Fungal Infection

Diagnosis and Management

Malcolm D. Richardson, David W. Warnock

• Publisher: Wiley-Blackwell
• Year: 2012
• ISBN:
  9781444361001
• Edition: 4
• Topic: Medicina
• Subtopic: Enfermedades infecciosas

Fungal Infection: Diagnosis and Management, 4th Edition is a concise and up-to-date guide to the clinical manifestations, laboratory diagnosis and management of superficial, subcutaneous and systemic fungal infections.

This highly acclaimed book has been extensively revised and updated throughout to ensure all drug and dosage recommendations are accurate and in agreement with current guidelines. A new chapter on infections caused by Pneumocystis jirovecii has been added. The book has been designed to enable rapid information retrieval and to help clinicians make informed decisions about diagnosis and patient management. Each chapter concludes with a list of recent key publications which have been carefully selected to facilitate efficient access to further information on specific aspects of fungal infections.

Clinical microbiologists, infectious disease specialists, as well as dermatologists, hematologists and oncologists, can depend on this contemporary text for authoritative information and the background necessary to understand fungal infections.

CHAPTER 1

Introduction

The last several decades have seen unprecedented changes in the pattern of fungal infections in humans. These diseases have assumed a much greater importance because of their increasing incidence in persons with the acquired immunodeficiency syndrome (AIDS), in recipients of solid organ or haematopoietic stem cell transplants (HSCT), in persons with haematological malignancies and in other debilitated or immunocompromised individuals. Although gains have been made in the treatment and prevention of fungal disease, major changes in health care practices have resulted in the emergence of new at-risk populations.

1.1 The nature of fungi

The fungi form a large, diverse group of organisms, most of which are found as saprophytes in the soil and on decomposing organic matter. They are eukaryotic, but differ from other groups, such as plants and animals, in several major respects. First, fungal cells are encased within a rigid cell wall, mostly composed of polysaccharides (glucan, mannan), chitin and glycoproteins in various combinations. This feature contrasts with animals, which have no cell walls, and plants, which have cellulose as the major cell wall component. Second, fungi are heterotrophic. This means that they are lacking in chlorophyll and therefore require preformed organic carbon compounds for their nutrition. Fungi obtain their nourishment by secreting enzymes for external digestion and by absorbing the released nutrients through their cell wall. Third, fungi are simpler in structure than plants or animals. There is no division of cells into organs or tissues. The basic structural unit of fungi is either a chain of tubular, filament-like cells (termed hypha) or an independent single cell (termed yeast). Fungal cell differentiation is no less sophisticated than is found in plants or animals, but it is different. Many fungal pathogens of humans and animals change their growth form during the process of tissue invasion. These dimorphic pathogens usually change from a multicellular hyphal form in the natural environment to a budding, single-celled yeast form in tissue.

In most multicellular fungi, the vegetative stage consists of a mass of branching hyphae, termed mycelium. Each individual hypha has a rigid cell wall and increases in length as a result of apical extension with mitotic cell division. In most fungi, the hyphae are septate, with more or less frequent cross walls. In the more primitive fungi, the hyphae usually remain aseptate (without cross walls). Fungi that exist in the form of microscopic multicellular mycelium are commonly called moulds.

Many fungi exist in the form of independent single cells. Most yeasts propagate by an asexual process called budding, in which the cell develops a protuberance from its surface. The bud enlarges and may become detached from the parent cell, or it may remain attached and itself produce another bud. In this way, a chain of cells may be produced. Under certain conditions, continued elongation of the parent cell before it buds results in a chain of elongated cells, termed pseudohypha. Some yeasts reproduce by fission of the cells. Yeasts are neither a natural nor a formal taxonomic group, but are a growth form shown in a wide range of unrelated fungi.

Moulds reproduce by means of microscopic propagules called either conidia or spores. Many fungi produce conidia that result from an asexual process (involving mitosis only). Except for the occasional mutation, these spores are identical to the parent. Asexual conidia are generally short-lived propagules that are produced in enormous numbers to ensure dispersion to new habitats. Many fungi are also capable of sexual reproduction (involving meiosis). Some species are self-fertile (homothallic) and able to form sexual structures within individual colonies. Most, however, are heterothallic and do not form their sexual structures unless two different mating strains come into contact. Meisosis then leads to the production of sexual spores. In some species, the sexual spores are borne singly on specialized generative cells and the whole structure is microscopic in size. In other cases, however, the spores are produced in millions in ‘fruiting bodies’ such as mushrooms. Many fungi can produce more than one type of spore, depending on the growth conditions, the precise method of spore production and type(s) of spore produced being unique to each species. Sexual reproduction and its accompanying structures form the main basis for classification of the fungi.

