Advances in the serological diagnosis of invasive Aspergillus infections in patients with haematological disorders (original) (raw)
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Mycoses, 2015
Rapid diagnosis and early treatment of invasive aspergillosis is crucial for the management of the patients with haematological malignancy. We evaluated 358 sera from 78 febrile neutropenic episodes in patient with invasive aspergillosis (IA) (one proven, 17 probable, and 60 possible) and 83 episodes in patients with no IA according to the EORTC/MSG criteria. Patient's specimens were tested by Mycassay Aspergillus PCR (first commercial real-time PCR test) and in house real-time PCR to investigate the presence of Aspergillus DNA, and by ELISA for detect the galactomannan (GM) antigen. We systematically investigated the medical background that can be effective on the test results. The hospitalisation period was longer in proven/ probable episodes when compared with no IA (P = 0.001) and possible episodes. With regard to duration of neutropenia, the differences between both proven/probable with no IA (P = 0.023) and possible with no IA (P = 0.002) were highly significant. Similarly, the rates of T cell suppressant therapy in group proven/probable and possible episodes were significantly higher than in no IA (P = 0.005). There are significant differences in the performance of GM and PCR-based tests among studies, and standardisation is required. Therefore, it can be useful to determine the effective factors on these tests. The use of larger volume of sera improved the performance of real-time PCR for detection of Aspergillus DNA in high-risk adult patients in the present study. Some host factors such as duration of neutropenia and administration of T cell suppressants related to the development of IA.
BMC Infectious Diseases, 2015
We assessed the diagnostic value of standard clinical methods and combined biomarker testing (galactomannan assay and polymerase chain reaction screening) in a prospective case-control study to detect invasive pulmonary aspergillosis in patients with hematological malignancies and prolonged neutropenia. Methods: In this observational study 162 biomarker analyses were performed on samples from 27 febrile neutropenic episodes. Sera were successively screened for galactomannan antigen and for Aspergillus fumigatus specific nucleic acid targets. Furthermore thoracic computed tomography scanning was performed along with bronchoscopy with lavage when clinically indicated. Patients were retrospectively stratified to define a case-group with "proven" or "probable" invasive pulmonary aspergillosis (25.93 %) and a control-group of patients with no evidence for of invasive pulmonary aspergillosis (74.07 %). In 44.44 % of episodes fever ceased in response to antibiotic treatment (group II). Empirical antifungal therapy was administered for episodes with persistent or relapsing fever (group I). 48.15 % of patients died during the study period. Postmortem histology was pursued in 53.85 % of fatalities.
Diagnosis and management of invasive aspergillosis in adult neutropenic haemato-oncology patients
2014
Background Invasive fungal disease (IFD) is difficult to diagnose. For clinical trials the European Organisation for Research in Treatment of Cancer (EORTC) and the Mycology Study Group (MSG) criteria are useful but there are few data on their value in clinical practice. The aims of this study were to: (1) investigate the incidence and risk factors of IFD; (2) assess the utility of galactomannan (GM), β-D glucan (BDG), the UK consensus fungal PCR, and lateral flow device (LFD) assays together with the safety and feasibility of biopsy; (3) assess the role of cytokines in the diagnosis and prognosis of IFD; (4) establish the prevalence of baseline CT abnormalities, and assess diagnostic CT features and spectrum of radiological signs. Methods Patients (N=203) were recruited prospectively and followed for a median (range) of 556 (12-730) days after chemotherapy or haematopoietic stem cell transplantation. Chest CT, Karnofsky score (KS), serum GM, and cytokine profiles were performed at baseline; during admission twice-weekly GM assays were performed on all patients. BDG, serum and whole blood consensus PCR, and LFD assays were performed on a selection of samples from different IFD categories. Neutropenic sepsis refractory to antimicrobials for ≥4 days triggered diagnostic CT and biopsy where feasible. All patients were on
PCR as a Screening Test for Invasive Aspergillosis in Haematological Patients: A Pilot Study
Mycopathologia, 2014
Invasive aspergillosis is a leading cause of morbidity and mortality in immunocompromised patients, particularly in individuals with haematological malignancy and in haematopoietic stem cell transplant recipients. Nowadays, the galactomannan (GM) assay has been widely used as an indication of invasive aspergillosis, even though the test is known to generate false-positive results. The aim of this study was to compare the performance of GM and real-time PCR (qPCR) to detected Aspergillus in blood samples obtained from high-risk haematological patients. Haematological patients were screened twice weekly with GM testing, which was performed by the Platelia ELISA kit. An additional sample of whole blood (4 ml) was obtained for the purpose of qPCR testing. Sixty-four samples from 12 patients with haematopoietic stem cell transplant or haematological malignancy were studied. The overall accordance between GM and qPCR tests was 96.9 % (62 samples). Only two samples showed contradictory results, with positive GM test and negative real-time PCR results. Based on the high concordance between GM and qPCR in terms of negative results, the main utility of qPCR could be in the confirmation of positive results seen with GM testing.
