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Blastomycosis and human immunodeficiency virus: three new cases and review.

Reports of blastomycosis in individuals infected with the human immunodeficiency virus (HIV) are increasing. We report on 3 patients co-infected with blastomycosis and HIV (to add to the previously reported 21), and review important clinical aspects and outcomes in all cases. The percentage of patients co-infected with blastomycosis and HIV who had disseminated blastomycosis (63%) was similar to the blastomycosis patients in the general population (67%); however, as a group the patients with HIV were severely immunosuppressed and fared poorly. Severe immunodeficiency was indicated by CD4 counts < 200/mm3 in 85% of co-infected patients. Central nervous system (CNS) involvement occurred in 46% of this group, approximately 5 to 10 times more frequently than in individuals not infected with HIV previously reported at 5% to 10%. The mortality rate from blastomycosis for patients with both HIV infection and blastomycosis is 54%, about 5 times the mortality rate of blastomycosis patients in the general population, previously reported at < 10%. Disseminated blastomycosis in individuals with HIV may appear as deep cutaneous ulcers, as was the case in two of our patients. Although blastomycosis is not an AIDS-defining infection, it may be reasonable to consider HIV testing and measurement of CD4 counts in patients with blastomycosis. Such testing could help identify individuals who are HIV positive but asymptomatic who have blastomycosis, as well as provide useful information regarding a possible association between CD4 cell deficiency and various clinical manifestations of blastomycosis. Patients with HIV and blastomycosis should be examined carefully for any evidence of CNS involvement. Lifetime therapy with ketoconazole or itraconazole is likely to be of benefit to patients with HIV who have been treated successfully for blastomycosis.

Adult↗

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.

Acquired Immunodeficiency Syndrome↗

Blastomycosis.

Blastomycosis is a rare but important fungal infection that occurs primarily in the south central and midwestern United States. Epidemics of blastomycosis related to a point-source exposure include patients of all ages and both sexes; however, cases of endemic blastomycosis are usually in young to middle-aged adults and are reported more for men than for women. Pneumonia is the most common manifestation of blastomycosis, and the lungs are almost always the organ initially infected. Skin, bone, prostate, and central nervous system are the next most frequently infected organs in descending order. Amphotericin B is curative, but because of its toxic effects, oral agents have been investigated as therapy for blastomycosis. ketoconazole should replace amphotericin B as therapy for blastomycosis that is not life threatening. Itraconazole is an experimental agent that is perhaps even more effective than ketoconazole. The therapeutic usefulness of fluconazole for blastomycosis remains unproven. For patients with life-threatening or central nervous system blastomycosis, amphotericin B remains the treatment of choice.

Amphotericin B↗

Blastomycosis in immunocompromised patients.

Among the endemic mycoses, blastomycosis has been least often associated with disorders of immune function, but the data presented herein suggest that blastomycosis may occur more commonly in immunocompromised patients than was previously recognized. We have observed a marked increased in the number of immunocompromised patients with blastomycosis over the last 15 years, increasing from about 3% of patients seen between 1956 and 1977 to almost 24% patients seen between 1978 and 1991. The disease appears to be much more aggressive in immunocompromised than in normal hosts. Almost 30% of the patients in our series died secondary to blastomycosis, with most deaths occurring within 5 weeks following the diagnosis. Furthermore, almost one third of those patients who died of other causes had evidence of persistent blastomycosis at death. Multiple organ and central nervous system involvement were relatively common in this series. For these reasons, early and aggressive therapy with amphotericin B is indicated for most immunocompromised patients with blastomycosis. Oral therapy with an azole compound should probably be reserved for patients who have responded to a primary course of amphotericin B but who require additional or long-term suppressive therapy. Until more data are available, the newer azoles should be used with caution as primary therapy in immunocompromised patients with blastomycosis, and considered only in patients with limited disease and a stable underlying condition. Caring for the immunocompromised patient poses many diagnostic and therapeutic challenges to the clinician, and among those patients who have been exposed to areas endemic for blastomycosis, B. dermatitidis must be regarded as a potentially important opportunistic pathogen.

