Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis

Rohrlich, Pierre‐Simon; Sarfati, J.; Mariani, Patricia; Duval, Michel; Carol, Agnès; Saint-Martin, Catherine; Bingen, Edouard; Latgé, Jean‐Paul; Vilmer, E

doi:10.1097/00006454-199603000-00011

Cited by 137 publications

(97 citation statements)

References 21 publications

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“…Early detection of suspected lesions on CT might have resulted in an earlier start of antifungal treatment. As antifungal treatment has been shown to suppress circulating GM levels (Rohrlich et al, 1996) and we observed that GM-positive serum often became negative as soon as antifungals were started, the early start of treatment may have prevented detectable antigenaemia in a number of patients. With a PPV of 73% and a NPV of 82%, GM detection in serum may still have some additional value for diagnosing IPA in the individual patient in our clinical setting.…”

Section: Discussionmentioning

confidence: 76%

“…In our study, CT's were performed systematically and early in all patients with IPA, with a mean of 5AE3 CT's per patient, and starting within 4 d after onset of fever. GM detection for diagnosing IPA has been investigated in several studies (Dupont et al, 1987;Verweij et al, 1995a,b;Rohrlich et al, 1996;Maertens et al, 1999Maertens et al, , 2001Salonen et al, 2000;Siemann & Koch-Dorfler 2001;Sulahian et al, 2001). The antigen can be detected by a latex agglutination test or by a sandwich ELISA, the latter of which has shown the higher sensitivity (Verweij et al, 1995b;Sulahian et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

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Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

Becker¹,

Lugtenburg²,

Cornelissen³

et al. 2003

Br J Haematol

189

123

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Summary. We determined the value of galactomannan (GM) detection in computerized tomography (CT)-based broncho-alveolar lavage (BAL) fluid and serum for the diagnosis of invasive pulmonary aspergillosis (IPA) in haemato-oncological patients with neutropenia. CT of the thorax and BAL were performed systematically at predefined clinical indications. GM was determined by sandwich enzyme-linked immunosorbent assay; the clinicians were unaware of the results. Of 160 patients, 17 patients (10AE6%) presented with proven, probable or suspected IPA. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of GM detection in CT-based BAL fluid were all 100%. For GM detection in serially sampled serum, the sensitivity was 47%, the specificity 93%, the PPV 73% and the NPV 82%. A non-blinded follow-up study was performed to validate these results. In this study, 22 of 198 patients (11AE1%) presented with IPA, and the sensitivity, specificity, PPV and NPV of GM detection in CT-based BAL fluid were 85%, 100%, 100% and 88% respectively. None of BAL fluids obtained after antifungal treatment of 3 d or more were positive. These results indicate that, when CT is used systematically and at an early stage, GM detection in CT-based BAL fluid has a high PPV for diagnosing IPA early in untreated patients.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

Becker¹,

Lugtenburg²,

Cornelissen³

et al. 2003

Br J Haematol

189

123

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“…The ELISA test using the MoAb EB-A2 has been investigated in recent years, 3,6,7,11,30 and two previous studies which compared the ELISA and the LA tests using the MoAb EB-A2, 6,7 showed the ELISA to be more sensitive (82.5-90% vs 27.5-70%), but less specific (84-81% vs 86-100%) than the LA test. Two different hypotheses might be advanced as possible causes of the lower specificity of the ELISA test: (1) a transient antigenemia induced by immunosuppressive therapy; or (2) a cross-reactivity with unidentified components in serum.…”

Section: Csamentioning

confidence: 99%

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

Machetti¹,

Feasi

Mordini

et al. 1998

Bone Marrow Transplant

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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...

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“…Galactomannan detection by the Platelia Aspergillus enzyme immunoassay (EIA) has proven to be a potentially promising tool for the early diagnosis of invasive aspergillosis. False-positive test results, however, have been reported for ϳ6 to 8% of neutropenic and hematopoietic stem cell transplant recipients, for 13% of liver transplant recipients, and for 20% of lung transplant recipients (4,5,9,10,12). Cytotoxic chemotherapeutic agents, autoreactive antibodies or paraproteins, or yet-unidentified serum components may account for the false-positive tests.…”

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confidence: 99%

Reactivity of Platelia Aspergillus Galactomannan Antigen with Piperacillin-Tazobactam: Clinical Implications Based on Achievable Concentrations in Serum

Singh

Obman

Husain

et al. 2004

Antimicrob Agents Chemother

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The possible reactivities of commonly used antibiotics of fungal, nonfungal, and nonmicrobial or synthetic sources with the Platelia Aspergillus galactomannan assay were assessed. For drugs that tested positive, the minimal concentration of the antibiotic in serum that yielded a positive test (index, >0.5) was determined. At undiluted concentrations, piperacillin and multiple lots of piperacillin-tazobactam tested positive, whereas amoxicillin, ampicillin-sulbactam, nafcillin, cefazolin, ceftazidime, erythromycin, gentamicin, and levofloxacin tested negative. All three lots of piperacillin-tazobactam and all bags within each lot tested positive, with a mean index value of 5.168. At achievable concentrations in serum, however, only one of three lots of piperacillin-tazobactam yielded a positive test. Concentrations of 75, 150, and 300 g/ml of serum tested positive with the Platelia Aspergillus enzyme immunoassay, whereas lower concentrations, mimicking the trough levels, tested negative. Thus, while achievable serum piperacillin-tazobactam concentrations may potentially result in a positive test for galactomannan, the timing of the collection of serum samples from patients may influence the test results, with reactivity being less likely in samples collected at trough levels or prior to the administration of a dose of the antibiotic.Galactomannan is a polysaccharide component of the cell wall of Aspergillus spp. that is released into the circulation in varying amounts during invasive aspergillosis (3, 7, 15). Galactomannan detection by the Platelia Aspergillus enzyme immunoassay (EIA) has proven to be a potentially promising tool for the early diagnosis of invasive aspergillosis. False-positive test results, however, have been reported for ϳ6 to 8% of neutropenic and hematopoietic stem cell transplant recipients, for 13% of liver transplant recipients, and for 20% of lung transplant recipients (4,5,9,10,12). Cytotoxic chemotherapeutic agents, autoreactive antibodies or paraproteins, or yet-unidentified serum components may account for the false-positive tests. The high rate of false EIA reactivity in neonates may result from cross-reactivity with the lipoteichoic acid of Bifidobacterium bifidum in the gut (P. E. Verweij, R. R. Klont, A. Warris, H. J. M. Op Den Camp, and M. A. S. MenninkKersten, Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. M-1027, 2003). Reactivity with the galactomannan of Paecilomyces and Penicillium spp. has been noted previously (13).In 1997, Ansorg et al. first reported that drugs of fungal origin, such as antibiotics and uricase, might be associated with false-positive test results (1a). Galactomannan was detected in a batch of ampicillin-sulbactam and in two batches of piperacillin (1a). Of our liver transplant recipients with false-positive test results, 55% had received these antibiotics (5). Recent reports from Europe have documented false-positive tests related to the use of piperacillin-tazobactam in patients with hematologic malignancy or those who had undergone b...

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Prospective sandwich enzyme-linked immunosorbent assay for serum galactomannan: early predictive value and clinical use in invasive aspergillosis

Cited by 137 publications

References 21 publications

Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

Galactomannan detection in computerized tomography‐based broncho‐alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis

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

Reactivity of Platelia Aspergillus Galactomannan Antigen with Piperacillin-Tazobactam: Clinical Implications Based on Achievable Concentrations in Serum

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