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Background: Glucomannan has been studied for various health benefits, but its effects on lipid profile in adults are not well understood. This meta-analysis aims to evaluate the impact of glucomannan supplementation on serum/plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), Apo B1, Apo A1, APO-B/ A1 ratio, and LDL-C/ HDL-C in adults., Methods: A comprehensive search was conducted across Scopus, PubMed, Embase, and Web of Science from inception to June 2024 to identify randomized controlled trials (RCTs) assessing glucomannan supplementation on lipid profile in adults. Data were extracted and analyzed using random effects model to determine the standardized mean differences (SMDs) and 95% confidence intervals (CIs) for each biomarker., Results: Glucomannan supplementation significantly decreased TC (SMD: -3.299; 95% CI: -4.955, -1.664, P < 0.001; I 2  = 95.41%, P-heterogeneity < 0.001), LDL-C (SMD: -2.993; 95% CI: -4.958, -1.028; P = 0.006; I 2  = 95.49%, P-heterogeneity < 0.001), and Apo B1 (SMD: -2.2; 95% CI: -3.58, -0.82; P = 0.01). However, glucomannan did not alter the levels of TG (SMD: -0.119; 95% CI: -1.076, 0.837, P = 0.789; I 2  = 91.63%, P-heterogeneity < 0.001), Apo A1 (SMD: -0.48; 95% CI: -6.27, 5.32; P = 0.76), APO-B/ A1 ratio (SMD: -1.15; 95% CI: -2.91, 0.61; P = 0.11), and LDL-C/ HDL-C ratio (SMD: -2.2; 95% CI: -7.28, 2.87; P = 0.2)., Conclusions: Glucomannan supplementation has a beneficial effect on the level of TC and LDL-C., (© 2024. The Author(s).)

Invasive Aspergillosis (IA) is a potentially lethal infection in high-risk haemato-oncology patients. Since traditional diagnostic methods have many inherent challenges, Polymerase Chain Reaction (PCR) has been used to diagnose IA. This prospective study evaluated a commercial AsperGenius multiplex real-time PCR for its clinical utility in diagnosing IA compared with galactomannan (GM) testing serum samples from haemato-oncology patients with clinically suspected IA. A total of 107 patients were recruited between April 2022 and March 2023. Serum samples (n = 113) collected from those patients for the routine diagnosis by GM Enzyme Linked Immuno-Sorbent Assay (ELISA) were subjected to PCR. The patients were categorised into probable, possible, and no IA based on revised (2020) and previous (2008) European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC-MSG) criteria. The performance characteristics of PCR and GM were calculated against the EORTC criteria by combining probable and possible cases as diseased groups. Among the 107 recruited patients, 93 were categorised into probable/possible IA (diseased group) and 14 into no IA group. The PCR was positive in 53 samples from 49 patients. The sensitivity and specificity of single positive PCR and GM were 51.61% [95% confidence interval, 41-62], 92.86% (66.1-99.8) and 26.88% (18.2-37.1), 92.86% (66.1-99.8), respectively. The combination-based strategy (GM and/or PCR positive) exhibited a moderate sensitivity of 62.37% (51-72.2) and a specificity of 85.71% (57.2-98.2). To conclude, the combined strategy of serum GM and/or PCR positivity, along with radiological findings that fulfilled the EORTC/MSG criteria, has improved the diagnosis of probable IA among high-risk haematological patients with clinically suspected IA., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Invasive aspergillosis affects solid organ transplant (SOT) recipients, carrying a high risk of mortality and morbidity in this population. Rapid and accurate diagnosis is essential to ensure the initiation of correct antifungal therapy. We aimed to evaluate the performance of the bronchoalveolar lavage (BAL) Eurofins Viracor Aspergillus PCR (AspPCR) in diagnosing invasive pulmonary aspergillosis (IPA) in SOT recipients., Methods: We conducted a multicenter retrospective study of SOT recipients in Arizona from February 2019 to December 2022 who had AspPCR done at the time of the clinical encounter. Probable IPA was defined as a positive BAL culture with Aspergillus spp. with clinical and imaging findings of IPA per EORTC/MSGERC criteria., Results: Ninety-nine SOT recipients with 131 encounters with BAL AspPCR testing were included. The median age was 66, the majority were White, non-Hispanics (60%), and males (66%). Among the participants, 93 lung transplant recipients with 87 of the encounters received antifungal prophylaxis active against Aspergillus spp. Sixty-four encounters had BAL galactomannan (GM), all of which had BAL GM <1 OD, and one case had a serum GM of 10 OD. Nine cases met the definition of IPA. The sensitivity of the BAL AspPCR was 67% (95% CI 30%-93%), and the specificity was 98% (95% CI 93%-99%)., Conclusion: BAL AspPCR had moderate sensitivity and high specificity in identifying IPA in our cohort of SOT recipients. Further studies in populations with a higher prevalence of IPA are needed to evaluate the performance of this test., (© 2024 Wiley Periodicals LLC.)

The Platelia Aspergillus Antigen immunoassay is the "gold standard" for Aspergillus galactomannan (GLM) measurement in sera and bronchoalveolar lavage (BAL) for the diagnosis of invasive pulmonary aspergillosis (IPA). We evaluated the performance of the Aspergillus GLM antigen Virclia Monotest compared to the Platelia assay. A total of 535 specimens [320 sera, 86 bronchial aspirates (BAs), 70 BAL, and 59 tracheal aspirates (TAs)] from 177 adult patients (72 hematological, 32 Intensive Care Unit, and 73 hospitalized in other wards) were processed for GLM testing upon clinical request. One patient had proven IPA, and 11 had probable disease. After excluding indeterminate Virclia results ( n = 38), 396 specimens yielded concordant results (56 positive and 340 negative) and 101 discordant results (Virclia positive/Platelia negative, n = 95). The overall agreement between immunoassays was higher for sera ( κ 0.56) than for BAL ( κ ≤ 0.24) or BAS and TA ( κ ≤ 0.22). When considering all specimen types in combination, the overall sensitivity and specificity of the Virclia assay for the diagnosis of proven/probable IPA were 100% and 65%, respectively, and for the Platelia immunoassay, sensitivity and specificity were 91.7% and 89.4%, respectively. The correlation between index values by both immunoassays was strong for serum/BAL ( ρ = 0.73; P < 0.001) and moderate for BAS/TA (Rho = 0.52; P = 0.001). The conversion of Virclia index values into the Platelia index could be derived by the formula y = (11.97 * X )/3.62 + X ). Data from GLM-positive serum/BAL clinical specimens fitted the regression model optimally ( R 2 = 0.94), whereas that of BAS and TA data did not ( R 2 = 0.11). Further studies are needed to determine whether the Virclia assay may be an alternative to the Platelia assay for GLM measurement in sera and lower respiratory tract specimens.IMPORTANCEGalactomannan detection in serum or bronchoalveolar fluid specimens is pivotal for the diagnosis of invasive pulmonary aspergillosis (IPA). The Platelia Aspergillus Antigen immunoassay has become the "gold standard" for Aspergillus GLM measurement. Here, we provide data suggesting that the Virclia Monotest assay, which displays several operational advantages compared with the Platelia assay, may become an alternative to the Platelia assay, although further studies are needed to validate this assumption. We also provide a formula allowing the conversion of Virclia index values into Platelia values. The study may contribute toward positioning the Virclia assay within the diagnostic algorithm of IPA., Competing Interests: The authors declare no conflict of interest.