Microbiology Research Journal International
Background: Invasive aspergillosis (IA) is a leading cause of death among immunocompromised patients, particularly those with hematological malignancies. The use of galactomannan (GM) antigen as a biological marker for screening of IA in high-risk patients is attractive and non-invasive tool that detect evidence of IA prior to the appearance of clinical manifestations. Objectives: The aim of this study was to compare the diagnostic value of the conventional blood culture technique to the serological detection of GM antigen using ELISA for screening of IA in neutropenic patients with hematological malignancies. Methods: Forty patients with haematological malignancies from those admitted to the Clinical Oncology Department of Menoufia University Hospitals (MUH) were enrolled and classified to have either proven (5/40; 12.5%), probable (10/40; 25%) or possible (25/40; 62.5%) invasive aspergillosis based on the clinical criteria provided by the European Organization for research and tre...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2016
We evaluated the usefulness of a serum Aspergillus PCR assay for the diagnosis and prognosis of invasive aspergillosis in a study involving 941 patients for a total of 5,146 serum samples. Fifty-one patients had proven/probable aspergillosis. We compared galactomannan, PCR, and mycological analysis of pulmonary samples in both neutropenic and non-neutropenic patients. PCR performed in serum yielded 66.7% sensitivity, 98.7% specificity, 75.6% positive predictive value and 98.0% negative predictive value while the galactomannan index yielded 78.4% sensitivity, 87.5% specificity, 27% positive predictive value and 98.6% negative predictive value. The inclusion of PCR in the EORTC/MSG mycological criteria permitted the reclassification of nine other cases from possible to probable aspergillosis and increased sensitivity to 71.7%. Combining the galactomannan index with serum PCR increased the detection rate of invasive aspergillosis with 88.2% sensitivity. PCR was systematically negative ...
Journal of Infection, 1997
The double sandwich ELISA detecting Aspergillus galactomannan (GM) was prospectively evaluated for the diagnosis of invasive aspergillosis (IA) in 50 haematological patients at risk for IA. Serum samples were collected once weekly as long as the risk factors persisted. Six patients had proven or probable IA (3 A. fiimigatus, 1 A. flavus, 1 A. niger, 1 A. ustus) and the GM titres were parallel to the clinical evolution of IA. Six of nine patients with suspected IA had at least two consecutive serum GM titres above I ng/ml and died with increasing titres, whereas the GMnegative patients survived. Positive GM titres did not anticipate the isolation of fungi. Unfortunately, positive GM titres did not anticipate the initiation of antifungal therapy, based on clinical suspicion. Moreover, if a true-positive result was defined as two consecutive positive serum samples, four patients out of 35 without proven, probable or suspected IA were positive. Then, the rate of false-positive results was high (12%) in the range previously reported. Nevertheless, the GM ELISA appears useful to assess IA and to follow the efficacy of antifungal treatment.