galactomannan and Fusariosis

A peptidogalactomannan (PGM) from Fusarium oxysporum was structurally characterized by a combination of chemical and spectroscopic methods, including one and two-dimensional nuclear magnetic resonance (1D and 2D NMR). The galactomannan component consists of a main chain containing (1→6)-linked β-D-galactofuranose residues with side chains containing (1→2)-linked α-D-Glcp, (1→2)-linked -β-D-Manp (1→2) and β-D-Manp terminal nonreducing end units and differs from that of Aspergillus fumigatus and Cladosporium resinae that present a main chain containing (1→6)-linked α-D-Manp residues presenting β-D-Galf as side chains of 3-4 units that are (1→5)-interlinked. The importance of the carbohydrate moiety of the F. oxysporum PGM was demonstrated. Periodate oxidation abolished much of the PGM antigenic activity. A strong decrease in reactivity was also observed with de-O-glycosylated PGM. In addition, de-O-glycosylated PGM was not able to inhibit F. oxysporum phagocytosis, suggesting that macrophages recognize and internalize F. oxysporum via PGM. F. oxysporum PGM triggered TNF-α release by macrophages. Chemical removal of O-linked oligosaccharides from PGM led to a significant increase of TNF-α cytokine levels, suggesting that their removal could exposure another PGM motifs able to induce a higher secretion of TNF-α levels. Interestingly, F. oxysporum conidia, intact and de-O-linked PGM were not able to induce IL-10 cytokine release. The difference in patient serum reativity using a PGM from F. oxysporum characterized in the present study as compared with a PGM from C. resinae, that presents the same epitopes recognized by serum from patients with aspergillosis, could be considered a potential diagnostic antigen and should be tested with more sera.

Topics: Antigens, Fungal; Cytokines; Epitopes; Fusariosis; Fusarium; Galactose; Glycopeptides; Macrophages; Magnetic Resonance Spectroscopy; Mannans; Oligosaccharides; Phagocytosis; Species Specificity

To compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF).. We retrospectively reviewed the charts of 36 patients with IA and 26 with IF diagnosed between 2006 and 2017 in haematologic patients, and compared baseline characteristics, coexisting exposures, clinical manifestations, treatment, and the outcome.. Fever was more frequent in IF (96.2% vs. 63.9%, p 0.003), whereas pneumonia (88.9% vs. 50.0%, p 0.001) and sinusitis (63.9% vs. 38.5%, p 0.048) were more frequent in IA. Skin lesions and positive blood cultures occurred exclusively in patients with IF. Among patients with pneumonia, the halo sign was more frequent in IA (62.5% vs. 23.1%, p 0.02). Serum galactomannan was positive in 88.6% of patients with IA and in 73.3% with IF (p 0.18), with no differences in the median number of positive tests and galactomannan values. Positive serum galactomannan plus lung infiltrates was the predominant clinical presentation in IA and occurred in four of 13 patients with IF and lung involvement. The 30-day survival was 77.7% in IA and 46.1% in IF (p 0.01).. IA and IF share the same epidemiologic scenario but different clinical presentations in the majority of cases, with disease in the airways in IA, and fever, metastatic skin lesions, and positive blood cultures in IF. However, a substantial proportion of patients with IF present with a clinical picture similar to IA, with fever, lung infiltrates, and positive serum galactomannan.

Topics: Adult; Aged; Aspergillosis; Female; Fever; Fusariosis; Galactose; Humans; Invasive Fungal Infections; Male; Mannans; Middle Aged; Pneumonia; Retrospective Studies; Young Adult

Compared with major invasive mycoses such as aspergillosis and candidiasis, the antifungal stewardship management strategies of other fungal diseases have different opportunities and considerations. Cryptococcosis, fusariosis and mucormycosis are globally prevalent invasive fungal diseases (IFDs), but are not currently included in antifungal prophylaxis guidelines for immunocompromised hosts. Since the implementation of biomarkers as part of diagnostic screening strategies, the concept of pre-emptive antifungal therapy has emerged for these IFDs. Management of cryptococcosis, the most common IFD worldwide, generally utilizes a pre-emptive or therapeutic strategy that does not involve prophylaxis or empirical antifungal treatment strategies. Antifungal stewardship outcomes for cryptococcosis may vary according to the availability of local resources. Invasive fusariosis, the second-most common form of non-Aspergillus mould infection among haematological malignancy patients, can be managed with pre-emptive (or diagnostic-driven) approaches based on the monitoring of serum galactomannan (GM) antigen in increased-risk populations. The success of antimicrobial stewardship programmes in decreasing the burden of invasive fusariosis in selected patient populations depends on the development and implementation of rapid diagnostic strategies for early and appropriate administration of therapy. Mucormycosis may emerge as a breakthrough IFD in haematology or solid organ transplant recipients receiving antifungals that lack activity against Mucorales. The concept of pre-emptive antifungal therapy has thus arisen for mucormycosis in the haematology setting because of the recent availability of circulating Mucorales DNA measurement. These examples demonstrate the challenges of implementing antifungal stewardship programmes in areas with limited resources, as well as in IFDs that are difficult to diagnose and treat.

