A case of chronic myelogenous leukemia with pulmonary aspergillosis diagnosed by the detection of circulating Aspergillus antigen]

Immunocompromised hosts usually develop invasive mycotic disease. Among many pathogenic fungi. Aspergillus spp, is the most common pathogen of respiratory infection. Early diagnosis of invasive type pulmonary aspergillosis is still difficult, and the treatment is usually difficult. Many investigations have recently suggested that detection of Aspergillus antigen from sera of the patients is useful for early diagnosis to save their lives. We have experienced a case diagnosed by the detection of circulating Aspergillus antigen by Pastorex Aspergillus, who was a 64-year-old female with the blastic crisis chronic myelogenous leukemia. After anti-leukemic chemotherapy, she suffered from pneumoniae with pleural effusions and severe hypoxia, which did not respond to antibiotics. At this point, her serum sample showed positive Aspergillus antigen by Pastorex Aspergillus. She was treated by intensive antifungal chemotherapy, and thereafter improved quickly. Titers of Pastorex Aspergillus were well correlated with her clinical course. The sensitivity of the test requires further improvement, but the specificity of the test is considered to be high enough for clinical use.     

Serial monitoring ofAspergillus antigen in the early diagnosis of invasive aspergillosis. Preliminary investigations with two examples

Summary A recently developed sandwich ELISA, which detectsAspergillus galactomannan, was tested retrospectively in serial serum samples from an allogeneic bone marrow transplant recipient with proven invasive aspergillosis (patient 1) and another with suspected disease (patient 2). Galactomannan was detected in the serum 4 and 28 days, respectively, before pulmonary infiltrates suggestive of fungal infection first became apparent on the chest X-ray.Aspergillus was detected by ELISA and PCR in BAL fluid samples from both patients, and in CSF from patient 1. The diagnosis was confirmed at autopsy for patient 1 by histopathology and the recovery ofAspergillus fumigatus from the lung and brain. Furthermore, in both patients the course of the antigen titer in the serum during antifungal treatment corresponded with the clinical outcome. These results confirm that the sandwich ELISA appears to be useful for the early diagnosis of invasive aspergillosis. The value of the test for monitoring the response to antifungal treatment remains to be established in prospective trials.     

Invasive pulmonary aspergillosis complicated by complete atrioventricular block and aspergillus pericarditis after induction chemotherapy in a patient with acute lymphoblastic leukemia

A 50-year-old man developed invasive pulmonary aspergillosis after induction chemotherapy for acute lymphoblastic leukemia. He was treated with 5-fluorocytosine and intravenous amphotericin B (AMPH-B). During antifungal therapy, he developed aspergillus pericarditis and complete atrioventricular (A-V) block. The pericardial effusion was decreased and the A-V block was improved after treatment with intravenous and intrapericardial instillation of AMPH-B. Because the patient's renal function deteriorated, AMPH-B was replaced with itraconazol after the latex agglutination (LA) test for an aspergillus-specific antigen showed a negative result. The patient, however, died from disseminated aspergillosis. Aspergillus DNA was detected in retrospective analysis of the serum which had been negative with the LA test. This case indicates that LA is not sufficient for diagnosis and post therapy evaluation of invasive aspergillosis. PCR or other methods should be used concomitantly with LA. Intrapericardial instillation of AMPH-B might be effective for patients with aspergillus pericarditis in whom surgical treatment is not indicated.     

Detection of Aspergillus species in blood and bronchoalveolar lavage samples from immunocompromised patients by means of 2-step polymerase chain reaction: clinical results.

Bronchoalveolar lavage (BAL) samples from 67 patients who were at high risk for invasive aspergillosis were examined using a recently developed 2-step polymerase chain reaction (PCR) that detects 相似文献   

Aspergillus antigen in serum, urine and bronchoalveolar lavage specimens of neutropenic patients in relation to clinical outcome

We have used a new, commercial enzyme-linked immunosorbent assay (ELISA, Platelia Aspergillus) to detect Aspergillus antigen in serum, urine and bronchoalveolar lavage (BAL) samples of 105 haematological patients who received empirical amphotericin B treatment for suspected fungal infection. 14% (60/419) of serum and 5% (18/373) of urine samples were positive. Ten-fold concentration of urine increased the number of positive samples to 31 (8%). The antigen was detected in 5 of 20 BAL samples, but fungal culture was negative in all of them. 22 patients had positive antigen test. Serum was positive in 17, urine in 7 and concentrated urine in 12 patients. Six patients had confirmed invasive aspergillosis. In all these patients, antigen was detected in serum, but urine was positive in only 2 patients. Patients whose antigen test turned negative during the amphotericin B treatment had significantly lower mortality than patients with persistently positive antigen test (2/10 vs. 8/8, p = 0.002). We conclude that Aspergillus galactomannan can be detected by ELISA in serum, urine and BAL samples of haematological patients, but the higher sensitivity of serum testing makes it preferable for screening. Disappearance of the antigen during antifungal therapy seems to correlate with good, and persistence with poor, clinical outcome.     

