ß-1,6-linked Galactofuranose- rich peptidogalactomannan of Fusarium oxysporum is important in the activation of macrophage mechanisms and as a potential diagnostic antigen.

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 ß-D-galactofuranose residues with side chains containing (1→2)-linked α-D-Glcp, (1→2)-linked -ß-D-Manp (1→2) and ß-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 ß-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.

Invasive mould disease in haematologic patients: comparison between fusariosis and aspergillosis.

OBJECTIVES: To compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Successful treatment of bilateral endogenous Fusarium solani endophthalmitis in a patient with acute lymphocytic leukaemia.

Fusarium spp. are an uncommon cause of fungaemia in immunocompromised and neutropenic patients that may hematogenously disseminate to the eyes. Herein, we describe a patient with acute lymphoblastic leukaemia and a prior history of extensive corticosteroid exposure who developed disseminated Fusarium solani infection following chemotherapy despite posaconazole prophylaxis. She was successfully treated with combination liposomal amphotericin B and voriconazole, intraocular injections of voriconazole, topical amphotericin B and bilateral vitrectomy. We also review published literature describing the management of endogenous Fusarium endophthalmitis in immunocompromised hosts.

Interleukin 17 expression in peripheral blood neutrophils from fungal keratitis patients and healthy cohorts in southern India.

Interleukin 17A (IL-17) production by peripheral blood neutrophils was examined in patients with fungal keratitis and in uninfected individuals in southern India, which has high levels of airborne Aspergillus and Fusarium conidia. Il17a gene expression and intracellular IL-17 were detected in all groups, although levels were significantly elevated in neutrophils from patients with keratitis. There were no significant differences in plasma IL-17 and IL-23 between patients with keratitis and uninfected individuals; however, combined data from all groups showed a correlation between the percentage IL-17 producing neutrophils and plasma IL-23, and between plasma IL-17 and IL-6 and IL-23.

The utility of bronchoalveolar lavage beta-D-glucan testing for the diagnosis of invasive fungal infections.

OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Invasive mycoses: diagnostic challenges.

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 ß-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.