epiglucan and Eye-Infections--Fungal

Pythiosis is an emerging infectious disease caused by the aquatic oomycete Pythium insidiosum, a fungal-like organism. It is believed that P. insidiosum's zoospores, its infected form, play major role in pathogenesis. Vascular and ocular infections are the most common clinical manifestation in humans. It is difficult to establish the diagnosis given its relatively rarity and difficulty to distinguish P. insidiosum from other molds. Delay in diagnosis and treatment has been associated with poor outcomes. High index of suspicion is the key, particularly in thalassemia patients with arterial insufficiency and patients with fungal keratitis/endophthalmitis without improvement on antifungal therapy. Tissue culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The combination of radical surgery, antifungal agents, and immunotherapy has been recommended. It was previously believed that surgery with negative surgical margins was the essential to survive in vascular pythiosis; however, it was recently found that patients could have residual disease despite documented negative surgical margins as infected clot may be dislodged to proximal arterial sites prior to surgery. Serum β-D-glucan (BG) has been used to monitor disease response after treatment initiation in vascular pythiosis. A significant decrease in BG levels within 2 weeks after surgery is indicative of the absence of residual infection. Unfortunately, monitoring tools for ocular pythiosis are not yet available. Itraconazole plus terbinafine have generally been used in P. insidiosum-infected patients; however, antibacterial agents, including azithromycin and linezolid, have also been used with favorable outcomes in ocular disease. Recently, azithromycin or clarithromycin plus doxycyclin were used in two relapsed vascular pythiosis patients with good outcomes.

Topics: Anti-Bacterial Agents; Antifungal Agents; beta-Glucans; Communicable Diseases, Emerging; Drug Combinations; Eye Infections, Fungal; Immunotherapy; Itraconazole; Oomycetes; Pathology, Molecular; Pythiosis; Pythium; Serologic Tests; Spores, Fungal; Terbinafine; Thalassemia; Vascular System Injuries

To review the literature on beta-D-glucan (BDG) testing in fungal endophthalmitis.. Review of primary literature using PubMed through April 2017 and presentation of an illustrative case report. A total of 231 articles were identified and 43 were ultimately chosen for review based on relevance and presence of ophthalmologic examination and objective data.. Beta-D-glucan is a major component of fungal cell walls. It is quantified using a calorimetry-based Fungitell assay based on modification of the limulus amebocyte lysate. Serum BDG levels are commonly used clinically in conjunction with other tests for early surveillance and diagnosis of invasive fungal infections. In the ophthalmic literature, elevated levels of BDG have been detected in vitreous fluid of patients undergoing vitrectomy for fungal endophthalmitis, tear fluid of patients with mycotic keratitis, and serum of a patient with bilateral endogenous subretinal abscesses. Elevated serum BDG levels appear to be highly associated with fungal endophthalmitis. Potential uses and considerations with regards to test limitations are discussed.. Beta-D-glucan testing may be used as an adjunct to support a diagnosis, initiate pharmacologic therapy or surgical intervention, and optimize overall clinical management in patients diagnosed with or under clinical suspicion for invasive fungal infections, including endophthalmitis. Additional clinical studies are necessary to fully characterize the utility of BDG testing in patients with fungal endophthalmitis.

Topics: beta-Glucans; Biomarkers; Diagnostic Tests, Routine; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Sensitivity and Specificity; Young Adult