Background: Rapid galactomannan tests, such as the sõna Aspergillus GM Lateral Flow Assay (GM-LFA) and the Aspergillus Galactomannan Ag VIRCLIA® Monotest (GM-Monotest), which are suitable for the analysis of single samples, have the potential to accelerate diagnosis of invasive aspergillosis (IA)., Objectives: To compare the performance of the GM-Monotest and the GM-LFA for the diagnosis of IA., Patients/methods: Two patient cohorts were analysed: adults who had received an allogeneic haematopoietic stem-cell transplant (alloHSCT-cohort) and patients with proven/probable IA from a 5-year period (cross-sectional IA-cohort). In the alloHSCT-cohort, weekly serum samples were tested, whereas in the cross-sectional IA-cohort sera and bronchoalveolar lavage fluids were analysed. The diagnostic performance was calculated using two definitions for positivity: (1) a single positive GM result and (2) at least two positive GM results from consecutive samples. IA classification followed EORTC/MSG 2019., Results: The alloHSCT-cohort included 101 patients. Four had proven/probable IA, 26 possible IA and 71 no IA. The specificity for one positive serum and two consecutively positive sera was 88.7% and 100% (GM-Monotest) and 85.9% and 98.6% (GM-LFA). Comparison of ROC curves in the alloHSCT-cohort showed no significant difference. The cross-sectional IA-cohort included 59 patients with proven/probable IA. The sensitivity for one positive sample and two consecutively positive samples was 83.1% and 55.1% (GM-Monotest) and 86.4% and 71.4% (GM-LFA)., Conclusions: Both assays showed comparable diagnostic performance with a higher sensitivity for the GM-LFA if two consecutive positive samples were required for positivity. However, due to poor reproducibility, positive GM-LFA results should always be confirmed., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Invasive pulmonary aspergillosis (IPA) in patients with diabetes mellitus has high incidence, especially in Type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) for IPA in patients with T2DM. A total of 66 patients with T2DM were included, including 21 IPA and 45 non-IPA patients, from January 2022 to December 2022. The demographic characteristics, comorbidities, laboratory test results, antibiotic treatment response, and 30-day mortality rate of patients were analyzed. The diagnostic accuracy of mNGS and conventional methods was compared, including sensitivity, specificity, positive predictive value and negative predictive value. The sensitivity and specificity of mNGS were 66.7% and 100.0%, respectively, which were significantly higher than those of fluorescence staining (42.1% and 100%), serum 1,3-β-D-glucan detection (38.1% and 90.9%), serum galactomannan detection (14.3% and 94.9%) and BALF galactomannan detection (47.3% and 70.7%). Although the sensitivity of BALF culture (75.0%) was higher than that of mNGS (66.7%), the turnover time of mNGS was significantly shorter than that of traditional culture (1.6 days vs. 5.0 days). The sensitivity of mNGS combined with BALF culture reached 100.0%. In addition, mNGS has a stronger ability to detect co-pathogens with IPA. 47.6% of T2DM patients with IPA were adjusted the initial antimicrobial therapy according to the mNGS results. This is the first study to focus on the diagnostic performance of mNGS in IPA infection in T2DM patients. MNGS can be used as a supplement to conventional methods for the diagnosis of IPA in patients with T2DM., (© 2024. The Author(s).)

Objective: To explore the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing invasive pulmonary aspergillosis (IPA) among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the intensive care unit (ICU)., Methods: A retrospective analysis was conducted on patients with AECOPD admitted to the ICU of Xinxiang Central Hospital in Henan Province, China, between March 2020 and September 2023, suspected of having IPA. Bronchoalveolar lavage fluid (BALF) samples were collected for fungal culture, the galactomannan (GM) test, and mNGS. Based on host factors, clinical features, and microbiological test results, patients were categorized into 62 cases of IPA and 64 cases of non-IPA. Statistical analysis was performed to compare the diagnostic efficacy of fungal culture, the serum and BALF GM test, and mNGS detection for IPA in patients with AECOPD., Results: 1. The sensitivity and specificity of mNGS in diagnosing IPA were 70.9% and 71.8% respectively, with the sensitivity of mNGS surpassing that of fungal culture (29.0%, P <0.01), serum GM test (35.4%, P <0.01), and BALF GM test (41.9%, P <0.05), albeit with slightly lower specificity compared to fungal culture (90.6%, P > 0.05), serum GM test (87.5%, P > 0.05), and BALF GM test (85.9%, P > 0.05).Combining fungal culture with the GM test and mNGS resulted in a sensitivity of 80.6% and a specificity of 92.2%, underscoring a superior diagnostic rate compared to any single detection method. 2.mNGS accurately distinguished strains of the Aspergillus genus. 3.The area under the ROC curves of mNGS was 0.73, indicating good diagnostic performance. 4.The detection duration for mNGS is shorter than that of traditional fungal culture and GM testing., Conclusion: mNGS presents a pragmatic and highly sensitive approach, serving as a valuable complementary tool to conventional microbiological tests (CMT). Our research demonstrated that, compared to fungal culture and GM testing, mNGS exhibits superior diagnostic capability for IPA among patients with AECOPD. Integration of mNGS with established conventional methods holds promise for improving the diagnosis rate of IPA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niu, Liu, Yang and Zhao.)

