Value of antigen detection using an enzyme immunoassay in the diagnosis and prediction of invasive aspergillosis in two adult and pediatric hematology units during a 4-year prospective study. Comparison of non-culture-based methods for detection of systemic fungal infections, with an emphasis on invasive Candida infections. Contribution of (1->3)-beta-D-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. Aspergillus antigen and PCR assays in bone marrow transplanted children. Application of nucleic acid sequence-based amplification for diagnosis of and monitoring the clinical course of invasive aspergillosis in patients with hematologic diseases. Prospective assessment of Platelia Aspergillus galactomannan antigen for the diagnosis of invasive aspergillosis in lung transplant recipients. Treatment with piperacillin-tazobactam and false-positive Aspergillus galactomannan antigen test results for patients with hematological malignancies. Comparison of an enzyme immunoassay and latex agglutination test for detection of galactomannan in the diagnosis of invasive aspergillosis. [Usefulness of galactomannan detection in the diagnosis and follow-up of hematological patients with invasive aspergillosis]. Usefulness of sequential Aspergillus galactomannan antigen detection combined with early radiologic evaluation for diagnosis of invasive pulmonary aspergillosis in patients undergoing allogeneic stem cell transplantation. Serum Aspergillus galactomannan antigen testing by sandwich ELISA: practical use in neutropenic patients. Detection of galactomannan antigenemia by enzyme immunoassay for the diagnosis of invasive aspergillosis: variables that affect performance. Prospective clinical evaluation of a LightCycler-mediated polymerase chain reaction assay, a nested-PCR assay and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients. Comparison of an enzyme immunoassay and a latex agglutination system for the diagnosis of invasive aspergillosis in bone marrow transplant recipients. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Comparison of serum galactomannan antigen detection and competitive polymerase chain reaction for diagnosing invasive aspergillosis. Development of a serum-based Taqman real-time PCR assay for diagnosis of invasive aspergillosis. [Value of Aspergillus galactomannan antigen detection in the diagnosis and follow-up of invasive aspergillosis in hematological patients]. Poor performance of galactomannan and mannan sandwich enzyme-linked immunosorbent assays in the diagnosis of invasive fungal infection. Prospective comparison of the diagnostic potential of real-time PCR, double-sandwich enzyme-linked immunosorbent assay for galactomannan, and a (1-->3)-beta-D-glucan test in weekly screening for invasive aspergillosis in patients with hematological disorders. Galactomannan antigenemia for the diagnosis of invasive aspergillosis in neutropenic patients with hematological disorders. Prevention and monitoring of invasive fungal infections in pediatric patients with cancer and hematologic disorders. Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients. Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis. Prospective evaluation of a polymerase chain reaction-ELISA targeted to Aspergillus fumigatus and Aspergillus flavus for the early diagnosis of invasive aspergillosis in patients with hematological malignancies. Comparison of antigen detection and PCR assay using bronchoalveolar lavage fluid for diagnosing invasive pulmonary aspergillosis in patients receiving treatment for hematological malignancies. Galactomannan antigen enzyme-linked immunosorbent assay for diagnosis of invasive aspergillosis after hematopoietic stem cell transplantation. The contribution of galactomannan detection in the diagnosis of invasive aspergillosis in bone marrow transplant recipients. Antifungal therapy decreases sensitivity of the Aspergillus galactomannan enzyme immunoassay. Comparison of PCR-ELISA and galactomannan detection for the diagnosis of invasive aspergillosis. Aspergillus antigen testing in bone marrow transplant recipients. Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. Optimization of the cutoff value for the Aspergillus double-sandwich enzyme immunoassay. Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients. Assessment of Platelia Aspergillus enzyme immunoassay for the diagnosis of invasive aspergillosis. Aspergillus antigenemia sandwich-enzyme immunoassay test as a serodiagnostic method for invasive aspergillosis in liver transplant recipients. Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies. Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies. Detection of Aspergillus galactomannan by enzyme immunoabsorbent assay in recipients of allogeneic hematopoietic stem cell transplantation: a prospective study.
Invasive aspergillosis (IA) is a well recognized, life-threatening infection in neutropenic patients and stem cell transplantation recipients. Early diagnosis is important to achieve the best outcome for these patients; however, definite proof often is difficult to obtain due to counterindicated invasive procedures.
                This study evaluated the specificity and sensitivity of the detection of galactomannan (GM) for the diagnostic and prediction of IA in 347 children from the Pediatric Hematology Service and 450 patients from the Bone Marrow Transplantation Unit at the Hôpital Saint-Louis in Paris. Serial screening of Aspergillus GM circulating antigen was evaluated using a double sandwich ELISA assay (Platelia Aspergillus) on 6209 sera. Among the patients studied, 53 presented with confirmed IA (n = 27 patients) or probable IA (n = 26 patients).
                Antigen was detected on at least two sequential sera in 48 of 53 patients, with a sensitivity of 90.6%. GM antigenemia was detected before the onset of radiologic signs in 31 of 48 patients (64.6%), with a mean of -8.4 days, and before clinical symptoms in 18 of 48 patients (39.6%), with a mean of -6.9 days. In patients without IA, 44 of 744 had positive antigenemia, resulting in a specificity of 94%. False positive results could not be related to the presence of a concurrent mucositis.
