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.
BACKGROUND
Current laboratory and radiological methods for diagnosis of invasive aspergillosis (IA) lack sensitivity and specificity.


METHODS
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).


RESULTS
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%.


CONCLUSIONS
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.
Florent
Martine
M
Service de Microbiologie, Hotel-Dieu, Assistance Publique-Hopitaux de Paris (AP-HP), Universite Paris Descartes, Paris, France.
Katsahian
Sandrine
S
Vekhoff
Anne
A
Levy
Vincent
V
Rio
Bernard
B
Marie
Jean-Pierre
JP
Bouvet
Anne
A
Cornet
Muriel
M
D001228:Aspergillosis / Q000150:complications / Q000175:diagnosis*; D001231:Aspergillus flavus / Q000235:genetics / Q000302:isolation & purification; D001232:Aspergillus fumigatus / Q000235:genetics / Q000302:isolation & purification; D004271:DNA, Fungal / Q000032:analysis; D042241:Early Diagnosis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D008351:Mannans / Q000097:blood; D025202:Molecular Diagnostic Techniques; D016133:Polymerase Chain Reaction / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D004271:DNA, Fungal; D008351:Mannans; C012990:galactomannan; D005690:Galactose