Background: The performance of serum galactomannan (GM) for the diagnosis of invasive aspergillosis (IA) has been studied mainly in adults. Paediatric data are scarce and based on small and heterogeneous cohorts., Objective: To evaluate the performance of serum GM for the diagnosis of IA in a paediatric oncologic population at high risk of IA and to clarify the impact of antifungal prophylaxis on this test., Methods: We performed a retrospective study from January 2014 to December 2020 in the paediatric oncologic haematologic department of the University Hospital of Bordeaux. The diagnosis of IA was made using the recommendations of the EORTC and the MSGERC., Results: Among the 329 periods at high risk of IA in 222 patients, the prevalence of IA was 1.8% (3 proven and 3 probable IA). In the total population, the sensitivity, and the positive predictive value (PPV) were respectively 50% and 17.6%. Under antifungal prophylaxis, the sensitivity and PPV dropped, respectively, to 33.3% and 14.3%. In this group, the post-test probability of IA was 2% for a negative serum GM and only 14%., Conclusion: In this large cohort of children at high risk of IA, the incidence of IA is low and the diagnostic performance of GM is poor, especially in the case of mould-active prophylaxis. Screening should be targeted rather than systematic and should be reserved for patients at highest risk for IA without mould-active prophylaxis. Combination with other tests such as Aspergillus PCR would increase the accuracy of GM in screening setting., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Purpose: Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia., Methods: We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021., Results: Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n = 74) and acute myeloid leukemia (n = 68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated., Conclusions: In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Patricia Cornejo-Juarez reports a relationship with Pfizer that includes: speaking and lecture fees. Patricia Cornejo-Juarez reports a relationship with Merck & Co Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: Serum galactomannan (GM) testing is essential for diagnosing invasive aspergillosis (IA), particularly in immunocompromised individuals. The global lack of on-site GM testing capacities necessitates cost-effective alternatives, such as .the clarus Aspergillus GM enzyme immunoassay prototype (clarus AGM prototype)., Methods: This single-centre, cross-sectional study compared the diagnostic performance of the clarus AGM prototype (IMMY, Norman, Oklahoma) with the serological gold standard (=Platelia AGM assay; Bio-Rad, Marnes-la-Cocquette, France). IA was classified according to modified 2020 EORTC/MSG consensus and 2024 FUNDICU criteria. In total, 300 prospectively (May-Dec 2023) and retrospectively (2012-2015) collected samples were included., Results: Among 300 samples from 232 patients, 49 (16%) were classified as proven (n = 1) or probable IA (n = 48). In non-IA cases (n = 250), one patient was classified as possible IA. With the manufacturer recommended cut-off of ≥0.2, sensitivity and specificity of the clarus AGM prototype were 27% (13/49; 95% confidence interval [CI]: 15%-41%) and 99% (248/250; 95% CI: 97%-100%), respectively, while sensitivity and specificity were 78% and 79% when using the optimised Youden's cut-off of 0.0045 ODI. ROC curve analysis demonstrated an area under the curve (AUC) of 0.829 (95% CI: 0.760-0.898) for the clarus AGM prototype in distinguishing between proven/probable IA and non-IA. The AUC for the Platelia AGM was 0.951 (95% CI: 0.909-994). Spearman's correlation analysis showed a weak correlation between the two assays (0.382; p < .001)., Conclusions: The weak correlation between the clarus AGM prototype and Platelia AGM highlights the need for further investigation into the clinical performance of the clarus AGM prototype, giving the different antigen epitopes addressed., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Objective: To diagnose invasive pulmonary aspergillosis (IPA), galactomannan (GM) detection in serum or bronchoalveolar lavage fluid (BALF) is widely used. However, the utility of proximal airway GM test (from induced sputum or tracheal aspirate) has not been well elucidated., Methods: In this retrospective cohort study, we evaluated the diagnostic performance of proximal airway GM in diagnosis of IPA including COVID-19 associated pulmonary aspergillosis (CAPA). Between January 2022 and January 2023, patients who had been tested for GM with clinical suspicion or for surveillance from any specimen (serum, induced sputum, tracheal aspirate, and BALF) were screened. IPA was diagnosed using EORTC/MSGERC criteria, and CAPA was diagnosed following the 2020 ECMM/ISHAM consensus criteria., Results: Of 624 patients with GM results, 70 met the criteria for proven/probable IPA and 427 had no IPA. The others included possible IPA and chronic form of aspergillosis. The sensitivities and specificities of serum, proximal airway, and BALF GM for proven/probable IPA versus no IPA were 78.9% and 70.6%, 93.1% and 78.7%, and 78.6% and 91.0%, respectively. Areas under the receiver operating characteristic curve (AUCs) were 0.742 for serum GM, 0.935 for proximal airway GM, and 0.849 for BALF GM (serum GM vs proximal airway GM, p = 0.014; proximal airway GM vs BALF GM, p = 0.334; serum GM vs BALF GM, p = 0.286)., Conclusion: This study demonstrates that the performance of GM test from non-invasive proximal airway samples is comparable or even better than those from serum and distal airway sample (BALF)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We evaluated the interest of systematic screening of serum fungal markers in patients hospitalized in a medical ward., Methods: We retrospectively analyzed all patients hospitalized in our infectious disease department from October 1st to October 31st, 2020 for COVID-19 without prior ICU admission, and for whom systematic screening of serum fungal markers was performed., Results: Thirty patients were included. The majority of patients received corticosteroids (96.7%). The galactomannan antigen assay was positive for 1/30 patients at D0, and 0/24, 0/16, 0/13 and 0/2 at D4, D7, D10 and D14 respectively. 1,3-ß-D-glucan was positive for 0/30, 1/24, 1/12, 0/12, 0/2 at D0, D4, D7, D10 and D14 respectively. No Aspergillus fumigatus PCR was positive. No cases of aspergillosis were retained., Conclusion: Our study does not support the interest of systematic screening of fungal markers in immunocompetent patients with COVID-19 in a conventional unit., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Cancer patients are at heightened risk for invasive aspergillosis (IA), a condition associated with elevated mortality risk. The JF5-based Aspergillus Galactomannoprotein Lateral Flow Device (AspLFD) offers rapid point-of-care testing (POCT) for IA. This study evaluated the diagnostic performance of AspLFD in cancer populations., Methods: This retrospective study examined cancer patient bronchoalveolar lavage fluid (BALF) and serum samples collected between September 2021 and January 2023. Both AspLFD and galactomannan (GM) assays were conducted, and the results were analysed by two independent researchers., Results: This study included 242 samples from 218 cancer patients, with 58 BALF and 184 serum samples. The overall agreement between AspLFD and GM assay results was 92.1%, with a kappa value of 0.552. AspLFD diagnosed proven/probable IA with a sensitivity and specificity of 91.7% and 95.3%, respectively, whereas GM exhibited sensitivity and specificity values of 83.3% and 93.7%, respectively. There were no statistical differences in the sensitivity and specificity between the two methods (P > 0.05). For serum analyses, AspLFD and GM exhibited similar sensitivity (66.7% vs. 66.7%, P > 0.05) and specificity (98.6% vs. 96.6%, P > 0.05) values. However, the sensitivity of the AspLFD was superior to the GM assay (100% vs. 88.9%) in BALF analyses but the difference was not statistically significant (P > 0.05), with no difference in specificity (83.7% vs. 83.7%, P > 0.05). In the solid-tumour cohort, both the AspLFD and GM assay exhibited high sensitivity (100% for both) and specificity (94.2% vs. 92.8%, P > 0.05)., Conclusion: The AspLFD demonstrated good performance in diagnosing IA in cancer patients, especially those with solid tumours. The AspLFD is thus an alternative POCT, particularly when GM evaluations are not readily available., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to identify the cause of false-positive serum Aspergillus antigen galactomannan (GM) results in our centre., Methods: We performed a case-control study aiming to elucidate the factors associated with false-positive GM results. Independent risk factors for false-positive GM were evaluated through a multivariable regression analysis. An interrupted time series analysis was used to evaluate the effectiveness of an intervention removing the identified factors., Results: Among 568 patients tested, GM was positive in 130 patients of whom 97 had false-positive GM (cases). These were compared with 427 patients with true-negative GM (controls). Administration of dextrose-containing fluids within 6 days before GM testing was an independent predictor for false-positive GM results (adjusted odds ratio [aOR], 18.60; 95% CI, 8.95-38.66. An analysis of GM presence in different dextrose-containing fluids revealed positivity in 34.8% (8 of 23) (manufacturer A) and 33.3% (5 of 15) (manufacturer B) of the samples. Investigation of the manufacturing process revealed that the saccharification process employed enzymes derived from Aspergillus niger. After identifying the root cause of false positivity, GM-containing dextrose fluid use was restricted. Interrupted time series analysis showed an immediate reduction of GM false-positivity (-6.5% per week, p = 0.045) and a declining trend (-0.33% per week, p = 0.005) postintervention., Conclusions: Administering dextrose-containing fluids was the primary factor causing false-positive serum Aspergillus antigen GM assay results. Our investigation led to a modification of the manufacturing process of the dextrose-containing fluids., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

