epiglucan and Fusariosis

The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI.. IF and IS are severe fungal infections for which diagnosis is often delayed. This meta-analysis shows that beta-glucan testing in serum had a sensitivity of about 80% for IF/IS and could detect the disease earlier compared to conventional diagnostic tests.

Topics: Animals; beta-Glucans; Fusariosis; Invasive Fungal Infections; Sensitivity and Specificity

Despite the availability of newer antifungal drugs, outcomes for patients with invasive fungal infections (IFIs) continue to be poor, in large part due to delayed diagnosis and initiation of appropriate antifungal therapy. Standard histopathologic diagnostic techniques are often untenable in at-risk patients, and culture-based diagnostics typically are too insensitive or nonspecific, or provide results after too long a delay for optimal IFI management. Newer surrogate markers of IFIs with improved sensitivity and specificity are needed to enable earlier diagnosis and, ideally, to provide prognostic information and/or permit therapeutic monitoring. Surrogate assays should also be accessible and easy to implement in the hospital. Several nonculture-based assays of newer surrogates are making their way into the medical setting or are currently under investigation. These new or up-and-coming surrogates include antigens/antibodies (mannan and antimannan antibodies) or fungal metabolites (d-arabinitol) for detection of invasive candidiasis, the Aspergillus cell wall component galactomannan used to detect invasive aspergillosis, or the fungal cell wall component and panfungal marker β-glucan. In addition, progress continues with use of polymerase chain reaction- or other nucleic acid- or molecular-based assays for diagnosis of either specific or generic IFIs, although the various methods must be better standardized before any of these approaches can be more fully implemented into the medical setting. Investigators are also beginning to explore the possibility of combining newer surrogate markers with each other or with more standard diagnostic approaches to improve sensitivity, specificity, and capacity for earlier diagnosis, at a time when fungal burden is still relatively low and more responsive to antifungal therapy.

Topics: Adult; Amphotericin B; Antifungal Agents; Antineoplastic Agents; beta-Glucans; Biomarkers; Female; Fusariosis; Humans; Immunocompromised Host; Leukemia, Myeloid, Acute; Meta-Analysis as Topic; Mycoses; Opportunistic Infections; Polymerase Chain Reaction

Invasive fusariosis (IF) usually presents with high fungal burden at diagnosis, and this may contribute to its high mortality rate. The use 1,3-beta-D-glucan (BDG) may help to establish the diagnosis at an earlier disease stage and to monitor treatment. To evaluate the performance of BDG in the diagnosis of IF and its kinetics in relation to the outcome, we retrospectively tested serum samples of 13 cases of IF, analysed the temporal relationship between the first positive BDG test and the date of the diagnosis of IF, and the kinetics of BDG in relation to patients' outcome. We selected 13 controls with similar underlying diseases as cases, at least two serum samples stored, and no invasive fungal disease. Twelve patients with IF had at least one positive BDG (median 4, range 1-16). The test was positive before the diagnosis of IF in 11 of the 12 patients (91.6%), at a median of 10 days (range 1-32). The median BDG value increased (from 109 to 316 pg/mL, P = 0.04) in patients who died by day 30, and did not change significantly (99-101 pg/mL, P = 0.60) in survivors. Using two consecutive BDG tests, sensitivity, specificity, and positive and negative predictive values were 85%, 69%, 7% and 99%, respectively. BDG is positive in the majority of patients with IF, usually before the diagnosis, but the low positive predictive value limits its use to diagnose IF earlier. Once therapy is started, decreasing BDG values suggests treatment response.

Topics: Adolescent; Adult; beta-Glucans; Female; Fusariosis; Humans; Male; Middle Aged; Predictive Value of Tests; Proteoglycans; Retrospective Studies; Sensitivity and Specificity; Survival Analysis; Time Factors; Young Adult

To investigate the utility of beta-D-glucan (BDG) testing in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive fungal infection (IFI), as compared to BAL galactomannan (GM).. We retrospectively reviewed medical records of 132 consecutive patients at the National Institutes of Health (NIH) in whom BAL BDG testing was performed for diagnosis of pneumonia. Using the European Organization for Research and Treatment of Cancer/Mycoses Study Group guidelines, we determined which patients had proven or probable IFI, and assessed the diagnostic performance of BAL BDG testing, relative to BAL GM. We also determined the reproducibility of the BDG assay in BAL via repeat testing of patient samples.. Ten patients had Pneumocystis pneumonia, and 34 patients had proven/probable IFI, including 14 with invasive aspergillosis (IA). BAL BDG was 100% sensitive for Pneumocystis. Although BAL BDG had similar sensitivity to BAL GM for the diagnosis of IA and IFI, it exhibited inferior specificity. Repeat testing demonstrated poor reproducibility of the BDG assay in BAL but not in serum.. BDG testing exhibits poor specificity and reproducibility in BAL. Identification of the BAL-specific factors that may interfere with the performance of the assay could improve the clinical usefulness of BAL BDG testing.

Topics: beta-Glucans; Bronchoalveolar Lavage Fluid; Female; Fusariosis; Galactose; Humans; Invasive Pulmonary Aspergillosis; Lung Diseases, Fungal; Male; Mannans; Mucormycosis; Paecilomyces; Pneumonia, Pneumocystis; Reproducibility of Results; Retrospective Studies; Scopulariopsis; Sensitivity and Specificity

Galactomannan (GM) is used to diagnose aspergillosis. We present a case of a hematopoietic stem cell transplantation recipient with fusariosis who received early antifungal treatment based on GM positivity. Additionally, 3 Fusarium isolates tested positive for GM. Fusarium is another mold containing GM. GM might be useful for diagnosing fusariosis in high-risk patients.

Topics: Antifungal Agents; beta-Glucans; Early Diagnosis; Fatal Outcome; Female; Fusariosis; Fusarium; Galactose; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Middle Aged

β-1,3-Glucan binding proteins (βGBPs) are soluble pattern recognition proteins/receptors that bind to β-1,3-glucans from fungi cell walls. In crustaceans, βGBPs are abundant plasmatic proteins produced by the hepatopancreas, and have been proved to play multiple biological functions. Here, we purified and characterized novel members of the βGBP family from the hemolymph of two Brazilian shrimps, Farfantepenaeus paulensis (FpβGBP) and Litopenaeus schmitti (LsβGBP). As observed for other crustacean species, FpβGBP and LsβGBP are monomeric proteins (∼100kDa) able to enhance the activation of the prophenoloxidase system, a potent antimicrobial defense conserved in arthropods. More interestingly, we provided here evidence for a novel biological activity for shrimp βGBPs: the agglutination of fungal cells. Finally, we investigated the modulation of the βGBP gene in F. paulensis shrimps experimentally infected with a cognate fungal pathogen, Fusarium solani. From our expression data, βGBP gene is constitutively expressed in hepatopancreas and not modulated upon a non-lethal fungal infection. Herein, we have improved our knowledge about the βGBP family by the characterization of a novel biological role for this multifunctional protein in shrimp.

Topics: Agglutination; Animals; beta-Glucans; Brazil; Carrier Proteins; Catechol Oxidase; Enzyme Precursors; Female; Fusariosis; Fusarium; Hemolymph; Hepatopancreas; Lectins; Male; Penaeidae; Protein Binding