To assess the diagnostic utility of (1→3)-β- d -glucan (BDG) in ocular fluid of patients with fungal endophthalmitis.. This prospective pilot single-center study evaluated aqueous and vitreous humor BDG levels of suspected fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls with the standard Fungitell assay and the Fungitell STAT assay. β- d -Glucan levels were compared using generalized linear models followed by post hoc pairwise comparisons.. Seven fungal endophthalmitis, 6 bacterial endophthalmitis, and 17 noninfectious ocular samples were evaluated. Mean aqueous BDG concentrations were 204, 11.0, and 9.6 pg/mL for fungal endophthalmitis, bacterial endophthalmitis, and noninfectious controls, respectively ( P = 0.01, fungal vs. bacterial; P = 0.0005, fungal vs. noninfectious controls). Mean vitreous BDG concentrations were 165, 30.3, and 5.4 pg/mL, respectively ( P = 0.001 for fungal vs. bacterial; P < 0.0001 for fungal vs. noninfectious controls). Mean vitreous BDG index (Fungitell STAT) values were 1.7, 0.4, and 0.3, respectively ( P = 0.001, fungal vs. bacterial; P = 0.0004, fungal vs. noninfectious controls). The Pearson correlation between BDG levels and BDG index was high (correlation coefficient = 0.99, P < 0.001).. Significantly elevated ocular BDG levels were found in fungal endophthalmitis compared with bacterial endophthalmitis and noninfectious controls. Our study suggests a potential utility for BDG testing in the diagnosis of fungal endophthalmitis, and a larger study is warranted.

Topics: beta-Glucans; Endophthalmitis; Eye Infections, Fungal; Glucans; Humans; Prospective Studies; Sensitivity and Specificity

To evaluate vitreous Galactomannan(GM) and 1,3 β-D-Glucan (BDG) levels in the diagnosis of fungal endophthalmitis, with emphasis on culture-negative cases.. Vitreous from 31 clinically suspected fungal endophthalmitis patients and 11 controls were evaluated for GM and BDG using ELISA Kits. The Receiver Operating Characteristic (ROC) curves and diagnostic significance was calculated.. The median vitreous GM in culture-positive (60.83pg/ml) and culture-negative (59.9pg/ml) samples were higher than the (51.2pg/ml) control group. The median vitreous BDG in culture-positive (1.47pg/ml) and culture-negative (1.52pg/ml) samples were also similar, and higher than the control group (1.18pg/ml). ROC analysis showed that at a cut-off of 51.35pg/ml, the sensitivity and specificity for GM were 0.88 and 0.73.Similarly, for BDG at a cut-off of 1.18pg/ml, the sensitivity and specificity were 0.94 and 0.82 respectively.. Vitreous GM and BDG above the indicated threshold level could suggest a fungal infection, even when cultures are negative.

Topics: beta-Glucans; Endophthalmitis; Eye Infections, Fungal; Glucans; Humans; Mannans; Sensitivity and Specificity

To evaluate the value of the β- d -glucan (BDG) testing of intraocular fluid for the diagnosis of fungal endophthalmitis (FE).. Twenty patients (22 eyes) with FE were diagnosed using both culture and nonculture methods. Intraocular fluid was collected for BDG testing, including 22 eyes of FE and 55 eyes of control group. Under different BDG cutoff points as the test-positives, the BDG sensitivity, specificity, positive predictive value, and negative predictive value for FE were analyzed.. The BDG testing value was 1,022.78 ± 1,362.40 pg/mL in the FE group, significantly higher than that of the control group (105.0 ± 180.80 pg/mL, P < 0.001). The area under the receiver operating characteristic (ROC) curve was 0.885 (95% confidence interval, 0.793-0.978; P < 0.001). With the prespecified BDG cutoff 107.83 pg/ml as the test-positive, sensitivity was 81.8%, specificity was 87.5%, and the Youden index was 0.693. When the BDG cutoff was depicted as 202.05 pg/mL, sensitivity reduced to 77.3%, specificity increased at 95.8%, and the Youden index reached the highest value of 0.731.. β- d -glucan testing of intraocular fluid demonstrated good sensitivity and specificity regarding the diagnosis of FE, which can provide earlier diagnosis to achieve better outcomes.

Topics: Aqueous Humor; beta-Glucans; Endophthalmitis; Eye Infections, Fungal; Glucans; Humans; ROC Curve; Sensitivity and Specificity

