MAJOR ARTICLE – Diagnosis of Invasive Aspergillosis Using a Galactomannan Assay: A Meta-Analysis

Source: Clin Infect Dis 15 May 2006 Vol.42 N.10 p.1417-1727

Christopher D. Pfeiffer,1 Jason P. Fine,2 and Nasia Safdar1

Departments of 1Medicine and 2Biostatistics, University of Wisconsin Medical School, Madison, Wisconsin

Background. A double-sandwich enzyme-linked immunosorbent galactomannan assay has been approved for surveillance for invasive aspergillosis in immunocompromised patients. We undertook a meta-analysis to assess the accuracy of a galactomannan assay for diagnosing invasive aspergillosis.

Methods. Studies of the galactomannan assay that used the European Organization for Research and Treatment of Cancer or similar criteria as a reference standard and provided data to calculate sensitivity and specificity were included. Pooled sensitivity and specificity and summary measures of accuracy, Q* (the upper left-most point on the summary receiver-operating characteristic curve), mean D (a log odds ratio), and Youden index were calculated. Subgroup analyses were performed to explore heterogeneity.

Results. Twenty-seven studies from 1966 to 28 February 2005 were included. Overall, the galactomannan assay had a sensitivity of 0.71 (95% confidence interval [CI], 0.68–0.74) and specificity of 0.89 (95% CI, 0.88–0.90) for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were 0.54 (95% CI, 0.41–0.65), 2.74 (95% CI, 21.12–3.36), and 0.80 (95% CI, 0.74–0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that the performance of the test differed by patient population and type of reference standard used. Significant heterogeneity was present.

Conclusions. The galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis in immunocompromised patients. The test is more useful in patients who have hematological malignancy or who have undergone hematopoietic cell transplantation than in solid-organ transplant recipients. Further studies with attention to the impact of antifungal therapy, rigorous assessment of false-positive test results, and assessment of the utility of the test under nonsurveillance conditions are needed.

Received 8 November 2005; accepted 19 December 2005; electronically published 14 April 2006.
Presented in part: 43rd Annual Meeting of the Infectious Diseases Society of America, San Francisco, California, 6–9 October 2005 [abstract 284].