Lecture 7: Mycoses Caused by Dimorphic Fungi, Part I

Transcription

1 BIOL 4849 Medical Mycology Summer 2006 Histoplasmosis Lecture 7: Mycoses Caused by Dimorphic Fungi, Part I u Most common endemic mycotic disease in the United States u Two different varieties (actually three) Q Histoplasma capsulatum var. capsulatum - found in the U.S. Q Histoplasma capsulatum var. capsulatum - causes African histoplasmosis which has a different clinical manifestation u H. capsulatum is a thermally dimorphic fungus Q <35 C - grows as mold Q 35 C-37 C - grows as a budding yeast u Endemic area Q Mississippi and Ohio River valleys Q Most people in this region are infected during childhood u Infection occurs worldwide Q H. capsulatum - associated with droppings of birds (e.g., chickens, blackbirds) and bats l Birds aren t infected, but can carry the pathogen l Bats are infected and secrete the fungus in their feces Q H. duboisii - ecological niche is unknown, but some cases associated with bats u Infection is typically via the inhalation of conidia leading to pulmonary involvement u Severity of disease is dependent upon the number of inhaled conidia Q Most cases are mild or asymptomatic Q Acute pulmonary/progessive form Q Systemic disease - immune compromised u Histoplasma Q Mold form produces two types of conidia - macroconidia (tuberculate) and microconidia Q Yeast form l Var. capsulatum - tiny, budding yeasts l Var. duboisii - larger budding yeasts in chains u Microconidia are inhaled and are subsequently phagocytized Q Grow as yeast cells in the phagolysosome, thereby surviving killing Q Macrophages transport the fungus throughout the body Page 1 of 5

2 u Clinical manifestations Q Acute pulmonary - most cases tend to be self-limiting l Sporadic l Epidemic l Chronic cavitary - occurs almost exclusively in older males with underlying pulmonary disease l Complications of pulmonary disease include mediastinal granuloma, fibrosing mediastiniti, broncholithiasis, and pericarditis Q Disseminated l Acute - occurs primarily in immunosuppressed patients and infants l Chronic progressive - typically occurs in non- immunocompromised mid-aged to older adults l Endocarditis - uncommon manifestation of disseminated disease Q Focal organ system involvement u Diagnosis l Central nervous system - resulting from disseminated disease or as an isolated manifestation of infection by H. capsulatum l Other organs F Osteoarticular F Gastrourinary tract F Ocular F Others Q Culture - up to 6 weeks l Conversion of mold to yeast phase l DNA probes Q Antigen tests/serology/skin tests Q Histopathology l Very small (2-4 µm) budding yeasts (not readily visible by H&E stain) l Yeasts often observed within macrophages Page 2 of 5

3 u Treatment Q Acute pulmonary disease l Most recover within one month without therapy l If recovery is longer, may require itraconazole l Complications of pulmonary disease (e.g., pericarditis), are more difficult to treat, if at all, and treatment often doesn t affect outcome Q Disseminated disease l Severe forms - amphotericin B l Less server forms - itraconazole Q Central nervous system infection - amphotericin B followed by azole therapy l Fluconazole - achieves high concentrations in tissue, but is less effective l Itraconazole - lower concentrations in tissues, but more effective l Administration of azoles Blastomycosis F At least 12 month course F Some patients need to be on life-long azole suppressive therapy u Endemic disease of the United States caused by Blastomyces dermatitidis u Thermally dimorphic Q 25 C - grows as mold Q 37 C - grows as a round, thick-walled budding yeast u Sexual state - Ajellomyces dermatitidis u Disease occurs in normal hosts Q Sporadic cases Q Epidemic cases u Endemic region includes most of the mid-western US and Canada along the Mississippi and Ohio rivers Q Environmental source not well known Q Associated with soil, particular in wet areas u Disease begins with the inhalation of spores Q Fungus appears to be readily susceptible to killing by macrophages in some individuals Q In individuals not clearing the fungus, the spores convert to budding yeasts in the lung and can spread hematogenously Q Can spontaneously resolve, only to reactivate later Page 3 of 5

4 u Clinical manifestations Q General information l Frequently misdiagnosed l One possible key to diagnosis - does the family dog have blastomycosis? l Not routinely transmissible from person-to-person or animal-to-person, though cases of: F Dog to human via bite F Sexual transmission via penile lesion l Adult males more likely to be infected than females; children rarely acquire blastomycosis Q Pulmonary disease l Presents as pneumoniae in most patients F Acute - appears similar to bacterial pneumoniae F Chronic - often mistaken, if not properly diagnosed, for tuberculosis or lung cancer l In contrast, come patients with pulmonary infiltrates may have no symptoms l Infrequently causes adult respiratory syndrome that leads to lung failure Q Extrapulmonary manifestations u Diagnosis l Cutaneous disease F May occur with or without pulmonary symptoms F Often misdiagnosed as skin cancer l Bone disease - affects up to 25% of patients l Joint disease l Genitourinary disease l Central nervous system disease l Other organs/tissues Q Culture of fungus within 2-4 weeks Q Direct microscopic observation of yeasts in specimens Q Skin testing and serology are poor in deriving a diagnosis Page 4 of 5

5 u Treament Q Non-life threatening infections l Ketoconazole l Fluconazole l Itraconazole - drug of choice; 6 month therapy Q Severe, life-threatening infections - initial therapy with amphotericin B, followed by itraconazole Page 5 of 5