A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation

Grim, Shellee A.; Proia, Laurie A.; Miller, Rachel; Alhyraba, M.; Costas‐Chavarri, Ainhoa; Oberholzer, José; Clark, Nina M.

doi:10.1111/j.1399-3062.2011.00658.x

Cited by 119 publications

(152 citation statements)

References 24 publications

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“…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).…”

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confidence: 99%

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Connolly¹,

Hage

Bariola

et al. 2012

Clin Vaccine Immunol

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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mentioning

confidence: 99%

Blastomyces dermatitidis Antigen Detection by Quantitative Enzyme Immunoassay

Connolly¹,

Hage

Bariola

et al. 2012

Clin Vaccine Immunol

104

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“…While immunocompetent subjects can usually contain the infection via cell-mediated immunity, immunocompromised patients are at higher risk to develop serious disease (2). In addition to direct exposure, immunocompromised patients can also acquire histoplasmosis by reactivation of a latent infection or from a donor organ following transplantation (3). Pneumonia is often the initial manifestation of infection in immunosuppressed patients, but once infected, disseminated infection can occur in more than 50% of patients with conditions such as organ transplantation and AIDS (3)(4)(5)(6).…”

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confidence: 99%

“…Serologic testing can be used to document exposure but is less useful for differentiating acute from prior infection and can be unreliable in the immunocompromised-patient populations, who are at the highest risk of disease. For these reasons, detection of histoplasma antigen in the urine has been proposed as a useful method for both diagnosis and monitoring therapeutic response, especially in immunocompromised patients (3).…”

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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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“…Scedosporium apiospermum and S. prolificans often require combination therapy using voriconazole and terbinafine, reductions in immunosuppression and occasionally debulking surgery if possible [252,275]. With increasing overseas travel, the endemic mycoses may need to be considered in a wide range of differential diagnoses given their variable clinical presentation [281,282]. An initial awareness of the relevant epidemiology is key, coupled with appropriate sero-testing and culture diagnostic methods for blood and tissue.…”

Section: Fungal Infectionsmentioning

confidence: 99%