Detection of
            <i>Histoplasma</i>
            Antigen by a Quantitative Enzyme Immunoassay

Connolly, Patricia; Durkin, Michelle; LeMonte, Ann M.; Hackett, Emily; Wheat, L. Joseph

doi:10.1128/cvi.00071-07

Cited by 184 publications

(183 citation statements)

References 12 publications

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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%

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Results from the polyclonal IVD assay and monoclonal LDT were compared to reference laboratory (MiraVista Diagnostics, Indianapolis, IN) results as the "gold standard." The MiraVista assay utilizes a polyclonal rabbit anti-H. capsulatum IgG as the capture antibody and a modified biotinylated polyclonal antibody as the detection antibody (11,12). The analytical sensitivity of each assay was evaluated using a panel of normal urine specimens spiked with 0 to 10 U of Histoplasma antigen derived from yeast phase culture filtrate.…”

Section: Methodsmentioning

confidence: 99%

“…The clinical sensitivity (Sn) and specificity (Sp) of the assay have been well characterized in a variety of populations (10)(11)(12)(13), and several generations of laboratory-developed tests (LDTs) based on the approach have been offered by one of the largest histoplasma reference laboratories in the United States (MiraVista Diagnostics, Indianapolis, IN). Because the reagents used in the assay are not commercially available, alternative assays have been evaluated by other investigators with varying success.…”

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confidence: 99%

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

2013

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Urinary histoplasma antigen measurement can be useful for diagnosing systemic histoplasmosis and for monitoring treatment response, especially in immunocompromised patients. However, testing has traditionally been limited to specialized reference laboratories, as immunoassay reagents for the antigen were not widely available. Recently, a polyclonal-antibody-based in vitro diagnostic (IVD) kit for histoplasma antigen detection was released, as well as monoclonal-antibody reagents against the target. We evaluated the analytical and clinical performance of the two reagents. Both assays were capable of detecting histoplasma antigen in urine samples over a wide dynamic range, although the monoclonal assay showed improved precision and analytical sensitivity relative to the polyclonal IVD. In a test set of clinically characterized patient samples, the monoclonal laboratory-developed test (LDT) demonstrated 90.5% sensitivity and 96.3% specificity versus 61.9% sensitivity and 79.3% specificity for the polyclonal IVD, with areas under the curve (AUCs) of 0.987 and 0.754, respectively. The major differences between the two assays were higher background reactivity in healthy donors with the polyclonal assay and an increased signal response in positive samples for the monoclonal assay. The impact of these differences on monitoring treatment response was evaluated in a series of patients undergoing treatment for histoplasmosis. While all the assays gave similar qualitative estimates of treatment response, responses were more evident using the monoclonal assay. In summary, we conclude that while multiple assays are available for measuring histoplasma antigen in urine, a monoclonal-antibody-based assay appears to provide improved analytical performance for management of immunocompromised histoplasmosis patients.

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“…Detection of circulating Histoplasma capsulatum polysaccharide antigen in urine and serum is used for rapid diagnosis. The sensitivity of the urine assay is approximately 90% among patients who have acquired immunodeficiency syndrome (AIDS) 1,3 .…”

Section: 000x Magnification -Giemsa Staining)mentioning

confidence: 99%

Disseminated histoplasmosis diagnosed in a peripheral blood smear

Maltos

Maia

Oliveira

2017

Rev. Soc. Bras. Med. Trop.

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FIGURE 1 -Peripheral blood smear -multiple yeasts in neutrophil (arrow). 1,000x magnification -Giemsa staining).A 40-year-old man with human immunodeficiency virus (HIV) infection, diagnosed in 2008, and irregular use of antiretroviral therapy, was admitted to the emergency room with diarrhea, asthenia, fever, and weight loss of 4kg in the previous 10 days. His evacuations were watery, with no mucus or blood. He was emaciated, with an axillary temperature of 38.3°C. Cardiopulmonary auscultation findings were normal, and the abdomen was not tender, without visceromegaly. The skin showed generalized hypo-and hyperchromic spots. The patient was hospitalized, and laboratory tests were performed. The complete blood count showed anemia, leucopenia, and a normal platelet count; the serum level of C-reactive protein was 43mg/dL (reference: ≤0.5mg/dL). The cluster of differentiation 4+ (CD4+) cell count was 6.0/mm 3 , and the viral load was undetectable. In the peripheral blood smear, neutrophils with multiple yeasts were observed, suggestive of Histoplasma capsulatum (Figure 1). He was treated with amphotericin B, which reached a cumulative dose of 840mg (in 40 days). He was discharged and prescribed itraconazole. After 3 months, he developed a disseminated cryptococcosis (treated with amphotericin B and fluconazole), and died 1 month later, following bacterial pneumonia with septic shock.Yeasts can grow in the blood of patients with disseminated histoplasmosis, and in severe acute cases, yeasts can be detected inside white blood cells on a peripheral blood smear or buffy coat preparation 1,2

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Detection of Histoplasma Antigen by a Quantitative Enzyme Immunoassay

Cited by 184 publications

References 12 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

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

Disseminated histoplasmosis diagnosed in a peripheral blood smear

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