An increasing number of fungal infections were reported post COVID-19 and many of them were caused by fungi of mixed aetiologies. This study was carried out to assess the utility of serum galactomannan (GM) assay in establishing the etiology of acute rhino-orbito-cerebral mycosis caused by Aspergillus spp. Two serum samples were obtained from 41 suspected post COVID-19 rhino-orbito-cerebral mycosis patients to perform GM assay. Serum GM assay was positive in 68.7% of the cases of proven aspergillosis at cut off OD = 1.0. Serum GM assay can be used as a supplementary test in the diagnosis of rhino-orbito-cerebral mycosis caused by Aspergillus spp., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Magnusiomyces and Geotrichum species are ascomycetous yeasts that can cause potentially life-threatening invasive fungal infections commonly referred to as geotrichosis. In this study, we aimed to estimate the incidence and mortality of these infections in a German tertiary care center. Furthermore, we evaluated the suitability of the fungal biomarkers galactomannan (GM) and β-1,3-d-glucan (BDG), which are both recommended as surrogate markers for Magnusiomyces capitatus infection by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM) joint clinical guidelines for the diagnosis and management of rare invasive yeast infections for detection of invasive geotrichosis. Cases meeting the inclusion criteria for invasive Magnusiomyces/Geotrichum infection were retrospectively identified. Serum samples and culture supernatants were analyzed with two commercially available fungal antigen tests (Platelia Aspergillus Ag EIA and Wako β-glucan test). For a control cohort, outpatient samples sent for lues testing were included. Thirty-eight cases of Magnusiomyces/Geotrichum infection were identified over an 11-year observation period. In the majority of cases, the fungus was isolated from intra-abdominal specimens of patients with a history of abdominal surgery/procedures ( n  = 32). All cases of fungemia occurred exclusively in haemato-oncologic patients ( n  = 14). Thirty-day survival was 42% in the fungemia and 43% in the intra-abdominal geotrichosis group. Serum samples were available for 23 patients (14 bloodstream and nine intra-abdominal infections). While BDG sensitivity was 65%, none of the sera was GM positive. This finding was supported by in vitro experiments analyzing fungal culture supernatants: M. capitatus secretes significant amounts of BDG but not GM. Specificity was 96% for BDG and 100% for GM. Magnusiomyces and Geotrichum infections are not limited to haemato-oncologic patients. Contrasting the current ESCMID/ECMM recommendation, our results indicate that GM is no suitable biomarker for the diagnosis of Magnusiomyces infection. Contrarily, BDG sensitivity is comparable to that of candidemia.

Objective: To study the utility of Galactomannan (GM) antigen as a screening marker for diagnosing invasive pulmonary aspergillosis (IPA) in coronavirus disease 2019 (COVID-19) patients., Patients and Methods: The serum samples from patients with severe COVID-19 diseases admitted to the Critical Care Unit were collected on the 5th day of admission for GM screening. The samples were analysed by enzyme linked immune sorbent assay (ELISA) and GM index of more than 1 was considered as positive. All GM positive patients were serially followed until discharge or death., Results: The GM was raised in serum of 12 out of 38 patients, indicating an incidence of possible COVID-19 associated IPA (CAPA) in 31.57% of patients. The median age of these CAPA patients was 56.5 years, males were significantly more affected than females. The inflammatory marker serum ferritin was raised in all 12 patients (median value of 713.74 ng/ml), while IL-6 was raised in 9 patients (median value of 54.13 ng/ml). None of these patients received antifungals. Their median length of hospital stay was 20 days (IQR: 12, 34 days). All these patients succumbed to the illness., Conclusions: The serum GM appears to be sensitive diagnostic tool to identify early IPA in COVID-19 patients and pre-emptive antifungal therapy could play a role in salvaging these patients.

Background: The use of galactomannan (GM) testing in plasma and bronchoalveolar lavage fluid (BALF) has improved the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with chronic obstructive pulmonary disease (COPD); however, the high false-positive rate leads to overdiagnosis. Pentraxin 3 (PTX3) as an indicator of inflammation plays an important role in resistance to Aspergillus infections. This study aimed to investigate the diagnostic value of PTX3 for diagnosing IPA with COPD., Methods: We retrospectively collected data on patients with suspected COPD and IPA who had been hospitalized in the Third Affiliated Hospital of Soochow University between September 2017 and November 2020. PTX3 and GM were measured using enzyme-linked immunosorbent assays., Results: A total of 165 patients were included in the study, of whom 35 had confirmed or probable IPA. The remaining 130 patients served as controls. The median plasma and BALF PTX3 levels were significantly higher in patients with IPA than in control patients (3.74 ng/mL vs. 1.29 ng/mL, P < 0.001; and 3.88 ng/mL vs. 1.58 ng/mL, P < 0.001 in plasma and BALF, respectively). The plasma GM, plasma PTX3, BALF GM, and BALF PTX3 assays had sensitivities of 60.0%, 77.1%, 78.6%, and 89.3%, respectively, and specificities of 73.8%, 69.2%, 80.7%, and 77.1%, respectively. The sensitivity of PTX3 in plasma and BALF was higher than that of GM. However, the specificity of PTX3 and GM did not differ significantly between the IPA group and the control group. The specificity of the assays for the diagnosis of IPA was > 90% in patients who were PTX3-positive and GM-positive in plasma and BALF., Conclusions: BALF and plasma PTX3 levels were significantly higher in COPD patients with IPA. The sensitivity of PTX3 was superior to that of GM for diagnosing IPA in patients with COPD. The combination of GM and PTX3 is useful for the diagnosis of IPA in patients with COPD., (© 2021. The Author(s).)

The aim of this study was to evaluate diagnostic means, host factors, delay of occurrence, and outcome of patients with COVID-19 pneumonia and fungal coinfections in the intensive care unit (ICU). From 1 February to 31 May 2020, we anonymously recorded COVID-19-associated pulmonary aspergillosis (CAPA), fungemia (CA-fungemia), and pneumocystosis (CA-PCP) from 36 centers, including results on fungal biomarkers in respiratory specimens and serum. We collected data from 154 episodes of CAPA, 81 of CA-fungemia, 17 of CA-PCP, and 5 of other mold infections from 244 patients (male/female [M/F] ratio = 3.5; mean age, 64.7 ± 10.8 years). CA-PCP occurred first after ICU admission (median, 1 day; interquartile range [IQR], 0 to 3 days), followed by CAPA (9 days; IQR, 5 to 13 days), and then CA-fungemia (16 days; IQR, 12 to 23 days) ( P < 10 -4 ). For CAPA, the presence of several mycological criteria was associated with death ( P < 10 -4 ). Serum galactomannan was rarely positive (<20%). The mortality rates were 76.7% (23/30) in patients with host factors for invasive fungal disease, 45.2% (14/31) in those with a preexisting pulmonary condition, and 36.6% (34/93) in the remaining patients ( P = 0.001). Antimold treatment did not alter prognosis ( P = 0.370). Candida albicans was responsible for 59.3% of CA-fungemias, with a global mortality of 45.7%. For CA-PCP, 58.8% of the episodes occurred in patients with known host factors of PCP, and the mortality rate was 29.5%. CAPA may be in part hospital acquired and could benefit from antifungal prescription at the first positive biomarker result. CA-fungemia appeared linked to ICU stay without COVID-19 specificity, while CA-PCP may not really be a concern in the ICU. Improved diagnostic strategy for fungal markers in ICU patients with COVID-19 should support these hypotheses. IMPORTANCE To diagnose fungal coinfections in patients with COVID-19 in the intensive care unit, it is necessary to implement the correct treatment and to prevent them if possible. For COVID-19-associated pulmonary aspergillosis (CAPA), respiratory specimens remain the best approach since serum biomarkers are rarely positive. Timing of occurrence suggests that CAPA could be hospital acquired. The associated mortality varies from 36.6% to 76.7% when no host factors or host factors of invasive fungal diseases are present, respectively. Fungemias occurred after 2 weeks in ICUs and are associated with a mortality rate of 45.7%. Candida albicans is the first yeast species recovered, with no specificity linked to COVID-19. Pneumocystosis was mainly found in patients with known immunodepression. The diagnosis occurred at the entry in ICUs and not afterwards, suggesting that if Pneumocystis jirovecii plays a role, it is upstream of the hospitalization in the ICU.