Serodiagnosis of invasive aspergillosis in patients with hematologic malignancy: validation of the Aspergillus fumigatus antigen radioimmunoassay

Six hundred sixteen sera from 79 hematology patients admitted on 152 occasions were analyzed for validation of the Aspergillus fumigatus antigen radioimmunoassay (RIA). Invasive aspergillosis developed on 24 admissions of 22 patients. Maximal antigenic activity was significantly higher in patients with invasive aspergillosis than in controls (P less than .0005). At the level of antigenic activity selected as the cutoff value, the sensitivity of the RIA was 74%, the specificity 90%, the positive predictive value 82%, and the negative predictive value 85%. Antigen was detected before invasive aspergillosis was suspected during 30% of admissions and before pathological or even preliminary microbiological evidence for disease in 46%. In 17 (77%) of the 22 episodes of pulmonary aspergillosis, the RIA would have been the first positive diagnostic test for aspergillosis or would have confirmed a diagnosis established by other means. Overall, the test would have been of clinical usefulness in diagnosis, management, and prognosis in 80% of 16 fatal cases.     

Invasive aspergillosis in two liver transplant recipients: diagnosis by SeptiFast

Abstract: We report the clinical features, diagnosis, and monitoring findings of invasive aspergillosis (IA) in 2 liver transplant recipients. Blood/serum samples and bronchoalveolar lavage (BAL) fluids were analyzed by a novel commercial polymerase chain reaction (PCR) assay (SeptiFast) and an Aspergillus galactomannan (GM) enzyme-linked immunoassay (EIA). The diagnosis of IA could be performed in <6 h with the detection of Aspergillus fumigatus DNA in blood and BAL fluid. High GM values (mean: 9.1, range: 7.3–10.8) in serum and BAL fluid confirmed the SeptiFast result. Follow-up of the SeptiFast findings and GM index correlated with the clinical course. The molecular detection of A. fumigatus -specific DNA and GM test in blood/serum and BAL samples appears to be a useful tool for prompt diagnosis of IA. Further prospective clinical trials are necessary to evaluate the accuracy of SeptiFast and the GM test in diagnosing IA.     

Antigen detection in the diagnosis of invasive aspergillosis. Utility in controlled, blinded trials

Two blinded, controlled trials were done to evaluate the usefulness of fungal antigen detection for the diagnosis of invasive aspergillosis. Detection of Aspergillus fumigatus carbohydrate by radioimmunoassay was compared with antibody detection by an enzyme-linked immunosorbent assay and with diagnostic microbiologic and histopathologic procedures. In the first trial, antigenemia was detected in 4 of 6 leukemic patients with invasive pulmonary aspergillosis, but not in 8 acute leukemic controls or in 24 normal controls. Fungal antigenemia persisted for 8 to 75 days in 4 patients and seroconversion occurred at the onset of pulmonary infiltrates in 3. Antibody to A. fumigatus was detected in 2 of the 6 patients with aspergillosis, but also in 2 leukemic controls and 6 normal controls. Aspergillus species were identified in four of seven bronchoscopies done in 5 patients with invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis. Prospective nasal cultures grew Aspergillus species in 4 of the 6 patients with invasive aspergillosis, but in only 1 patient was this information available before a histologic diagnosis was made. In a second trial, antigenemia was detected in 2 patients with invasive aspergillosis, and in 1 with possible invasive aspergillosis, but not in 9 controls. This study indicates that the radioimmunoassay for A. fumigatus antigen is a highly specific and moderately sensitive serodiagnostic test for invasive pulmonary aspergillosis.     

Invasive pulmonary aspergillosis diagnosed early by polymerase chain reaction assay.

We compared the usefulness of a polymerase chain reaction (PCR) assay for the early diagnosis of invasive pulmonary aspergillosis with the serodiagnosis of sufficient concentrations of galactomannan using the same serum samples. A patient was treated with prednisolone for the management of hepatitis. Computed tomography (CT) scan of the chest showed the nodular shadow with a cavity containing a clear fungus ball. DNA of Aspergillus spp. from a serum sample was detected and using the same serum sample, both latex agglutination and sandwich enzyme-linked immunosorbent assay (ELISA) of galactomannan were negative. PCR assay provides an early diagnosis of invasive pulmonary aspergillosis compared with ELISA of galactomannan.     

