Galactomannan detection for invasive aspergillosis in immunocompromized patients.
BACKGROUND
Invasive aspergillosis (IA) is the most common life-threatening opportunistic invasive mycosis in immunocompromized patients. A test for IA needs to be not too invasive and not too big a burden for the already weakened patient. The serum galactomannan ELISA seems to have potential for both requirements.


OBJECTIVE
To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of IA.


METHODS
We searched MEDLINE, EMBASE and Web of Science with both Medical Headings and text words for both aspergillosis and the sandwich ELISA. We checked reference lists of included studies and review articles for additional studies.


METHODS
Cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of IA in patients with neutropenia or patients whose neutrophils are functionally compromised were included. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).


METHODS
Two review authors independently assessed quality and extracted data


RESULTS
Thirty studies were included in the meta-analyses, with a median prevalence of IA (proven or probable) of 7.7%. Seven of these (901 patients) reported results for an Optical Density Index (ODI) of 0.5 as cut-off value. The overall sensitivity in these studies was 78% (61% to 89%) and overall specificity was 81% (72% to 88%). Twelve studies (1744 patients) reported the results for cut-off value of 1.0 ODI, overall sensitivity was 75% (59% to 86%) and mean specificity 91% (84% to 95%). Seventeen studies (2600 patients) reported the results for cut-off value 1.5 ODI, sensitivity was 64% (50% to 77%) and mean specificity 95% (91% to 97%).


CONCLUSIONS
At a cut-off value 0.5 ODI in a population of 100 patients with a disease prevalence of 8% (overall median prevalence), 2 patients who have IA, will be missed (sensitivity 78%, 22% false negatives), and 17 patients will be treated or further referred unnecessarily (specificity of 81%, 19% false negatives). If we use the test at cut-off value 1.5 in the same population, that will mean that 3 IA patients will be missed (sensitivity 64%, 36% false negatives) and 5 patients will be treated or referred unnecessarily (specificity of 95%, 5% false negatives). These numbers should however be interpreted with caution, because the results were very heterogeneous.
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, J1B-210, P.O. Box 22700 , AMSTERDAM, Netherlands, 1100 DE. m.m.leeflang@amc.uva.nl
Mariska M
MM
Leeflang
Yvette J
YJ
Debets-Ossenkopp
Caroline E
CE
Visser
Rob J P M
RJ
Scholten
Lotty
L
Hooft
Henk A
HA
Bijlmer
Johannes B
JB
Reitsma
Patrick Mm
PM
Bossuyt
Christina M
CM
Vandenbroucke-Grauls
D001228:Aspergillosis / Q000175:diagnosis* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D016867:Immunocompromised Host; D008351:Mannans / Q000097:blood*; D009894:Opportunistic Infections / Q000175:diagnosis* / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D012680:Sensitivity and Specificity
D015415:Biomarkers; D008351:Mannans; C012990:galactomannan; D005690:Galactose