Background: Detection of galactomannan (GM) from bronchoalveolar lavage fluid (BALF) or serum is broadly used for diagnosis of invasive aspergillosis (IA), although the sensitivity of GM from serum is lower in non-neutropenic patients. We evaluated the Aspergillus galactomannan Lateral Flow assay (LFA) with digital readout from serum in a mixed cohort of patients., Methods: We performed a retrospective two-centre study evaluating the LFA from serum of patients with clinical suspicion of IA obtained between 2015 and 2021 at the University of California San Diego and the Medical University of Graz. The sensitivity and specificity was calculated for proven/probable aspergillosis versus no aspergillosis. Correlation with same-sample GM was calculated using Spearman correlation analysis and kappa statistics., Results: In total, 122 serum samples from 122 patients were analysed, including proven IA (n = 1), probable IA or coronavirus-associated pulmonary aspergillosis (CAPA) (n = 27), and no IA/CAPA/non-classifiable (n = 94). At a 0.5 ODI cut-off, the sensitivity and specificity of the LFA was 78.6% and 80.5%. Spearman correlation analysis showed a strong correlation between serum LFA ODI and serum GM ODI (ρ 0.459, p < .0001). Kappa was 0.611 when both LFA and GM were used with a 0.5 ODI cut-off, showing substantial agreement (p < .001)., Discussion: The LFA with digital read out from serum showed good performance for the diagnosis of probable/proven aspergillosis, with substantial agreement to GM from serum. Like the LFA from BALF, the LFA from serum may serve as a more rapid test compared to conventional GM, particularly in settings where GM is not readily available., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Among immunologically normal hosts, patients with chronic obstructive pulmonary disease (COPD) are considered to be at high risk of invasive pulmonary aspergillosis (IPA), and early diagnosis and treatment are the key to improving the prognosis of patients. Here we aimed to evaluate whether interleukin (IL)-6 and IL-8 might be used in the detection and diagnosis of IPA in patients with COPD. We prospectively collected 106 patients with COPD and divided them into non-IPA (n=74), probable/possible IPA (n=26) and proven IPA (n=6). Platelia Aspergillus kit was used to detect galactomannan in bronchoalveolar lavage fluid (BALF), and serum and ELISA kit was used to detect IL-6 and IL-8 levels. Diagnostic efficiency of IL-6, IL-8 and galactomannan in serum and BALF was evaluated by receiver operating characteristic curve. Compared with the non-IPA group, the proven/probable IPA group showed significantly elevated levels of IL-6 and IL-8 in both serum and BALF, which were positively correlated with galactomannan levels. The sensitivity and specificity of IL-6 for diagnosing IPA were 74.32% and 81.25% (cut-off at 92.82 pg/mL, area under the curve (AUC)=0.8366) in serum and 68.92% and 71.88% (cut-off at 229.4 pg/mL, AUC=0.7694) in BALF. The sensitivity and specificity of IL-8 for diagnosing IPA were 83.78% and 81.25% (cut-off at 93.46 pg/mL, AUC=0.8756) in serum and 85.14% and 75.00% (cut-off at 325.4 pg/mL, AUC=0.8252) in BALF. The elevated levels of IL-6 and IL-8 in patients with IPA with COPD could be used as auxiliary indicators to diagnose IPA in addition to galactomannan., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Invasive pulmonary aspergillosis (IPA) is mainly caused by Aspergillus fumigatus and other Aspergillus species. Galactomannan (GM) is a polysaccharide antigen that exists primarily in the cell walls of Aspergillus species. GM may be released into the blood and other body fluids even in the early stages of Aspergillus invasion; therefore, detection of the GM antigen level can be useful in making an early diagnosis of IPA.

Background and Objectives: There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA., Methods: This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study., Results: A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n = 24) or BAL fungal culture results (n = 8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193])., Conclusion: Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection., (© 2021 Wiley-VCH GmbH.)

Invasive aspergillosis (IA) is an increasingly recognised phenomenon in critically ill patients in the intensive care unit, including in patients with severe influenza and severe coronavirus disease 2019 (COVID-19) infection. To date, there are no consensus criteria on how to define IA in the ICU population, although several criteria are used, including the AspICU criteria and new consensus criteria to categorise COVID-19-associated pulmonary aspergillosis (CAPA). In this review, we describe the epidemiology of IA in critically ill patients, most common definitions used to define IA in this population, and most common clinical specimens obtained for establishing a mycological diagnosis of IA in the critically ill. We also review the most common diagnostic tests used to diagnose IA in this population, and lastly discuss the most common clinical presentation and imaging findings of IA in the critically ill and discuss areas of further needed investigation., (© 2021 Wiley-VCH GmbH.)

