Plasmalyte as a cause of false-positive results for Aspergillus galactomannan in bronchoalveolar lavage fluid.
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Antigens, Fungal↗
Biomedical subjects
L Joseph Wheat
Publications and source records attributed to L Joseph Wheat.
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↗
Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who failed fluconazole.
OBJECTIVES: To determine the activity of newer triazoles against strains of Histoplasma capsulatum resistant to fluconazole. METHODS: Susceptibility testing was performed on 17 paired pre- and post-treatment H. capsulatum isolates from patients with AIDS who failed fluconazole. RESULTS: The median MICs of fluconazole, voriconazole, and posaconazole and ravuconazole for the pre-treatment isolates were 1 mg/L, 0.015 mg/L and <0.007 mg/L, respectively. A 4-fold or greater increase in the MIC of fluconazole and voriconazole was observed in 12 and 7 of the post-treatment isolates, respectively; the median fold increases in MIC were 8 and 2.1, respectively. No MIC increases were observed for posaconazole and ravuconazole. One pair of isolates exhibiting reduced susceptibility was examined in more detail. A single amino acid substitution (at tyrosine 136) was identified in the active site of the CYP51 protein from the post-treatment isolate, which is presumed to be responsible for reduced susceptibility to voriconazole and fluconazole, analogous to recent observations in Candida albicans. CONCLUSIONS: These findings support careful monitoring for relapse in patients receiving voriconazole treatment for histoplasmosis, particularly in those who were previously treated with fluconazole.
AIDS-Related Opportunistic Infections↗
Urine polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis.
We developed a colorimetric microtiter plate polymerase chain reaction enzyme immunoassay (PCR-EIA) for the detection of Histoplasma capsulatum in urine. The specificity of the PCR assay was confirmed using H. capsulatum (positive control) and Blastomyces dermatitidis (negative control) isolates. The analytical sensitivity of the PCR assay was determined by testing urine samples spiked with freshly grown H. capsulatum organisms and was 2 yeasts per reaction in urine and 0.2 yeasts per reaction in urine sediment after centrifugation. Fifty-one urine specimens positive for H. capsulatum antigen and 25 urine specimens from healthy volunteers were tested blindly. Patient specimens also were cultured for H. capsulatum. The PCR assay was positive in 4 (7.8%) of 51 urine specimens containing antigen and negative in urine specimens from healthy volunteers. The positive PCR results occurred in 4 of 5 urine specimens that were positive by culture, and each exhibited high level of antigenuria (>20 U). Urine cultures were not positive in 24 urine specimens with an antigenuria of 1-19.9 U, but were positive in 5 of 27 urine specimens with antigenuria >20 U. Thus, positive PCR results in urine specimens correlate with positive culture results, but not with antigenuria. The low sensitivity of this PCR assay in urine limits its use in the diagnosis of disseminated histoplasmosis.
Antigens, Fungal↗
Urine antigen detection of blastomycosis in pediatric patients.
Blastomycosis is an uncommonly recognized disease in pediatric patients. We describe 4 cases of pediatric blastomycosis that presented to our children's hospital, 2 with isolated pulmonary blastomycosis and 2 with disseminated blastomycosis. Because of variable clinical presentations and morbidity if treatment is delayed, physicians must maintain a high index of suspicion and obtain appropriate diagnostic tests promptly. For the first time, we report the effect of therapy on Blastomyces antigen clearance. In our experience, the urine antigen detection for B. dermatitidis is useful for diagnosis and follow up during therapy.
Adolescent↗
Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature.
We reviewed the clinical, microbiologic, and outcome characteristics of 72 patients with human immunodeficiency virus (HIV)-associated histoplasmosis (4 newly described) reported in Europe over 20 years (1984-2004). Seven cases (9.7%) were acquired in Europe (autochthonous), whereas the majority involved a history of travel or arrival from endemic areas. The diagnosis of progressive disseminated histoplasmosis (PDH) was made during life in 63 patients (87.5%) and was the acquired immunodeficiency syndrome (AIDS)-presenting illness in 44 (61.1%). Disease was widespread in 66 patients (91.7%) and localized in 6 (8.3%), with the skin being the most frequent site of localized infection. Overall skin involvement was reported in 47.2% of the patients regardless of whether histoplasmosis was acquired in Africa or South America. Reticulonodular or diffuse interstial infiltrates occurred in 52.8%. The diagnosis was made during life by histopathology plus culture in 44 patients (69.8%), histopathology alone in 18 (28.5%), and culture alone in 1 (1.5%). During the induction phase amphotericin B and itraconazole (74.6%) were the single most frequently used drugs. Both drugs were also used either in combination (10.2%) or in sequential therapy (11.8%). Cumulative mortality rate during the induction phase of treatment was 15.2%. Overall, 37 patients died (57.8%); death occurred early in the course in 18 (28.1%). Seven of 40 patients (17.5%) who responded to therapy subsequently relapsed. Autopsy data in 13 patients confirmed the widespread disseminated nature of histoplasmosis (85%) among AIDS patients with a median of 4.5 organs involved. The results of the present report highlight the need to consider the diagnosis of PDH among patients with AIDS in Europe presenting with a febrile illness who have traveled to or who originated from an endemic area.
