antigen were found in 13% using RIA and 21% using CF. Only 50% of patients with active mycoses (Groups 2 and 3) had elevated CF titers to a homologous antigen, whereas the RIA test was positive in 19 of 20 patients (95%). Elevated titers to 1 or more antigens was found in Groups 1 and 4, and frequent cross-reactions among the antigens occurred with both tests, indicating low specificities for both RIA and CF. The RIA is a sensitive and rapid screening test for histoplasmosis and blastomycosis, and a negative RIA using the 3 antigens tested makes the diagnosis of active infection very unlikely in immunologically competent patients.

Adolescent↗
PubMed1986

The use of ketoconazole in the treatment of blastomycosis.

We retrospectively reviewed our experience using ketoconazole in the therapy of blastomycosis. Over the course of 30 months, blastomycosis was diagnosed in 11 patients. Their clinical presentations ranged from the asymptomatic pulmonary nodule to the adult respiratory distress syndrome. Six of 8 patients treated with ketoconazole completed a 6-month course of 400 mg daily. Seventeen to 40 months after completion of therapy, the patients who had completed 6 months of therapy were well. Ketoconazole should play a major role in the therapy of blastomycosis because of its efficacy and because its administrative costs are lower than those of amphotericin B. It can be recommended for patients who have been symptomatic for longer than 3 wk and are not improving and for those who undergo resection of an asymptomatic pulmonary nodule. Amphotericin B remains the drug of choice in patients with life-threatening illness who require ventilatory assistance, have developed renal failure, or have central nervous system involvement. Severely immunocompromised patients with disseminated disease should also be treated with amphotericin B. Patients treated with ketoconazole should have close medical follow-up.

Adult↗
PubMed1987

Chronic murine pulmonary blastomycosis induced by intratracheally inoculated Blastomyces dermatitidis conidia.

Groups of 6-wk-old male BALB/cByJ mice were injected intratracheally (IT) with viable conidia from Blastomyces dermatitidis strains (FW or CR) harvested from 2-wk-old cultures (Pine-Drouhet agar at 30 degrees C) and separated from hyphal elements by polycarbonate filtration (5 micron). Inocula (0.05 ml) were 93 to 97% conidia in nonpyrogenic normal saline (NPNS) with greater than 90% viability. Quantitative cultures of the lungs and trachea of mice killed immediately after injection of 10(4) conidia (FW) confirmed that the inoculum was evenly distributed between the lungs, with virtually no conidia retained in the trachea. Animals were observed for 354 days for weight change, mortality, extrapulmonary dissemination and histopathologic changes. Mice inoculated with 10(4) FW began dying on Day 44, with a median survival of 92 days. A decrease in mean weight compared with that in control mice was noted by Day 55. In contrast, mice inoculated with 10(4) CR or NPNS neither died with blastomycosis nor lost weight in 329 days. Variation of the FW inoculum by tenfold increments produced comparable dose-dependent alterations in both mortality rate and weight change curves. Fifty percent survival was 32, 36, 92, or 172 days for mice inoculated with 10(6), 10(5), 10(4), or 10(3) conidia, respectively. Dissemination from the lungs to the liver, spleen, kidney, testis, and brain was found in the cachectic mice that were killed. Pathologic features of pulmonary and disseminated infections were comparable to those in human disease. This quantitative, reproducible model of chronic murine blastomycosis mimics the human disease in many respects and should provide a basis for future studies of the immunology, pathogenesis, and therapy of chronic blastomycosis.

Animals↗
PubMed2000

Pulmonary function following blastomycosis in childhood.

In order to determine the pulmonary outcome following blastomycosis during childhood, we compiled a case series of hospitalized patients from a retrospective review with later recall for pulmonary function testing, coupled with prospective measurements of pulmonary function in three patients, at a tertiary care children's hospital. A convenience sample of five of 17 patients hospitalized with pulmonary blastomycosis, whose mean age at the time of diagnosis was 10.6 +/- 5.5 years, was recalled at a mean of 4.5 +/- 3.5 years after diagnosis. Three patients more recently hospitalized underwent serial pulmonary function testing (PFT) prospectively from as soon after the acute infection as their condition permitted. All but two patients had normal PFT when last seen. The two patients with persistent pulmonary sequelae were among those followed up prospectively and had more severe clinical and radiographic pictures at the outset. Pulmonary function in children who suffered from pulmonary blastomycosis is normal in most patients at follow-up years later. Severe radiographic disease and slow recovery over months portend long-term sequelae.

Adolescent↗
PubMed1989

Subcutaneous blastomycosis: diagnosis by fine-needle aspiration cytology.

Blastomycosis is a rare disease. Fine-needle aspiration of nodules and neck masses is generally well accepted for head and neck cancer. This method has recently been used to make a rapid diagnosis of blastomycosis so that therapy could be instituted before the usual 4 to 6 week delay that is necessary for fungal cultures to mature. We believe this technique is reliable, provided the services of an experienced cytopathologist are available. The current treatment for blastomycosis is amphotericin B or ketoconazole, though newer antifungal agents hold promise for the treatment of this disease in the future.

Biopsy, Needle↗
PubMed2002

Delayed diagnosis of osseous blastomycosis in two patients following environmental exposure in nonendemic areas.

Blastomycosis generally results from inhalation of Blastomyces dermatitidis conidia following exposure to contaminated soil in an endemic area. Primary infections commonly involve the lungs, although secondary dissemination to other body sites may occur. We describe 2 cases of osseous blastomycosis in people living outside the endemic areas. Both patients reported exposure to soilfollowing injury to the knee from occupational activities. Mold isolated from each case was identified as B dermatitidis by micromorphologic characteristics including yeast conversion testing and by a positive AccuProbe Blastomyces dermatitidis test (GenProbe, San Diego, CA). Retrospective review of histologic slides, initially reported as negative, identified rare poorly staining, broad-based budding yeast forms in each case. Both patients were treated successfully with itraconazole with no evidence of recurrent infection after 1 year These cases illustrate the importance of considering blastomycosis in the differential diagnosis of bony lesions, even though the patient may live outside an endemic area for B dermatitidis.

Adult↗
PubMed1985

Failure of ketoconazole in an immunosuppressed patient with pulmonary blastomycosis.

A renal transplant recipient presented with pulmonary blastomycosis. Because of recent data suggesting a role for ketoconazole in the treatment of blastomycosis and concern for preserving her functioning renal transplant, she was started on therapy with ketoconazole, 400 mg daily. After four months of continuous therapy, she developed skin and laryngeal involvement requiring emergency tracheostomy; subsequent therapy with amphotericin B resulted in resolution of her disease. This is an example of life-threatening progression of blastomycosis in an immunosuppressed patient during ketoconazole therapy.

Adult↗