Background: The prevalence of fungal infection (FI) in developing countries is high, but the diagnosis of FI is still challenging to determine, so it is needed evaluation of biomarkers other than microbiological culture, because the culture has low sensitivity, high cost, not available in every laboratory and needs a long time. The detection of human galactomannan Aspergillus antigen (GAL) and 1,3-beta-D-glucan (BDG) on the fungal cell wall could be the promising biomarkers for fungal infection. Neutropenia, lymphopenia and CD4T cells in the immunocompromised patients are essential factors, but these cell associations with BDG and GAL levels have not been evaluated yet. The study aimed to evaluate GAL and BDG for detecting fungal infection and their association with total leucocyte count, neutrophil, monocyte, lymphocyte and CD4T cells., Method: A cross-sectional study was conducted among 86 patient with suspected FI. Fungal infection established using EORTC/MSG criteria. Serology test performed using ELISA. Leucocyte cells were measured using a haematology autoanalyser, and CD4T cells were analysed using BD FACSPresto. Statistical analysis obtained using Spearman's correlation coefficient, ROC curve analysis and 2 × 2 contingency table., Results: Serum Galactomannan and BDG had a significant correlation with CD4T cells and total lymphocyte count (p < 0.05). The cut-off OD GAL >0.3 had sensitivity 54.6%, specificity 87.5% and AUC 0.71; meanwhile, the BDG cut-off >115.78 pg/ mL had sensitivity 71.2%, specificity 52.4% and AUC 0.63 for detecting fungal infection., Conclusions: The immunocompromised patients can undergo GAL for determining the diagnose of FI. The lower the CD4T cells and total lymphocyte count, the higher the GAL and BDG serum levels., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Coronavirus disease 2019 or COVID-19 is a new infectious disease responsible for potentially severe respiratory impairment associated with initial immunosuppression. Similarly to influenza, several authors have described a higher risk of fungal infection after COVID-19, in particular for invasive pulmonary aspergillosis. The main objective here is to define the prevalence of invasive pulmonary aspergillosis (IPA) in a cohort of COVID-19 patients with moderate to severe acute respiratory disease syndrome (ARDS)., Material and Methods: We conducted a large monocentric retrospective study investigating all the ventilated COVID-19 patients with ARDS hospitalized at Valenciennes' general hospital, France, between March 15, 2020 and April 30, 2020. In the center a systematic IPA screening strategy was carried out for all ARDS patients, with weekly tests of serum galactomannan and beta-D-glucan. Bronchoalveolar lavage with culture and chest CT scan were performed when the serum assays were positives., Results: A total of 54 patients were studied. Their median age was 65 years, and 37 of the patients (71%) were male. Two patients had chronic immunosuppression and among all the patients, only 2 non-immunocompromised presented a putative IPA during their stay., Conclusion: The prevalence of IPA in this cohort of COVID-19 patients (3.7%) is not higher than what is described in the other ARDS populations in the literature. These results are however different from the previous publications on COVID-19 patients and must therefore be confirmed by larger and multicentric studies., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Aspergillus species meet the most important group of invasive fungal diseases (IFD) in immunosuppressed patients. Galactomannan is a polysaccharide antigen located in the wall structure of Aspergillus. The most commonly used method for antigen detection is enzyme-linked immunoassay (ELISA). Aspergillus galactomannan lateral flow assay (LFA) constitutes one of the new methods in the diagnosis of invasive aspergillosis (IA). The goal of this study was to demonstrate efficacy of LFA in our patients and to compare it to synchronous ELISA results., Methods: Galactomannan antigen was examined using both LFA and ELISA in serum samples taken from patients who were followed up in our haematology clinic. All patients are classified in subgroups as 'proven', 'probable' and 'possible' patients according to the last EORTC / MSG guideline. Patients who met the 'proven' IA criteria were included in the study as the gold standard., Results: A total of 87 patients were included in the study. Majority of patients had acute myeloid leukaemia (AML) (56.3%). Eleven (12.6%) were in 'proven' IA group. LFA test showed a superior diagnostic performance compared with ELISA (LFA AUC  = 0.934 vs ELISA AUC  = 0.545; p < .001). The LFA had a sensitivity of 90.9% and a specificity of 90.8% for '0.5 ODI' in predicting IA (PPV = 55.8%; NPV = 98.6%; p < .001)., Conclusion: The most important finding of this study is that the specificity of LFA was found to be higher for cut-off value of 0.5. It is recommended to combine the methods in many studies to provide a better early diagnosis for IA., (© 2021 Wiley-VCH GmbH.)

Abstract: The incidence of invasive pulmonary aspergillosis (IPA) is increasing higher in non-neutropenic patients. This study aimed to assess the diagnostic performance of bronchoalveolar lavage fluid (BALF). Galactomannan (GM), serum GM, and 1,3-β-d-glucan (BDG) in non-neutropenic respiratory disease patients with IPA.A total of 333 non-neutropenic patients suspected IPA were recruited from Xiamen University Zhong Shan hospital between January 2016 and February 2019. One, 33, and 92 cases were diagnosed with proven, and possible IPA.BALF and serum GM were both elevated in the possible IPA group and the probable/proven IPA group (p < 0.001). BALF and serum GM showed a fair correlation in the possible IPA group (r = 0.286, p = 0.008), and moderate correlation in the probable/proven IPA group (r = 0.466, p = 0.005). When the cutoff value was 0.5, the sensitivity and negative likelihood ratio of BALF GM were superior to serum GM (78.3% vs 47.8%, 96.7% vs 91.6%). The specificity and positive likelihood ratio of BALF GM were slightly weaker than serum GM (91.8% vs 95.4%, 56.7% vs 85.0%). When the cutoff value was 1.0, the sensitivity and negative predictive value of BALF GM were better than serum GM (73.9% vs 26.1%, 94.5% vs 88.8%), and the specificity of were equivalent (99.2%). The optimal cutoff value of BALF GM was 0.6, wherein the sensitivity reached 78.3% and the specificity reached 95.4%. Given the extremely low sensitivity of serum BDG at different cutoff values (≥10 μg/mL = 5.3%, ≥20 μg/mL = 2.1%), it cannot be used as a preferred biomarker.The diagnostic performance of BALF GM was superior to other biomarkers and the optimal cutoff value was 0.6., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the diagnostic performance of galactomannan (GM) detection in serum and bronchoalveolar lavage fluid (BALF) for invasive pulmonary aspergillosis (IPA) in non-neutropenic patients., Methods: A total of 291 non-neutropenic patients in the Second Xiangya Hospital of Central South University were included. According to the 2019 EORTC/MSG guidelines, all cases were divided into an IPA group (n = 24) and a non-IPA group (n = 267). Receiver operating characteristic (ROC) curves were drawn to compare the diagnostic efficiency of GM detection in BALF and serum., Results: According to the receiver operating characteristic curves of BALF and serum GM, the areas under the curve were 0.961 and 0.699, respectively. The optimal BALF GM detection was found when the cutoff value was set to 0.87, whereas the sensitivity and specificity were 91.7% and 92.5%, respectively., Conclusions: BALF GM detection is more sensitive than serum GM detection for diagnosing IPA, and the optimal cutoff value for BALF GM is 0.87., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of the present study was to investigate the values of the serum (1,3)-β-D-glucan test (G test) alone, the galactomannan test (GM test) alone, and their combination in the diagnosis of invasive fungal rhinosinusitis (IFRS)., Methods: The present study retrospectively analysed the clinical data of 98 patients who were preliminarily diagnosed with "space-occupying lesions in nose". Of these 98 patients, 88 received the G test, 55 received the GM test, and 45 received both. A pathology analysis was used as the gold standard to diagnose IFRS. All data were analysed using SPSS 19.0., Results: The sensitivities (Se) of the G and GM tests alone were 60.0% and 28.6%, respectively, whereas the specificities (Sp) were 92.3% and 93.8%, respectively. Moreover, the positive predictive values (PPV) of the G and GM tests alone were 50.0% and 40.0%, respectively, and the negative predictive values (NPV) were 94.7% and 90.0%, respectively. In addition, the diagnostic odds ratios (DOR) were 18.0 and 6.0, respectively, and the Kappa values were 0.48 (P < 0.05) and 0.25 (P > 0.05), respectively. When the G and GM tests were parallel combined, the Se was 66.7%, the Sp was 92.3%, the PPV was 57.1%, the NPV was 94.7%, the DOR was 24.0, and the Kappa value was 0.55 (P < 0.05). The present study was unable to evaluate the serial diagnosis due to the lack of patients testing positive., Conclusions: The G/GM tests exhibited low Se and PPV when used to diagnose IFRS, while high Sp and NPV. Parallel diagnosis improved the diagnostic Se and DOR values., (Copyright © 2020. Published by Elsevier Inc.)