Adult↗
Histoplasmosis: a review for clinicians from non-endemic areas.
Histoplasmosis is an important systemic mycosis in the Americas, Asia, and Africa. Increasingly cases are recognised in nonendemic areas. Proper management requires recognition of the clinical syndromes caused by Histoplasma capsulatum infection, familiarity with the uses and limitations of the diagnostic tests, an understanding of the indications for treatment and role of specific antifungal agents. This review will address these issues with the goal of providing physicians in non-endemic areas sufficient information to suspect, diagnose, and treat patients with histoplasmosis.
Histoplasmosis↗
Improvements in diagnosis of histoplasmosis.
Understanding the uses and limitations of a battery of laboratory methods is essential to diagnose histoplasmosis. Antigen detection and serology are valuable adjuncts to histopathology and culture. Improvements incorporated into the second-generation Histoplasma antigen assay have increased its sensitivity and specificity for diagnosis of histoplasmosis. More recently, the antigen assay has been modified to provide quantitation, which improves reproducibility and facilitates monitoring antigen clearance during treatment. Furthermore, detection of antigen in bronchoalveolar lavage fluid increases the sensitivity for diagnosis of pulmonary histoplasmosis. Serological tests for antibodies are also useful, but may be falsely negative in immunosuppressed patients. In addition, elevated antibody titres persist for several years following initial infection, complicating their interpretation. Although histopathology may provide for rapid diagnosis, its sensitivity is < 50% in patients with disseminated disease and even lower in pulmonary histoplasmosis. Polymerase chain reaction has been described, but sensitivity is less than that of histopathology. Culture, although highly specific, has notable limitations, including insensitivity, a need for invasive procedures and delayed growth. This review provides the background for understanding the role of a battery of diagnostic methods in histoplasmosis. Tests facilitating a rapid diagnosis are expected to improve the outcome in patients with severe disease.
Animals↗
Infliximab does not affect dendritic cells' mediated lymphoproliferative response to Histoplasma capsulatum.
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Antibodies, Monoclonal↗
Gastrointestinal histoplasmosis.
Gastrointestinal histoplasmosis (GIH) is an uncommon disease with protean manifestations. It may occur as a result of mediastinal histoplasmosis or in the setting of progressive dissemination. GIH may be misdiagnosed as inflammatory bowel disease, malignancy, or other intestinal diseases leading to inappropriate therapies and unnecessary surgical interventions. Patients with bowel obstruction, perforation, or bleeding, and systemic findings suggestive of histoplasmosis should be evaluated for GIH. This is especially true for immunosuppressed patients, especially those with AIDS. Diagnosis first requires consideration of histoplasmosis in the differential in patients with the above types of gastrointestinal abnormalities, and second, familiarity with a battery of mycologic and serologic tests. Progressive disseminated histoplasmosis (PDH) is lethal if left untreated, and treatment is highly effective. This review will focus on the clinical and histopathologic features of GIH, the approach to diagnosis, and recommendations for treatment.
Gastrointestinal Diseases↗
Safety of discontinuation of maintenance therapy for disseminated histoplasmosis after immunologic response to antiretroviral therapy.
We performed a prospective observational study to assess the safety of stopping maintenance therapy for disseminated histoplasmosis among human immunodeficiency virus infected patients after response to antiretroviral therapy. All subjects received at least 12 months of antifungal therapy and 6 months of antiretroviral therapy before entry. Negative results of fungal blood cultures, urine and serum Histoplasma antigen level of <4.1 units, and CD4+ T cell count of >150 cells/mm3 were required for eligibility. Thirty-two subjects were enrolled; the median CD4+ T cell count at study entry was 289 cells/mm3. No relapses of histoplasmosis occurred after a median duration of follow-up of 24 months. This corresponded to an observed relapse rate of 0 cases per 65 person-years. The median CD4+ T cell count at final study visit was 338 cells/mm3. Discontinuation of antifungal maintenance therapy appears to be safe for patients with acquired immunodeficiency syndrome with previously treated disseminated histoplasmosis and sustained immunologic improvement in response to antiretroviral therapy.
AIDS-Related Opportunistic Infections↗
Therapy for severe histoplasmosis: what's best?
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Amphotericin B↗
Pulmonary histoplasmosis syndromes: recognition, diagnosis, and management.
