Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Hage, Chadi A.; Kirsch, Emily J.; Stump, Timothy E.; Kauffman, Carol A.; Goldman, Mitchell; Connolly, Patricia; Johnson, Philip C.; Wheat, L. Joseph; Baddley, John W.

doi:10.1128/cvi.00389-10

Cited by 64 publications

(42 citation statements)

References 13 publications

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“…Antigenemia and antigenuria steadily declined during itraconazole therapy in dogs with blastomycosis (10). Antigen cleared more rapidly in serum than in urine, similar to what was observed in humans with histoplasmosis (8). The findings of the present study and these other reports support the rationale for a larger study using antigen to monitor therapy in humans.…”

Section: Discussionsupporting

confidence: 79%

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Connolly¹,

Hage

Bariola

et al. 2012

Clin Vaccine Immunol

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104

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The second-generation MVista Blastomyces antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative Blastomyces antigen assay and detection of antigen in serum. Calibrators containing known concentrations of Blastomyces galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture-or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.A ntigen detection is a useful method for diagnosis of blastomycosis. The sensitivity has been reported to be over 90% and specificity has been reported to be 100% in healthy subjects, but cross-reactions occur in most patients with histoplasmosis (6). In a recent report of 59 patients with proven blastomycosis (4), culture was positive in 86%, histopathology in 81%, antigen in 74%, cytopathology in 38%, and immunodiffusion for antibody in 32% (4). Antigen detection was considered to be a "reliable method to make an accurate and rapid diagnosis of blastomycosis, particularly when a large burden of disease is present, and when cytological analysis is performed at less-experienced centers" (4). Blastomyces antigen detection was also reported to be useful for diagnosis of blastomycosis in solid organ transplant patients (7).Because of interassay variability, specimens obtained earlier have been tested simultaneously with current specimens to assess the change in antigen levels. In a Histoplasma antigen assay, quantification of galactomannan antigen eliminated the need to test the previously obtained specimen with the current specimen to determine change in antigen level (5). In a recent study, quantification and improved detection of antigen in serum following EDTA treatment at 104°C in the t...

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Section: Discussionsupporting

confidence: 79%

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Connolly¹,

Hage

Bariola

et al. 2012

Clin Vaccine Immunol

Self Cite

104

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“…On the other hand, antigen tests are available for both of these fungal infections, can be performed on both urine and serum, and have superior sensitivities (83.3 to 91.8% for histoplasmosis and 92.9% for blastomycosis) (100,101). Also, a recent study showed that H. capsulatum antigenemia, but not antigenuria, decreases rapidly after clearance of the infection in AIDS patients with disseminated disease, thus having the potential to be used to monitor the response to treatment (102). Note that the H. capsulatum antigen test has a high sensitivity for both AIDS patients and patients with other causes of immune deficiency, such as solid organ transplant recipients (103), while its sensitivity for nonimmunocompromised individuals is relatively lower in cases of disseminated histoplasmosis (100).…”

Section: Other Fungal Infectionsmentioning

confidence: 99%

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

et al. 2014

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SUMMARY Invasive fungal infections constitute a serious threat to an ever-growing population of immunocompromised individuals and other individuals at risk. Traditional diagnostic methods, such as histopathology and culture, which are still considered the gold standards, have low sensitivity, which underscores the need for the development of new means of detecting fungal infectious agents. Indeed, novel serologic and molecular techniques have been developed and are currently under clinical evaluation. Tests like the galactomannan antigen test for aspergillosis and the β-glucan test for invasive Candida spp. and molds, as well as other antigen and antibody tests, for Cryptococcus spp., Pneumocystis spp., and dimorphic fungi, have already been established as important diagnostic approaches and are implemented in routine clinical practice. On the other hand, PCR and other molecular approaches, such as matrix-assisted laser desorption ionization (MALDI) and fluorescence in situ hybridization (FISH), have proved promising in clinical trials but still need to undergo standardization before their clinical use can become widespread. The purpose of this review is to highlight the different diagnostic approaches that are currently utilized or under development for invasive fungal infections and to identify their performance characteristics and the challenges associated with their use.

