Discussion
Galactomannan is a polysaccharide component of Aspergillus cell
walls,and it is released during tissue invasion by Aspergillus hyphae.
Beta-D-glucan (BDG) is present in the cell walls of almost all
pathogenic fungi, such as Candida, Aspergillus, and several other genera
(except Mucorales and Cryptococcus). These two serologic biomarkers have
been introduced for the diagnosis of invasive aspergillosis (IA) over
the last four decades.
The concentration of serum GM in vivo is determined not only by the rate
of production and secretion by the growing fungus but also by the rate
of uptake in the bloodstream, as well as the rate of elimination from
the circulation. A meta-analysis from Mayo Clinic in 2018 shows that
serum GM had a moderate mean sensitivity of 0.71 and high specificity of
0.89. Increasing the cut-off index increased specificity and decreased
sensitivity. A serum GM cut-off of 1.0 seems to provide optimal
sensitivity of 0.79 and specificity of 0.88[1]. In
another study, the sensitivity, in particular, was very heterogeneous at
the cut-off values of 0.5, 1.0, and 1.5 optical density index.
Currently, due to the large number of false positives, a higher cut-off
of 1.0 is proposed[2]. Even so, the GM test is
difficult to be considered a gold standard of IA
diagnosis.The major sources of
circulating BDG are invasive fungal disease, iatrogenic contamination,
intestinal translocation, intestinal contents: mycobiome and BDG
translocation, hepatic function, bacterial infections, and
manufacturing-associated contamination. A meta-analysis showed that the
BDG assay in ICU patients at risk for IC or candidemia had a mean
sensitivity of 0.81 and mean specificity of
0.60[1]. The
negative predictive value of BDG is very high,and it could not identify
Aspergillus infection.So the BDG test is clearly less close to being a
diagnostic gold standard of invasive fungal disease than the GM
testThe limitation of BDG-based tests
lies in their inability to identify pathogenic microbial species.
Overall, serologic examination is not considered sufficient for a proven
diagnosis. Microscopic examination, culture, and PCR sequencing are also
required, according to the recent EORTC/MSG
guidelines[3]. Invasive fungal diseases do not
have specific symptoms, signs, or imaging findings. Some studies have
evaluated the early diagnostic value of serum GM tests combined with
computed tomography for invasive pulmonary aspergillosis. The diagnostic
and follow-up performance of the two biomarkers were further improved by
using them as a combination of tests (parallel analysis improves
sensitivity and negative predictive value) or continuous monitoring
(serial analysis improves specificity and positive predictive value). In
this report, pain appeared earliest and persisted in the progression of
the disease; imaging studies provided localization but were not
diagnostic. At the early stage of the disease, the BDG assay and GM test
showed a slight increase, but the presence of Candida in the sputum
examination made us consider them as false positives. Fortunately, we
persisted in monitoring the serological changes dynamically and made the
decision to treat with voriconazole. Serological tests were sensitive
and varied with the severity of the illness and remained valuable for
observation even after the disappearance of symptoms and imaging
changes.
It is known that treating Aspergillus infections in the central nervous
system requires longer periods of drug therapy[4].
When the patient stopped taking the medication, the GM test values began
to rise, raising concerns about a possible resurgence of aspergillosis.
The current guidelines do not exhaustively describe these rare clinical
cases, and the optimum duration of antifungal treatment and follow-up
remains uncertain.
Only about half of all invasive fungal infections are diagnosed
pre-death,the value of the GM test is not sensitive and specific enough
to be considered a diagnostic gold standard, according to many
sources.However, when used it in
combination with BDG, CT, and MR imaging and observed dynamically,it
demonstrates significant value during the course of Aspergillus
infections and therapeutic management.