Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients

Abstract

Summary:The performance of two Aspergillus antigenemia systems, the sandwich enzyme-linked immunosorbent assay (ELISA), Platelia Aspergillus test, and the latex agglutination (LA), Pastorex Aspergillus test, in the diagnosis of invasive aspergillosis were compared by testing 364 serum samples from 22 bone marrow transplant (BMT) recipients. Sensitivity and specificity for the ELISA test were 60% and 82% respectively, vs 40% and 94% for the LA test. In the two patients found positive with both methods, the ELISA test became positive earlier than the LA test or remained positive after the LA test had become negative. These results encourage further evaluation of the Platelia Aspergillus test, to assess its role in the management of invasive aspergillosis in BMT patients. Keywords: invasive aspergillosis; galactomannan; antigen detectionIn recent years, considerable progress has been achieved in the management of bacterial and viral infections in bone marrow transplant (BMT) recipients. By contrast, little progress has been made in the management of fungal infections, especially aspergillosis. 1 This is probably due both to the frequent impossibility of obtaining a reliable diagnosis of aspergillosis at an early stage of the disease and to the relatively poor efficacy of the presently available antifungal armamentarium. As a result, indirect diagnostic methods have received considerable attention in order to overcome these limitations. So far, no method has proven sufficiently sensitive and specific to allow a diagnosis of aspergillosis at an early stage. 2 However, several authors have pointed out that this might be due, at least in part, to how the tests have been used in clinical practice and to the criteria adopted by clinicians in the interpretation of results. 2 A precommercial version of a sandwich enzymelinked immunosorbent assay (ELISA) for detection of cirCorrespondence: C Viscoli, Unità di Malattie dell'Ospite Compromesso, Istituto Nazionale per la Ricerca sul Cancro-Genova, Largo Rosanna Benzi, 10-16132 Genova, Italy Received 22 May 1997; accepted 17 December 1997 culating galactomannan, a polysaccharide component of the fungal cell wall, has been recently described. 3 The test employs the same monoclonal antibody (MoAb) EB-A2 used in the latex agglutination (LA) test (Pastorex Aspergillus; Sanofi Diagnostic, Pasteur, France), but the ELISA system detects galactomannan in serum at a concentration of 1 ng/ml, whereas the LA test has a 15 ng/ml threshold.We have compared sensitivity and specificity of the new ELISA detection system with that of the LA system in the diagnosis of invasive aspergillosis in BMT patients. With the aim of improving the sensitivity and the specificity of the tests, we prospectively collected consecutive serum samples in patients at high risk of aspergillosis, regardless of the presence or absence of clinical symptoms. Patients and methodsDuring a 6-month period, 22 allogeneic BMTs from matched donors, followed at the Bone Marrow Transplant Unit of the Haematology Department of S...

Diagnostic aspects of invasive Aspergillus infections in allogeneic BMT recipients

“…10,11 Neither antigen tests [12][13][14][15][16] nor culture or microscopy of sputum 17,18 were used for the diagnostics of Aspergillus infections during the study period.…”

Aspergillose - Stand des Wissens zu Diagnose, Therapie, Umweltbedingungen - Ein Assessment. Endbericht

“…Dadurch können noch Galaktomannankonzentrationen in der Größenordnung von 1-5 ng/ml nachgewiesen werden (Stynen et al 1995). Der Sandwich-ELISA wird häufig in einem früheren Stadium der Erkrankung als der Latex-Agglutinationstest positiv (Sulahian et al 1996, Machetti et al 1998; in manchen Fällen konnte damit Galaktomannan im Serum bereits vor Auftreten klinischer und radiologischer Zeichen der Infektion nachgewiesen werden (Rohrlich et al 1996. Im Tiermodell konnte gezeigt werden, dass die Galaktomannankonzentration im Serum auch mit der "Pilzlast" im Lungengewebe korreliert (Andriole 1993, Stynen et al 1995 (Sulahian et.…”

Diagnosis of Invasive Fungal Infections – Current Limitations of Classical and New Diagnostic Methods

“…83,93 While a positive test in a lung transplant recipient with a clinical illness compatible with invasive aspergillosis may be considered highly suggestive of this infection, a negative test does not rule out aspergillosis. 64 The sensitivity of the test has been typically lower in non-neutropaenic patients (15% to 30%) and may be related to lower circulating galactomannan levels.…”

“…77,78 Studies evaluating the role of galactomannan assay in the diagnosis of invasive aspergillosis have largely been conducted with leukaemia patients or haematopoietic stem-cell transplantation (HSCT) recipients. 77,78,[82][83][84][85][86][87][88][89] After initial clinical studies suggested a high sensitivity and specificity, 73,76,78,79,90,91 further studies revealed high rates of false-positive results among paediatric patients and neonates. 81,92,93 In one study, rates of false-positive results as high as 83% were observed 93 that may be related to cross-reactivity with Bifidobacterium bifidum, found in large inocula in the guts of breast-and formula-fed infants.…”