Topics: Antifungal Agents; Biomarkers; Cryptococcosis; Fusariosis; Galactose; Humans; Immunocompromised Host; Invasive Fungal Infections; Mannans; Mucormycosis

Cross-reactivity of Fusarium species with serum galactomannan antigen (GMI) test has been observed. We sought to evaluate if GMI could help to early diagnose invasive fusariosis and to monitor treatment response. We reviewed the records of all patients with invasive fusariosis between 2008 and 2012 in three Brazilian hospitals. We selected patients who had at least 1 GMI test within 2 days before or after the date of the first clinical manifestation of fusariosis, and analyzed the temporal relationship between the first positive GMI test and the date of the diagnosis of invasive fusariosis, and the kinetics of GMI in relation to patients' response to treatment. We also selected 18 controls to determine the sensitivity and specificity of the test. Among 18 patients, 15 (83%) had at least one positive GMI (median 4, range 1-15). The sensitivity and specificity of was 83% and 67%, respectively. GMI was positive before the diagnosis of invasive fusariosis in 11 of the 15 cases (73%), at a median of 10 days (range 3-39), and after the diagnosis in 4 cases. GMI became negative in 8 of the 15 patients; 3 of these 8 patients (37.5%) were alive 90 days after the diagnosis of fusariosis compared with 2 of 7 (29%) who did not normalize GMI (p = 1.0). GMI is frequently positive in invasive fusariosis, and becomes positive before diagnosis in most patients. These findings may have important implications for the choice of antifungal therapy in settings with high prevalence of invasive fusariosis.

Topics: Antifungal Agents; Aspergillus; Biomarkers; Brazil; Cross Reactions; Early Diagnosis; Fusariosis; Galactose; Humans; Kinetics; Mannans; Prognosis; Retrospective Studies; Sensitivity and Specificity

Disseminated infections caused by members of the Fusarium fujikuroi species complex (FFSC) occur regularly in immunocompromised patients. Here, we present the first human case caused by FFSC-member Fusarium andiyazi. Fever, respiratory symptoms and abnormal computerised tomography findings developed in a 65-year-old man with acute myelogenous leukaemia who was under posaconazole prophylaxis during his remission-induction chemotherapy. During the course of infection, two consecutive blood galactomannan values were found to be positive, and two blood cultures yielded strains resembling Fusarium species, according to morphological appearance. The aetiological agent proved to be F. andiyazi based on multilocus sequence typing. The sequencing of the internal transcribed spacer region did not resolve the closely related members of the FFSC, but additional data on partial sequence of transcription elongation factor 1 alpha subunit did. A detailed morphological study confirmed the identification of F. andiyazi, which had previously only been reported as a plant pathogen affecting various food crops.

Topics: Aged; Antigens, Fungal; Aspergillus; Cross Reactions; Diagnosis, Differential; DNA, Fungal; DNA, Ribosomal Spacer; Fusariosis; Fusarium; Galactose; Humans; Immunoenzyme Techniques; Leukemia, Myeloid, Acute; Male; Mannans; Multilocus Sequence Typing; Tomography, X-Ray Computed

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

Nine of 11 hematological patients with disseminated/deep-seated Fusarium infection tested at least twice for Aspergillus galactomannan (GM) had repeated positive results in the absence of Aspergillus isolation in culture. The centrifuged supernatants of 12 Fusarium isolates were tested by a GM enzyme-linked immunosorbent assay (EIA). All the isolates produced positive reactions when tested undiluted. These results show cross-reactivity of Fusarium spp. with Aspergillus GM that may constitute a drawback with respect to the specificity of the Platelia EIA.

Topics: Adult; Aspergillosis; Aspergillus; Child; Child, Preschool; Clinical Laboratory Techniques; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Female; Fusariosis; Fusarium; Galactose; Humans; Male; Mannans; Middle Aged; Young Adult

To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin.. Retrospective, non-interventional study conducted in three University Hospitals.. Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis (n = 3), empirical therapy (n = 9) or directed therapy for candidemia (n = 5) or aspergillosis (n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis.. Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin.

Topics: Adult; Aged; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; France; Fusariosis; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hospitals, University; Humans; Lipopeptides; Male; Mannans; Middle Aged; Mucormycosis; Pulmonary Aspergillosis

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