                This large, prospective study allowed the authors to define better the conditions for the use of GM immunocapture ELISA in surveying patients who are at high risk for IA. The presence of antigen has a good diagnostic value mainly when there is an increase in the titer on two consecutive sera samples. A repeated negative result is a strong argument against the diagnosis of IA; however, an awareness of the possibility of unexplained false negative results is important. The accepted limitations associated with classic culture techniques for the diagnosis of invasive fungal infections have lead to the emergence of many non-culture-based methods. With superior sensitivities and quicker turnaround times, non-culture-based methods may aid the diagnosis of invasive fungal infections. In this review of the diagnostic service, we assessed the performances of two antigen detection techniques (enzyme-linked immunosorbent assay [ELISA] and latex agglutination) with a molecular method for the detection of invasive Candida infection and invasive aspergillosis. The specificities for all three assays were high (> or = 97%), although the Candida PCR method had enhanced sensitivity over both ELISA and latex agglutination with values of 95%, 75%, and 25%, respectively. However, calculating significant sensitivity values for the Aspergillus detection methods was not feasible due to a low number of proven/probable cases. Despite enhanced sensitivity, the PCR method failed to detect nucleic acid in a probable case of invasive Candida infection that was detected by ELISA. In conclusion, both PCR and ELISA techniques should be used in unison to aid the detection of invasive fungal infections. Two noninvasive diagnostic tests, (1-->3)-beta-D-glucan (BG) (Glucatell) and galactomannan (GM) (Platelia Aspergillus), were used retrospectively in a twice-weekly screening for the diagnosis of invasive aspergillosis (IA) in 40 treatment episodes (one hospital visit per patient) in 40 neutropenic adult patients at high risk for IA. Five proven IA cases, three probable IA cases, and three possible IA cases were diagnosed. Diagnostic levels of both BG and GM were detected in 100% of patients with proven IA cases and in 66% of patients with probable IA cases. The kinetics of both markers in patients with IA were similar. The sensitivity, specificity, and positive and negative predictive values for GM and BG were identical, namely, 87.5, 89.6, 70, and 96.3%, respectively. False-positive reactions occurred at a rate of 10.3% in both tests, but the patients showing false-positive results were different in each test. Both tests anticipated the clinical diagnosis, computed tomography abnormalities, and the initiation of antifungal therapy in most patients, but BG tended to become positive earlier than GM. A combination of the two tests improved the specificity (to 100%) and positive predictive value (to 100%) of each individual test without affecting the sensitivity and negative predictive values. In conclusion, BG and GM detection are useful tests for the diagnosis of IA in high-risk hematological patients, but a combination of the two tests was very useful to identify false-positive reactions by each test. Screening for Aspergillus antigen and DNA has been introduced for the early diagnosis of invasive aspergillosis (IA) in adults, but data in children at risk are scarce. Seventeen 1-108 month-old children were screened for Aspergillus antigenaemia by a commercial assay before and after bone marrow transplantation (BMT). Seventy-one serum samples were examined retrospectively by a novel nested PCR assay. Results of both assays were correlated with clinical, radiological and microbiological findings used for the definition of invasive aspergillosis by the European Organisation for Research and Treatment of Cancer (EORTC). Three cases of probable or possible IA were defined, and in 14 children invasive aspergillosis was ruled out. In 10 children, Aspergillus antigen was detected in at least two consecutive serum samples, a microbiological EORTC criteria of IA. Specific DNA was detected in 8 antigen-positive and 2 antigen-negative sera. A positive predictive value of 20% was calculated for both assays. Hence, a high rate of positive results of antigen Elisa and PCR assays in BMT children are due to transient antigenaemia and fungaemia without clinical relevance. According to our data, prospective studies in well defined pediatric patients are urgently needed to determine the value of serial Aspergillus PCR assays for the early diagnosis of invasive aspergillosis in children at risk. We evaluated nucleic acid sequence-based amplification (NASBA) and a galactomannan enzyme immunosorbent assay (GM-EIA) for the diagnosis of invasive aspergillosis (IA) in neutropenic febrile patients and for monitoring of its clinical course and outcome. Blood samples were collected twice per week from 128 patients with hematologic diseases during periods of neutropenic fever after undergoing chemotherapy or hematopoietic stem cell transplantation. A total of 448 blood samples were tested.
                There were 14 patients with IA (2 patients with proven IA and 12 with probable IA). The median index of the initial NASBA in the IA group was more than 10-fold higher than that in the non-IA group. Galactomannan antigenemia (index, >0.5) was detected with a sensitivity of 86%. In receiver-operator characteristic analysis, the cutoff index of NASBA for the presumptive diagnosis of IA was determined to be 5.0. Combination of these 2 parameters (either a GM-EIA index of >or=0.5 or a NASBA index of >or=5.0) improved the sensitivity of diagnosis to 100%. There was a close relationship between patient outcome and the kinetics of NASBA values: failure of negative conversion during treatment resulted in death in almost all cases.
