Mycology Lec. 4 Dr. Manahil

Endemic mycoses (systemic)   Fungal infection caused by agents that are highly virulent, can invade deeply into tissues and organs. The main disease and their etiological agents are: Histoplasmosis Histoplasm capsulatum. Blastomycosis Blastomyces dermatiditis. Coccidioidomycosis Coccidioides immitis. Paracoccidioidomycosis Paracoccidioides brasiliensis

Histoplasma capsulatum Is a dimorphic, soil saprophytics fungus. The mycosis (disease) caused by H. capsulatum known as histoplasmosis, which is an intracellular, not contagious, and man is infected by inhalation of spores. Severity of the disease related to the intensity of exposure . Histoplasmosis is the most prevalent pulmonary mycotic infection in humans. The disease is endemic in the United States but reported from different countries, and Iraq.

Pathogenesis After inhalation, the conidia (spores) develop into yeast cells and are engulfed by alveolar macrophages, where they are able to replicate. Within macrophages, the yeasts may disseminate to reticuloendothelial tissues such as liver, spleen, bone marrow, and lymph nodes. The initial inflammatory reaction becomes granulomatous.

Clinical types Asymptomatic infection which is present in about 95% of the exposed patients. The cell-mediated immune response leads to the secretion of cytokines that activate macrophage to inhibit intracellular growth of the yeasts. Acute pulmonary This type is a self-limited flu-like syndrome, with fever, chills, myalgias, and nonproductive cough. These symptoms resolve spontaneously without therapy, and the granulomatous nodules in the lungs or other sites heal with calcification.

Chronic pulmonary is usually a reactivation process, breakin gdown of a dormant lesion that may havebeen acquired years before. Severe disseminated histoplasmosis The reticuloendothelial system mainly involved with enlarged spleen and liver, high fever, anemia, and a high mortality rate if no antifungal therapy used. Primary cutaneous these are mostly laboratory acquired infection. Local, self limiting ulcers develop.

Laboratory diagnosis Direct examination Culture The media used are: B.H.I. agar with blood, Yeast extract phosphate agar, Sabouraud's agar

For the conversion of mold to yeast form, Blood glucose cysteine (BGC) agar or BHI agar with blood are commonly used media, the incubation at 37oC. Exoantigen test or nucleic acid probe test is used for rapidly confirm the final identification. For serodiagnosis, the two tests that are widely available, the immunodiffusion assay and complement fixation test.   Treatment Amphotricin B. Ketoconazole or itraconzole.

Blastomyces dermatitidis Is a dimorphic fungus. Blastomyces dermatitidis cause blastomycosis, a chronic infection with granulomatous and suppurative lesions that is initiated in the lungs. The disease is endemic for humans and dogs in the Eastern United States, but it was reported from Africa, South America, Asia, and recently from Iraq.

Pathogenesis Infection occurs by inhaling the conidia of the fungus into the alveoli, then transform at body temp. to the yeast phase, and reproduce by budding. This transformation provides a survival advantage to the infecting fungus as the thick cell wall of the yeasts provides resistance to phagocytosis and induce expression of an immune-modulating virulence factor (BAD-I) on the cell surface. The evoked pyogranulomatous inflammatory response has an initial influx of neutrophils, followed by macrophage and granuloma formation.

Clinical findings Pulmonary: About 50% of patients are asymptomatic Subacute to chronic pulmonary form: The common symptoms of this form are fever, productive or dry cough, chest pain. The lesions may be cavitary, nodular, fibrotic or mass like in appearance. Extrapulmonary: dissemination occur in patients with chronic illness and in those who are immunocompromised. When dissemination occurs, skin lesions are most common. Reactivation of the disease occur after pulmonary infection.

Diagnostic laboratory tests Specimen sputum, pus, urine, and biopsies from lesions. Microscopic appearance: Culture: The identification is confirmed by conversion of the mold form to yeast after cultivation on enriched media and incubated at 37°C for 10- 15 days. Serology: serologic tests are not useful for the diagnosis of blastomycosis as other endemic mycosis Treatment Amphotericin B. Itraconazole is effective.