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40.
Pazos C., Ponto
J., and Del Palacio
A. Contribution
of (1→3)-ß-D-glucan
chromogenic assay
to diagnosis and
therapeutic monitoring
of invasive aspergillosis
in neutropenic
adult patients:
A comparison with
serial screening
for circulating
galactomanna.
Journal of Clinical
Microbiology 43(1):
299-305 (2005)
Back To Top
1. Diagnosis
of fungal infection:
new technologies
for the mycology
laboratory.
Alexander BD.
transplant Infectious
Diseases Services,
Clinical Mycology
Laboratory, Duke
University
Medical
Center,
Durham,
NC
27710,
USA.
alexa011@mc.duke.edu
Abstract: The dramatic increase in nosocomial invasive mycoses over the past two decades has led to increased interest in the area of antifungal development. Unfortunately, the infusion of new diagnostic technology into the clinical mycology laboratory has lagged behind. Although newer, automated, continuous-monitoring blood culture systems are as sensitive as the older, manual "gold standard" system, the recovery of fungi from blood, as well as other clinical specimens, remains an insensitive marker for invasive fungal infection. Antigen assays for the rapid diagnosis of invasive fungal infections are in development, and galactomannan and glucan are two such promising antigens. Glucan may be present in the blood of patients with infection secondary to a wide variety of fungal pathogens, including Candida, Aspergillus, Fusarium, Saccharomyces, trichosporon and Acremonium species. Early data suggest galactomannan may be present in the blood in detectable levels very early in the course of invasive aspergillosis. The galactomannan assay currently undergoing evaluations may actually be positive prior to the clinical suspicion for infection and may be useful in monitoring therapeutic response as well; however, the etiology of false-positive results following cytotoxic chemotherapy still has to be elucidated. PCR assays are also being developed in the research laboratory, however, the PCR assays will require a significant amount of adaptation and validation before they are ready for clinical care. Well-planned studies to evaluate the performance characteristics as well as appropriate clinical and cost-effective application of these new tests are needed.
Back To TopT Miyazaki, S Kohno, K Mitsutake, S Maesaki, K Tanaka, N Ishikawa, and K Hara
Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
(1→3)-ß-D-Glucan is one of the major structural components of fungi, and it seems that it can be detected by the fractionated (1→3)-ß-D-glucan-sensitive component from a Limulus lysate, factor G. We evaluated the concentration of (1→3)-ß-D-glucan by using factor G and other fungal antigens in 24 patients with clinical evidence of mycosis and 36 healthy subjects. The mean concentration of (1→3)-ß-D-glucan in the plasma of the healthy subjects was found to be 2.7 +/- 1.9 pg/mL (range, < 6.9 pg/mL), and it was found to be substantially higher in all 11 patients with candidemia (mean, 2,207.4 pg/mL; range, 325.4 to 8,449.0 pg/mL). Eight of those 11 patients with candidemia (73%) were positive for the Cand-Tec heat-labile candida antigen and only 3 patients (27%) were positive for mannan antigen. Three patients with invasive pulmonary aspergillosis were positive for galactomannan and had, in addition, high concentrations of (1→3)-ß-D-glucan (mean, 323.3 pg/mL; range, 27.0 to 894.0 pg/mL). All 10 patients with cryptococcosis (including 2 patients with probable cryptococcosis) were positive for cryptococcal antigen by the Eiken latex test; however, (1→3)-ß-D-glucan levels were not elevated in these patients (mean, 7.0 pg/mL; range, < 16.5 pg/mL). Our results indicated that (1→3)-ß-D-glucan levels are elevated in patients with candidiasis and aspergillosis but not in those with cryptococcosis.
Back To Top3. Impact
of diagnostic
markers on early
antifungal therapy.
Jones BL,McLintock LA.