Adult↗

Blastomycosis in northeast Tennessee.

STUDY OBJECTIVES: To study the epidemiologic and clinical features of blastomycosis in northeast Tennessee. DESIGN: Retrospective review of blastomycosis cases in the region from 1980 through 1995. SETTING: Hospitals located in the Tri-Cities region of northeast Tennessee. PATIENTS: Seventy-two patients with confirmed blastomycosis infection. INTERVENTIONS: None. RESULTS: During the 1980 to 1995 study period, we documented 72 cases of blastomycosis. The mean age was 52 years (range, 13 to 86 years), most were male (69.4%), and nine were immunocompromised. A possible environmental exposure was noted for 28 patients. Pulmonary involvement represented the most common site of infection (61 cases), but multiorgan involvement was common (17 cases). Most patients with pulmonary blastomycosis (66%) presented with a chronic illness, and radiologic findings usually revealed local consolidation or a mass-like lesion. Nine patients developed ARDS with an associated mortality rate of 89%, compared with a 10% mortality for non-ARDS pulmonary cases. Antifungal treatment regimens varied widely, with amphotericin B often used for sicker patients. An epidemiologic evaluation revealed that the mean yearly incidence rate for blastomycosis quadrupled between 1980 and 1987 (0.31 cases/ 100,000 population) and 1988 to 1995 (1.23 cases/100,000 population) (p=0.00001). Most new blastomycosis cases in the 1988 to 1995 period occurred in three counties in the region where significant new construction projects have been underway. CONCLUSION: Blastomycosis is endemic in northeast Tennessee and the number of cases is increasing, coinciding with major new construction in the region. Clinicians in the area must be alert to this condition.

Adolescent↗

Evaluation of risk factors for blastomycosis in dogs: 857 cases (1980-1990)

An epidemiologic study was conducted by use of the Veterinary Medical Data Base to investigate risk factors for blastomycosis in dogs. From January 1980 through June 1990, 971 cases of blastomycosis in dogs from 22 North American veterinary teaching hospitals were identified. Of these cases, 114 (11.7%) were excluded from the study because of incomplete information regarding age, body weight, sex, and neuter status. A control group of 417,079 dogs was selected that included all other dogs with medical conditions unrelated to blastomycosis for which records were submitted to the data base during the same period. The prevalence of blastomycosis in dogs was 205/100,000 admissions during the study period. When veterinary teaching hospitals were grouped on the basis of their general geographic location, dogs in the East South central, East North central, West South central, and South Atlantic regions had a significantly (P < 0.05) increased risk of acquiring blastomycosis, compared with that of dogs in the Mountain/Pacific region. When teaching hospitals from all geographic regions were considered, dogs had a significantly (P < 0.05) increased risk of acquiring blastomycosis in autumn, compared with that in spring. Sporting dogs and hounds, as defined by the American Kennel Club, were at increased risk for blastomycosis. At highest risk were Bluetick Coonhounds, Treeing-walker Coonhounds, Pointers, and Weimaraners, compared with mixed-breed dogs. Ages of dogs with blastomycosis tended to be normally distributed. Generally, the highest-risk group was composed of sexually intact male dogs, 2 to 4 years old, weighing 22.7 to 34.1 kg. This same pattern was observed for sporting dogs and hounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Utility of anti-WI-1 serological testing in the diagnosis of blastomycosis in Wisconsin residents.

