Biomarkers for Invasive Aspergillosis: The Challenges Continue

Abstract

The incidence of invasive aspergillosis (IA), an opportunistic infection in immuno compromised individuals, is rising, but its early diagnosis remains challenging and treatment options are limited. Hence there is an urgent need to improve existing diagnostic procedures as well as develop novel approaches. The clinical usefulness of galactomannan and βdglucan, widely used assays detecting cellwall antigens of Aspergillus, is unclear and depends on clinicians' awareness of their practical limitations. This leaves room for new methods that utilize genomic, proteomic and metabolomics approaches as well as novel detection procedures, for example point ofcare lateralflow devices. Each of these strategies has its own limitations and it is likely that a combination of methods will be required to achieve optimal performance for the diagnosis of IA and subsequent appropriate patient management.

The current status of avian aspergillosis diagnoses: Veterinary practice to novel research avenues

“…The specificity and sensitivity of the GM assay in human patients are widely documented (Table ) . Although generally reliable and applicable to both bronchoalveolar lavage (BAL) and noninvasive serum samples, other factors such as concurrent patient treatment can confound the results . The full spectrum of interferences associated with the GM assay is still uncertain; however, antifungal administration could limit fungal growth and thus inhibits GM release, and antibiotics may contain trace amounts of GM or contaminants that cross‐react with the GM antibody .…”

“…Obstacles to routine implementation come from exogenous spore colonization, and workup steps and reagents that can introduce contaminants and cause false‐positive results. Clinical samples that inhibit PCR reagents and small PCR reagent working volumes can cause false‐negative results . Nevertheless, PCR is widely used in aspergillosis diagnostics and too numerous to mention in this review.…”

“…PCR does have some drawbacks . False positives can occur because of the ubiquitous presence of Aspergillus spores that could contaminate clinical samples or PCR reagents.…”

“…Real‐time nucleic acid sequence‐based amplification (NASBA) is an isothermal RNA amplification method that can detect Aspergillus . This technique is as sensitive as PCR with fewer primer restrictions compared with qPCR, but its ability to diagnose IA has not been evaluated in clinical medicine.…”

Recent progress in developing proximity ligation assays for pathogen detection

“…Its main advantages are: its sensitivity, the ease with which specific primers can be synthesized and incorporated into new tests and its potential for detecting acute disease prior to the formation of a detectable serological response. The main disadvantage is that the detection of a pathogen's nucleic acid does not necessarily indicate the pathogen's viability, for example, when applied to the early detection of invasive Aspergillus in immunosuppressed patients [3]. Furthermore, residual DNA may informahealthcare.com 10.1586/14737159.2015.1044440 Ó 2015 Informa UK Ltd persist for weeks after successful treatment [4], tests can require expensive instrumentation and skilled personnel, and contamination is an ever-present danger.…”