Early diagnosis of invasive aspergillosis (IA) is facilitated by detection of galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) using an enzyme-linked immunosorbent assay (ELISA). Although accurate, false positive results have been reported with these tests in numerous contexts. We report for the first time the occurrence of false positive GM ELISA due to nocardiosis, initially in a clinical sample of BALF from a patient with pulmonary nocardiosis, and subsequently corroborated by in vitro reactivity of 26% of tested isolates. Since patients at risk for IA are also at risk for nocardiosis, this finding has important clinical implications., Lay Summary: Early diagnosis of aspergillosis has been facilitated by the routine use of antibody-based detection of galactomannan in various bodily fluids. We report for the first time the occurrence of false positive results of this assay in the context of nocardiosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardized diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11 March and 14 July 2020, the UK National Mycology Reference Laboratory received 1,267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-β-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavage specimens, tracheal aspirates, and sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus -specific PCR, and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA, especially when only limited clinical samples are available for testing, and the importance of a multimodal diagnostic approach involving regular and repeat testing of both serum and respiratory samples., (© Crown copyright 2020.)

Although patients with severe immunodeficiency and hematological malignancies has been considered at highest risk for invasive fungal infection, patients with severe pneumonia due to influenza, and severe acute respiratory syndrome coronavirus (SARS-CoV) are also at a higher risk of developing invasive pulmonary aspergillosis (IPA). Recently, reports of IPA have also emerged among SARS-CoV-2 infected patients admitted to intensive care units (ICUs). Here, we report a fatal case of probable IPA in an acute myeloid leukemia patient co-infected with SARS-CoV-2 and complicated by acute respiratory distress syndrome (ARDS). Probable IPA is supported by multiple pulmonary nodules with ground glass opacities which indicate halo sign and positive serum galactomannan results. Screening studies are needed to evaluate the prevalence of IPA in immunocompromised patients infected with SARS-CoV-2. Consequently, testing for the presence of Aspergillus in lower respiratory secretions and galactomannan in consecutive serum samples of COVID-19 patients with timely and targeted antifungal therapy based on early clinical suspicion of IPA are highly recommended.

Objective: The aim of this study is to characterize chest CT findings of neutropenic patients with proven/probable invasive pulmonary aspergillosis (IPA)., Methods: Hematological cancer patients admitted to our institution (2007-2017) were retrospectively enrolled if the diagnostic criteria of proven/probable IPA during the neutropenia were met (EORTC/MSG). Galactomannan (GM) was routinely measured in serum and chest CT-scan was routinely performed in case of recurrent/persistent fever. Bronchoscopy was performed in case of chest CT-scan abnormalities. Chest CT-scan and GM dosage were analyzed at the time of IPA suspicion. Chest lesions were classified using a clinical report form by two expert radiologists., Results: 35 patients were identified. Peribronchial focal lesions were observed in 29 IPA (82.9%) by the first radiologist and in 31 (88.5%) by the second ( k = 0.768). 12 weeks mortality was 20%., Conclusion: Peribronchial focal lesions are a common finding in early-IPA whatever the GM value during neutropenia and our findings reinforce the efficiency of a preemptive approach., Advances in Knowledge;: Peribronchial focal lesions, which are classically described in airway invasive aspergillosis, are a common finding in early-IPA in hematological cancer patients with prolonged neutropenia regardless of the GM value, and such peribronchial lesions should reinforce the possibility of IPA.

Background: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population., Objectives: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN., Patients/methods: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds., Results: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04)., Conclusions: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN., (© 2020 Blackwell Verlag GmbH.)

Early detection of Aspergillus infection has the potential to facilitate a more effective management of invasive disease. Data from probable/proven cases of invasive aspergillosis (IA) with a positive galactomannan enzyme-linked immunosorbent assay (GM) bronchoalveolar lavage fluid (BALF) was analyzed in respect to serum GM and/or polymerase chain reaction (PCR) screening of blood samples prior to, or concurrent with bronchoscopy. Concurrent serum GM testing is less sensitive than BALF itself. Nevertheless screening of blood using GM or PCR testing detected IA cases earlier (GM: 42% or PCR: 56%), particularly when combined (GM/PCR: 73%). Therefore, regular screening facilitates and improves early detection of IA in patients suffering from acute leukemia., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The aim of this study was to evaluate the diagnostic utility of serum galactomannan (GM) positivity for invasive aspergillosis (IA) in children. Positive GM results between January 2015 and August 2017 were reviewed retrospectively in children with hematologic malignancies. Single and consecutive positive GM results were evaluated according to the different galactomannan index (GMI) (>0.5, >0.7, >1.0 and >1.5) values. There were 104 positive GM results of 70 patients. IA was identified in 29 patients (41.4%) (2 proven and 27 probable). For a single positive GMI of >0.5, >0.7, >1.0, and >1.5, the numbers were 104, 76, 57, and 32 and the positive predictive values (PPVs) were 39.4%, 43.2%, 47.2%, and 50.0%, respectively. The single GM positivity at different thresholds showed no difference between the IA and non-IA group (P>0.05). For 2 consecutive positive GMI values of >0.5, >0.7, >1.0, and >1.5, the numbers were 34, 20, 13, and 4, and the PPVs were 58.8%, 65.0%, 84.6%, and 100.0%, respectively. In the IA group, positivity was higher at all thresholds (P<0.05). According to our findings, consecutive GM positivity has higher PPVs independently from the cutoff value chosen. In pediatric patients with high risk, consecutive sampling should be preferred.

Invasive fungal diseases are associated with significant morbidity and mortality, particularly in immunocompromised individuals. Early and accurate diagnosis is crucial for effective treatment. Despite traditional methods such as microbiological culture, histopathology, radiology and direct microscopy are available, antigen/antibody-based diagnostics are emerging for diagnosis of invasive fungal infections (IFI). Fungal cell wall is a unique structure composed of polysaccharides that are well correlated with fungal burden during fungal infections. Based on this feature, cell wall polysaccharides have been explored as antigens in IFIs diagnostics such as the galactomannan assay, mannan test, β-glucan assay and cryptococcal CrAg test. Herein, we provide an overview on the cell wall polysaccharides from three opportunistic pathogens: Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans, and their applications for IFIs diagnosis. The clinical outcome of newly developed cell wall polysaccharides-based diagnostics is also discussed., (© 2020 Blackwell Verlag GmbH.)

