| FungiI. OverviewFungi are a diverse group of saprophytic (derives nourishment from dead organic matter) and parasitic eukaryotic organisms. Although formerly considered to be plants, they are now generally assigned their own kingdom, Mycota. Virtually all organisms are subject to fungal infection. Of some 100,000 fungal species, only about 100 have pathogenic potential for humans; of these, only a few species account for most clinically important fungal infections (Figure 20.1). Human fungal diseases (mycoses) are classified by the location on or in the body where the infection occurs. They are called cutaneous when limited to the epidermis, subcutaneous when the infection penetrates significantly beneath the skin, and systemic when the infection is deep within the body or disseminated to internal organs. Systemic mycoses can be further divided into those that are caused by true pathogenic fungi capable of infecting healthy individuals, and those that are opportunistic, infecting primarily those individuals who have predisposing conditions such as immunodeficiency or debilitating diseases (for example, diabetes, leukemia, and Hodgkin and other lymphomas). Fungi produce and secrete a variety of unusual metabolic products, some of which, when ingested, are highly toxic to animals, including humans. Thus, fungi can cause poisonings as well as infections. Lastly, fungal spores are important as human allergenic agents.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.1 Classification of pathogenic
fungi (figure continues on next page). Classification of pathogenic
fungi.
| </tr></table>II. Characteristics of Major Fungal GroupsFungi can be distinguished from other infectious organisms such as bacteria or viruses because they are eukaryotes (that is, they have a membrane-enclosed nucleus). Their characteristic structures, habitats, and modes of growth and reproduction are used to distinguish between different groups of fungi.P.204A. Cell wall and membrane componentsThe fungal cell wall and cell membrane are fundamentally different from those of bacteria and other eukaryotes. Fungal cell walls are composed largely of chitin, a polymer of N-acetylglucosamine,1 rather than peptidoglycan—a characteristic component of bacterial cell walls. Fungi are, therefore, unaffected by antibiotics (for example, penicillin) that inhibit peptidoglycan synthesis. The fungal membrane contains ergosterol, rather than the cholesterol found in mammalian membranes. These chemical characteristics are useful in targeting chemotherapeutic agents against fungal infections. Many such agents interfere with fungal membrane synthesis or function. For example, amphotericin B and nystatin bind to ergosterol present in cell membranes of fungal cells. There they form pores that disrupt membrane function, resulting in cell death. Imidazole antifungal drugs (clotrimazole, ketoconazole, miconazole) and triazole antifungal agents (fluconazole and itraconazole) interact with C-14 خ±-demethylase to block demethylation of lanosterol to ergosterol. Ergosterol is a vital component of the cell membrane of fungi, and disruption of its biosynthesis results in cell death.B. Habitat and nutritionAll fungi are heterotrophs; that is, they require some preformed organic carbon source for growth. Fungi do not ingest food particles as do organisms such as protozoa (see p. 217), but depend upon transport of soluble nutrients across their cell membranes. To obtain these soluble nutrients, fungi secrete degradative enzymes (for example, cellulases, proteases, nucleases) into their immediate environment. It is this ability that enables fungi to live saprophytically on organic waste. Therefore, the natural habitat of almost all fungi is soil or water containing decaying organic matter. [Note: Some fungi can be parasitic on living organisms. However, these parasitic infections usually originate from the individual's contact with fungus-infested soil, an exception being Candida, which is part of the normal human mucosal flora (see p. 7).]<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.2 A. Filamentous (mold-like)
fungi (light micrograph). B. Budding yeast-like fungi (scanning electron
micrograph).
| </tr></table>C. Modes of fungal growthMost fungi exist in one of two basic morphologic forms (that is, either as filamentous mold or unicellular yeast). However, some fungi are dimorphic (that is, they switch between these two forms in response to environmental conditions).- Filamentous (mold like) fungi: The vegetative body, or thallus, of mold-like fungi is typically a mass of threads with many branches (Figure 20.2A). This mass is called a mycelium, which grows by branching and tip elongation. The threads (hyphae) are actually tubular cells that, in some fungi, are partitioned into segments (septate); whereas, in other fungi, the hyphae are uninterrupted by crosswalls (nonseptate). Even in septate fungi, however, the septae are perforated so that the cytoplasm of the hyphae is continuous. When hyphal filaments become densely packed, the P.205mycelium may have the appearance of a cohesive tissue. An example of this is the body of a mushroom.