                If either GM-EIA or NASBA results suggest IA, the diagnostic yield for IA could be improved, and NASBA could be a useful marker for predicting the clinical course and outcome of treatment. The clinical utility of Platelia trade mark Aspergillus galactomannan antigen for the early diagnosis of invasive aspergillosis was prospectively assessed in 70 consecutive lung transplant recipients. Sera were collected twice weekly and tested for galactomannan. Invasive aspergillosis was documented in 17.1% (12/70) of the patients. Using the generalized estimating equation model, at the cutoff value of >or= 0.5, the sensitivity of the test was 30%, specificity 93% with positive and negative likelihood ratios of 4.2 and 0.75, respectively. Increasing the cutoff value to >or= 0.66 yielded a sensitivity of 30%, specificity of 95%, and positive and negative likelihood ratios of 5.5 and 0.74. A total of 14 patients had false-positive tests, including nine who had cystic fibrosis or chronic obstructive pulmonary disease. False-positive tests occurred within 3 days of transplantation in 43% (6/14) of the patients, and within 7 days in 64% (9/14). Thus, the test demonstrated excellent specificity, but a low sensitivity for the diagnosis of aspergillosis in this patient population. Patients with cystic fibrosis or chronic obstructive pulmonary disease may transiently have a positive test in the early post-transplant period. We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 through June 2003, 42 (19.3%) had > or =1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay. Aspergillus antigenemia was followed up in 215 consecutively observed bone marrow transplant (BMT) patients over a period of two years, using both a latex agglutination test and a sandwich immunocapture enzyme immunoassay (EIA) with a rat antigalactomannan monoclonal antibody as capture and detector antibody. For each patient, sequential sera (3 to 20) were obtained before and after BMT. No positivity was observed before BMT. After BMT, the EIA and latex agglutination test were positive in 19 and 4 patients respectively of 25 patients with confirmed aspergillosis and 14 and 7 of 15 patients with probable aspergillosis. In 19 of 25 patients with confirmed aspergillosis and 9 of 15 patients with probable aspergillosis, the EIA was more sensitive and detected infection earlier than the latex test. In all positive cases, antigenemia rapidly increased in sequential samples and remained strongly positive. In 31 of 169 (19%) BMT patients without clinical signs of aspergillosis, the EIA was occasionally positive in samples taken within the first month after BMT, giving a specificity of 81% in these patients. In non-BMT patients suffering from other diseases (n = 77), the specificity was 98.7%. The overall positive and negative predictive values for the EIA were 54% and 95% respectively. These results favour the use of EIA for early diagnosis and monitoring of aspergillosis in BMT patients, although the predictive value of transient positivity remains to be ascertained. The usefulness of galactomannan detection using the Platelia Aspergillus test for the diagnosis of invasive aspergillosis was studied in 849 sera from 54 hematological patients with prolonged neutropenia, which were classified according to the risk for invasive aspergillosis. Three patients developed a proven invasive aspergillosis, one a probable invasive aspergillosis and 17 patients a possible invasive aspergillosis. Thirty-three patients showed no evidence of invasive aspergillosis. All patients with proven invasive aspergillosis had a high risk for invasive aspergillosis, while the one having probable invasive aspergillosis had intermediate risk. Detection of galactomannan in this study showed a sensitivity of 66.7% for patients with proven invasive aspergillosis and 50% for patients with proven and probable invasive aspergillosis. The specificity was 98% or higher in all groups studied. The predictive positive and negative values for patients with proven invasive aspergillosis were 66.7% and 98%, respectively. A rise in the concentration of galactomannan was observed in patients who failed to respond to the antifungal treatment. Galactomannan antigenemia preceded post-mortem histological diagnosis of invasive aspergillosis in two patients by 17 and 81 days, respectively. In conclusion, detection of galactomannan by the Platelia Aspergillus test allows for a specific and relatively sensitive diagnosis of invasive aspergillosis in hematological patients with a high and intermediate risk for invasive aspergillosis. Early diagnosis of invasive pulmonary aspergillosis (IPA) is important as prompt treatment with antifungal drugs may increase patient survival. Our study investigated the efficiency of routine testing of the Aspergillus galactomannan antigen (AGA) test in combination with chest CT scans for IPA diagnosis.
                From February 2002 to June 2004, 74 hemato-oncologic patients undergoing allogeneic stem cell transplantation were prospectively studied with serum AGA twice weekly from admission until death or discharge and weekly afterward when possible. Chest CT scans were performed when fever of unknown origin had lasted beyond 3 days of antibacterial therapy.
                Seven patients were classified with possible IPA and two patients, proven IPA. Fourteen patients showed positive results for AGA (OD index>or=1.0 on two subsequent sera). The sensitivity and specificity of the test were 100% and 93%, respectively; the positive and negative predictive values were 64% and 100%, respectively. All patients with possible/proven IPA showed abnormal CT signs; in four cases, imaging signs followed AGA positivity (median 5 days), whereas in five cases they preceded serologic positivity (median, 8 days). In the nine patients with IPA, antifungal therapy was promptly instituted, including lipid formulations of amphotericin B (n=5) or caspofungin (n=4). In only two of the nine patients (22%) with IPA, the primary cause of death was fungal infection.
