Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies.
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ABSTRACT:
SUBMITTER: Reischies FM
PROVIDER: S-EPMC4767980 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
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Project description:Mortality associated with invasive aspergillosis (IA) remains high, partly because of delayed diagnosis. Detection of microbial exoantigens, released in serum and other body fluids during infection, may help timely diagnosis. In course of IA, Aspergillus galactomannan (GM), a well established polysaccharide biomarker, is released in body fluids including urine. Urine is an abundant, safely collected specimen, well-suited for point-of-care (POC) testing, which could play an increasing role in screening for early disease. Our main objective was to demonstrate GM antigenuria as a clinically relevant biological phenomenon in IA and establish proof-of-concept that it could be translated to POC diagnosis. Utilizing a novel IgM monoclonal antibody (MAb476) that recognizes GM-like antigens from Aspergillus and other molds, we demonstrated antigenuria in an experimental animal IA model (guinea pig), as well as in human patients. In addition, we investigated the chemical nature of the urinary excreted antigen in human samples, characterized antigen detection in urine by immunoassays, described a putative assay inhibitor in urine, and indicated means of alleviation of the inhibition. We also designed and used a lateral flow immunochromatographic assay to detect urinary excreted antigen in a limited number of IA patient urine samples. In this study, we establish that POC diagnosis of IA based on urinary GM detection is feasible. Prospective studies will be necessary to establish the performance characteristics of an optimized device and define its optimal clinical use.
| S-EPMC3416763 | biostudies-literature
Project description:BackgroundThe pathogenesis of invasive aspergillosis (IA) is still unknown, but its progression is rapid and mortality rate remains high. Bronchoalveolar lavage fluid (BALF) galactomannan (GM) analysis has been used to diagnose IA. This study is aimed at making an accurate estimate of the whole accuracy of BALF-GM in diagnosing IA.MethodsAfter a systematic review of the study, a bivariate meta-analysis was used to summarize the specificity (SPE), the sensitivity (SEN), the positive likelihood ratios (PLR), and the negative likelihood ratios (NLR) of BALF-GM in diagnosing IA. The overall test performance was summarized using a layered summary receiver operating characteristic (SROC) curve. Subgroup analysis was performed to explore the heterogeneity between studies.ResultsA total of 65 studies that are in line with the inclusion criteria were included. The summary estimates of BALF-GM analysis are divided into four categories. The first is the proven+probable vs. possible+no IA, with an SPE, 0.87 (95% CI, 0.85-0.98); SEN, 0.81 (95% CI, 0.76-0.84); PLR, 9.78 (5.78-16.56); and NLR, 0.20 (0.14-0.29). The AUC was 0.94. The BALF-GM test for proven+probable vs. no IA showed SPE, 0.88 (95% CI, 0.87-0.90); SEN, 0.82 (95% CI, 0.78-0.85); PLR, 6.56 (4.93-8.75); and NLR, 0.24 (0.17-0.33). The AUC was 0.93. The BALF-GM test for proven+probable+possible vs. no IA showed SPE, 0.82 (95% CI, 0.79-0.95); SEN, 0.59 (95% CI, 0.55-0.63); PLR, 3.60 (2.07-6.25); and NLR, 0.31 (0.15-0.61). The AUC was 0.86. The analyses for others showed SPE, 0.85 (95% CI, 0.83-0.87); SEN, 0.89 (95% CI, 0.86-0.91); PLR, 6.91 (4.67-10.22); and NLR, 0.18 (0.13-0.26). The AUC was 0.94.ConclusionsThe findings of this BALF-GM test resulted in some impact on the diagnosis of IA. The BALF-GM assay is considered a method for diagnosing IA with high SEN and SPE. However, the patients' underlying diseases may affect the accuracy of diagnosis. When the cutoff is greater than 1, the sensitivity will be higher.
| S-EPMC7723495 | biostudies-literature
Project description:BackgroundProteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy.MethodsWe conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared.ResultsIn this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671-0.847, P < 0.001). After a median follow-up of 29.88 (14.65-51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31-6.08; P = 0.008].ConclusionsIn IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.