- Yeast-like fungi: These fungi exist as populations of single, unconnected, spheroid cells, not unlike many bacteria, although they are some ten times larger than a typical bacterial cell (Figure 20.2B). Yeast-like fungi generally reproduce by budding.
Some fungal species, especially those that cause systemic mycoses, are dimorphic, being usually yeast-like in one environment and mold-like in another. Examples of conditions that affect the choice of morphology are temperature and carbon dioxide levels.D. SporulationSporulation is the principal means by which fungi reproduce and spread through the environment. Fungal spores are metabolically dormant, protected cells, released by the mycelium in enormous numbers. They can be borne by air or water to new sites, where they germinate and establish colonies. Spores can be generated either asexually or sexually (Figure 20.3).<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.3 Examples of: A. Asexual
sporulation. B. Sexual sporulation. Both spores are Aspergillus
nidulans.
| </tr></table>P.206- Asexual sporulation: Asexual spores (conidia) are formed by mitosis in or on specialized hyphae (conidiophores, Figure 20.3A). The color of a typical fungal colony seen on bread, fruit, or culture plate is caused by the conidia, which can number tens of millions per cm3 of surface. Because they are easily detached from their underlying mycelial mats, conidia can become airborne and, therefore, are a major source of fungal infection (see p. 209).
- Sexual sporulation: This process is initiated when a haploid nucleus from each of two compatible strains of the same species fuse to form a transient diploid (Figure 20.3B). The products of meiosis of this transient diploid become sexual spores (ascospores). Compared to asexual sporulation, sexual sporulation is relatively rare among human fungal pathogens. Spores, especially sexual spores, often have a characteristic shape and surface ornamentation pattern that may serve as the primary or only means of species identification.
E. Laboratory identificationMost fungi can be propagated on any nutrient agar surface. The standard medium is Sabouraud dextrose agar, which, because of its low pH (5.0), inhibits bacterial growth while allowing fungal colonies to form (Figure 20.4). Various antibacterial antibiotics can also be added to the medium to further inhibit bacterial colony formation. Cultures can be started from spores or hyphal fragments. Clinical samples may be pus, blood, spinal fluid, sputum, tissue biopsies, or skin scrapings. Identification is usually based on the microscopic morphology of conidial structures. Serologic tests and immunofluorescent techniques are also useful in identification of fungi from clinical isolates.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.4 Colonies of Nocardia asteroides grown on Sabouraud dextrose
agar.
| </tr></table>III. Cutaneous MycosesAlso called dermatophytoses, these common diseases are caused by a group of related fungi, the dermatophytes. Dermatophytes fall into three genera, each with many species: Trichophyton, Epidermophyton, and Microsporum.A. EpidemiologyThe causative organisms of the dermatophytoses are often distinguished according to their natural habitats: anthropophilic (residing on human skin), zoophilic (residing on the skin of domestic and farm animals), or geophilic (residing in the soil). Most human infections are by anthropophilic and zoophilic organisms. Transmission from human to human or animal to human is by infected skin scales.B. PathologyA defining characteristic of the dermatophytes is the ability to use keratin as a source of nutrition. This ability allows them to infect keratinized tissues and structures, such as skin, hair, and nails. There P.207is some specificity, however. Whereas all three genera attack the skin, Microsporum does not infect nails and Epidermophyton does not infect hair. None invade underlying, nonkeratinized tissue.C. Clinical significanceDermatophytoses are characterized by itching, scaling skin patches that can become inflamed and weeping. Specific diseases are usually identified according to affected tissue (for example, scalp, pubic area, or feet), but a given disease can be caused by any one of several organisms, and some organisms can cause more than one disease depending, for example, on the site of infection or condition of the skin. The following are the most commonly encountered dermatophytoses.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.5 Cutaneous
mycoses.
| </tr></table>- Tinea pedis (athlete's foot): Organisms most often isolated from infected tissue are Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum. The infected tissue is initially between the toes, but can spread to the nails, which become yellow and brittle. Skin fissures can lead to secondary bacterial infections, with consequent lymph node inflammation (Figure 20.5A).
