Evaluation of Commercially Available Reagents for Diagnosis of Histoplasmosis Infection in Immunocompromised Patients

Zhang, Xiaochun; Gibson, Bill; Daly, Thomas M.

doi:10.1128/jcm.02298-13

Cited by 42 publications

(35 citation statements)

References 20 publications

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“…The sensitivity and specificity of this assay were found to be lower than those of the MiraVista assay (11). A subsequently developed analyte-specific reagent (ASR) H. capsulatum antigen EIA (IMMY) has shown improved performance characteristics (12), as well as high agreement with the MiraVista EIA (13).…”

Section: Antigen Detectionmentioning

confidence: 98%

Laboratory Diagnostics for Histoplasmosis

2017

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The diagnosis of histoplasmosis is based on a multifaceted approach that includes clinical, radiographic, and laboratory evidence of disease. The gold standards for laboratory diagnosis include demonstration of yeast on pathological examination of tissue and isolation of the mold in the culture of clinical specimens; however, antigen detection has provided a rapid, noninvasive, and highly sensitive method for diagnosis and is a useful marker of treatment response. Molecular methods with improved sensitivity on clinical specimens are being developed but are not yet ready for widespread clinical use. This review synthesizes currently available laboratory diagnostics for histoplasmosis, with an emphasis on complexities of testing and performance in various clinical contexts.

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Section: Antigen Detectionmentioning

confidence: 98%

Laboratory Diagnostics for Histoplasmosis

2017

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“…The clinical significance of the fluctuating MVista EIA values was not readily apparent, as the patient remained asymptomatic with antifungal therapy. The overall disparity in quantitative antigen levels between the two assays is likely due to the different detection antibodies and target antigens used; the IMMY GM ASR employs a monoclonal antibody to Histoplasma galactomannan, whereas the MVista EIA utilizes a polyclonal antibody to a Histoplasma polysaccharide antigen (15,20).…”

Section: Discussionmentioning

confidence: 99%

“…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. Finally, while an FDA-cleared assay for detection of His-toplasma urinary Ag (UAg), the Alpha Histoplasma antigen EIA (IMMY), is available, the performance of this assay has been reported to be poor (15).…”

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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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“…Care must be taken not to compare titers derived from different kits given the lack of standardization among manufacturers. [62,63]. Antigen detection assays are especially useful for establishing a diagnosis in immunosuppressed patients and patients with progressive disseminated disease (i.e., those with higher fungal burden), while they are less sensitive in detection of isolated pulmonary histoplasmosis.…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%