1.2 Classification and nomenclature of fungi and fungal diseases

The fungal kingdom is one of the six kingdoms of life. It is organized in a hierarchical manner and is currently divided into seven phyla, which include the Ascomycota and Basidiomycota. The phylum name Zygomycota is no longer accepted because of its polyphyletic nature. In its place, the phylum Glomeromycota and four subphyla, including the Mucoromycotina and Entomophthoromycotina, have been created pending further resolution of taxonomic questions. Historically, fungal classification has largely been based on morphological features, in particular the method of sexual spore production. In some fungi, however, the asexual stage (termed the anamorph) has proved so successful as a means of rapid dispersal to new habitats, that the sexual stage (termed the teleomorph) has diminished or even disappeared. In these fungi, the shape of the asexual spores and the arrangement of the spore-bearing structures have been of major importance in classification and identification. With the advent of DNA sequence analysis, fungal species are now defined as groups of organisms with concordant sequences at multiple different genetic loci, rather than organisms that share common morphological characteristics or organisms that can mate with one another. Even in the absence of the sexual stage, it is now often possible to assign asexual, anamorphic or mitosporic fungi to genera within the phyla Ascomycota or Basidiomycota on the basis of DNA sequence analysis.

The scientific names of fungi are subject to the International Botanical Code of Nomenclature, a convention that dates from the time when biologists regarded these organisms as ‘lower plants’. In general, the correct name for any species is the earliest name published in line with the requirements of the Code. Any later names are termed synonyms. To avoid confusion, however, the Code allows for certain exceptions. The most significant of these is when an earlier generic name has been overlooked, a later name is in general use, and a reversion to the earlier name would cause problems. Another reason for renaming a fungus is when new research necessitates the transfer of a species from one genus to another, or establishes it as the type of a new genus. Such changes are quite in order, but with the provision that the specific epithet should remain unchanged.

Many fungi bear two names, one designating their sexual stage and the other their asexual stage. Often this is because the anamorphic and teleomorphic stages were described and named at different times without the connection between them being recognized. The Code of Nomenclature permits this practice, and while the name of the teleomorph takes precedence and covers both stages, the name given to an anamorph may be used as appropriate. Thus, it is permissible to refer to a fungus by its asexual designation if this is the stage that is usually obtained in culture.

Unlike the names of fungi, the names of fungal diseases are not subject to strict international control. Their usage tends to reflect local practice. One popular method has been to derive disease names from the generic names of the causal organisms: for example, aspergillosis, cryptococcosis, histoplasmosis, etc. However, if the fungus changes its name, then the disease name has to be changed as well. For example, the term zygomycosis has been used for decades to describe infections caused by members of the class Zygomycetes. With the recent abolition of this class, the more precise terms mucormycosis and entomophtoromycosis have begun to supplant zygomycosis to describe diseases caused by species belonging to the orders Mucorales and Entomophthorales, respectively (see Chapters 13 and 20).

In 1992, a sub-committee of the International Society for Human and Animal Mycology recommended that the practice of forming disease names from the names of their causes should be avoided and that, whenever possible, individual diseases should be named in the form ‘pathology A due to (or caused by) fungus B’. This recommendation was not intended to apply to long-established disease names, such as aspergillosis, rather it was intended to offer a more flexible approach to nomenclature.

There is also much to be said for the practice of grouping together mycotic diseases of similar origins under single headings. One of the broadest and most useful of these collective names is the term ‘phaeohyphomycosis’, which is used to refer to a range of superficial, subcutaneous and systemic infections caused by any brown-pigmented mould that adopts a septate hyphal form in host tissue (see Chapter 25). The number of organisms implicated as aetiological agents of phaeohyphomycosis has increased from 16 in 1975 to more than 250 at the present time. Often these fungi have been given different names at different times, and the use of the collective disease name has helped to reduce the confusion in the literature. The term ‘hyalohyphomycosis’ is another collective name that is increasing in usage. This term is used to describe infections caused by colourless (hyaline) moulds that adopt a septate hyphal form in tissue (see Chapter 23). To date, more than 70 different organisms have been implicated, including a number of important emerging fungal pathogens, such as Fusarium species, that are not the cause of otherwise-named diseases, such as aspergillosis.

1.3 Fungi as human pathogens

There are at least 100,000 named species of fungi. However, fewer than 500 have been associated with human disease, and no more than 100 are capable of causing infection in otherwise normal individuals. The remainder is only able to produce disease in hosts that are debilitated or immunocompromised in some way. Most human infections are caused by fungi that grow as saprophytes in the environment and are acquired through inhalation, ingestion or traumatic implantation. Some yeasts are human commensals and cause endogenous infections when there is some imbalance in the host. Many fungal diseases have a worldwide distribution, but some are endemic to specific geographical regions, usually because the aetiological agents are saprophytes restricted in their distribution by environmental conditions.

Fungal infections can be classified into a number of broad groups according to the initial site of infection. Grouping the diseases in this manner brings out clearly the degree of parasitic adaptation of the different groups of fungi and the way in which the site affected is related to the route by which the fungus enters the host.

1.3.1 The superficial mycoses

These are infections limited to the outermost layers of the skin, the nails and hair, and the mucous membranes. The principal infections in this group are the dermatophytoses and superficial forms of candidosis. These diseases affect millions of individuals worldwide, but there are regional variations. They are readily diagnosed, and usually respond well to treatment.