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“…Also, unlike other diagnostic methods, monitoring of quantitative Histoplasma antigen values in urine and/or serum can be used to follow treatment responses and to monitor disease progression (13,14). The primary limitation of the MVista assay is the requirement that all specimens be submitted to MiraVista Diagnostics for testing, which can delay result reporting and affect patient management.…”

mentioning

confidence: 99%

Reevaluation of Commercial Reagents for Detection of Histoplasma capsulatum Antigen in Urine

et al. 2015

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Detection of the Histoplasma capsulatum urinary antigen (UAg) is among the most sensitive and rapid means to diagnose histoplasmosis. Previously, we evaluated analyte-specific reagents (ASR) manufactured by IMMY (Norman, OK) for detection of Histoplasma galactomannan (GM) in urine using an enzyme immunoassay (EIA), and we showed low positive agreement (64.5%) with the MiraVista (MVista) Histoplasma antigen (Ag) quantitative EIA (MiraVista Diagnostics, Indianapolis, IN). Here we reevaluated the IMMY GM ASR following modification of our original assay protocol and introduction of an indeterminate range. A total of 150 prospectively collected urine samples were tested with both the IMMY and MVista EIAs, and clinical histories were recorded for all study subjects. The IMMY GM ASR showed positive and negative agreements of 82.3% (14/17 samples) and 100% (121/121 samples), respectively (with exclusion of 12 indeterminate results), and overall agreement of 90% (135/150 samples) with respect to the MVista EIA. Of the three patients with negative IMMY GM ASR results and positive MVista EIA results, testing was performed for initial diagnostic purposes for one patient (<0.4 ng/ml by the MVista EIA) and UAg levels were being monitored for the remaining two patients (both <0.7 ng/ml by the MVista EIA). The MVista EIA results were positive for 6/12 samples that tested indeterminate by the IMMY GM ASR. We also show that the IMMY GM ASR can be used to serially monitor Histoplasma UAg levels. In conclusion, we demonstrate that, with modification, the IMMY GM ASR is a reliable rapid assay for detection of Histoplasma UAg. Localized largely along the Ohio River and Mississippi River valleys, Histoplasma capsulatum continues to be a significant cause of morbidity and death, particularly among individuals with weakened cellular immunity and those over the age of 65 years (1, 2). Despite the high rates of exposure (60 to 90%) among residents of these regions of endemicity, otherwise healthy individuals are able to control infections with minimal disease manifestations (3, 4). However, immunocompromised patients exposed to H. capsulatum typically present with a nonspecific febrile illness, which can rapidly progress to pneumonia, respiratory insufficiency, disseminated disease, and death (2, 5). Histoplasmosis can be treated effectively with proper antifungal management, but timely diagnosis is essential.Due to the nonspecific clinical presentation of histoplasmosis, as well as lengthy, costly, and potentially toxic therapeutic regimens, laboratory testing to confirm the diagnosis is critical. Many methods are available for this purpose, including culture, nucleic acid amplification testing (NAAT), histopathological examination, and antibody and antigen (Ag) detection. The individual performance characteristics of these methods vary, with their overall clinical utility being largely dependent on disease presentation (localized versus disseminated), level of patient immunosuppression, and symptom duration prior to testing. Briefly, wh...

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Histoplasma Antigen Clearance during Treatment of Histoplasmosis in Patients with AIDS Determined by a Quantitative Antigen Enzyme Immunoassay

Cited by 64 publications

References 13 publications

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Molecular and Nonmolecular Diagnostic Methods for Invasive Fungal Infections

Reevaluation of Commercial Reagents for Detection of Histoplasma capsulatum Antigen in Urine

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