Advances in diagnosis

Ref ID: 19448

Author:

A. H. Groll

Author address:

University Children’s Hospital M€unster, Germany

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Successful management of invasive fungal diseases (IFDs) relies on
early recognition and rapid initiation of the appropriate treatment.
Apart from a sound understanding of patient populations at risk, the
presentation of IFDs and the local epidemiology, a careful history
and physical examination provide direction for further work up of
the individual patient. Standard diagnostic procedures include blood
cultures for yeasts and certain moulds; cultures and microscopic
examination of appropriate diagnostic specimens; and imaging stud-
ies as guided by clinical findings. Considering the increasing diversity
of fungal pathogens in high risk patients, the differences in the activ-
ity of the available antifungal agents and the looming threat of resis-
tance, identification of the infecting isolate at the species level and
information on drug resistance are mandatory to provide state of the
art patient care. While microscopy and culture remain standard
tools, however, difficulties to obtain an appropriate specimen, long
time of culturing and negative or inconclusive results all limit an effi-
cient and rapid microbiological diagnosis. Modern imaging studies,
detection of circulating fungal cell wall components and fungal
nucleic acids in blood and other body fluids may enhance the labora-
tory diagnosis of IFDs and have been included in the EORTC/MSG
fungal disease definitions. Nevertheless, their validity and usefulness
in paediatric patients are less well evaluated and require separate
assessment.
Imaging studies. In high-risk granulocytopaenic adults with acute
leukaemia or allogeneic haematopoietic stem cell transplantation
(HSCT), serial high-resolution computed tomography (CT) imaging
has been shown to positively impact on early diagnosis and outcome
of invasive pulmonary aspergillosis. However, CT findings character-
istic in adults, such as the ’halo’ and ’air crescent’ signs, appear to
be rather infrequent in paediatric patients with pulmonary aspergillo-
sis for reasons that are not yet understood. As a consequence, in
granulocytopaenic paediatric patients at high risk to develop IFDs,
any radiological finding needs to be considered to represent invasive
pulmonary mould infection and should prompt further microbiologi-
cal work up and treatment. Hepatosplenic candidiasis can be detected
early by ultrasound or magnetic resonance imaging (MRT) in context
with the appropriate clinical presentation, and MRI and CT are use-
ful to investigate other sites and to guide diagnostic and surgical
interventions.
Detection of fungal cell wall antigens. Based on their performance in
adults, two antigen detection methods have been included in the
MSG/EORTC criteria. The galactomannan antigen ELISA (Platelia
Aspergillus; BioRad, Marnes-la-Coquette, France) allows for the detec-
tion Aspergillus galactomannan (GM) in serum, bronchoalveolar
lavage (BAL) fluid and cerebrospinal fluid (CSF). While cross-reac-
tions with other fungal organisms are rare, false-positive results can
be caused by contaminating GM in -lactam-antibiotics, dietary GM in
pasta, cereals and formula milk. Prospective monitoring of GM in
children at high risk for IFD may be considered for early diagnosis of
invasive aspergillosis: A combined analysis of five paediatric studies
revealed a sensitivity of 0.76 and a specificity of 0.86, which is in
the range of the performance values reported for adults. Based on
adult and additional paediatric data, GM measured in BAL fluid -GM
appears to be a useful adjunctive diagnostic tool for invasive pulmo-
nary aspergillosis; limited data also suggest the utility of GM testing
in the CSF for diagnosis invasive aspergillosis of the CNS. All studies
thus far indicate no differences in diagnostic threshold values
between paediatric and adult patients.
The beta-D glucan (BG) assay has been studied in adult patients
with fungal infections. Due to the presence of (1,3)-D-glucan in most
opportunistic fungi, this test is non-specific, but highly sensitive for
detection of invasive fungal pathogens; false-positive results may
occur by several ways. Particularly in neonates, the assay is very
promising for the diagnosis of invasive candidiasis. However, valida-
tion of the two commercially available assays (FungitellTM, Associ-
ates of Cape Cod Inc, Falmouth, USA; Fungitec GTM, Seikagaku
Corp., Tokyo, Japan) with definition of cut-off values in paediatric
patients is pending, and therefore, the BG assaymay not be used on a
routine basis for clinical decision making in children.
Detection of fungal nucleic acids. Polymerase chain reaction (PCR)
may be a powerful tool for early diagnosis of IFIs. Standardized meth-
ods have been developed and are currently evaluated for inclusion in
the MSG/EORTC criteria. No studies have addressed the issue in neo-
nates; in children, PCR has not been specifically studied but is proba-
bly as good as in adults. Twice weekly screening in blood of high
risk patients and specific detection of fungal pathogens in tissue spec-
imens have emerged as the most feasible clinical applications to date.

Abstract Number: w04-2

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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