Galactomannan detection in broncho-alveolar lavage fluid for invasive aspergillosis in immunocompromised patients.

Abstract

Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test. To assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook. We searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies. We included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classification as reference standard. Two review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment. We included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%. The optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.