                The combination of AGA detection and early chest CT scans might be considered useful tools to detect minimal changes of IPA. Based on these findings, aggressive antifungal therapy should be initiated. 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. fumigatus, 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 1 ng/ml and died with increasing titres, whereas the GM-negative 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. Invasive aspergillosis (IA) is a frequent complication of blood or marrow transplantation. Previous studies have reported that the Aspergillus galactomannan enzyme immunoassay (GM EIA) may be a useful diagnostic tool for IA, but its sensitivity is variable. We examined the performance of the GM EIA in 986 serum samples from 67 patients. Results demonstrated that decreasing the index cutoff for positivity to 0.5 increased its sensitivity, with minimal loss of specificity. The low cutoff increased the duration of test positivity before diagnosis by clinical means. Sensitivity was highest in patients who did not receive preventative mold-active antifungals (87.5%). A rabbit model demonstrated that the level of circulating antigen correlated with the tissue fungus burden. A quantifiable response to antifungal therapy in clinical samples and the rabbit model supports the development of this assay for early diagnosis and therapeutic monitoring. The 0.5 cutoff may allow for better performance as an early diagnostic test. Invasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCycler polymerase chain reaction (PCR) assay, a nested-PCR assay and a galactomannan (GM) enzyme-linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested-PCR assay and GM testing was performed at regular intervals. Positive nested-PCR results were quantified by a LightCycler PCR assay. Patient episodes were stratified according to the 2002 European Organization for Research and Treatment of Cancer/Mycosis Study Group consensus criteria and the PCR and serology results were correlated with the clinical diagnostic classification. Sensitivity and specificity rates for the nested-PCR assay were up to 63.6% [95% confidence interval (CI): 30.8-89%) and 63.5% (95% CI: 53.4-72.7%) respectively, and 33.3% and 98.9% (95% CI: 7.5-70.1% and 94.2-99.9%) for GM respectively. The LightCycler PCR assay yielded positive results in 21.4%, lacking discrimination by quantification across the different clinical categories. In this prospective comparison, PCR was superior to GM with respect to sensitivity rates. In patients at high risk for IA, positive results for Aspergillus by PCR of blood samples are highly suggestive for IA and contribute to the diagnosis. 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. 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 (10.6%) 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 (11.1%) 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. To improve the diagnosis of invasive aspergillosis (IA), we retrospectively compared competitive polymerase chain reaction (PCR) and sandwich ELISA for detection of serum galactomannan (GM) antigen. We studied 281 serum samples collected weekly during the period at risk for IA from 41 selected hematology patients. Twenty-two patients had confirmed, probable, or suspected IA, according to clinical and mycologic data. Fifteen of them had positive GM titers (87 samples) and 12 had positive PCRs (20 samples). Nineteen of the 20 PCR-positive samples were also GM-positive. Of the 19 patients without IA (83 samples), one had 3 GM-false-positive samples. Neither test anticipated the initiation of antifungal therapy on the basis of clinical suspicion. Both tests were more likely to be positive before death. This study suggests that PCR on serum samples is not more sensitive than GM detection. However, PCR can improve the specificity of the GM test. Together, these noninvasive tests should improve the diagnosis of IA. We compared an Aspergillus fumigatus-specific Taqman real-time PCR assay for the diagnosis of invasive aspergillosis (IA) with the enzyme-linked immunosorbent assay Platelia Aspergillus method. Patients with proven or probable IA had positive results with at least one of the two methods. The PCR method seems to be more specific, and a combination of the two should improve the diagnosis of IA. Serum galactomannan detection is considered to be a useful test for early diagnosis and follow-up of invasive aspergillosis. From February to September 2002, adult patients hospitalized in our Hematology Unit for receiving intensive chemotherapy and/or hematopoietic stem cell transplant were prospectively studied. We analyzed a total of 760 samples obtained from 100 patients. Eleven patients (11%) having a positive result (OD index >1.5 ng/ml) in two consecutive Platelia Aspergillus tests were considered galactomannan-positive cases. On the other hand, 12 patients (12%) were diagnosed of proven or probable invasive aspergillosis. Sensitivity (66.6%), specificity (95.5%), positive predictive value (72.7%) and negative predictive value (96.7%) were comparable to those of larger series. Galactomannan positivity allowed also to anticipate invasive aspergillosis diagnosis (from two to 17 days before radiographic findings and from two to 15 days before mycological culture). Moreover, kinetics of antigenemia could be useful for assessing therapeutic response. Once accepted galactomannan test as a diagnostic criterium for invasive aspergillosis knowing potential causes of false positive results is of paramount importance. nan The establishment of an optimal noninvasive method for diagnosing invasive aspergillosis (IA) is needed to improve the management of this life-threatening infection in patients with hematological disorders, and a number of noninvasive tests for IA that target different fungal components, including galactomannan, (1-->3)-beta-d-glucan (BDG), and Aspergillus DNA, have been developed. In this study, we prospectively evaluated the diagnostic potential of three noninvasive tests for IA that were used in a weekly screening strategy: the double-sandwich enzyme-linked immunosorbent assay (ELISA) for galactomannan (Platelia Aspergillus), a real-time PCR assay for Aspergillus DNA (GeniQ-Asper), and an assay for BDG (beta-glucan Wako). We analyzed 149 consecutive treatment episodes in 96 patients with hematological disorders who were at high risk for IA and diagnosed 9 proven IA cases, 2 probable IA cases, and 13 possible invasive fugal infections. In a receiver-operating characteristic (ROC) analysis, the area under the ROC curve was greatest for ELISA, using two consecutive positive results (0.97; P = 0.036 for ELISA versus PCR, P = 0.055 for ELISA versus BDG). Based on the ROC curve, the cutoff for the ELISA could be reduced to an optical density index (O.D.I.) of 0.6. With the use of this cutoff for ELISA and cutoffs for PCR and BDG that give a comparable level of specificity, the sensitivity/specificity/positive predictive value/negative predictive value of the ELISA and the PCR and BDG tests were 1.00/0.93/0.55/1.00, 0.55/0.93/0.40/0.96, and 0.55/0.93/0.40/0.96, respectively. In conclusion, among these weekly screening tests for IA, the double-sandwich ELISA test was the most sensitive at predicting the diagnosis of IA in high-risk patients with hematological disorders, using a reduced cutoff of 0.6 O.D.I. Invasive aspergillosis (IA) is among the most common invasive fungal infections in neutropenic patients with hematological disorders in the authors' institution, King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand Previous studies have reported the Aspergillus galactomannan enzyme immunosorbent assay (GMEIA) may be a useful diagnostic tool for IA. The authors evaluated the performance of the GM EIA for the diagnosis and monitoring of the course of IA in KCMH.
