Large Scale Evaluation of the Immuno-Mycologics Inc. (IMMY) Lateral Flow and Enzyme-linked Immunoassays for the detection of Cryptococcal Antigen in Serum and Cerebrospinal Fluid.

ARUP Laboratories, Salt Lake City, UT.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.47). 10/2012; 20(1). DOI: 10.1128/CVI.00536-12
Source: PubMed


Cryptococcosis is a systemic infection caused by the pathogenic yeasts Cryptococcus neoformans and C. gattii. Detection of cryptococcal capsular antigen (CrAg) in serum and cerebrospinal fluid (CSF) plays an important diagnostic role. We prospectively compared the new IMMY lateral flow assay (LFA) and enzyme immunoassay (EIA) to our current CrAg test (Premier EIA, Meridian Bioscience Inc.). Discordant samples were retested with the Latex-Cryptococcus antigen test (IMMY) and using serotype-specific monoclonal antibodies (mAbs). A total of 589 serum and 411 CSF specimens were tested in parallel. Qualitative agreement across assays was 97.7%. In all, 56 (41 serum and 15 CSF) were positive and 921 (527 serum and 394 CSF) were negative by all three assays. The 23 discrepant specimens were all Meridian EIA negative. Of 23 discordant specimens, 20 (87.0%) were positive by both the IMMY LFA and EIA, 2 were LFA positive only and 1 EIA positive only. Eleven discrepant specimens had adequate volume for latex agglutination (LA) testing; 8 were LA positive and 3 LA negative. LA negative samples (2 CSF and 1 serum) had low IMMY LFA/EIA titers (≤ 1:10). Serotype-specific mAb analysis of the LA positive samples suggested that these specimens contain CrAg epitopes similar to those of serotype C strains. In conclusion, the IMMY assays showed excellent overall concordance with the Meridian EIA. Assay performance differences were related to issues of analytic sensitivity and possible serotype bias. Incomplete access to patient-level data combined with low specimen volumes limited our ability to fully resolve discrepant results.

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Available from: Brandon Paul Neary, Jan 13, 2015
    • "This suggests a higher sensitivity of the IMMY-LFA compared to immunoagglutination assays. This is consistent with two recent large studies, performed on 421 sera from HIV patients in Colombia and 589 sera and 411 CSF in the United States, respectively[18,19]. The negative case that we report in this article might be due to the low fungus load of C. neoformans (10 cfu/mL), which might be close to the detection limit (Fig. 1). "

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    • "The assay provides a result in less than 10 minutes and requires no special storage or prior laboratory expertise. Of four prospective and retrospective studies, the CrAg LFA showed excellent diagnostic accuracy when compared to culture and CrAg LA or EA [9, 14–16]. On CSF and peripheral blood samples, sensitivity ranged from 96% to 100% and specificity was 92% to 100%. "
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    ABSTRACT: Despite access to antiretroviral therapy, mortality from cryptococcal meningitis (CM) is high among persons with advanced HIV infection in sub-Saharan Africa. Cryptococcal antigen (CrAg) is present several weeks to months before the onset of symptoms of meningitis and can be screened to prevent life threatening meningitis. Recently, the World Health Organisation recommended that a new rapid CrAg lateral flow ''dipstick" assay (LFA) is to be used to screen HIV-infected persons with CD4 counts of less than 100 cells/µL. In this paper, we describe two cases of cryptococcosis with differing outcomes. In the first case, the new CrAg LFA was used as part of a screen and preemptive treatment strategy to prevent CM. In the second case, our patient had no access to the CrAg LFA and subsequently developed life threatening meningitis. To the best of our knowledge, this is the first case report of cryptococcosis diagnosed using this novel assay.
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    ABSTRACT: To study the clinical manifestations of cryptococcosis, its diagnostic features, and treatment results in patients with hemoblastoses. The study included adult patients with cryptococcosis treated at the Hematology Research Center (HRC) in 2005 to 2011. The diagnosis of cryptococcosis was established on the basis of isolation of Cryptococcus neoformans from a blood culture or determination of positive cryptococcal antigen in the cerebrospinal fluid (CSF) of patients with infection symptoms. During 7 years, 19 patients aged 19 to 68 years (median 47 years) were diagnosed as having cryptococcosis. In the pattern of cryptococcosis, there was a preponderance of patients with lymphoma (31%) and those with acute lymphoblastic leukemia (26%) at the stages of hemoblastosis remission induction (32%) and consolidation (26%). The diagnosis was made in 9 (47%) patients at the Intensive Care Department, HRC. The major risk factors of cryptococcosis were previous cytostatic drug exposure (68%), use of immunosuppressive and glucocorticoid drugs (63%), and granulocytopenia (42%). Seventeen (78%) patients were diagnosed with cryptococcal meningitis or meningoencephalitis; 1 patient had cryptococcal sepsis and 1 patient had possible cryptococcal pneumonia. All the patients were given antifungal agents. Amphotericin B, fluconazole, and a combination of antimycotics were used as first-line drugs in 16 (84%), 1 (5.5%), and 2 (10.5%), respectively. When their health became better, the patients were treated with voriconazole or fluconazole. Within 30 days after the diagnosis of cryptococcosis, 5 (26%) patients died; of them 2 had tumor progression concurrent with infection. In cryptococcosis, the central nervous system is predominantly involved in the infectious process. The determination of cryptococcal antigen in CSF is a necessary diagnostic component in meningitis and meningoencephalitis in patients with blood system tumors, lymphatic ones in particular. When cryptococcosis is timely diagnosed and treated, its mortality, when the tumor is controlled, is lower than that in other invasive mycoses.
    No preview · Article · Jan 2013 · Terapevticheskii arkhiv
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