- Tinea corporis (ringworm): Organisms most often isolated are E. floccosum and several species of Trichophyton and Microsporum. Lesions appear as advancing annular rings with scaly centers (Figure 20.5B). The periphery of the ring, which is the site of active fungal growth, is usually inflamed and vesiculated. Although any site on the body can be affected, lesions most often occur on nonhairy areas of the trunk.
- Tinea capitis (scalp ringworm): Several species of Trichophyton and Microsporum have been isolated from scalp ringworm lesions, the predominant infecting species depending on the geographic location of the patient. In the United States, for example, the predominant infecting species is Trichophyton tonsurans. Disease manifestations range from small, scaling patches, to involvement of the entire scalp with extensive hair loss (Figure 20.5C). The hair shafts can become invaded by Microsporum hyphae, as manifested by their green fluorescence in long-wave ultraviolet light (Wood lamp).
- Tinea cruris (“jock itchâ€): Causative organisms are E. floccosum and T. rubrum. Disease manifestations are similar to ringworm, except that lesions occur in the moist groin area, where they can spread from the upper thighs to the genitals (Figure 20.5D).
- Tinea unguium (onychomycosis): The causative organism is most often T. rubrum. The nails are thickened, discolored, and brittle. Treatment must be continued for three to four months until all infected portions of the nail grow out and are trimmed off (Figure 20.5E).
P.208D. TreatmentRemoval of infected skin, followed by topical application of antifungal antibiotics such as miconazole or clotrimazole, is the first course of treatment. Refractory infections usually respond well to oral griseofulvin and itraconazole. Infections of the hair and nails usually require systemic (oral) therapy. Terbinafine is the drug of choice for onychomycosis.IV. Subcutaneous MycosesSubcutaneous mycoses are fungal infections of the dermis, subcutaneous tissue, and bone. Causative organisms reside in the soil and decaying or live vegetation.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.6 Subcutaneous mycoses. A.
Sporotrichosis. The forearm of a gardener exhibiting the cutaneouslymphatic form
of sporotrichosis. B. Chromomycosis. Multiple plaques on the lower leg. C.
Mycetoma of the arm.
| </tr></table>A. EpidemiologySubcutaneous fungal infections are almost always acquired through traumatic lacerations or puncture wounds. Sporotrichosis, for example, is often acquired from the prick of a thorn. As expected, these infections are more common in individuals who have frequent contact with soil and vegetation and wear little protective clothing.The subcutaneous mycoses are not transmissible from human to human under ordinary conditions.B. Clinical SignificanceWith the rare exception of sporotrichosis, which shows a broad geographic distribution in the United States, the common subcutaneous mycoses discussed below are confined to tropical and subtropical regions.- Sporotrichosis: This infection, characterized by a granulomatous ulcer at the puncture site, may produce secondary lesions along the draining lymphatics (Figure 20.6A). The causative organism, Sporothrix schenckii, is a dimorphic fungus that exhibits the yeast form in infected tissue (see Figure 20.7) and the mycelial form upon laboratory culture. In most patients, the disease is self-limiting, but may persist in a chronic form. Oral itraconazole is the drug of choice.
- Chromomycosis (also called chromoblastomycosis): This infection is characterized by warty nodules that spread slowly along the lymphatics and develop crusty abscesses (Figure 20.6B). Pathogens causing this mycosis include several species of pigmented soil fungi, for example, Phialophora and Cladosporium, and the infection is most commonly seen in the tropics. Treatment is difficult. Surgical removal of small lesions is effective, but must P.209be performed cautiously and with wide margins to prevent dissemination. More advanced stages of the disease are treated with itraconazole and terbinafine.
- Mycetoma (Madura foot): Mycetoma appears as a localized abscess, usually on the feet, that discharges pus, serum, and blood through sinuses (in this usage, sinus means “abnormal channelâ€). The infection can spread to the underlying bone and results in crippling deformities (Figure 20.6C). The pathogenic agents are various soil fungi or actinomycetes (see p. 163), depending on the climate of the geographic area. Most common are Madurella grisea and Actinomadura madurae. Mycetomas appear similar to the lesions of chromomycosis, but the defining characteristic of mycetoma is the presence of colored grains, composed of compacted hyphae, in the exudate. The color of the grains (black, white, red, or yellow) is characteristic of the causative organism and, therefore, useful in identifying the particular pathogen. There is no effective chemotherapy for fungal mycetoma; the treatment is usually surgical excision.