                The authors prospectively performed the study from June 2002 to January 2004 in a consecutive series of adult neutropenic patients with hematological disorders who were at risk for developing IA. During hospitalization, serum galactomannan levels were measured once or twice weekly using the Platellia Aspergillus EIA test kit. The sensitivity and specificity of the GM EIA were calculated according to the proportion of patients with true and false positive and negative tests.
                There were 50 treatment episodes in 44 patients with 5 proven, 12 probable, and 33 possible or no IA. The cutoff GM index of > 0.75 was determined with a sensitivity of 94.1% and a specificity of 78.8%. There was a close relationship between clinical outcome and the kinetics of GM indices.
                The GM EIA is a useful diagnostic toolfor the diagnosis and monitoring of the course oflA in the presented institute. The occurrence of invasive fungal infection (IFIs) in a pediatric hematology/oncology unit after renovation of the ventilation system, and initiating routine azole antifungal prophylaxis was monitored. In addition, the value of serial screening for Aspergillus galactomannan (GM) for diagnosing invasive aspergillosis was assessed.
                A total of 98 consecutive high-risk pediatric patients were prospectively surveyed for signs of IFI and weekly monitored for serum GM. The data was not made available to treating physicians.
                Only 2 patients had proven and 27 possible IFI based on the European Organization for Research and Treatment of Cancer/Mycoses Study Group definitions. The incidence of proven IFI was 1/31 (3.2%) in the allogeneic stem cell transplant (SCT) (Aspergillus spp), 0/26 in the autologous SCT, and 1/60 (1.6%) in the induction therapy group (C. krusei). GM was detected at least in one tested sample in 12/98 patients (12.2%), in five patients in two or more sequential samples. In the latter group, IFI was proven in one patient and could not be excluded in the others. Four of the five patients belonged to the 31 allogeneic and one to the 26 autologous SCT patients. In patients with only one positive GM test none developed signs of IFI and only one received empirical amphotericin B.
                With the currently used preventative and prophylactic measures, IFI is uncommon in children with high-risk for infection. Regular screening for GM could be useful among allogeneic SCT patients and two positive samples should prompt further investigative procedures and pre-emptive antifungal therapy.
                (c) 2006 Wiley-Liss, Inc. To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients.
                The study was conducted in four patient groups: those with fever of unknown origin (FUO) during neutropenia, suspected pulmonary infection (PI), or nonpulmonary aspergillosis (NPA) and those undergoing surveillance (S) after hematopoietic stem-cell transplantation (HSCT). IA was classified as definite, probable, or possible, according to European Organization for Research and Treatment of Cancer/Mycosis Study Group definitions.
                A total of 3,294 serum samples were collected during 797 episodes (FUO, 261; PI, 297; NPA, 28; and surveillance, 211), and 153 episodes of IA were diagnosed (31 definite, 67 probable, and 55 possible). Three episodes were first suspected from galactomannan ELISA; the remaining 150 cases were diagnosed from clinical or radiologic evidence. Sensitivity of the ELISA was 64.5%, 16.4%, and 25.5% in definite, probable, and possible episodes of IA, respectively, and was lower in patients positive for anti-Aspergillus antibodies than in antibody-negative patients. Most false-positive results occurred in children and in allogeneic HSCT (allo-HSCT) patients. Overall specificity of the ELISA was 94.8%. It was lower in children compared with adults (P <.0001) and in allo-HSCT patients compared with non-allo-HSCT adults (P =.0002). Lowering the ELISA cutoff value from 1.500 to 0.700 seemed more relevant for non-allo-HSCT adults (sensitivity, 73.1%, 44.3%, and 44.7% in definite, probable, and possible IA, respectively; specificity, 94%).
                Galactomannan ELISA seems less sensitive than previously described, and sensitivity can be further reduced by the presence of anti-Aspergillus antibodies. A new cutoff value for the ELISA of 0.700 is proposed for non-allo-HSCT adults. The effectiveness of galactomannan detection with the Platelia test was evaluated in a prospective study of 3,327 sera from 807 patients. The specificity was 99.6% (748 of 751 cases). For the groups of patients with proven and probable invasive aspergillosis, the sensitivity was 50.0% (17 of 34 cases). The disappointing sensitivity associated with the presence of rare false-positive cases underlines the limits of this test. Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity.
                We prospectively evaluated the diagnostic value of twice-weekly screening for circulating Aspergillus fumigatus and A. flavus DNA with a polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA).