| S-EPMC8918683 | biostudies-literature
Project description:PurposeThe detection of galactomannan (GM) in bronchoalveolar lavage (BAL) fluid is an important surrogate marker for the early diagnosis and therapeutic monitoring of invasive aspergillosis (IA), regardless of the involved species of Aspergillus. Here, we utilized the Platelia Aspergillus GM enzyme immunoassay (Bio-Rad) to evaluate the GM index in BAL fluid samples from patients with proven, probable or putative IA due to Aspergillusflavus versus Aspergillusfumigatus.MethodologyIn a prospective study between 2009 and 2015, 116 BAL samples were collected from suspected IA patients referred to two university hospitals in Tehran, Iran.Key findingsAccording to European Organization for Research and Treatment of Cancer and Mycoses Study Group and Blot criteria, 35 patients were classified as IA patients, of which 33 cases tested positive for GM above 0.5 and, among these patients, 22 had a GM index ≥1. Twenty-eight were culture positive for A. flavus and seven for A. fumigatus. The GM index for A. flavus cases was between 0.5-6.5 and those of A. fumigatus ranged from 1 to 6.5. The sensitivity and specificity of a GM index ≥0.5 in cases with A. flavus were 86 and 88 % and for A. fumigatus patients were 100 and 73 %, respectively.ConclusionOverall, the mean GM index in patients with A. fumigatus (3.1) was significantly higher than those of A. flavus (1.6; P-value=0.031) and the sensitivity of GM lower for A. flavus when compared to A. fumigatus. This finding has implications for diagnosis in hospitals and countries with a high proportion of A. flavus infections.
| S-EPMC5737110 | biostudies-literature
Project description:The optimal cut-off value of the optical density index of the galactomannan antigen assays (GM) for diagnosing invasive pulmonary aspergillosis in hematological patients is a disputed topic. This article conducts a systematic review with a meta-analysis to establish which optical density index (ODI) cut-off value should be implemented into clinical practice. Pubmed, Embase and Cochrane databases were searched (N = 27). The pooled data, using a generalized linear mixed model with binomial distribution, resulted in an overall serum sensitivity of 0.76 and a specificity of 0.92. For serum ODI 0.5 there was a pooled sensitivity of 0.92 and a specificity of 0.84. The pooled data of all broncho-alveolar lavage (BAL) studies resulted in an overall sensitivity of 0.80 and a specificity of 0.95. For BAL ODI 0.5, there was a pooled sensitivity of 0.75 and a specificity of 0.88. For the BAL ODI 1.0 pooling, the studies resulted in a sensitivity of 0.75 and a specificity of 0.96. Serum ODI of 0.5 and BAL ODI of 1.0 are the most suitable cut-offs for clinical practice. However, our study affirms that the evidence for the use of GM in clinical practice for the hematological malignancy patient is currently insufficient and more research is needed to determine the diagnostic value of GM.
| S-EPMC10305130 | biostudies-literature
Project description:The monitoring and prediction of treatment responses to invasive aspergillosis (IA) are difficult. We determined whether serum galactomannan index (GMI) trends early in the course of disease may be useful in predicting eventual clinical outcomes. For the subjects recruited into the multicenter Global Aspergillosis Study, serial GMIs were measured at baseline and at weeks 1, 2, and 4 following antifungal treatment. Clinical response and survival at 12 weeks were the outcome measures. GMI trends were analyzed by using the generalized estimation equation approach. GMI cutoffs were evaluated by using receiver-operating curve analyses incorporating pre- and posttest probabilities. Of the 202 study patients diagnosed with IA, 71 (35.1%) had a baseline GMI of ? 0.5. Week 1 GMI was significantly lower for the eventual responders to treatment at week 12 than for the nonresponders (GMIs of 0.62 ± 0.12 and 1.15 ± 0.22, respectively; P = 0.035). A GMI reduction of >35% between baseline and week 1 predicted a probability of a satisfactory clinical response. For IA patients with pretreatment GMIs of <0.5 (n = 131; 64.9%), GMI ought to remain low during treatment, and a rising absolute GMI to >0.5 at week 2 despite antifungal treatment heralded a poor clinical outcome. Here, every 0.1-unit increase in the GMI between baseline and week 2 increased the likelihood of an unsatisfactory clinical response by 21.6% (P = 0.018). In summary, clinical outcomes may be anticipated by charting early GMI trends during the first 2 weeks of antifungal therapy. These findings have significant implications for the management of IA.
| S-EPMC3405588 | biostudies-literature
Project description:BackgroundA rapid and reliable diagnostic test is needed to reduce mortality through early diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies.ObjectiveTo evaluate the efficacy of serum and bronchoalveolar lavage (BAL) Aspergillus galactomannan lateral flow assay (GM-LFA) in IA diagnosis and determine the correlation of GM-LFA with GM enzyme immunoassay (GM-EIA) in patients with hematological malignancies.MethodsIn this prospective multicenter study, we used serum and BAL fluid samples from patients with hematological malignancies and suspected IA and performed GM-LFA and GM-EIA. According to the EORTC/MSGERC criteria, patients were grouped as proven (n = 6), probable (n = 22), possible IA (n = 55), or no IA (n = 88). The performance of serum GM-LFA at 0.5 optical density index (ODI) and area under the curve (AUC) were calculated. Spearman's correlation analysis and kappa statistics were performed to determine the agreement between the tests.ResultsGM-LFA showed an AUC of 0.832 in proven/probable IA (sensitivity [SEN], specificity [SPE], negative predictive value [NPV], and diagnostic accuracy were 75%, 100%, 92.6%, and 93.9%, respectively, at a 0.5 ODI) versus that in no IA. A moderate positive correlation was noted between the GM-LFA and GM-EIA scores (p = 0.01). The observed agreement between the tests at 0.5 ODI was almost perfect (p < 0.001). After excluding patients who received mold-active antifungal prophylaxis or treatment, the SEN, SPE, NPV, and diagnostic accuracy for proven/probable IA were 76.2%, 100%, 93.3%, and 94.5%, respectively.ConclusionsSerum GM-LFA demonstrated high discriminatory power and good diagnostic performance for IA in patients with hematological malignancies.
