The 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,”). 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 pathology

Entry 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 1).

Fig1. Systemic mycoses.

B. Clinical significance

 In spite of the seemingly grave nature of potentially systemic dis ease, most cases of coccidioidomycosis, histoplasmosis, and para coccidioidomycosis in otherwise healthy patients present only mild symptoms and are self-limiting. In immunosuppressed patients, however, the same infections can be life threatening.

 1. Coccidioidomycosis: Caused by Coccidioides immitis, most cases of coccidioidomycosis occur in the arid areas of southwest ern United States (Figure 2) and Central and South America. Initial infection with C. immitis can cause fever with varying degrees of respiratory illness (called “Valley fever” because of its prevalence in the San Joaquin Valley of the southwestern United States). In the soil, the fungus generates spores by septation of hyphal filaments (arthrospores). These spores become readily air borne and enter the lungs, where they germinate and develop into large (20 to 40 μm) spherules filled with many endospores. Rupture of the spherule releases the endospores, each of which can spread by the bloodstream and then form a new spherule. In cases of disseminated disease, lesions occur most often in the bones and the central nervous system, where they result in meningitis. The spores from the hyphal filaments are easily spread, so cultivation carries a significant risk of accidental infection of laboratory personnel.

Fig2. Geographic prevalence of coccidioidomycosis in the United States.

2. Histoplasmosis: Histoplasmosis is caused by Histoplasma capsulatum. In the soil, the fungus generates conidia, which, when air borne, enter the lungs and germinate into yeast-like cells. These yeast cells are engulfed by macrophages, in which they multiply. Pulmonary infections may be acute but relatively benign and self-limiting, or they can be chronic, progressive, and fatal. Dissemination is rare but can occur in older adults, the very young, and patients with deficiencies in T-cell function. Disseminated dis ease 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 (4 to 6 weeks), or by detection of exoantigen in urine specimens. The disease occurs worldwide but is most prevalent in central North America, especially the Ohio and Mississippi River Valleys (Figure 3). 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. The wide range of clinical manifestations of histoplasmosis makes it a particularly complex disease, often resembling tuberculosis.

Fig3. Endemic areas of histoplasmosis in North America.

3. Blastomycosis: Blastomyces dermatitidis causes blastomycosis. 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 unipolar, broad-based buds. Although initial pulmonary infections (Figure 4) rarely disseminate to other sites, when dissemination does occur, secondary sites include skin (70 percent), bone (30 percent), and the genitourinary tract (20 percent), where they manifest as ulcerated granulomas. Definitive diagnosis is accomplished by isolation and culture of the organism. Identifiable colonies can be obtained in 1 to 3 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.

Fig4. Chest radiograph showing a diffuse reticulonodular infiltrate of the lungs in a male landscaper. Broncho alveolar lavage recovered Blastomyces dermatitidis.

4. Paracoccidioidomycosis: Also called South American blastomycosis, paracoccidioidomycosis 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 appearance resembling a ship’s steering wheel, caused by the presence of multiple buds (see Figure 1). The disease is restricted to Central and South America, and over 90 percent of patients with symptomatic disease are mature males. It is speculated that estrogen may inhibit formation of the yeast form.

C. Laboratory identification

These 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. Histological examination of body fluids (sputum, pus, draining fistulas) for the presence of yeasts, hyphae, or conidia allows for rapid identification of the fungal etiological agent prior to the availability of culture results. A rapid 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. The exoantigen test can also be applied to urine specimens collected from patients suffering from histoplasmosis. Polymerase chain reaction is another rapid, accurate diagnostic method that detects specific fungal DNA sequences.

 D. Treatment

 Systemic mycoses are usually treated with amphotericin B, sometimes in combination with flucytosine. Ketoconazole, fluconazole and intraconazole are also used, depending on the infecting organism and the stage and site of the disease.

مواضيع ذات صلة

Reproduction in fungi

Dermatophytoses

الفطريات الجلدية Dermatophytes

الفيومونيسينات Fumonisins

جنس Aspergillus

SUBCUTANEOUS MYCOSES

FUNGAL TOXINS & ALLERGIES

سموم ستريوفيريدين Citreoviridin المنتجة بواسطة فطر Penicillium

مكافحة السموم الفطرية

تأثير الفطريات والسموم الفطرية على الدواجن

مؤثرات وأضرار بعض السموم الفطرية

التسمم الفطري Mycotoxicosis