To evaluate serum beta-D-glucan (BDG) as a biomarker for endogenous fungal eye infection.. Retrospective case-control study of 88 patients with a BDG test and eye examination at UPenn (2013-2018). Cases had endogenous fungal chorioretinitis or endophthalmitis diagnosed by eye examination and confirmed with positive culture; controls were without these fungal eye findings. Charts were reviewed for BDG values, blood/vitreous cultures, and eye examinations. Outcomes were BDG sensitivity, specificity, positive predictive value, and negative predictive value for fungal chorioretinitis or endophthalmitis, using prespecified BDG cut-off points of ≥80, ≥250, and ≥500 pg/mL as test positive.. Cases included six chorioretinitis and four endophthalmitis patients. Controls included 78 patients without chorioretinitis or endophthalmitis. Defining BDG ≥80 pg/mL as test positive, the BDG sensitivity (95% confidence interval) was 66.7% (22.3%-95.7%) for chorioretinitis and 100% (39.8%-100%) for endophthalmitis. The specificity was 74.4% (63.2%-83.6%) when BDG values ≥80 pg/mL were test positive, and 85.9% (76.2%-92.7%) when values ≥250 pg/mL were test positive. For a 1% endophthalmitis prevalence and BDG cut-off value of ≥80 pg/mL, the positive predictive value was 3.8% (2.4%-5.2%) and negative predictive value was 100% (99.1%-100%).. For endogenous fungal endophthalmitis, BDG's sensitivity and specificity seem good and the negative predictive value is high; a larger ophthalmic study is indicated.

Topics: Adult; beta-Glucans; Biomarkers; Case-Control Studies; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; ROC Curve

BACKGROUND In clinical practice, the presentation of fungal endophthalmitis is often occult and confusing, so it is difficult to make an early diagnosis. The aim of this study was to evaluate the utility of ß-d-glucan (BDG) testing in diagnosis, management, and prognosis of fungal endophthalmitis. CASE REPORT We present a retrospective, observational case series of 5 fungal endophthalmitis cases, 3 of which were endogenous and 2 exogenous. There were significantly elevated BDG levels in all cases, which was consistent with the pathological diagnosis. Four cases were diagnosed as fungal endophthalmitis through smear or culture and gene chip analysis of intraocular fluid. CONCLUSIONS Fungal endophthalmitis is rare, and its diagnosis is difficult because of its occult nature. Therefore, BDG testing may be required as an auxiliary examination for the early diagnosis of fungal endophthalmitis. Compared to cultures and smears, intraocular fluid BDG testing has a higher sensitivity for detecting fungal endophthalmitis.

Topics: Adult; Aged; Aqueous Humor; beta-Glucans; Child, Preschool; China; Diagnostic Tests, Routine; Endophthalmitis; Eye Infections, Fungal; Female; Humans; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity

Ocular pythiosis is the second most common form of human pythiosis, and the rates of evisceration/enucleation in Thailand are 55-79%. This prospective study was conducted to evaluate treatment outcomes of the combination therapy protocol and the potential use of serum (1→3)-β-glucan (BG) and Pythium insidiosum-specific antibody (Pi-Ab) as an aid to diagnosis and monitoring of ocular pythiosis. Thirty patients were enrolled in the study and 14 (non-globe salvage) required evisceration/enucleation. The globe salvage group was significantly younger, and first ocular surgeries were performed significantly sooner than in the non-globe salvage group. Serum BG and Pi-Ab levels were similar among the 2 groups over time. In vitro susceptibility testing of antifungal agents revealed relatively high minimum inhibitory concentrations and lack of synergistic effect. Serum BG and Pi-Ab would not be useful in diagnosis and monitoring of ocular pythiosis. Until effective antimicrobial agents are discovered, ocular surgeries are still the mainstay therapy in Thailand.

Topics: Adult; Antibodies, Fungal; Antifungal Agents; Antigens, Fungal; beta-Glucans; Combined Modality Therapy; Diagnostic Tests, Routine; Eye Infections, Fungal; Female; Humans; Immunologic Factors; Male; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Proteoglycans; Pythiosis; Pythium; Thailand; Treatment Outcome; Young Adult