WI-1, a 120-kD protein found in the outer cell wall of Blastomyces dermatitidis, has been purified, labeled with 125I, and used as a target in a radioimmunoassay (RIA). In an assessment of the usefulness of anti-WI-1 serology in the diagnosis of blastomycosis, the RIA was used to test four panels of sera from residents of Wisconsin, a state in which blastomycosis is endemic. Twenty-four (75%) of 32 patients whose blastomycosis had been reported to the Wisconsin Division of Health had at least one serum sample positive for antibody to WI-1; 25 (93%) of 27 serum samples obtained from these patients within 60 days of diagnosis were positive. In an effort to simulate clinical practice, 132 serum samples were assayed from another 107 patients in whom blastomycosis was being considered as a cause of illness. The result was positive for at least one sample from 83% of the 23 patients with confirmed blastomycosis and from 5% of the 84 patients from whom the fungus was not documented. Serum samples from another five patients with blastomycosis identified during investigation of a 1990 outbreak in Oconto Falls, Wisconsin, also gave a positive result, whereas none of the serum specimens from 57 healthy family members or neighbors did so. Only three (0.56%) of 535 serum samples from random blood donors residing in two counties with a high annual incidence of blastomycosis were positive for antibody to WI-1. Modification of the RIA so that IgM rather than IgG antibody was detected did not enhance diagnostic sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical presentation, radiographic findings, and diagnostic methods of pulmonary blastomycosis: a review of 100 consecutive cases.

BACKGROUND: We sought to determine the relationship among radiographic findings, clinical presentation, and diagnostic testing of pulmonary blastomycosis. METHODS: We reviewed the medical records of 100 consecutive patients with pulmonary blastomycosis. RESULTS: Air-space infiltrates were the usual radiographic finding of pulmonary blastomycosis. Mass-like infiltrates were associated more with chronic than acute presentations. Air-space and mass-like infiltrate were predominately involved in the upper lobes. Sputum analysis made the initial diagnosis of blastomycosis most often. Acute and chronic presentations were not different between immunosuppressed patients and the remainder of the patients. In addition, infiltrates on chest radiographs in immunosuppressed patients were similar to the other patients. CONCLUSIONS: In an endemic area, pulmonary blastomycosis should be considered for any pulmonary infiltrate, especially in the upper lobes. Sputum analysis in most cases aids in the diagnosis, but bronchoscopy and/or tissue biopsy should be considered if the suspicion of blastomycosis is high and sputum analysis is inconclusive, negative, or not possible. Follow-up with chest radiographs after antifungal therapy is reasonable until complete resolution or fibrotic changes in patients with pulmonary blastomycosis.

Acute Disease↗

Lymphocyte subpopulations of blood and alveolar lavage in blastomycosis.

Patients with blastomycosis were found to have differing lymphocyte populations depending on the extent of disease manifestations and whether or not therapy had been started. Patients with recovering pulmonary blastomycosis who had been receiving antifungal treatment for at least four weeks had lymphocyte subpopulations no different from control donors. Patients with treated extrapulmonary blastomycosis had similar T helper (TH) to T suppressor (TS) ratios compared to recovering pulmonary patients and control subjects; this ratio gives a false impression because extrapulmonary blastomycosis patients had a reduced absolute number of lymphocytes with either marker. In bronchoalveolar lavage fluid, pulmonary blastomycosis patients who were clinically improved while receiving antifungal therapy had fewer TH cells and a greater number of lymphocytes with the TS marker than did control subjects. Patients with pulmonary blastomycosis prior to therapy had a smaller TH/S ratio than the other groups in peripheral blood primarily due to a reduction in the circulating TH fraction in both absolute numbers of cells and in the percentage of total T lymphocytes. Pulmonary blastomycosis patients re-evaluated after at least four weeks of antifungal therapy had TH/S ratios that were similar to normal persons. This increase in TH lymphocytes corresponded to clinical improvement and in a temporal correlation to that described for the development of specific immunity in this illness.

Adult↗

Evidence of subclinical blastomycosis in forestry workers in northern Minnesota and northern Wisconsin.