Pulmonary manifestations are the hallmark of histoplasmosis. Clinical syndromes range from asymptomatic infection to diffuse alveolar disease causing respiratory difficulty and even death. Serologic tests for antibodies and antigen detection are especially helpful in the diagnosis of histoplasmosis but are frequently overlooked. Detection of Histoplasma capsulatum antigen in bronchoalveolar lavage fluid may be particularly helpful in patients with acute pulmonary histoplasmosis or disseminated disease with pulmonary involvement. Topics of special importance for pulmonary disease specialists include the approach to the exclusion of histoplasmosis in the evaluation of patients with suspected sarcoidosis, differentiation of pulmonary histoplasmosis and malignancy in those with lung masses or mediastinal lymphadenopathy, and recognition and management of chronic pulmonary and mediastinal manifestations of histoplasmosis. Although histoplasmosis is mild and self-limited in most healthy individuals, antifungal therapy is indicated in those with acute diffuse pulmonary infection, chronic pulmonary histoplasmosis, progressive disseminated disease, and perhaps mediastinal adenitis accompanied by obstructive symptoms. Antifungal therapy to prevent reactivation of histoplasmosis during immunosuppressive therapy, or transition of mediastinal adenitis to fibrosing mediastinitis, although controversial, is not recommended. Several new drugs active against H. capsulatum offer alternatives in patients failing or intolerant of current therapies.
Journal Article↗
A large histoplasmosis outbreak among high school students in Indiana, 2001.
BACKGROUND: A histoplasmosis outbreak occurred in an Indiana high school in November-December 2001. METHODS: To describe the risk factors for this outbreak, we conducted a cohort study of all available students and staff (N = 682) and an environmental investigation. RESULTS: Of the 523 (77%) persons who displayed serologic evidence of recent Histoplasma capsulatum infection, 355 (68%) developed symptoms consistent with acute pulmonary histoplasmosis. Rototilling of soil in a school courtyard known to be a bird roosting site had been performed during school hours on November 12, 2001, 14 days before both the peak of the onset of illness and a rise in student absenteeism. Being a student (odds ratio, 3.3; 95% confidence interval, 2.2-5.0) and being a student in a classroom near the courtyard during the rototilling (odds ratio, 3.1; 95% confidence interval, 1.8-5.2) were independently associated with infection and symptomatic illness. H. capsulatum was isolated from environmental samples, including soil from the courtyard and dust collected from a filter of a heating, ventilating and air-conditioning system. CONCLUSIONS: Soil-disrupting activities within a school courtyard caused the largest outbreak to date of histoplasmosis among adolescents. Improved efforts are needed to educate the community in endemic areas about histoplasmosis to prevent the occurrence of such outbreaks in the future. In addition, increased awareness among health care providers of this disease would facilitate appropriate diagnosis and treatment.
Adolescent↗
Combination therapy for aspergillosis: is it needed, and which combination?
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Animals↗
Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy.
Anti-tumor necrosis factor-alpha (TNF-alpha) antibodies are frequently used to treat inflammatory diseases. However, these drugs also have immunosuppressive effects. We report on three patients who developed disseminated histoplasmosis on therapy with TNF-alpha inhibitors. In vitro assays were used to characterize the role of these agents in host defense against Histoplasma capsulatum. Intracellular proliferation of H. capsulatum was measured in alveolar macrophages and peripheral monocytes of normal volunteers in the presence and absence of the TNF-alpha antibody, infliximab. Both infliximab and control antibody enhanced fungal growth in monocytes and alveolar macrophages, suggesting this was a nonspecific antibody response. Despite similar intracellular fungal loads in the presence of both antibodies, lymphocyte proliferation in response to blood monocytes and alveolar macrophages infected with H. capsulatum was inhibited by the addition of physiologic doses of infliximab, whereas control antibody had no effect. The production of H. capsulatum-induced interferon-gamma and TNF-alpha was assessed in 5-day cultures containing lymphocytes and alveolar macrophages or monocytes. Interferon-gamma secretion was significantly reduced in the presence of infliximab. In summary, patients receiving anti-TNF-alpha therapy are at risk for developing disseminated histoplasmosis. This may be due to a defect in the TH1 arm of cellular immunity.
Adolescent↗
Current diagnosis of histoplasmosis.
Histoplasmosis is a common infection endemic in many regions of America, Asia, India and Africa, with sporadic cases also occurring throughout the world. Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose histoplasmosis. Research is needed to reduce false-negative and false-positive results, and to improve the identification of the organism in tissues. Approaches to the diagnosis of histoplasmosis and areas that require further research will be reviewed.
Antigens, Fungal↗
Histoplasmosis.
The diagnosis of histoplasmosis depends on recognition of the different clinical manifestations of infection, accompanied by knowledge of the accuracy and limitations of tests used for diagnosis of fungal infections. Although most infections are asymptomatic, histoplasmosis can be severe, or even fatal, in patients who have experienced a heavy exposure, have underlying immune defects, or develop progressive disease that is not recognized and treated. This article provides an up-to-date clinical review of histoplasmosis, focusing on recognition, diagnosis, and management.
AIDS-Related Opportunistic Infections↗