Fungal diagnosis: how do we do it and can we do better?

Abstract

Background: Morbidity and mortality remain high for patients with invasive fungal infections (IFIs) despite an increasing number of antifungals and other treatments. Many studies indicate that delayed or inaccurate diagnosis and treatment are major causes of poor outcomes in patients with IFIs.

Objective: The aim of the current paper is to provide a review of traditional and newer approaches to the diagnosis of IFIs, with a particular focus on invasive candidiasis (IC) and aspergillosis (IA). Recent studies from the author's institution are highlighted, along with an advancement in cryptococcal meningitis diagnosis that should improve the care of AIDS and its opportunistic infection in many developing countries.

Findings: Currently available tools for the diagnosis of IFIs include traditional methods like histopathology, culture, and radiology, and newer antigen- and PCR-based diagnostic assays. Attempts have also been made to predict IFIs based on colonization or other factors, including genetic polymorphisms impacting IFI susceptibility in high-risk patients. Biopsy with histopathologic analysis is often not possible in patients suspected of pulmonary aspergillosis due to increased bleeding risk, and blood cultures for IC, IA, or other IFIs are hindered by poor sensitivity and slow turnaround time which delays diagnosis. Radiology is often used to predict IFI but suffers from inability to differentiate certain pathogens and does not generally provide certainty of IFI diagnosis. Newer antigen-based diagnostics for early diagnosis include the β-glucan assay for IFIs, galactomannan assay for IA, and a recent variation on the traditional cryptococcal antigen (CRAG) test with a Lateral Flow Assay for invasive cryptococcosis. PCR-based diagnostics represent additional tools with high sensitivity for the rapid diagnosis of IFIs, although better standardization of these methods is still required for their routine clinical use.

Conclusion: Better understanding of the strengths and weaknesses of currently available diagnostic tools, and further devising linked strategies to best implement them either alone or in combination, would greatly improve early and accurate diagnosis of IFIs and improve their successful management.