<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.7 Tissue section showing the
budding yeast Sporothrix
schenckii.
| </tr></table>V. Systemic MycosesThe organisms responsible for systemic mycoses fall into two general categories: 1) those that infect normal healthy individuals (“true†pathogens), and 2) those that primarily infect debilitated, and/or immunocompromised individuals (“opportunistic pathogens,†see p. 385). In the United States, coccidioidomycosis, histoplasmosis, and blastomycosis are the most common systemic mycotic infections in the immunocompetent host. These infections occur in defined geographic areas where fungal pathogens are found in the soil and can be aerosolized. Clinical manifestations closely resemble those seen in tuberculosis in that asymptomatic primary pulmonary infection is common, whereas chronic pulmonary or disseminated infection is rare. The fungi causing these diseases are uniformly dimorphic, exhibiting the yeast form in infected tissue, and the mycelial form in culture or in their natural environment.A. Epidemiology and pathologyEntry into the host is by inhalation of airborne spores, which germinate in the lungs. From the lungs, dissemination can occur to any organ of the body where the fungi can invade and destroy tissue (Figure 20.
.B. Clinical significanceIn spite of the seemingly grave nature of potentially systemic disease, most cases of coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis in otherwise healthy patients present only mild symptoms and are self-limiting. In immunosuppressed patients, however, the same infections can be life-threatening.P.210<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.8 Systemic
mycoses.
| </tr></table>P.211- Coccidioidomycosis is caused by Coccidioides immitis. Most cases of coccidioidomycosis occur in the arid areas of southwestern United States (Figure 20.9) and Central and South America. In the soil, the fungus generates spores by septation of hyphal filaments (arthrospores). These spores become readily airborne and enter the lungs, where they germinate and develop into large (twenty to forty آµm) spherules filled with many endospores. Rupture of the spherule releases the endospores, each of which can form a new spherule. In cases of disseminated disease, lesions occur most often in the bones and the central nervous system (CNS) where they result in meningitis.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.9 Geographic prevalence of
coccidioidomycosis in the United
States.
| </tr></table> - Histoplasmosis is caused by Histoplasma capsulatum. In the soil, the fungus generates conidia, which, when airborne, enter the lungs and germinate into yeast-like cells. These yeast cells become engulfed by macrophages in which they multiply. Pulmonary infections may be acute but relatively benign and self-limiting, or chronic, progressive, and fatal. Dissemination is rare. Disseminated disease results in invasion of cells of the reticuloendothelial system, which distinguishes this organism as the only fungus to exhibit intracellular parasitism. Definitive diagnosis is by isolation and culture of the organism, which is a slow process taking four to six weeks, or by detection of exoantigen, which can be completed in several days. The disease occurs worldwide, but is most prevalent in central North America, especially the Ohio and Mississippi River Valleys (Figure 20.10). Soils that are laden with bird, chicken, or bat droppings are a rich source of H. capsulatum spores. Local epidemics of the disease can occur, in particular, in areas where construction has disturbed bird, chicken, and bat roosts. AIDS patients who live in or travel through endemic areas are especially at risk.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.10 Endemic areas of
histoplasmosis in North America.
| </tr></table> - Blastomycosis is caused by Blastomyces dermatitidis. Like Histoplasma, the fungus produces microconidia, most often in the soil, which become airborne and enter the lungs. There they germinate into thick-walled yeast cells that often appear with buds. Initial pulmonary infections (Figure 20.11) rarely disseminate to other sites; however, when dissemination occurs, secondary sites include skin (seventy percent), bone (thirty percent), and genitourinary tract (twenty percent), where they manifest as ulcerated granulomas. Definitive diagnosis is accomplished by isolation and culture of the organism. Identifiable colonies can be obtained in one to three weeks, but identity can be established more rapidly by subjecting the young mycelial colonies to an exoantigen test. Infections are most common in the South Central and South Eastern United States, and are much more common in adult males than in females or children.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.11 Chest radiograph showing a
diffuse reticulonodular infiltrate of the lungs in a male landscaper.