Department of
Medical Microbiology,
North Glasgow
Hospitals University
NHS trust, Royal
Infirmary, University
of Glasgow, Glasgow,
UK. b.l.jones@clinmed.gla.ac.uk
Purpose of
Review The
early treatment
of invasive fungal
infection is critical
but is hampered
by the non-specific
nature of clinical
and radiological
signs and the
insensitivity
of current laboratory
diagnostic methods.
If mortality due
to invasive fungal
infection is to
be reduced, new,
preemptive therapeutic
strategies, targeting
those patients
at highest risk,
are required and
these will depend
on the development
of rapid, sensitive
diagnostic methods.
Such methods have
become available
in the form of
high-resolution
computed tomography
scanning and serological
and molecular
techniques and
in this review
the authors describe
recent studies
assessing the
utility of these
methods and consider
their role in
management strategies.
Recent Findings: Sensitive assays for the detection of fungal DNA and antigens such as galactomannan and glucan have been prospectively evaluated in the clinical setting and enable identification of patients at an earlier stage of infection. However, the sensitivity and specificity of the assays vary considerably in different studies, depending on several factors including patient selection and clinical application of the test, and issues regarding the release and circulation of galactomannan and fungal DNA remain to be clarified.
Summary:
Rapid serological
and molecular
diagnostic methods
facilitate the
early diagnosis
of invasive fungal
infection and
would appear to
be most useful
when used prospectively
to screen high-risk
patients. However,
in order to determine
the optimal approach
to treatment it
is essential that
these tests are
incorporated into
management strategies
and their impact
on incidence of
invasive fungal
infection and
clinical outcome
evaluated in further
clinical trials.
Back To Top
4. Beta-D-glucan
as a diagnostic
adjunct for invasive
fungal infections:
validation, cutoff
development, and
performance in patients
with acute myelogenous
leukemia and myelodysplastic
syndrome.
Odabasi Z, Mattiuzzi
G, Estey E, Kantarjian
H, Saeki F, Ridge
RJ, Ketchum PA,
Finkelman MA, Rex
JH, Ostrosky-Zeichner
L.
Laboratory of Medical
Mycology, University
of Texas-Houston
Medical School,
Houston,
TX,
USA.
The Glucatell (1→3)-ß-D-glucan
(BG) detection assay
(Associates of Cape
Cod) was studied
as a diagnostic
adjunct for invasive
fungal infections
(IFIs). On the basis
of findings from
a preliminary study
of 30 candidemic
subjects and 30
healthy adults,
a serum BG level
of >or=60 pg/mL
was chosen as the
cutoff. Testing
was performed with
serial serum samples
obtained from 283
subjects with acute
myeloid leukemia
or myelodysplastic
syndrome who were
receiving antifungal
prophylaxis. At
least 1 serum sample
was positive for
BG at a median of
10 days before the
clinical diagnosis
in 100% of subjects
with a proven or
probable IFI. IFIs
included candidiasis,
fusariosis, trichosporonosis,
and aspergillosis.
Absence of a positive
BG finding had a
100% negative predictive
value, and the specificity
of the test was
90% for a single
positive test result
and >or=96% for
>or=2 sequential
positive results.
The Glucatell serum
BG detection assay
is highly sensitive
and specific as
a diagnostic adjunct
for IFI.
Back To Top
Obayashi, T., Yoshida, M., Mori, T., Goto, H. Yasuoka, A., Iwasaki, H., Teshima, H., Kohno, S., Horichi, A., Ito, A., Yamaguchi, H., Shimada, K., and Kawai, T. (1995)
Summary
(1→3)-ß-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G , a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide.
With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% 9172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon.
Determination
of plasma (1→3)-ß-D-glucan
with factor G
is a highly sensitive
and specific test
for invasive deep
mycosis and fungal
febrile episodes,
and will substantially
benefit immunocompromised
patients.
Back To Top
6. (1→3)-ß-D-glucan in patients with pulmonary aspergilloma.
