Utility of Aspergillus Antigen Detection in Specimens Other than Serum Specimens

Department of Medical Microbiology, University Medical Center St. Radboud, Nijmegen, The Netherlands.
Clinical Infectious Diseases (Impact Factor: 8.89). 12/2004; 39(10):1467-74. DOI: 10.1086/425317
Source: PubMed

ABSTRACT The detection of circulating galactomannan in serum is an important tool for the early diagnosis of invasive aspergillosis. A commercial enzyme-linked immunosorbent assay (Platelia Aspergillus; BioRad) was shown to be both highly sensitive and specific for detection of galactomannan in serum samples. Despite the fact that this assay is validated for serum samples, specimens of other body fluids are increasingly used for detection of galactomannan, including urine, bronchoalveolar lavage fluid, and cerebrospinal fluid. Review of the literature shows that galactomannan can be detected in each of these samples from patients with invasive aspergillosis with higher sensitivity than is the case with culture, as well as early in the course of infection. However, the evidence thus far is based on case reports--predominantly retrospective studies--that often include heterogeneous patient populations and limited numbers of cases of proven infection. Clearly, well-designed prospective studies with systematic sampling and use of consensus case definitions are needed to compare the performance of antigen detection in samples other than serum specimens with that in serum specimens.

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    • "Galactomannan is relatively specific for Aspergillus species45, and can be detected in urine, bronchoalveolar lavage fluid cerebrospinal fluid and other specimens with enzyme immunoassay. Various sensitivity rates from 30 to 100 per cent, and similarly wide-ranging specificities from 38 to 98 per cent have been reported for GM4647. Factors that limit the specificity of this test are immune reactivity with other fungi such as Penicillium spp. "
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    ABSTRACT: Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections.
    The Indian Journal of Medical Research 02/2014; 139(2):195-204. · 1.40 Impact Factor
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    • "We next tested the affinity of EB-A2, a monoclonal antibody that binds Galf residues with high specificity, towards galactomannoproteins extracted from the disruptant strains (Fig. 2B). Clinical screening with EB-A2 is considered to be a highly sensitive and specific assay for early detection of invasive aspergillosis (Klont et al., 2004), and the specificity of EB-A2 for Galf antigen is well characterized (Stynen et al., 1992; Yuen et al., 2001; Leitao et al., 2003; Morelle et al., 2005). The main epitope of EB-A2 is reportedly a tetrasaccharide of β1,5-linked Galf (galactofuran side-chain) (Stynen et al., 1992); however, EB-A2 also reacts with a single terminal nonreducing Galf residue in N-glycans and terminal β1,5- linked Galf residues in O-glycans (Yuen et al., 2001; Leitao et al., 2003; Morelle et al., 2005). "
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    ABSTRACT: The cells walls of filamentous fungi in the genus Aspergillus have galactofuranose-containing polysaccharides and glycoconjugates, including O-glycans, N-glycans, fungal-type galactomannan, and glycosylinositolphosphoceramide, which are important for cell wall integrity. Here, we attempted to identify galactofuranosyltransferases that couple galactofuranose monomers onto other wall components in Aspergillus nidulans. Using reverse-genetic and biochemical approaches, we identified that the AN8677 gene encoded a galactofuranosyltransferase, which we called GfsA, involved in galactofuranose (Galf) antigen biosynthesis. Disruption of gfsA reduced binding of β-Galf-specific antibody EB-A2 to O-glycosylated WscA protein and galactomannoproteins. The results of an in-vitro galactofuranose antigen synthase assay revealed that GfsA has β1,5- or β1,6- galactofuranosyltransferase activity for O-glycans in glycoproteins, uses UDP-D-galactofuranose as a sugar donor, and requires a divalent manganese cation for activity. GfsA was found to be localized at the Golgi apparatus based on cellular fractionation experiments. ΔgfsA cells exhibited an abnormal morphology characterized by poor hyphal extension, hyphal curvature, and limited formation of conidia. Several gfsA orthologs were identified in members of the Pezizomycotina subphylum of Ascomycota, including the human pathogen Aspergillus fumigatus. To our knowledge, this is the first characterization of a fungal β-galactofuranosyltransferase, which was shown to be involved in galactofuranose antigen biosynthesis of O-glycans in the Golgi.
    Molecular Microbiology 10/2013; 90(5). DOI:10.1111/mmi.12416 · 4.42 Impact Factor
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    • "In an attempt to improve sensitivity of diagnostic tests for IPA, several authors have investigated the utility of GM antigen detection in bronchoalveolar lavage (BAL) specimens (Becker et al., 2003; Clancy et al., 2007; Husain et al., 2007; Klont et al., 2004; Maertens et al., 2009; Meersseman et al., 2008; Musher et al., 2004; Nguyen et al., 2007; Penack et al., 2008; Sanguinetti et al., 2003; Siemann and Koch- Dorfler, 2001; Verweij et al., 1995). These results have been promising, with sensitivities ranging from 60% to 100% (Clancy et al., 2007; Husain et al., 2007). "
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    ABSTRACT: We conducted a single-center retrospective cohort study to determine the performance characteristics of the galactomannan (GM) assay in bronchoalveolar lavage (BAL) in patients with hematologic malignancies. Patients were classified as proven, probable, possible, or no invasive pulmonary aspergillosis (IPA), according to international guidelines. A total of 173 BAL samples from 145 patients were included. There were 5 proven, 7 probable, and 35 possible cases of IPA. Using a GM index cutoff of ≥ 0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 100%, 78%, 26%, and 100%, respectively. Using a GM index cutoff of ≥ 2.0, the sensitivity and NPV remained 100%, but specificity and PPV increased to 93% and 50%, respectively. The BAL GM assay is a highly sensitive screening test for IPA in patients with hematologic malignancies. Increasing the cutoff value to 2.0 would improve the performance of this assay.
    Diagnostic microbiology and infectious disease 10/2010; 68(2):132-9. DOI:10.1016/j.diagmicrobio.2010.03.017 · 2.46 Impact Factor
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