Screening for Aspergillus spp. using polymerase chain reaction of whole blood samples from patients with haematological malignancies

Sensitive screening for Aspergillus spp. using polymerase chain reaction (PCR) of whole blood samples in patients with haematological disorders has not been performed to date. In a 2-year study, 121 patients admitted to the University Hospital of Innsbruck for cancer chemotherapy without clinical signs of fungal infection were prospectively screened for Aspergillus spp. In 28 out of 121 (23%) patients, Aspergillus DNAaemia was detected. Of these patients, 16 (57%) were positive only once for Aspergillus DNA, but positivity was never associated with invasive aspergillosis. PCR positive episodes were short and resolved without antifungal treatment. Five patients (18%) had intermittent PCR positive results. Seven (25%) patients presented at least two consecutive positive PCR results; one of these patients developed invasive aspergillosis and another two were strongly suspected as having aspergillosis. Based on the criteria of the European Organization for Research and Treatment of Cancer case definitions, sensitivity and specificity of serial PCR monitoring were 75% and 96%. Positive PCR results became negative shortly after commencement of antifungal treatment, but the changes did not correlate with clinical responsiveness to treatment in three patients. Our results indicate the potential usefulness of PCR for screening for Aspergillus spp. in patients at risk, but without antifungal treatment.     

Oxalic acid level in bronchoalveolar lavage fluid from patients with invasive pulmonary aspergillosis

Oxalic acid is a fermentation product of Aspergillus. We have measured the oxalic acid level in bronchoalveolar lavage fluids recovered from immunocompromised patients with and without invasive pulmonary aspergillosis. These levels were significantly higher in patients with invasive aspergillosis than in patients with pneumonitis of other causes. Thus, the determination of oxalic acid in bronchoalveolar lavage could be a presumptive argument for invasive aspergillosis until positive fungal cultures or histologic diagnosis; its potential value in monitoring the course of invasive pulmonary aspergillosis, particularly under treatment, has to be confirmed in more patients.     

Multiple Brain Abscesses Due to Aspergillus Fumigatus in a Patient With Liver Cirrhosis: A Case Report

Invasive cerebral aspergillosis always developed in immunocompromised host. Early diagnosis may save life in this critical condition; however, it is difficult to reach. Herein, we presented an unusual case of invasive cerebral aspergillosis in a cirrhotic patient.A 47-year-old man presented with progressive deterioration of consciousness for three days. The patient had a history of alcoholic liver cirrhosis, Child-Pugh class C. Magnetic resonance imaging (MRI) of brain showed multi-focal parenchymal lesions, which was consistent with multiple brain abscesses. The diagnosis of invasive cerebral aspergillosis was made by molecular based laboratory methods including Aspergillus galactomannan antigen assay and oligonucleotide array. Despite treatment with the antifungal agent, Amphotericin B, the patient died at the ninth day of hospitalization.Our findings suggest that liver cirrhosis can be one of risk factors of invasive cerebral aspergillosis, and support the diagnosing usefulness of MRI, Aspergillus galactomannan antigen assay, and oligonucleotide array.     

Clinical evaluation of a polymerase chain reaction assay to detect Aspergillus species in bronchoalveolar lavage samples of neutropenic patients

The increasing incidence of invasive aspergillosis, a life-threatening infection in immunocompromised patients, emphasizes the need to improve the currently limited diagnostic tools. Using a recently developed two-step polymerase chain reaction (PCR) assay to detect 10 fg of Aspergillus DNA, corresponding to 1-5 colony-forming units (CFU)/ml of spiked samples in vitro, we prospectively examined 197 bronchoalveolar lavage (BAL) samples from 176 subjects, including 141 neutropenic, febrile patients with lung infiltrates, at risk for invasive fungal disease. Underlying diseases of these patients were haematological malignancies; 93 patients suffered from acute leukaemias. Thirty-one of these immunocompromised patients (17.6%) were PCR positive, correlating with positive BAL culture, positive histology from lung surgery or from autopsy, positive computerized tomography scans or positive galactomannan enzyme-linked immunosorbent assay. Six patients (4.3%) of this group had positive PCR results without any correlation to clinical or other diagnostic data, probably owing to contamination of the samples by ubiquitous Aspergillus spores. The samples of two patients (1.4%) with a subsequent histologically proven mould infection were PCR negative. All 102 immunocompromised patients (72.3%) with a negative PCR showed no evidence of invasive fungal disease. From 35 patients without immunodeficiency, four (11.4%) showed positive results, without evidence of invasive or non-invasive pulmonary aspergillosis. In this haematological population, the sensitivity and specificity values of the test reached 93.9% and 94.4%, the positive predictive value 83.8%, the negative predictive value 98.1%. Our data support the considerable clinical value of this PCR assay for confirming and improving diagnosis of pulmonary aspergillosis in high-risk patients.     