Yuasa K., and Goto H. (1997)
Division of Hematology, Department of Medicine and Department of Clinical Pathology, Jichi Medical School, Minamikawachi-machi, Tochigi-ken, Japan, 329-04
Abstract:
To elucidate the
role of (1→3)-ß-D-glucan
in pulmonary aspergilloma,
serum concentrations
of (1→3)-ß-D-glucan
were measured
repeatedly for
as long as 10
months in eight
patients. In four
patients with
inactive disease,
concentrations
of (1→3)-ß-D-glucan
were in the normal
range.The concentrations
of (1→3)-ß-D-glucan
increased in two
patients, although
the disease was
inactive. This
increase might
show the earliest
stage of the invasive
process of the
disease. In two
other patients
with active disease,
(1→3)-ß-D-glucan
increased. Other
parameters, such
as galactomannan,
immunodiffusion
and a radio-allergosorbent
test, as well
as inflammatory
markers such as
C-reactive protein
and the leukocyte
count, did not
show any consistent
tendency in regard
to the activity
of the disease.
Thus, a (1→3)-ß-D-glucan
assay may add
valuable data
for evaluating
the disease activity
and understanding
the disease process
of pulmonary aspergilloma.
Back To Top
Yoshida M, Obayashi T, Iwama A, Ito M, Tsunoda S, Suzuki T, Muroi K, Ohta M, Sakamoto S, Miura Y. (1997)
Department of Medicine, Jichi Medical School, Tochigi-ken, Japan.
Abstract:
(1→3)-ß-D-glucan,
a characteristic
fungal molecule,
is known to increase
in blood in invasive
candidiasis, aspergillosis
and cryptococcosis.
This report shows
that the plasma
glucan concentration
was also elevated
in four patients
infected with
Fusarium, trichosporon
beigelii, Saccharomyces
cerevisiae and
Acremonium. In
three of the patients,
the elevation
preceded positive
blood cultures
by 5-17 days,
and in one of
them it even preceded
the onset of fever
by 6 days. In
a fourth patient,
the glucan level
decreased with
clinical improvement.
Plasma (1→3)-ß-D-glucan
determination
appears to be
useful also for
diagnosis and
follow-up of these
unusual deep mycoses.
Back To Top
Pazos C, Ponton J, Del Palacio A.
Unidad de Micologia, Departamento de Microbiologia, Hospital Universitario 12 de Octubre, Avenida de Cordoba s/n, 28041 Madrid, Spain. pazos.c@terra.es
Abstract:
Two noninvasive
diagnostic tests,
(1→3)-ß-D-glucan
(BG) (Glucatell)
and galactomannan
(GM) (Platelia
Aspergillus),
were used retrospectively
in a twice-weekly
screening for
the diagnosis
of invasive aspergillosis
(IA) in 40 treatment
episodes (one
hospital visit
per patient) in
40 neutropenic
adult patients
at high risk for
IA. Five proven
IA cases, three
probable IA cases,
and three possible
IA cases were
diagnosed. Diagnostic
levels of both
BG and GM were
detected in 100%
of patients with
proven IA cases
and in 66% of
patients with
probable IA cases.
The kinetics of
both markers in
patients with
IA were similar.
The sensitivity,
specificity, and
positive and negative
predictive values
for GM and BG
were identical,
namely, 87.5,
89.6, 70, and
96.3%, respectively.
False-positive
reactions occurred
at a rate of 10.3%
in both tests,
but the patients
showing false-positive
results were different
in each test.
Both tests anticipated
the clinical diagnosis,
computed tomography
abnormalities,
and the initiation
of antifungal
therapy in most
patients, but
BG tended to become
positive earlier
than GM. A combination
of the two tests
improved the specificity
(to 100%) and
positive predictive
value (to 100%)
of each individual
test without affecting
the sensitivity
and negative predictive
values. In conclusion,
BG and GM detection
are useful tests
for the diagnosis
of IA in high-risk
hematological
patients, but
a combination
of the two tests was very useful
to identify false-positive
reactions by each
test.
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