| S-EPMC10241129 | biostudies-literature
Project description:Fungal infections represent a serious complication for immunosuppressed patients resulting in an increased morbidity and mortality. A non-concurrent prospective study was performed to evaluate the factors associated to invasive fungal infection (IFI) in patients with hematological malignancies admitted to the University Hospital in San Juan, Puerto Rico from January 1st, 2011 through June 15th, 2014. The medical records of 84 patients were evaluated. Fifty-nine patients with IFI and twenty-five without IFI. The majority were men between 35 to 55 years old. The main hematological diagnosis was acute myelogenous leukemia (AML) followed by acute lymphoblastic leukemia (ALL). Seventy-percent developed IFI. The most common fungi were C. albicans followed by non-albicans species, Fusarium and, Aspergillus species, respectively. About 63% of the patients with AML and 81% without AML had IFI. Those who received steroids were more likely to develop IFI. After adjusting for AML and age, the odds of IFI among patients using steroids were 3.33 higher than those not using steroids. Patients who were exposed to different antifungal medication had 72% lower odds to develop IFI.
| S-EPMC5980240 | biostudies-other
Project description:Invasive mold infections (IMI) are among the most devastating complications following chemotherapy and hematopoietic stem cell transplantation (HSCT), with high mortality rates. Yet, the molecular basis for human susceptibility to invasive aspergillosis (IA) and mucormycosis remain poorly understood. Herein, we aimed to characterize the immune profile of individuals with hematological malignancies (n = 18) who developed IMI during the course of chemotherapy or HSCT, and compared it to that of hematological patients who had no evidence of invasive fungal infection (n = 16). First, we measured the expression of the pattern recognition receptors pentraxin 3, dectin-1, and Toll-like receptors (TLR) 2 and 4 in peripheral blood of chemotherapy and HSCT recipients with IMI. Compared to hematological controls, individuals with IA and mucormycosis had defective expression of dectin-1; in addition, patients with mucormycosis had decreased TLR2 and increased TLR4 expression. Since fungal recognition via dectin-1 favors T helper 17 responses and the latter are highly dependent on activation of the signal transducer and activator of transcription (STAT) 3, we next used phospho-flow cytometry to measure the phosphorylation of the transcription factors STAT1 and STAT3 in response to interferon-gamma (IFN-γ) and interleukin (IL)-6, respectively. While IFN-γ/STAT1 signaling was similar between groups, naïve T cells from patients with IA, but not those with mucormycosis, exhibited reduced responsiveness to IL-6 as measured by STAT3 phosphorylation. Furthermore, IL-6 increased Aspergillus-induced IL-17 production in culture supernatants from healthy and hematological controls but not in patients with IA. Altogether, these observations suggest an important role for dectin-1 and the IL-6/STAT3 pathway in protective immunity against Aspergillus.
| S-EPMC4383538 | biostudies-literature
Project description:BackgroundInvasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies in the setting of profound neutropenia and/or hematopoietic stem cell transplantation. Early diagnosis and therapy has been shown to improve outcomes, but reaching a definitive diagnosis quickly can be problematic. Recently, galactomannan testing of bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA, but widespread experience and consensus on optical density (OD) cut-offs remain lacking.MethodsWe performed a prospective case-control study to determine an optimal BAL galactomannan OD cutoff for IPA in at-risk patients with hematological diagnoses. Cases were subjects with hematological diagnoses who met established definitions for proven or probable IPA. There were two control groups: subjects with hematological diagnoses who did not meet definitions for proven or probable IPA and subjects with non-hematological diagnoses who had no evidence of aspergillosis. Following bronchoscopy and BAL, galactomannan testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions.ResultsThere were 10 cases and 52 controls. Cases had higher BAL fluid galactomannan OD indices (median 4.1, range 1.1-7.7) compared with controls (median 0.3, range 0.1-1.1). ROC analysis demonstrated an optimum OD index cutoff of 1.1, with high specificity (98.1%) and sensitivity (100%) for diagnosing IPA.ConclusionsOur results also support BAL galactomannan testing as a reasonably safe test with higher sensitivity compared to serum galactomannan testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid over-diagnosis of IPA, and a standardized method of collection should be established before results can be compared between centers.
| S-EPMC2837869 | biostudies-literature