Aspergillus galactomannan detection in the diagnosis of invasive aspergillosis in cancer patients.
OBJECTIVE
To assess the Aspergillus galactomannan enzyme-linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in adult and pediatric oncohematologic patients.


METHODS
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.


RESULTS
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%).


CONCLUSIONS
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.
Herbrecht
Raoul
R
Département d'Hématologie et d'Oncologie, Hôpitaux Universitaires de Strasbourg, France. raoul.herbrecht@chru-strasbourg.fr
Letscher-Bru
Valérie
V
Oprea
Corina
C
Lioure
Bruno
B
Waller
Jocelyn
J
Campos
France
F
Villard
Odile
O
Liu
Kun-Lun
KL
Natarajan-Amé
Shanti
S
Lutz
Patrick
P
Dufour
Patrick
P
Bergerat
Jean-Pierre
JP
Candolfi
Ermanno
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000908:Antibodies, Fungal / Q000302:isolation & purification; D001228:Aspergillosis / Q000175:diagnosis* / Q000382:microbiology*; D001230:Aspergillus / Q000201:enzymology / Q000276:immunology / Q000302:isolation & purification*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005334:Fever / Q000209:etiology* / Q000382:microbiology; D006801:Humans; D007223:Infant; D008297:Male; D008361:Mannosidases / Q000378:metabolism*; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D009503:Neutropenia / Q000150:complications / Q000209:etiology; D012680:Sensitivity and Specificity
D000908:Antibodies, Fungal; D008361:Mannosidases; C109435:galactomannanase