Bronchoalveolar lavage recovered Blastomyces
dermatitidis.
| </tr></table>P.212 - Paracoccidioidomycosis, also called South American blastomycosis, is caused by Paracoccidioides brasiliensis. The clinical presentation is much like that of histoplasmosis and blastomycosis except that the most common secondary site of infection is the mucosa of the mouth and nose, where painful, destructive lesions may develop. Like other dimorphic pathogens, morphologic identification via conidia is slow, but the yeast form observed in infected tissue or exudates has a characteristic ship's steering wheel appearance caused by the presence of multiple buds (see Figure 20.. The disease is restricted to Central and South America, and over ninety percent of patients with symptomatic disease are mature males. It is speculated that female sex hormones may inhibit formation of the yeast form.
<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.12 Commonly reported pathogens
from urinary tract infections in patients in adult medical intensive care
units.
| </tr></table>The wide range of clinical manifestations of histoplasmosis makes it a particularly complex disease, often resembling tuberculosis.C. Laboratory identificationThese diseases are not communicable from one person to another. However, laboratory cultures should be handled cautiously, especially those of C. immitis, because under culture conditions the fungi revert to the spore-bearing, infectious form. Because these organisms have slow growth rates, morphologic identification of the characteristic conidia can take several weeks. A rapid and simple method for identifying the four systemic pathogens discussed above is the exoantigen test in which cell-free antigens produced by young mycelial colonies (or liquid cultures) are detected by immunodiffusion assay. A rapid and accurate diagnostic method uses nucleic acid probes that detect specific fungal sequences.D. TreatmentSystemic mycoses are usually treated with amphotericin B, sometimes in combination with flucytosine. Ketoconazole, fluconazole, and itraconazole are also used, depending on the stage and site of the disease.VI. Opportunistic MycosesOpportunistic mycoses afflict debilitated or immunocompromised individuals, and are rare in healthy individuals. The use of immunosuppressive drugs for organ transplantation, widespread use of chemotherapy in cancer treatment, and the high frequency of immunodeficient individuals caused by the AIDS epidemic have resulted in significant expansion of the immunocompromised population, as well as increasing the spectrum of opportunistic fungal pathogens.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.13 Candida
albicans.
| </tr></table>Fungal infections represent approximately fifteen percent of all nosocomial infections in intensive care units in the United States, with Candida species being the most commonly occurring fungal pathogen (Figure 20.12).P.213The opportunistic mycoses most commonly encountered today include the following.- Candidiasis (candidosis) is caused by the yeast Candida albicans, and other Candida species, which are normal body flora found in the skin, mouth, vagina, and intestines. Although considered a yeast, C. albicans is dimorphic, and can form a true mycelium (Figure 20.13). Infections occur when competing bacterial flora are eliminated, for example, by antibacterial antibiotics, allowing the yeast to overgrow. Candida infections have various manifestations depending on the site. For example, oral candidiasis (thrush) presents as raised, white plaques on the oral mucosa, tongue, or gums (Figure 20.14). The plaques can become confluent and ulcerated and spread to the throat. Most HIV-positive individuals eventually develop oral candidiasis, which often spreads to the esophagus. The latter condition is considered an indicator of full-blown AIDS. Vaginal candidiasis presents as itching and burning pain of the vulva and vagina, accompanied by a thick or thin white discharge. HIV-positive females often experience recurrent vaginal candidiasis. Systemic candidiasis is a potentially life-threatening infection that occurs in debilitated individuals, cancer patients (with neutropenia secondary to chemotherapy), individuals on systemic corticosteroids, and patients treated with broad-spectrum antibiotics. Systemic candidiasis may involve the gastrointestinal tract, kidneys, liver, and spleen. Both oral and vaginal infections are treated topically with nystatin or clotrimazole. Oral systemic antifungal agents such as ketoconazole, fluconazole, and itraconazole are preferred for ease of administration and increased efficacy. Amphotericin B by itself or in combination with flucytosine is used in systemic disease.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.14 Oral candidiasis
(thrush).