                Among the 201 adult patients with hematological malignancies who were included in the study, 55 IA cases were diagnosed. On the basis of the analysis of 1205 serum samples from 167 patients, the sensitivity, specificity, and positive and negative predictive values of the PCR-ELISA for proven and probable IA cases were 63.6%, 89.7%, 63.6%, and 89.7%, respectively, when samples with 2 consecutive positive results were used. The use of a combination of the PCR-ELISA and a galactomannan (GM) assay increased the sensitivity to 83.3%, increased the negative predictive value to 97.6%, and decreased the specificity to 69.8%. In most patients with IA, PCR-ELISA positivity anticipated or was simultaneous with the initiation of antifungal therapy, the abnormalities found by computed tomography, the mycological/histological diagnosis, and the GM positivity. Overall, 56.3% of the patients had at least 1 positive sample, and the false single-positive rate was 44.8%.
                In addition to serial screening for GM antigenemia and radiological surveillance, PCR-ELISA may improve the rates of early diagnosis of IA and the management of patients with hematological malignancies. The performance of a sandwich enzyme-linked immunosorbent assay (ELISA) which detects Aspergillus galactomannan (GM) was evaluated in bronchoalveolar lavage (BAL) fluid samples from 19 patients who were treated for hematological malignancies and who were suspected of having invasive pulmonary aspergillosis (IPA). All patients had fever and pulmonary infiltrates on the chest roentgenogram on the day that the BAL fluid was obtained. The ELISA results were compared with the results of culture and Aspergillus genus-specific PCR analysis of BAL fluid samples. ELISA was also performed with serum samples. Aspergillus species were detected by PCR or ELISA with BAL fluid samples from five of seven patients who had radiological evidence of IPA. Serum ELISA results were positive for all patients with ELISA-positive BAL fluid, and for four patients the serum ELISA was positive before the BAL fluid was obtained. PCR and ELISA were positive for 2 and 1 of 10 BAL fluid samples, respectively, obtained from patients without radiological evidence of IPA, and 5 and 2 of 35 BAL fluid samples, respectively, obtained from nonneutropenic patients. This preliminary investigation suggests that GM may be detected by ELISA in BAL fluid samples from patients at risk of IPA, but that monitoring of serum GM levels may allow for the earlier diagnosis of IPA. However, further evaluation in prospective studies is required. Invasive aspergillosis is difficult to diagnose in patients undergoing hematopoietic stem cell transplantation (HSCT). In 2003, a serum enzyme-linked immunosorbent assay (ELISA) test for the detection of galactomannan (a glycoprotein found on the Aspergillus cell wall) became available in the United States. In 2004, patients undergoing HSCT were screened biweekly with the galactomannan ELISA at our institution. We performed a retrospective chart review of 121 SCT patients who underwent galactomannan testing. Thirteen of the patients (10.7%) had at least 1 positive galactomannan ELISA, and 4 had multiple positive tests. When calculated in reference to a proved or probable diagnosis of aspergillosis, the galactomannan ELISA had a sensitivity of 0.50 and a specificity of 0.94. The positive predictive value was 0.46, and the negative predictive value was 0.94. Galactomannan ELISA had fewer false-positive and false-negative results in pediatric patients than in adult patients. In 4 of the 12 cases of invasive aspergillosis, the galactomannan ELISA was positive before other microbiologic evidence of aspergillosis was available. In these cases, a positive ELISA predated culture and cytologic evidence of invasive aspergillosis by a mean of 5 days (range, 1-8 days). Our findings indicate that a biweekly serum galactomannan ELISA is a highly specific diagnostic tool for detecting invasive aspergillosis in patients undergoing HSCT. When used regularly, the ELISA may allow for earlier diagnosis of invasive aspergillosis in some patients. The test is troubled by a low sensitivity and high frequency of false-negative tests. Until recently, accurate microbiological diagnosis of invasive aspergillosis (IA) was seldom established in HSCT recipients. Blood samples are rarely positive for Aspergillus species, the reliability of the cultures depends of the specimen (if taken from a normally sterile site or not) and biopsy samples require invasive procedures, rarely recommended in patients with severe thrombocytopenia. Implementing the international consensus defining the microbiological criteria for the diagnosis of Aspergillus infection, we retrospectively evaluated the role of serum galactomannan (GM) detection by EIA to diagnose IA among HSCT patients with proven invasive fungal infection (IFI) and the impact of serum storage in GM concentrations. The EIA assay allowed categorizing as "probable" 5 of the 10 cases of "possible" aspergillosis (50%). Considering a lower cut-off level for the reaction (1.0), 80% of the cases could be categorized as "probable" aspergillosis. Positive or undetermined results were detected one to 4 months before the diagnosis of IA in eight of the 11 patients (72.7%) with proven IFI. Retesting the stored samples after a second storage for four years, we could observe lower reactivity in 20% of the samples. The detection of galactomannan by the EIA test represents a major advance in the diagnosis of IA in HSCT recipients at high risk of IA. A better understanding of the kinetics of the GM in different clinical situations is necessary to maximize the benefit of the test in Aspergillus surveillance. Reported sensitivity of the galactomannan enzyme immunoassay as an early diagnostic test for invasive aspergillosis (IA) has been widely variable, ranging from 29% to 100% in earlier clinical studies.