The dermatophytes are limited to the keratinized tissues of the epidermis, hair and nail. Most are unable to survive as free-living saprophytes in competition with other keratinophilic organisms in the environment and thus are dependent on passage from host to host for their survival. These obligate pathogens seem to have evolved from unspecialized saprophytic forms. In the process, most are now no longer capable of sexual reproduction and some are even incapable of asexual reproduction. In general, these organisms have become well adapted to humans, evoking little or no inflammatory reaction from the host. Only dermatophyte infections are truly contagious.

The aetiological agents of candidosis, like the dermatophytes, are largely dependent on the living host for their survival, but differ from them in the manner by which this is achieved. These organisms, of which Candida albicans is the most important, are normal commensal inhabitants of the human digestive tract or skin. Acquisition of these organisms from another host seldom results in overt disease, but rather results in the setting-up of a commensal relationship with the new host. These organisms do not produce disease unless some change in the circumstances of the host lowers its natural defences. In this situation, endogenous infection from the host's own reservoir of the organism may result in mucosal, cutaneous or systemic infection.

Other common superficial infections include pityriasis versicolor, a mild and often recurrent infection of the stratum corneum, caused by lipophilic yeasts of the genus Malassezia. These organisms are skin commensals. Disease is probably related to host and environmental factors. Pityriasis versicolor is most common in hot, humid tropical climates.

1.3.2 The subcutaneous mycoses

These are infections of the dermis, subcutaneous tissues and adjacent bones that generally show slow localized spread. They usually result from the traumatic implantation of saprophytic fungi from soil or vegetation. More widespread dissemination of the infection, through the blood or lymphatics, is uncommon, and usually only occurs if the host is in some way debilitated or immunocompromised. The principal subcutaneous mycoses are mycetoma, sporotrichosis, phaeohyphomycosis and chromoblastomycosis. These infections are most frequently encountered among the rural populations of the tropical and sub-tropical regions of the world, where individuals go barefoot and wear the minimum of clothing.

1.3.3 The systemic mycoses

Deep-seated fungal infections usually originate in the lungs, but may spread to many other organs. These infections are most commonly acquired as a result of inhaling spores of organisms that grow as saprophytes in the environment, or as pathogens on plants.

The organisms that cause systemic fungal infection can be divided into two distinct groups: the true pathogens and the opportunists. The first of these groups is comprised of a handful of organisms, mostly dimorphic fungi that are able to invade and develop in the tissues of a normal host with no recognizable predisposition. The principal diseases are blastomycosis, coccidioidomycosis, histoplasmosis and paracoccidioidomycosis. The second group, the opportunists, consists of less virulent and less well-adapted organisms that are only able to invade the tissues of an immunocompromised host. Although new species of fungi are regularly being identified as causes of disease in immunocompromised patients, five diseases still account for most reported infections: aspergillosis, candidosis, cryptococcosis, mucormycosis and pneumocystosis.

In many instances, infections with true pathogenic fungi are asymptomatic or mild and of short duration. Most cases occur in geographical regions where the aetiological agents are found in nature and follow inhalation of spores that have been released into the environment. Individuals who recover from these infections may enjoy marked and lasting resistance to reinfection, while the few patients with chronic or residual disease often have a serious underlying illness.

In addition to their well-recognized manifestations in otherwise normal persons, infections with true pathogenic fungi have emerged as important diseases in immunocompromised individuals. Histoplasmosis and coccidioidomycosis, for instance, have been recognized as AIDS-defining illnesses. Both diseases have been seen in ...

Table of contents

• Cover
• Title Page
• Copyright
• Preface to the fourth edition
• Preface to the first edition
• Acknowledgements
• Chapter 1: Introduction
• Chapter 2: Laboratory diagnosis of fungal infection
• Chapter 3: Antifungal drugs
• Chapter 4: Dermatophytosis
• Chapter 5: Superficial candidosis
• Chapter 6: Other cutaneous fungal infections
• Chapter 7: Mould infections of nails
• Chapter 8: Keratomycosis
• Chapter 9: Otomycosis
• Chapter 10: Aspergillosis
• Chapter 11: Invasive candidosis
• Chapter 12: Cryptococcosis
• Chapter 13: Mucormycosis
• Chapter 14: Pneumocystosis
• Chapter 15: Blastomycosis
• Chapter 16: Coccidioidomycosis
• Chapter 17: Histoplasmosis
• Chapter 18: Paracoccidioidomycosis
• Chapter 19: Chromoblastomycosis
• Chapter 20: Entomophthoromycosis
• Chapter 21: Mycetoma
• Chapter 22: Sporotrichosis
• Chapter 23: Hyalohyphomycosis
• Chapter 24: Penicillium marneffei infection
• Chapter 25: Phaeohyphomycosis
• Chapter 26: Other invasive yeast infections
• Chapter 27: Unusual fungal and pseudofungal infections
• Select bibliography
• Index