| </tr></table> - Cryptococcosis is caused by the yeast Cryptococcus neoformans (Figure 20.15), which is found worldwide. The organism is especially abundant in soil containing bird (especially pigeon) droppings, although the birds are not infected. The organism has a characteristic thick capsule that surrounds the budding yeast cell, which is observable on a background of India ink. A positive India ink test on cerebral spinal fluid (CSF) can give a quick diagnosis of cryptococcal meningitis, but false negatives are common. The most common form of cryptococcosis is a mild, subclinical lung infection. In immunocompromised patients, the infection often disseminates to the brain and meninges, with fatal consequences. However, about half of patients with cryptococcal meningitis have no obvious immunologic defect.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.15 Cryptococcosis
neoformans.
| </tr></table><table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.16 Aspergillus
species.
| </tr></table>The antifungal drugs used to treat cryptococcosis are amphotericin B and flucytosine, the precise treatment regimen depending on the stage P.214of disease, site of infection, and whether the patient has AIDS. Fluconazole is the drug of choice for prevention of cryptococcal meningitis in AIDS patients.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.17 Fungus
ball.
| </tr></table> - Aspergillosis is caused by several species of the genus Aspergillus, but primarily by Aspergillus fumigatus. Aspergillus is rarely pathogenic in the normal host, but can produce disease in immunosuppressed individuals and patients treated with broad-spectrum antibiotics. The disease has a worldwide distribution. Aspergilli are ubiquitous, growing only as filamentous molds (Figure 20.16) and producing prodigious numbers of conidiospores. They reside in dust and the soil, decomposing organic matter. In fact, hospital outbreaks affecting neutropenic patients (that is, those with decreased neutrophils in their blood) have been traced to dust from neighboring construction work. Aspergillosis manifests itself in several forms, depending in part on the immunologic state of health of the patient.
- Acute aspergillus infections: The most severe, and often fatal, form of aspergillosis is acute invasive infection of the lung, from which the infection can be disseminated to the brain, gastrointestinal tract, and other organs. A less severe, noninvasive lung infection gives rise to a fungus ball (aspergilloma), a mass of hyphal tissue that can form in lung cavities derived from prior diseases, such as tuberculosis (Figure 20.17). Although the lung is the most common primary site of infection, the eye, ear, nasal sinuses, and skin can also be primary sites.
- Diagnosis and treatment: Definitive diagnosis of an aspergillus infection is afforded by detection of hyphal masses, and isolation of the organism from clinical samples. Aspergillus hyphae characteristically form V-shaped branches (septate hyphae that branch at a 45-degree angle, see Figure 20.16) that are distinguished from Mucor species, which form right-angle branches. Also, septae are present in aspergillus hyphae but absent from mucor hyphae. In culture, the spore-bearing structures of the aspergilli are unmistakable but, because these organisms are so ubiquitous, external contamination of clinical samples can give false-positives. Treatment of aspergillus infections is typically by amphotericin B and surgical removal of fungal masses or infected tissue. The antifungal drugs miconazole, ketoconazole, and fluconazole have not proved useful, although itraconazole has been used with some effectiveness for Aspergillus osteomyelitis.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>
| [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.18 Rhizopus
oryzae.
| </tr></table>
Mucormycosis is caused most often by Rhizopus oryzae (also called R. arrhizus, Figure 20.18) and less often by other members of the Order Mucorales, such as Absidia corymbifera and Rhizomucor pusillus. Like the aspergilli, these organisms are ubiquitous in nature, and their spores are found in great abundance on rotting fruit and old bread. Mucor infections occur worldwide, but are almost entirely restricted to individuals with some underlying predisposing condition, such as burns, leukemias, or acidotic states such as diabetes mellitus. The most common form of the disease, which can be fatal within one week, is rhinocerebral mucormycosis, in which the infection begins in the nasal mucosa or sinuses and progresses to P.215the orbits, palate, and brain. Because the disease is so aggressive, many cases are not diagnosed until after death. Treatment is based on high-dose amphotericin B, but must be accompanied, when possible, by surgical debridement of necrotic tissue, and correction of the underlying predisposing condition. Antifungal drugs other than amphotericin have not proven useful. With early diagnosis and optimal treatment, about half of diabetic patients survive rhinocerebral mucormycosis; however, prognosis is very poor for leukemic patients.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.19 Pneumocystis
jiroveci.