                Studies performed to date have analyzed performance using per-patient calculations, limiting their ability to measure the impact of clinical variables that change over time, such as receipt of preventive antifungal therapy. In our study, performance of the test was calculated in per-patient and per-test analyses in a large cohort of patients at high risk for IA from 2 North American centers. A total of 272 serum samples obtained from 46 patients with IA and 3005 serum samples obtained from 269 control patients were analyzed using multiple index cutoff values to define positivity.
                Per-patient calculations yielded sensitivities of 43% and 70% using index cutoff values of 1.5 and 0.5, respectively; specificity decreased from 93% with use of the 1.5 index cutoff to 70% with use of the 0.5 index cutoff. Per-test calculations yielded sensitivities of 31% and 59% and specificities of 99% and 92% using index cutoff values of 1.5 and 0.5, respectively. Receipt of mold-active antifungal drugs on the day of testing decreased sensitivity; samples obtained from patients not receiving prophylactic or empirical antifungal drugs yielded a sensitivity of 89% and a specificity of 92% (with use of an index cutoff value of 0.5).
                These findings have direct implications for preventive strategies, because the diagnostic utility of the antigen assay is compromised during receipt of prophylactic or empirical antifungal therapies. To compare PCR with galactomannan antigen detection for the diagnosis of invasive aspergillosis (IA).
                We prospectively collected serial blood samples from haematological patients at risk of IA, and analysed their samples retrospectively for galactomannan (GM) antigen using the Platelia test and for aspergillus DNA using an in-house PCR-ELISA assay. Matched GM and PCR analyses were performed on 263 samples from 25 patients. Patients were classified for potential IA according to international consensus criteria, with five patients classified as positive (four proven, one probable) and 20 classified as negative (seven possible, 13 no evidence IA).
                All five patients with IA were positive by PCR with positive results in 24 of 82 samples, whereas three of five patients were positive by GM with four of 82 samples being positive. Three of 20 patients without IA were positive by PCR in 18 of 181 samples, whereas corresponding results for GM detection were one of 20 and one of 181, respectively. Adjustment of ELISA cut-off values and/or the requirement for two consecutive samples to be positive generated different results; however, lowering the positivity index (PI) for GM detection to 0.5 did not improve the sensitivity of the assay. Optimal results for PCR detection and GM were: 100% and 60% sensitivity, 85% and 95% specificity, 0.625 and 0.75 positive predictive value, and 1.0 and 0.8 negative predictive value, with a false-positive sample rate of 8 and 0.4%, positive likelihood ratio of 6.66 and 11.99 and negative likelihood ratio of 0 and 0.42, respectively.
                This PCR method is very sensitive for the diagnosis of IA but is associated with a moderate rate of false positives; the GM assay exhibited poor sensitivity but high specificity. Further evaluation of PCR assays for the diagnosis of IA and other invasive fungal infections is warranted. To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test.
                In total, 2026 serum samples from 104 bone marrow transplant recipients were tested. These comprised 67 sera from seven patients who had died with confirmed IA, 268 sera from nine patients who had died with suspected IA, and 1691 sera from 88 patients with no clinical, radiological, or microbiological signs of IA.
                The ELISA was more sensitive than the LA test. All patients who were ELISA positive were also LA positive, and a positive LA result never preceded a positive ELISA. Twelve of 16 patients with confirmed or suspected IA were ELISA positive on two or more occasions, compared with 10 of 15 who were LA positive. ELISA was positive before LA in five patients (range, 2-14 days), and became positive on the same day in the remainder. Aspergillus antigen was detected by ELISA a median of 15 days before death (range, 4-233). Clinical and/or radiological evidence of IA was noted in all patients, and a positive ELISA was never the sole criterion for introduction of antifungal treatment. Two samples (one from each of two patients without IA) gave false positive results.
                The aspergillus ELISA is a specific indicator of invasive aspergillosis if the criterion of two positive samples is required to confirm the diagnosis. However, the test is insufficiently sensitive to diagnose aspergillosis before other symptoms or signs are apparent, and hence is unlikely to lead to earlier initiation of antifungal treatment. It is therefore unsuitable for screening of asymptomatic patients at risk of invasive aspergillosis, but does have a useful role in confirming the diagnosis in symptomatic patients. Screening for galactomannan (GM) has been adopted by many European centers as part of the management plan for allogeneic stem cell transplant recipients. However, the temporal onset of GM antigenemia remains unknown. A series of allogeneic stem cell transplant recipients were monitored prospectively, and the relationship between antigenemia and other diagnostic triggers for initiation of antifungal therapy was analyzed. GM detection had a sensitivity of 94.4% and a specificity of 98.8%. Positive and negative predictive values were 94.4% and 98.8%, respectively. This statistical profile was better than that of other triggers, including unexplained fever, new pulmonary infiltrates, isolation of Aspergillus species, and abnormalities seen on computed tomography. Antigenemia preceded diagnosis on the basis of radiologic examination or Aspergillus isolation by 8 and 9 days in 80% and 88.8% of patients, respectively. Antigenemia preceded therapy in 83.3% of patients. Detection of GM was especially useful when patients were receiving steroid treatment or when coexisting conditions masked the diagnosis of invasive aspergillosis. Prospective screening for GM allows earlier diagnosis of aspergillosis than do conventional diagnostic criteria. Many health care centers worldwide use the Platelia Aspergillus enzyme immunoassay (PA-EIA; Bio-Rad Laboratories) for diagnosis of invasive aspergillosis (IA). A cutoff optical density (OD) index of 1.5 was originally recommended by the manufacturer, but in practice, most institutions use lower cutoff values. Moreover, a cutoff OD index of 0.5 was recently approved in the United States. In the present study, we set out to optimize the cutoff level by performing a retrospective analysis of PA-EIA values for samples that had been obtained prospectively from adult patients at risk for IA at 2 European health care centers.