What is the clinical significance of positive blood cultures with Aspergillus sp in hematopoietic stem cell transplant recipients? A 23 year experience

Hematopoietic stem cell (HSC) transplantation is the most frequent underlying predisposing condition to invasive aspergillosis. However, the significance of positive blood culture with Aspergillus sp in this particular population remains uncertain. We retrospectively reviewed all blood cultures performed in 1453 patients who received HSC transplant at our institution between 1980 and 2002. We identified 19 patients with positive blood cultures with Aspergillus sp. Only one of these patients had clinical, histologic or microbiologic evidence of invasive aspergillosis. Thus, even in a population at highest risk for invasive aspergillosis, positive blood cultures with Aspergillus sp remain unusual, and cannot be readily associated with invasive aspergillosis. A case by case assessment by treating physicians of the clinical and radiologic parameters should be systematically made to establish the significance of aspergillemia. Single bottle positivity, obtained with the lysis-centrifugation blood culture system, is a common indicator of pseudoaspergillemia.     

Infection-associated hemophagocytic syndrome among patients with dengue shock syndrome and invasive aspergillosis: a case series and review of the literature

The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis.     

Polymerase chain reaction detection of aspergillus DNA in experimental models of invasive aspergillosis

To determine the sensitivity of polymerase chain reaction (PCR) assays for the diagnosis of invasive aspergillosis, results of quantitative culture, PCR-ELISA, and a quantitative LightCycler assay (Roche Diagnostics) of blood and organ specimens of experimentally infected mice and rabbits were compared. By PCR-ELISA, 297 of 379 murine lung specimens were positive, but only 235 of 379 were culture positive. Whereas 64 culture-negative lungs were positive by PCR, Aspergillus was grown from only 2 PCR-negative samples. The PCR assay was 19.4 times more sensitive than culture. None of the 68 blood cultures from mice and rabbits were positive for Aspergillus fumigatus, whereas PCR detected Aspergillus DNA in 17 of 68 blood samples. Quantitative PCR analysis of blood samples showed a fungus load of 10(1)-10(2) cfu/mL of blood. The data confirm the superior sensitivity of PCR for the diagnosis of experimental Aspergillus infections.     

Comparison of serial diagnostic tests in a patient with invasive aspergillosis

Studies on a liver transplant recipient with fatal disseminated aspergillosis are described. The concentration of IgG antibodies to Aspergillus rose sharply with the onset of fever and changes in the chest X-ray, reaching a peak on day 10. Thereafter, antibody concentrations fell and were within the normal range by day 21, when Aspergillus was first isolated from an endotracheal aspirate and one day before death. The fall in antibodies preceded a rise in circulating immune complexes but Aspergillus antigens were not detected in the serum. Serial quantitative assay for antibodies to Aspergillus may be more appropriate than culture or attempts to detect antigen in the early diagnosis of invasive aspergillosis in immunocompromised patients.     

Combined real‐time PCR and galactomannan surveillance improves diagnosis of invasive aspergillosis in high risk patients with haematological malignancies

Invasive aspergillosis (IA) is a leading complication of intensive treatment for haematological malignancies. Earlier diagnosis should facilitate effective antifungal therapy and prevent progression to invasive disease, which is often lethal. Polymerase chain reaction (PCR) assays, targeting the 28S and ITS ribosomal gene regions respectively, were evaluated for early detection of Aspergillus DNA and for diagnostic utility in patients receiving treatment in two busy haematopoietic stem cell transplant centres. Patients undergoing intensive chemotherapy, autologous or allogeneic transplant were eligible for inclusion in the study. EDTA blood and serum samples for circulating Aspergillus biomarkers, including galactomannan (GM), were collected twice‐weekly on a prospective basis from all study patients who were categorized according to international consensus criteria for defining invasive fungal disease (IFD). Of 278 patients recruited there were 44 probable IA cases and only one proven case. Moderate sensitivity and specificity, poor positive predictive value (50–80%), but good negative predictive value (>80–90%) were common to both PCR assays. Overall biomarker performance could be improved by combining positive results of either PCR assay with GM taken within a 12‐d period. The addition of PCR to GM monitoring in high‐risk patients with haematological malignancies provides greater diagnostic accuracy in invasive aspergillosis.     

Aspergillus antigen detection in bronchoalveolar lavage fluid from patients with invasive aspergillosis and aspergillomas

Improved diagnostic techniques have been needed for pulmonary aspergillosis, a common opportunistic fungal infection with a high mortality rate. Radioimmunoassay was used in this study to detect Aspergillus antigen in bronchoalveolar lavage fluid. In four patients with invasive aspergillosis or aspergillomas, Aspergillus antigen was detected in bronchoalveolar lavage fluid. In two patients, results of fungal cultures were negative or delayed. The specificity of antigen detection in bronchoalveolar lavage fluid was 91 percent in 35 control patients with a variety of pulmonary disorders. The technique of radioimmunoassay detection of microbial antigen in bronchoalveolar lavage fluid appears promising for the diagnosis of aspergillosis.     

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation

We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest X-rays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT.