Diagnosis of Fungal Infections (Infectious Disease and Therapy)

425 Pages·2007·6.98 MB·English

by  Johan A. Maertens, Kieren A. Marr

Diagnosis
of
Fungal
Infections
Maertens edited by
•
Marr Johan A. Maertens
Kieren A. Marr
Diagnosis of Fungal Infections
Diagnosis
of
Fungal
Infections
Diagnosis
of
Fungal
Infections
Edited by
Johan A. Maertens
Universitaire Ziekenhuizen Leuven
Leuven, Belgium
Kieren A. Marr
Oregon Health and Science University
Portland, Oregon, USA
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Library of Congress Cataloging-in-Publication Data
Diagnosis of fungal infections / edited by Johan A. Maertens, Kieren A. Marr.
p. ; cm. – (Infectious disease and therapy ; v. 47)
Includes bibliographical references.
ISBN-13: 978-0-8247-2933-2 (hardcover : alk. paper)
ISBN-10: 0-8247-2933-1 (hardcover : alk. paper)
1. Mycoses–Diagnosis. I. Maertens, Johan A. II. Marr, Kieren A. III. Series.
[DNLM: 1. Mycoses–diagnosis. W1 IN406HMN v.47 2007 / WC 450 D536 2007]
RC117.D47 2007
616.9’69075–dc22 2007023321
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Preface
Fungal infections are a leading cause of death in multiple different patient
populations; experience over the last few decades has been that these organisms
are a leading cause of transplant-related mortality after stem cell transplantation,
a frequent complication of organ transplantation, a leading cause of death in
people with advanced human immunodeficiency virus disease, and a common
cause of bloodstream infection among the hospitalized population. New studies
are indicating that known fungi are involved as inciters in disease states not
previously thought to be infectious (e.g., asthma and sinusitis), and “new”
organisms are being discovered. Recognition of these organisms as important
complications of the immunosuppressed state has generated much basic and
clinical research since the 1980s and recent development of several new
antifungal drugs. Despite these efforts and advancements, high mortality is at
least in part resultant from difficulties in establishing confirmed diagnoses.
Diagnostic difficulties have led to potentially inappropriate “empirical”
antifungal administration strategies and over-utilization of antifungals and lack
of appropriate therapy in the setting of established disease. Currently,
appreciation of emerging resistance to several antifungal drugs complicates
treatment decisions in the absence of microbial diagnoses. It appears that the field
is largely at an impasse, awaiting development of new diagnostics.
Establishing the diagnosis of fungal infections is complicated, in part
because these organisms are typically difficult to recover in the laboratory, either
by laboratory culture, or by histopathological identification. Laboratory recovery
of fungi has been improved in some settings; for instance, blood culture of
Candida species has been facilitated with improvements in culture systems.
However, other organisms remain elusive. For instance, filamentous organisms
continue to be difficult to recover in culture, even in the presence of documented
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iv Preface
disease with visualized fungal fragments under the microscope. Recent
observations suggest that there may be ways to improve laboratory cultivation
of such organisms by adjusting growth conditions; however, optimized culture
conditions appear to be relatively far from current practice. Other fungi, such as
Pneumocystis, have never been cultivated in either clinical or basic research
laboratories; we obviously have much to learn about fungal cultivation in the
laboratory.
Given the complexities in obtaining diagnoses based on isolating
organisms in the laboratory, efforts are now focused on developing diagnostics
based on serologic tests, antigen identification, and advanced methods for
detecting fungal nucleic acids. These tests have been in use for identifying
endemic fungi, such as Histoplasma, for quite some time, and efforts have led
towards relative optimization. However, other tests that detect Candida species
and filamentous organisms are relatively younger in development and use, with
differences in local and regional expertise guiding a great deal of variability in
utilization. Other molecular tests that rely on polymerase chain reaction for
identification of nucleic acids have become increasingly explored in research
laboratories and are reaching some clinical microbiology laboratories. Much
needs to be learned in order to most effectively use these types of tests for
adjunctive diagnostics and for development of preventative strategies.
This book is focused on fungal diagnostics; it is timely in both the
increasing toll of fungal infections worldwide, and in the heterogeneity of
diagnostic practices. We have attempted to provide both a historical perspective
and an update on state-of-the-art diagnostics, in both the general sense (Part I),
and with considering the approach to specific infections (Part II).
In Part I, considerations of fungal diagnostics are discussed, with chapters
that are focused on general methods. Establishing a clinical diagnosis with
consideration of signs and symptoms is the first topic. Conventional diagnostics
tools, including the roles of clinical microbiology and pathology laboratories,
are discussed in the next chapter. Radiology, which is the staple for identification
of fungal pneumonias, is addressed in one complete chapter. Following chapters
deal with serodiagnostics, use of fungal metabolites, and molecular diagnostics;
these chapters are not microbe-specific, but address multiple issues and tests
across different pathogenic fungi.
Part II provides a more complete and detailed discussion of diagnostic
methods for the most common superficial and invasive fungal infections.
Specific chapters address superficial infections, mould infections, Candida and
Cryptococcus infections, Pneumocystis, and endemic mycoses. These chapters
all provide historical perspectives, as well as state-of-the-art approaches to
diagnosing infectious complications in different hosts. Chapter 13 addresses the
increasingly appreciated complication of fungal involvement in hypersensitivity
and allergic conditions. The final chapter in the book raises perhaps the most
“futuristic” issue concerning fungal diagnosis, which is molecular identification
of emerging fungal pathogens, and our increasing understanding that as yet
Preface v
undiscovered organisms are the cause of disease states that have been historically
considered to be non-infectious conditions. This topic is an apropos ending to
summarize the general theme of the book, which is that we have learned a great
deal, but we still have a great deal more to learn about fungal diagnostics.
This monograph is intended to offer both practical advice and to spur
thoughts leading to new research. Our hope is that this will be found useful to
laboratorians as well as clinicians of all varieties. The authors have provided
both detailed reviews and thorough references. We acknowledge, at the onset,
that there is much to be learned; with this in mind, we hope that this can be an
effective platform from which gaps in knowledge can be identified and,
subsequently, filled.
Johan A. Maertens, M.D.
Kieren A. Marr, M.D.