| </tr></table>Pneumocystis jiroveci pneumonia is caused by the unicellular eukaryote, P. jiroveci (formerly, P. carinii). Before the use of immunosuppressive drugs and the onset of the AIDS epidemic, infection with this organism was a rare occurrence. It is one of the most common opportunistic diseases of individuals infected with HIV-1 (see Figure 33.10, p. 388) and almost 100 percent fatal if untreated.Classification: Previously, P. jiroveci had been considered a protozoan, but recent molecular homology studies of both protein and nucleic acid sequences strongly indicate that P. jiroveci is a fungus related to the ascomycetous yeasts. However ergosterol, which is an essential component of most fungal membranes, is lacking in P. jiroveci. It has so far not been possible to cultivate P. jiroveci in culture, limiting understanding of its life cycle.<table class="FIGURE" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr><tr>Figure 20.20 Pneumocystis
pneumonia.
| </tr></table>Pathology: The infectious form and the natural reservoir of this organism have not been identified, but they must be ubiquitous in nature because almost 100 percent of children worldwide have antipneumocystis antibodies. The disease is not transmitted from person to person. Instead, development of P. jiroveci in immunodeficient patients is thought to be by activation of preexisting dormant cells in the lungs. The encysted forms induce inflammation of alveoli, resulting in production of an exudate that blocks gas exchange. Figure 20.20 shows typical radiographic findings in Pneumocystis pneumonia.Diagnosis and treatment: Because P. jiroveci cannot be cultivated, diagnosis is based on microscopic examination of biopsied lung tissue or washings. The most effective therapy is a combination of sulfamethoxazole and trimethoprim, which is also used prophylactically to prevent infection in AIDS patients. Aggressive treatment can spare about half of patients.In AIDS patients, cryptococcosis, the second most common fungal infection (after candidiasis), is potentially the most serious.Because the mechanism of action of many antifungal drugs, such as amphotericin, involves interfering with ergosterol synthesis or function, these drugs are useless for ergosterol-lacking fungi.P.216Study QuestionsChoose the ONE correct answer20.1 A component of the cell membrane of most fungi isA. cholesterol.B. chitin.C. ergosterol.D. peptidoglycan.E. keratin.[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]Correct answer = C. Ergosterol in fungi is the functional equivalent of cholesterol in higher organisms. Peptidoglycan is a component of the bacterial cell wall, whereas chitin is a component of the cell wall of fungi. [Note: Chitin also comprises the exoskeletons of insects and crustacea.] Keratin is the major protein of hair and nails.20.2 A physician visiting a rural Latin American village finds that many mature males but few immature males or females of any age are afflicted by a particular fungal disease. What is likely to be the diagnosis?A. MycetomaB. BlastomycosisC. ParacoccidioidomycosisD. MucormycosisE. Histoplasmosis[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]Correct answer = C. For some reason, possibly hormonal, this disease favors mature males.20.3 A fungus that can attack hair isA. Trichophyton.B. Rhizopus.C. Microsporum.D. Sporothrix.E. Epidermophyton.[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]Correct answer = C. All attack skin, but only Microsporum attacks hair.20.4 A farmer in Mississippi presents with a chronic cough. Chest radiograph reveals an opaque mass. Biopsy of the lung shows macrophages with multiple yeast forms. Which one of the following diagnoses is most likely?A. CoccidioidomycosisB. HistoplasmosisC. BlastomycosisD. ParacoccidioidomycosisE. Sporotrichosis[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]Correct answer = B. Histoplasmosis is caused by Histoplasma capsulatum. In the soil, the fungus generates conidia, which, when airborne, enter the lungs and germinate into yeast-like cells. These yeast cells become engulfed by macrophages in which they multiply. Pulmonary infections may be acute but relatively benign and self-limiting or chronic, progressive and fatal. Dissemination is rare. The disseminated disease results in invasion of cells of the reticuloendothelial system, which distinguishes this organism as the only fungus to exhibit intracellular parasitism. The disease occurs worldwide, but is most prevalent in central North America, especially the Ohio and Mississippi River Valleys.<table border="0" cellpadding="0" cellspacing="0"><tr>[ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذه الصورة] | </tr></table>
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