To investigate the expression and function of the mannose receptor (MR) and to explore its interaction with dectin-1 in human corneal epithelial cells (HCECs) exposed to Aspergillus fumigatus.. HCECs were stimulated with A. fumigatus for 0, 4, 8, 12, 16, and 24 hours. MR expression was tested by the polymerase chain reaction, Western blot, and immunohistochemistry. HCECs were pretreated with 2 μg/mL MR-blocking antibody. The expressions of p38, phosphorylated p38 (p-p38), and the downstream cytokines (TNF-α and IL-1β) and dectin-1 were tested by the polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. HCECs were pretreated with dectin-1 agonists (curdlan, 100 μg/mL) and inhibitors (laminarin, 10 μg/mL), and the expression of the MR was tested.. MR expression was upregulated after stimulation with A. fumigatus. MR mRNA and protein levels began to rise at 8 and 16 hours, respectively. Stronger immunostaining of the MR was observed in fungal-infected corneal epithelium than in normal corneal epithelium. Aspergillus fumigatus increased the production of TNF-α (11-fold, 4-fold of the control), IL-1β (4.7-fold, 3-fold of the control), p-p38 (2.1-fold of the control), and dectin-1 (2.3-fold, 2-fold of the control) in mRNA and protein levels. The MR antibody significantly suppressed the expression of TNF-α (28%, 50% reduction), IL-1β (38%, 42% reduction), p-p38 (38% reduction), and dectin-1 (48%, 47% reduction). Curdlan increased the production of the MR (1.5-fold, 1.9-fold of the control), whereas laminarin decreased the expression of the MR (50%, 60% reduction) induced by A. fumigatus.. HCECs express the MR, and A. fumigatus infection can increase MR expression. A. fumigatus induces the expression of inflammatory cytokines through the MR and p38 MAPK pathway. The expression of dectin-1 and the MR had mutual influence.

Topics: Aspergillosis; Aspergillus fumigatus; beta-Glucans; Blotting, Western; Corneal Ulcer; Cytokines; Drug Interactions; Enzyme-Linked Immunosorbent Assay; Epithelium, Corneal; Eye Infections, Fungal; Humans; Lectins, C-Type; Mannose Receptor; Mannose-Binding Lectins; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Polysaccharides; Real-Time Polymerase Chain Reaction; Receptors, Cell Surface; Tissue Donors; Up-Regulation

Ocular candidiasis is a major complication of Candida bloodstream infection (BSI). This study was performed to reveal the clinical characteristics of ocular candidiasis. Of the 220 patients with Candida BSI, 204 cases received ophthalmology consultations between January 2005 and December 2011 at 2 teaching hospitals. Fifty-four (26.5%) cases had findings consistent with the diagnosis of ocular candidiasis. Of these 54 cases, 43 (79.6%) were diagnosed within 7 days after a positive blood culture. Among ocular candidiasis cases, more cases were due to Candida albicans (P =0.034 odds ratio [OR]; 3.68 95% confidence interval [CI] 1.11-12.2) and had higher β-d-glucan values (P = 0.001 OR; 9.99 95% CI 2.60-21.3). We need to consider fundoscopic examination to be performed within the first 7 days of therapy, especially for those patients who have C. albicans BSIs and higher β-d-glucan values. Additionally, follow-up fundoscopic examination should be considered before stopping therapy for high-risk patients.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Candidemia; Candidiasis; Diagnostic Techniques, Ophthalmological; Eye Infections, Fungal; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors

Increased concentration of (1,3)-beta-D-glucan, one of the major components of fungal cell walls, is detected in the serum of systemic fungal infection. In our study, the concentration of (1,3)-beta-D-glucan was measured in the tear fluid of patients with mycotic keratitis.. Tear fluid was collected from patients with fungal keratitis (n = 4) and bacterial corneal ulcers (n = 4) with or without corneal scraping. In addition, tear fluid was collected from patients without corneal diseases.. The concentration of (1,3)-beta-D-glucan in tear fluid collected without corneal scraping was 4.0 +/- 3.5, 5.8 +/- 2.6, 184 +/- 128 pg/ml in the control, bacterial corneal ulcer, and mycotic keratitis samples respectively. The concentration of (1,3)-beta-D-glucan in tear fluid collected after scraping the corneal lesions with a tip of glass capillary was 4.4 +/- 1.3, 8.2 +/- 5.2 and >1,000 pg/ml in the control, bacterial ulcer, and mycotic keratitis samples respectively.. A significant increase in (1,3)-beta-D-glucan was detected in tear samples from patients with mycotic keratitis. Measuring the concentration of (1,3)-beta-D-glucan in tear fluid might be helpful in the diagnosis of mycotic keratitis.