                In total, 239 treatment episodes were included of which there were 19 episodes of proven IA and 19 episodes of probable IA. Per-episode and per-test analyses and receiver operating characteristic curves were used to determine the optimal cutoff value.
                In the per-episode analysis, lowering the cutoff OD index for positivity from 1.5 to 0.5 increased the overall sensitivity by 21% (from 76.3% to 97.4%) but decreased the overall specificity by 7% (from 97.5% to 90.5%). Requiring 2 consecutive samples with an OD index > or = 0.5 resulted in the highest test accuracy, with an improved positive predictive value. At a cutoff OD index of 0.5, the antigen test result was positive during the week before conventional diagnosis in 65% of cases and during the week of diagnosis in 79.5% of cases.
                A cutoff OD index of 0.5--identical to the approved cutoff in the United States--improves the overall performance of the PA-EIA for adult hematology patients. The recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0.8 and (b) a 'dynamic' cut-off at 0.5. A single assay with an optical density (OD) index > or = 0.8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD > or = 0.5 ('dynamic' threshold) increased the specificity and the PPV to 98.6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling. This study investigated the diagnostic value of Platelia Aspergillus enzyme immunoassay (EIA) for galactomannan (GM) antigen in patients at risk of invasive aspergillosis (IA), and its association with clinical course and outcome.
                A total of 304 blood samples were collected from 189 patients at risk of IA during a 1-year period at a tertiary referral center. Classification of IA was made on the basis of the European Organization for Research and Treatment of Cancer case definitions.
                Of the 189 patients, 5 had proven IA, 9 had probable IA, 26 had possible IA, and 149 had no IA. Diagnostic levels of GM were detected in 80% of proven and in 77% of probable IA cases. The overall sensitivity, specificity, and positive and negative predictive values for this assay, using a 1.5 index cut-off value, were 78.6%, 93.9%, 55.0%, and 97.9%, respectively. With the 0.5 index cut-off value, the sensitivity would increase to 100%. A close relationship was found between clinical course and the kinetics of GM indices in survivors.
                The Platelia Aspergillus EIA is a useful screening test for the detection of IA. Regular monitoring of the kinetics of GM-EIA indices is a useful predictor of clinical course and outcome. Invasive aspergillosis (IA) is an important cause of mortality in liver transplant patients. Clinical and microbiological diagnosis is difficult, and it is frequently achieved only after autopsy. Early diagnosis and antifungal therapy could improve the survival of these patients.
                A retrospective case-control study of IA in liver transplant recipients (OLT) was performed to determine the value of the detection of galactomannan Aspergillus antigen in serum using a sandwich-ELISA test (Platelia, Sanofi Diagnostic Pasteur). Stored frozen serum specimens obtained during the posttransplantation period were used.
                Fourteen cases of IA were diagnosed in 240 OLT recipients (IA incidence: 5.8%) during 5 years with 13 deaths (mortality: 93%). Nine case patients and 33 control patients met the criteria required for being considered "valid" for antigenemia analysis. In five of the nine case patients, a serum sample was positive for Aspergillus antigenemia detection. The median value was 5.7 ng/ml (range: 1.6-6.6). Sensitivity of the test was 55.6%, specificity was 93.9%, the positive predictive value was 71.4%, and the negative predictive value was 88.6%. The likelihood ratio of a positive test was 9.2.
                Galactomannan detection in serum could be useful for an early diagnosis of IA in OLT recipients. The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA.
                We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations.
                Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0.
                Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy. Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied.
                In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group.
                We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT.
                We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM. Invasive aspergillosis (IA) has become the leading infectious cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This is partially because of the lack of a sensitive, specific, and noninvasive diagnostic test. New diagnostic tests for IA, such as the detection of Aspergillus galactomannan antigen (AGA) by sandwich enzyme-linked immunoabsorbent assay (ELISA), have recently been described. This study validates the usefulness of this diagnostic tool in the allo-HSCT setting.
                From January 1999 to January 2001, all consecutive adult patients undergoing allo-HSCT were prospectively studied with a galactomannan antigenemia assay (ELISA test) twice weekly from admission until death or discharge, and weekly afterward if the patient received immunosuppressive therapy. Proven, probable, and possible IA were defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria.
                During the 2 years of study, 74 patients underwent an allo-HSCT. A total of 832 serum samples were collected. According to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria, it was ascertained that 66 patients did not fulfill any criteria of IA, 2 patients were classified with possible IA, 5 patients were classified with probable IA, and 1 patient was classified with proven IA. Fourteen samples were positive for AGA, all from patients with IA. The sensitivity and specificity of the test were 75% and 100%, respectively. The positive predictive and negative predictive values were 100% and 97%, respectively.
                In this study, AGA detection was clearly related to IA. Although the ELISA test did not have any role in the anticipation of the diagnosis, it clarifies the diagnosis of IA in allo-HSCT.