Surveillance of Aspergillus galactomannan antigenemia for invasive aspergillosis by enzyme-linked immunosorbent assay in neutropenic patients treated for hematological malignancies.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Ulusakarya
A
A
Department of Medicine, Institut Gustave-Roussy, Villejuif, France.
Chachaty
E
E
Vantelon
J M
JM
Youssef
A
A
Tancrède
C
C
Pico
J L
JL
Bourhis
J H
JH
Fenaux
P
P
Munck
J N
JN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000946:Antigens, Fungal / Q000097:blood*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001228:Aspergillosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D001230:Aspergillus / Q000302:isolation & purification*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications; D015470:Leukemia, Myeloid, Acute / Q000150:complications; D008228:Lymphoma, Non-Hodgkin / Q000150:complications; D008297:Male; D008351:Mannans / Q000276:immunology*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000382:microbiology*
D000946:Antigens, Fungal; D000970:Antineoplastic Agents; D008351:Mannans; C012990:galactomannan; D005690:Galactose