Point-of-care diagnostics for invasive aspergillosis: nearing the finish line

ABSTRACT

Introduction

The spectrum of disease caused by Aspergillus spp. is dependent on the immune system of the host, with invasive aspergillosis (IA) its most severe manifestation. Early and reliable diagnosis of Aspergillus disease is important to decrease associated morbidity and mortality from IA.

Areas covered

The following review searched Pub Med for literature published since 2007 and will give an update on the current point-of-care diagnostic strategies for the diagnosis of IA, discuss needed areas of improvement for these tests, and future directions.

Expert opinion

Several new diagnostic tests for IA – including point-of-care tests – are now available to complement conventional galactomannan (GM) testing. In particular, the Aspergillus-specific Lateral Flow Device (LFD) test and the sōna Aspergillus GM Lateral Flow Assay (LFA) are promising for the diagnosis of IA in patients with hematologic malignancy, although further evaluation in the non-hematology setting is needed. In addition, a true point-of-care test, particularly for easily obtained specimens like serum or urine that can be done at the bedside or in the Clinic in a matter of minutes is needed, such as the lateral flow dipstick test, which is under current evaluation. Lastly, improved diagnostic algorithms to diagnose IA in non-neutropenic patients is needed.

KEYWORDS:

• Lateral flow device test
• lateral flow assay
• lateral flow dipstick
• bronchoalveolar lavage
• serum
• urine
• BDG
• automated reader

Article highlights

• Conventional Galactomannan ELISA testing is limited by long processing times, and on a global level only a small proportion of mycology laboratories can actually offer GM testing.

• Point-of-care diagnostic test for IPA are now commercially available and two tests are CE-marked, the LFA and LFD tests.

• These tests have been shown to reliably diagnose IPA in patients with hematological malignancies, and performance can be further improved by automatic readout of test results.

• More data for both CE-marked tests are needed outside the hematological malignancy setting, particularly evaluating performance in BALF but also serum, as reliable serum markers for IPA in non-neutropenic patients are lacking.

• Reliable serum markers for IPA in non-neutropenic patients would be particularly valuable for patients with COVID-19, where IPA occurs frequently, but bronchoscopy is rarely performed due to fear of transmission by this droplet-creating procedure.

• Both the LFA and LFD have potential to diagnose IPA on their own and can also complement GM and culture as well as other novel biomarkers for optimizing diagnostic performance for IPA.

• Only the LFD offers true point-of-care diagnosis at the bedside without sample treatment and only for non-hemorrhagic and non-viscous BALF samples. True bedside diagnostic tests that can be performed on a variety of clinical samples are needed.

• Reliable consensus definitions are needed for classifying IA in patients outside the hematology setting.

Declaration of interest

Martin Hoenigl has declared receiving research funding from Gilead and Pfizer. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer declarations

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.