A Multicenter Evaluation of Tests for Diagnosis of Histoplasmosis

Hage, Chadi A.; Ribes, Julie A.; Wengenack, Nancy L.; Baddour, Larry M.; Assi, Maha; McKinsey, David S.; Hammoud, Kassem; Alapat, Daisy; Babady, N. Esther; Parker, Michelle; Fuller, D.; Noor, Aliya; Davis, Thomas E.; Rodgers, Mark; Connolly, Patricia; Haddad, Boutros El; Wheat, L. Joseph

doi:10.1093/cid/cir435

Cited by 330 publications

(338 citation statements)

References 16 publications

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“…Serological assays for detection of antibodies to H. capsulatum are advantageous, as they are performed with an easily accessible specimen source (e.g., serum) and provide high specificity (Ͼ90%); however, false-negative results may occur for patients with recent infections and those with compromised immunity (3, 11). Furthermore, low-level seropositivity following exposure or resolved infection is not uncommon and may be diagnostically confounding.Among the many available laboratory methods, detection of H. capsulatum antigen (Ag), specifically with the MiraVista (MVista) Histoplasma Ag quantitative enzyme immunoassay (EIA) (MiraVista Diagnostics, Indianapolis, IN), provides a high level of sensitivity for clinical disease in both acute and disseminated cases of infection (75 to 80% and Ͼ90%, respectively) (3,11,12). 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).…”

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

et al. 2015

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“…One patient had antigenemia and antigenuria and one patient had antigenuria alone. One patient had both positive histoplasma and blastomyces urinary antigens however due to high cross reactivity reactions of these fungi (as high as 90%) [6] as well as clinical picture; the patient was felt to have infectious process consistent with SPH. In one patient (case number 1), nodal material was sent for flow cytometry, which was negative for a monoclonal population of lymphocytes.…”

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confidence: 99%

The Use of Endobronchial Ultrasound in the Diagnosis of Subacute Pulmonary Histoplasmosis

Ferguson

Egressy

Mohammed

2012

Chest

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“…An earlier study on antigen detection in dogs with blastomycosis revealed a sensitivity value of 94% in urine specimens and a value of 87% in serum specimens [7]. A multicenter evaluation on histoplasmosis antigen detection revealed 91.8% of 158 patients with disseminated histoplasmosis, 83.3% of 6 patients with acute histoplamosis, 30.4% of 46 patients with sub-acute hisotplasmosis, and 87.5% of 8 patients with chronic pulmonary histoplasmosis; antigenemia was present in 100% of 31 tested cases of disseminated histoplasmosis [18]. In another study on Coccidioides antigen detection, antigenuria was detected in 50% of patients.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years other investigators have been approaching the problem of immunodiagnosis and have produced encouraging results with antigen detection assays as second-generation assays have been developed [7,[14][15][16][17][18]. Our laboratory has been focusing on the use of the competitive enzyme-linked immunosorbent assay (ELISA) in B. dermatitidis antigen detection studies in urine specimens from dogs with diagnosed blastomycosis [11].…”

Section: Introductionmentioning

confidence: 99%

Antigen Detection in Canine Blastomycosis: Comparison of Different Antibody-Antigen Combinations in Two Competitive ELISAs

Andrae

Birch²,

Bybee³

et al. 2012

OJMM

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This present study was designed to evaluate four different Blastomyces dermatitidis antibody-antigen combinations (B5896 and T-58 antibodies and B5896 and WI-R antigens) for the detection of antigen in 36 urine specimens from dogs with blastomycosis using a standard indirect ELISA (STD) and a biotin-streptavidin ELISA (B-SA). The antigen detection sensitivity values ranged from 81% (B-SA: T-58 Ab + WI-R Ag) to 100% (STD and B-SA: B5896 Ab + WI-R Ag; B5896 Ab + B5896 Ag) with the antibody-antigen combinations in the two assays. Optimal detection was evidenced when the B5896 Ab was allowed to react with the urine specimens for 30 min at 37˚C and then placed in the B-SA ELISA plates containing the B5896 Ag. The greatest absorbance value obtained with this antibody-antigen combination was 0.903 (range of 0.596 -0.903) as compared to the control value of 1.246. The difference between the control absorbance and the test absorbance values was 0.343 which was considerably greater than the control-test values with the other combinations. This study thus showed that the results obtained in antigen detection assays are dependent upon the antibody used to react with the urine specimens as well as the antigen used in the enzyme immunoassay.

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A Multicenter Evaluation of Tests for Diagnosis of Histoplasmosis

Abstract: The sensitivity of antigen detection in disseminated histoplasmosis is higher in immunocompromised patients than in immunocompetent patients and in patients with more severe illness. The sensitivity for detection of antigenemia is similar to that for antigenuria in disseminated infection.

Cited by 330 publications

References 16 publications

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

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

The Use of Endobronchial Ultrasound in the Diagnosis of Subacute Pulmonary Histoplasmosis

Antigen Detection in Canine Blastomycosis: Comparison of Different Antibody-Antigen Combinations in Two Competitive ELISAs

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