scholarly journals Comparison of β-D-Glucan and Galactomannan in Serum for Detection of Invasive Aspergillosis: Retrospective Analysis with Focus on Early Diagnosis

2020 ◽  
Vol 6 (4) ◽  
pp. 253
Author(s):  
Karl Dichtl ◽  
Johannes Forster ◽  
Steffen Ormanns ◽  
Heidi Horns ◽  
Sebastian Suerbaum ◽  
...  

The early diagnosis of invasive aspergillosis (IA) relies mainly on computed tomography imaging and testing for fungal biomarkers such as galactomannan (GM). We compared an established ELISA for the detection of GM with a turbidimetric assay for detection of the panfungal biomarker β-D-glucan (BDG) for early diagnosis of IA. A total of 226 serum specimens from 47 proven and seven probable IA cases were analysed. Sensitivity was calculated for samples obtained closest to the day of IA-diagnosis (d0). Additional analyses were performed by including samples obtained during the presumed course of disease. Most IA cases involved the respiratory system (63%), and Aspergillus fumigatus was the most frequently isolated species (59%). For proven cases, sensitivity of BDG/GM analysis was 57%/40%. Including all samples dating from –6 to +1 weeks from d0 increased sensitivities to 74%/51%. Sensitivity of BDG testing was as high as or higher than GM testing for all subgroups and time intervals analysed. BDG testing was less specific (90–93%) than GM testing (99–100%). Combining BDG and GM testing resulted in sensitivity/specificity of 70%/91%. Often, BDG testing was positive before GM testing. Our study backs the use of BDG for diagnosis of suspected IA. We suggest combining BDG and GM to improve the overall sensitivity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4982-4982
Author(s):  
Ai-ning Sun ◽  
Jun Wang ◽  
De Pei Wu ◽  
Su-ning Chen

Abstract Objective To evaluate the value of galactomannan(GM) detection and nest PCR for early diagnosis of invasive aspergillosis (IA) in patients with hematological disease. Methods GM ELISA and nest PCR was performed to serially screen for circulating galactomannan(GM) and DNA of Aspergillus ssp. Respectively, 96 patients were grouped according to case definitions of the EORTC, including 5 proven IA and 28 probable IA cases. Samples of the patients included serum twice weekly(326) and bronchoalveolar lavage fluid(BALF 12). Sensitivity, specificity and predictive values were calculated respectively and compared. Results According to the receiver operator characteristic curve(ROC), using a reduced cutoff of 0.5 O.D.I of two-positive GM test result, we can achieved the most optimal results. The sensitivity, specificity, positive predictive value (PPV)and negative predictive value (NPV) of the ELISA test were 85.7%,91.6%,85.7%,91.6%respectively. While for the BALF samples, a increased cutoff 1.0 maybe improve the value of this diagnosis, with sensitivity 50% and specificity 100%.Quantitive results of the serum-based GM antigen can represent the status of IA and were correlated with the prognosis Of IA.Galactomannanemia preceded the development of characteristic findings on CT about 6 days. The nest PCR assay amplifies specifically a region of the 18S rRNA gene that is highly conserved in Aspergillus species and allows detection of down to 5.0 fg/ml of Aspergillus DNA. When two-positive results were used to define an episode as ‘PCR positive’, the sensitivity, specificity, PPV and NPV of the PCR test were 92.9%, 100%,100%,96.0% respectively. For the BALF samples, the sensitivity and specificity decreased to 75%and 60%. The frequency of the consecutively positive results of a patient was correlated with prognosis Of IA. The antifungal therapy usually causes a intermittent positive PCR results. Positve PCR results preceded the development of characteristic findings on CT about 9 days. Conclusion The cutoff 0.5 of two-positive serum-based GM ELISA test result is the most optimal cutoff value. GM ELISA test is a rapid,reliable method for early diagnosis and treatment of IA, with good sensitivity(85.7%)and specificity(91.6%). GM ELISA test is a good direction for preemptive antifungal therapy in patients with hematological disease at risk. Using two-positive results to define an episode as ‘PCR positive’, great sensitivity(92.9%)and specificity(100%) could be achieved. The serum-based PCR test is useful for screening for Aspergillus spp. in patients with hematological disease at risk but without antifungal treatment.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3833-3833
Author(s):  
Muriel Cornet ◽  
Sandrine Katsahian ◽  
Anne Vekhoff ◽  
Vincent Levy ◽  
Bernard Rio ◽  
...  