PURPOSE: To investigate the incidence of remote subclinical blastomycosis in a high-risk population of forestry workers. PATIENTS AND METHODS: The study consisted of 39 male forestry workers from northern Minnesota and northern Wisconsin, areas endemic for blastomycosis but not for histoplasmosis. All subjects were histoplasmin skin test-negative, and none had ever been diagnosed with blastomycosis or pneumonia. An antigen-specific lymphocyte stimulation assay was performed to determine the presence of blastomycosis. RESULTS: Peripheral blood lymphocytes from 12 of 39 subjects demonstrated specific antigen-induced proliferation when stimulated with a purified alkali- and water-soluble antigen derived from the cell wall of Blastomyces dermatitidis. CONCLUSION: The finding that 30% of these men had evidence of previous blastomycosis suggests that subclinical cases do occur sporadically, and are probably more common than diagnosed symptomatic cases. This is similar to histoplasmosis, in which the majority of infections are subclinical. However, the reservoir of persons with previous undiagnosed blastomycosis is probably small compared to the huge number of persons (perhaps 30 million) with prior histoplasmosis.

Adult↗

Itraconazole therapy for blastomycosis and histoplasmosis. NIAID Mycoses Study Group.

OBJECTIVE: To assess the efficacy and toxicity of orally administered itraconazole in the treatment of nonmeningeal, nonlife-threatening forms of blastomycosis and histoplasmosis. DESIGN: Prospective, nonrandomized, open trial. SETTING: Multicenter trial at 14 university referral centers. PATIENTS: Eighty-five patients with culture or histopathologic evidence of blastomycosis (48 patients) or histoplasmosis (37 patients). Patients receiving other systemic antifungal therapy were excluded. INTERVENTIONS: Itraconazole was administered orally at doses of 200 to 400 mg/d. Patients in whom treatment was considered a success were treated for a median duration of 6.2 months (blastomycosis) and 9.0 months (histoplasmosis). Disease activity was assessed at baseline; drug efficacy and toxicity were evaluated at monthly intervals during therapy, and efficacy was evaluated at regular follow-up visits after completion of therapy. The median duration of posttreatment evaluation for successfully treated patients was 11.9 months (blastomycosis) and 12.1 months (histoplasmosis). MEASUREMENTS AND MAIN RESULTS: Among the 48 patients with blastomycosis, success was documented in 43 (90%). The success rate for patients treated for more than 2 months was 95% (38 of 40). Among the 37 patients with histoplasmosis, success was documented in 30 (81%). The success rate for patients treated for more than 2 months was 86% (30 of 35). All patients with histoplasmosis in whom treatment failed had chronic cavitary pulmonary disease. Toxicity was minor; only 25 (29%) patients experienced any side effects, and itraconazole toxicity necessitated stopping therapy in only 1 patient. CONCLUSIONS: Itraconazole is a highly effective therapy for nonmeningeal, nonlife-threatening blastomycosis and histoplasmosis. The drug is associated with minimal toxicity.

Adult↗

Blastomycosis and pregnancy.

Blastomycosis is an exceedingly uncommon complication of pregnancy, rarely encountered by the practicing obstetrician. However, recognizing its presence during pregnancy and expeditiously initiating appropriate therapy is of critical importance to the mother and fetus. Mississippi has the highest prevalence of blastomycosis in North America. Nevertheless, there have been only three pregnancies complicated by this fungal disease at the University of Mississippi Medical Center (Jackson, MS) during two decades. During the same time frame there were another 120 blastomycotic patients treated at the University of Mississippi Medical Center. As a condition of partial immunodepression, a nonobligatory opportunistic fungal disease like blastomycosis can complicate pregnancy. From data on our three patients and 16 other published cases, it seems that fetal risk exceeds maternal risk. There were a total of 20 babies born from mothers with blastomycosis. Only two babies (10%) had transplacental infection and both succumbed to blastomycosis. None of the 18 affected mothers for whom data was available died of the disease. Furthermore, there was never progression in the mothers, with 14 complete cures and considerable postpartum regressions of lesions in the other four women. Even the three women who received no treatment had either noticeable improvement or total regression of the disease after delivery. One of the two stillborns with blastomycosis was born to an untreated mother.

Adolescent↗

Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for nonlife-threatening non-CNS blastomycosis.

Amphotericin B↗