Diagnosing Invasive Pulmonary Aspergillosis in Hematology Patients: a Retrospective Multicenter Evaluation of a Novel Lateral Flow Device

Abstract

Invasive pulmonary aspergillosis (IPA) is a potentially lethal infection in patients with hematological diseases or following allogeneic stem cell transplantation. Early diagnosis is essential, as delayed treatment results in increased mortality. Recently, a lateral flow device (LFD) for the diagnosis of IPA was CE marked and made commercially available by OLM Diagnostics. We retrospectively analyzed bronchoalveolar lavage fluid (BALf) collected from adult hematology patients from 4 centers in The Netherlands and Belgium. Galactomannan was retested in all samples. All samples were applied to an LFD and read out visually by two independent researchers blinded to the diagnosis of the patient. All samples were also read out using a digital reader. We included 11 patients with proven IPA, 68 patients with probable IPA, 44 patients with possible IPA, and 124 patients with no signs of IPA (controls). In cases of proven IPA versus controls, sensitivity and specificity were 0.82 and 0.86 for visual readout and 0.82 and 0.96 for digital readout, respectively. When comparing patients with proven and probable IPA as cases versus controls, sensitivity and specificity were found to be 0.71 and 0.86, respectively. When excluding serum and BALf galactomannan as mycological criteria from the 2008 European Organization for Research and Treatment of Cancer Invasive Fungal Infections Cooperative Group (EORTC)/Mycoses Study Group of the National Institute of Allergy and Infectious Diseases (MSG) consensus definitions, the LFD was less specific than galactomannan when comparing subjects with proven and probable IPA to controls (0.86 versus 0.96; P = 0.005) but had similar sensitivity (0.76 versus 0.85; P = 0.18). In conclusions, in this large study of the CE-marked LFD in BALf from hematology patients, the LFD had a good performance for the diagnosis of IPA.

Keywords: diagnosis; galactomannan; invasive aspergillosis; lateral flow device.

FIG 1

Lateral flow devices, showing from left to right a negative result, followed by increasing test line intensity. The control line is visible at the top, while the test line appears below the control line.

FIG 2

Receiver operating characteristic (ROC) curves of the lateral flow devices in different subgroups of invasive pulmonary aspergillosis (IPA). (a) Proven IPA versus controls. (b) Proven or probable IPA versus controls, galactomannan (GM) positive ≥ 1.0. (c) Proven or probable IPA versus controls, GM positive ≥ 0.5. (d) Proven or probable IPA versus controls, GM excluded as mycological criterion.

FIG 3

Jitterplot of the galactomannan optical density index versus the intensity of the lateral flow device for all included patients. (a) Overview of all measurements. (b) Zoomed-in detail of measurements with galactomannan optical density index of ≤4.0.

FIG 4

Negative predictive value (NPV) and positive predictive value (PPV) as a function of prevalence of the tested population, in cases of proven IPA versus controls (a) and in cases of proven and probable IPA versus controls (b). The red line marks the estimated prevalence used in our study (30%).