Abstract Purpose: Prospective evaluation of a PCR-ELISA method for the early diagnosis of invasive aspergillosis (IA) in hematological patients. Patients and Methods: The PCR-ELISA assay was evaluated using 1,494 sera samples from 201 hematological adult patients. Monitoring was performed twice weekly during 256 consecutive high-risk treatment periods. Results: Underlying diseases were acute leukemia 52.7%, lymphoma 20.9%, multiple myeloma 12.4%. Eighty four patients (41.8%) were stem cell transplant recipients. Fifty-five patients were diagnosed with IA. PCR-ELISA positivity (i) preceded the empirical antifungal therapy in 20/31 patients (median 10.5 days), (ii) preceded or was simultaneous to the radiological diagnosis by chest CT in 21/31 patients (median 8 days), (iii) preceded the mycological/histological diagnosis in 7/12 patients (median 70 days) and, (iv) anticipated or was simultaneous to the galactomannan (GM) antigen positivity in 50% (median 16.5 days) and in 89 % of the patients (median 33 days) using a 0.5 and a 1.5 optical density index (ODI) cut-off for the GM assay, respectively. For at least two positive samples the sensitivity, specificity, positive and negative predictive values of the PCR-ELISA assay, were 63.6%, 82.2%, 57.4% and 85.7%, respectively. When the PCR-ELISA and GM detections were combined, values of the combined test for at least two positive samples with either assay were 80%, 47.3%, 36.4%, 86.2% using the 0.5 GM ODI cutoff, and 67.3%, 82.2%, 58.7% and 87% using the 1.5 GM ODI cutoff. Conclusion: In addition to serial screening with GM antigenemia and chest CT surveillance, the PCR-ELISA assay may improve the early diagnosis of IA.


2021 ◽  
Vol 7 (3) ◽  
pp. 211
Author(s):  
Maria Siopi ◽  
Stamatis Karakatsanis ◽  
Christoforos Roumpakis ◽  
Konstantinos Korantanis ◽  
Elina Eldeik ◽  
...  

As conventional microbiological documentation of invasive aspergillosis (IA) is difficult to obtain, serum fungal biomarkers are important adjunctive diagnostic tools. Positivity rates and the kinetic profiles of galactomannan (GM), 1,3-β-D-glucan (BDG) and Aspergillus DNA (PCR) were studied in high-risk patients with hematologic malignancies. GM, BDG and PCR data from serial serum specimens (n = 240) from 93 adult hematology patients with probable (n = 8), possible (n = 25) and no (n = 60) IA were retrospectively analyzed. Positivity rates and sensitivity/specificity/positive/negative predictive values (NPV) of each fungal biomarker alone and in combination were estimated. The three markers were compared head-to-head and correlated with various biochemical, demographic and patient characteristics. The positivity rates for patients with probable/possible/no IA were 88%/8%/0 % for GM (X2 = 55, p < 0.001), 62%/46%/35% for BDG (X2 = 2.5, p = 0.29), 62%/33%/27% for PCR (X2 = 3.9, p = 0.15), 50%/4%/0% for GM + BDG and GM + PCR (X2 = 31, p < 0.001), 50%/8%/22% for BDG + PCR (X2 = 6.5, p = 0.038) and 38%/4%/0% for GM + BDG + PCR (X2 = 21, p < 0.001). Higher agreement (76%) and negative correlation (rs = -0.47, p = 0.0017) was found between GM index and PCR Ct values. The sensitivity and NPV was 45-55% and 90-92% when biomarkers assessed alone and increased to 75-90% and 93-97%, respectively when combined. Weak significant correlations were found between GM, PCR and BDG results with renal/liver function markers (r = 0.11–0.57) with most GM+ and PCR+ samples found in the first and second week of clinical assessment, respectively and BDG later on. Different positivity rates, time profiles and performances were found for the three biomarkers advocating the combination of GM with PCR for the early diagnosis of IA, whereas the high NPV of combined biomarkerscould help excluding IA.


1987 ◽  
Vol 33 (3) ◽  
pp. 358-362 ◽  
Author(s):  
A H Wu ◽  
T G Gornet ◽  
V H Wu ◽  
R E Brockie ◽  
A Nishikawa

Abstract We compared the clinical sensitivity, specificity, and diagnostic efficiency of measuring creatine kinase-3 (MM) isoenzyme sub-types (CK, EC 2.7.3.2) with the measurement of CK-2 (MB) isoenzymes for the diagnosis of acute myocardial infarction. Serial blood collections at 3-h intervals from 35 patients with acute myocardial infarction were examined. In attempts to reperfuse their coronary arteries, some of these patients were treated with pharmacological thrombolysis (streptokinase, tissue plasminogen activator), with or without coronary angioplasty. The infarction patients were divided into two groups: patients who were successfully treated with thrombolytic agents (i.e., they achieved coronary reperfusion), and patients who were treated unsuccessfully or who were not treated acutely. We also examined blood from 34 non-infarction patients. We measured CK-3 sub-types by both anion-exchange liquid chromatography and a modified high-voltage electrophoresis method, and CK-2 by immunoprecipitation. Our results show that during the first few critical 3 to 9 h after onset of chest pain, measurement of CK-3 sub-types has the highest diagnostic efficiency; in contrast, CK-2 has the highest efficiency during the 10- to 21-h time intervals. Thus early diagnosis of acute myocardial infarction can be based on rapid assays of CK-3 sub-types.


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