Objective: In invasive aspergillosis (IA), monitoring response to antifungal treatment is challenging. We aimed to explore if routine blood parameters help to anticipate outcomes following IA., Methods: Post hoc secondary analysis of two multicenter randomized trials was performed. The Global Comparative Aspergillosis Study (GCA, n = 123) and the Combination Antifungal Study (CAS, n = 251) constituted the discovery and validation cohorts respectively. The outcome measures were response to treatment and survival to 12 weeks. Interval platelet, galactomannan index (GMI) and C-reactive protein (CRP) levels prior and during antifungal treatment were analysed using logistic regression, Kaplan-Meier survival and receiver operating characteristic (ROC) analyses., Results: The 12-week survival was 70.7% and 63.7% for the GCA and CAS cohorts respectively. In the GCA cohort, every 10 × 10 9 /L platelet count increase at week 2 and 4 improved 12-week survival odds by 6-18% (odds ratio (OR) 1.06-1.18, 95% confidence interval (CI) 1.02-1.33). Survival odds also improved 13% with every 10 mg/dL CRP drop at week 1 and 2 (OR 0.87, 95% CI 0.78-0.97). In the CAS cohort, week 2 platelet count was also associated with 12-week survival with 10% improved odds for every 10 × 10 9 /L platelet increase (OR, 1.10, 95% CI 1.04-1.15). A GMI drop of 0.1 unit was additionally found to increase the odds of treatment response by 3% at the baseline of week 0 (OR 0.97, 95% CI 0.95-0.99). Week 2 platelet and CRP levels performed better than GMI on ROC analyses for survival (area under ROC curve 0.76, 0.87 and 0.67 respectively). A baseline platelet count higher than 30 × 10 9 /L clearly identified patients with >75% survival probability., Conclusions: Higher serial platelets were associated with overall survival while GMI trends were linked to IA treatment response. Routine and simple laboratory indices may aid follow-up of response in IA patients., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Invasive pulmonary aspergillosis (IPA) optimal duration of antifungal treatment is not known. In a joint effort, four international scientific societies/groups performed a survey to capture current practices in European haematology centres regarding management of IPA. We conducted a cross-sectional internet-based questionnaire survey in 2017 to assess practices in sixteen European countries concerning IPA management in haematology patients including tools to evaluate treatment response, duration and discontinuation. The following four groups/societies were involved in the project: European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG), Infectious Diseases Working Party-European Society for Blood and Bone Marrow Transplantation (IDWP-EBMT), European Organisation for Research and Treatment-Infectious Disease group (EORTC-IDG) and Sorveglianza Epidemiologica Infezioni nelle Emopatie (SEIFEM). A total of 112 physicians from 14/16 countries answered the survey. Galactomannan antigen was available in serum and bronchoalveolar lavage in most centres (106/112 [95%] and 97/112 [87%], respectively), quantitative Aspergillus PCR in 27/112 (24%) centres, β-D-glucan in 24/112 (21%) and positron emission tomography in 50/112 (45%). Treatment duration differed between haematological malignancies, with a median duration of 6 weeks [IQR 3-12] for patients with AML, 11 [4-12] for patients with allogenic stem cell transplantation and GvHD and 6 [3-12] for patients with lymphoproliferative disease. Treatment duration significantly differed according to country. Essential IPA biomarkers are not available in all European countries, and treatment duration is highly variable according to country. It will be important to provide guidelines to help with IPA treatment cessation with algorithms according to biomarker availability., (© 2020 Blackwell Verlag GmbH.)

Background: At present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients., Methods: Fifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves., Results: The positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P <  0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873)., Conclusions: Serum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Objective: To assess the utility of galactomannan and beta-D-glucan assays in the diagnosis of invasive aspergillosis in clinically suspected cases, and to compare their diagnostic potential to determine whether a combination of the two may result in an early and specific diagnosis., Methods: The descriptive cross-sectional case-control study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from April 1, 2017, to March 31, 2018, and comprised serum samples from clinically suspected invasive aspergillosis patients and healthy controls. The sera were tested for galactomannan and beta-D-glucan detection. Proven, probable and possible categories of invasive aspergillosis according to European Organisation for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Galactomannan antigen was detected using a one-stage immunoenzymatic sandwich microplate assay. Beta-D-Glucan antigen was detected using a protease zymogen-based colorimetric assay. Sensitivity and positive / negative likelihood ratio of both the cases and the controls were calculated and compared., Results: Of the 178 subjects, 119(67%) were cases and 59(33%) were controls. Beta-D-glucan assay was more sensitive than galactomannan assay (91.6% versus 80.67%) whereas galactomannan assay was more specific than beta-D-glucan assay (86.44% versus 76.27%) in the diagnosis of invasive aspergillosis. The sensitivities of both assays decreased with decreasing probability of invasive aspergillosis, i.e., maximum sensitivities of both beta-D-glucan and galactomannan assays were for proven cases (100% versus 87.5%), followed by probable cases (89.29% versus 85.71%), and possible cases (91.57% versus 78.31%)., Conclusions: Both beta-D-glucan and galactomannan assays seemed to play an encouraging role in the diagnosis of invasive aspergillosis in high-risk clinically suspected cases, with the former assay being more sensitive and the latter assay being more specific.

Background: Progressive disseminated histoplasmosis (PDH) is an important cause of mortality in persons living with HIV (PLHIV), especially in countries where patients have limited access to antiretroviral therapies and diagnostic testing., Objective: A lateral flow assay (LFA) to detect Histoplasma capsulatum antigen in serum developed by MiraVista ® was evaluated., Methods: We tested 75 serum samples: 24 from PLHIV and culture-proven PDH and 51 from PLHIV with other fungal and bacterial infections as well as people without HIV. LFA devices were read manually (read by eye) and by an automated reader., Results: When the LFA was read manually, sensitivity was 96% and specificity was 90%. When an automated reader was used, sensitivity was 92% and specificity was 94%. The Kappa index comparing manual and automated reader was 0.90. Cross-reactions were observed principally in samples from patients with proven diagnosis of paracoccidioidomycosis., Conclusions: The MiraVista ® Diagnostics Histoplasma antigen LFA had high analytical performance and good agreement between manual and automated reader. This LFA allows Histoplasma antigen testing with minimal laboratory equipment and infrastructure requirements., (© 2019 Blackwell Verlag GmbH.)

Talaromyces (Penicillium) marneffei is an emerging pathogen that causes significant morbidity and mortality in immunocompromised patients in endemic regions such as southeast Asia. The diagnosis of disseminated T. marneffei infection remains challenging in clinical practice. In the study, a well-validated real-time quantitative polymerase chain reaction (qPCR) target region of ITS1-5.8S-ITS2 and a Platelia galactomannan (GM) assay were compared for their diagnostic performance using serum samples from patients with or without human immunodeficiency virus (HIV). The results showed that this novel qPCR method is highly sensitive and specific for T. marneffei DNA detection in serum samples, and the limit of detection and species-specificity of qPCR were five copies of DNA and 100%, respectively. For detection in serum samples from 36 talaromycosis patients, the sensitivity of qPCR was 86.11% (31/36), including 20/20 (100%) patients with fungemia and 11/16 (68.75%) patients without fungemia. For the GM assay, the sensitivity was 80.56% (29/36) when the GM optical density cutoff index was ≥0.5, including 19/20 (95%) patients with fungemia and 10/16 (62.5%) patients without fungemia. These results indicate that the novel qPCR and GM assays can be used as a valuable tool in the diagnosis of T. marneffei infection. Serum samples are convenient hematological specimens for T. marneffei DNA quantification. Combining the GM assay and qPCR is more scientific and appropriate for diagnosing T. marneffei infection in endemic areas., (© The Author(s) 2019. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)