Topics: beta-Glucans; Corneal Ulcer; Eye Infections, Bacterial; Eye Infections, Fungal; Humans; Keratitis; Osmolar Concentration; Proteoglycans; Tears

Endotoxemia has been reported as a mechanism for the fatal sequela after heatstroke. Subsequent disseminated fungal infection in a heatstroke patient has been also described. Beta-D-glucan, a constituent of the fungal cell wall, is an early diagnostic measure for fungal infection. In a heatstroke case, we examined for the first time levels of serum beta-d-glucan and endotoxin. A 34-year-old man with a body temperature of 43.5 degrees C was admitted in a state of shock. Prior to the development of disseminated intravascular coagulopathy (DIC), a remarkable elevation of serum beta-D-glucan level to 116 pg/mL (normal level<6.0 pg/mL) was revealed on the first day of admission. However, serum endotoxin was not detected when using a method that excluded beta-D-glucan contamination from endotoxin measurement (normal level<1.0 pg/mL). This change of beta-D-glucan level was accompanied by a depressed neutrophil function, especially in phagocytosis of 34% (normal range 70-90%) but not in bacterocidal function (81% versus a normal range of 70-100%). After intensive care including continuous hemodiafiltration, the patient regained consciousness but remained ataxic due to cerebellar infarction, which might have resulted from DIC, and subsequent bilateral fungal oculitis were revealed 45 days after admission. This case report demonstrates the elevation of serum beta-D-glucan but normal endotoxin levels after heatstroke, which may prompt further study to re-examine the serum levels of endotoxin in such catastrophic insults.

Topics: Adult; beta-Glucans; Brain Infarction; Cerebellar Diseases; Cerebellum; Disseminated Intravascular Coagulation; Endotoxins; Eye Infections, Fungal; Fungemia; Heat Stroke; Humans; Male; Neutrophils; Phagocytosis

Major problems in the management of keratomycosis stem from the difficulty of its diagnosis and limited choice of antifungal agents. In the present paper we propose a new method of detecting (1,3)-beta-D-glucan, one of the major components of fungal cell wall, in tears from an animal model of keratomycosis. In addition, we investigated the efficacy of topical application of micafungin, a new antifungal agent that inhibits the activity of (1,3)-beta-D-glucan synthase in this animal model.. Candida albicans (5 x 10(5) organisms) was inoculated into the corneal stroma of 20 New Zealand White rabbits. The animals were randomly assigned to two groups and treated with subconjunctival injection of 0.5 mL of saline or 0.1% micafungin every day for 3 weeks. The clinical course of keratomycosis in both groups was compared. Before and 3 weeks after the injection of saline or micafungin, 5 microL of tears in each eye were collected by capillary tube. The concentration of (1,3)-beta-D-glucan was quantitatively measured by modified Limulus test.. The concentration of (1,3)-beta-D-glucan was significantly higher in keratomycosis model animals than in controls (mean +/- SD, 17.4 +/- 9.4 pg/mL and 2.8 +/- 1.8 pg/mL, respectively) at 21 days after treatment. Subconjunctival injection of micafungin had no significant effect on ocular lesions of keratomycosis until 9 days, after which ocular lesions significantly improved. Subconjunctival application of micafungin decreased the concentration of (1,3)-beta-D-glucan in tears to 4.9 +/- 3.0 pg/mL at 21 days after treatment.. Increased levels of (1,3)-beta-D-glucan in tears were detected in this model of keratomycosis. Measuring the concentration of (1,3)-beta-D-glucan in tears may be a reliable noninvasive method for the diagnosis of keratomycosis. Topical application of micafungin was effective in the treatment of keratomycosis.

Topics: Animals; beta-Glucans; Candidiasis; Corneal Diseases; Echinocandins; Eye Infections, Fungal; Glucosyltransferases; Limulus Test; Lipopeptides; Lipoproteins; Male; Micafungin; Peptides, Cyclic; Rabbits; Tears