1. Systemic mycoses Systemic fungal infections are uncommon Natural immunity is high; physiologic barriers include: 1. Skin and mucus membranes 2. Tissue temperature - fungi grow better at less than 37°C (mesophiles) 3. Redox potential- in vivo conditions too reducing for most fungi

2. Infection requires a large inoculum and is affected by the resistance of the host • infection often occurs in endemic areas • most infections are asymptomatic or self-limiting • in immune-compromised hosts, infections are more often fatal (distinction between infection and disease)

3. Systemic fungal disease is most often associated with three organisms • 1. Coccidioides immitis • 2. Histoplasma capsulatum • Blastomyces dermatitidis • paracoccidioides

4. Coccidioidomycosis(Vally fever) • Coccidioidesimmitisis considered to be the most virulent of fungal pathogens. • Restricted to hot, semi-arid areas of SW USA and Mexico. • Grows in the soil, but inhalation of a single spore can initiate infection. Conidia In infected tissues, C. immitis appears as a mixture of hyphae and spherules. Spherules

5. Coccidioidomycosis:Normally a benign, sub-clinical upper respiratory infection In a small percentage of cases, organism disseminates from the lungs to a variety of organs, particularly the CNS, meanings, skin, soft tissues, and bone.

6. In infected tissues, organism is seen as a mixture of spherules and endospores.

7. Risk factors for disseminated coccidioidomycosis 1. Race: Filipinos > African American> Caucasian 2. Age: Extremes more susceptible 3. Sex: Males more susceptible 4. Pregnancy 5. Immunosuppression Diagnosis 1. Suppurative or granulatomas inflammation 2. Spherule or endospores seen on pathology 3. Culture of microorganisms 4. Complement fixation assay (in cerebrospinal fluid) Treatment Amphotericin B, Fluconazole

8. Blastomycosis Granulomatousmycotic infection that predominantly involves lungs and skin; but can spread to other organs. Most prevalent in males 40-60 years of age and children. Blastomyces dermatitidis Dimorphic organism originates in the soil and infection ensues by inhalation of spores. Converts to yeast in animal hosts or at 37oin vitro.

9. Blastomycosis • Encounter: Most cases are in southern, central, and southeastern USA. Infection is by inhalation of spores. • Spread: The pulmonary infection is either self -limited or progressive. Dissemination often occurs to the skin and to the bone - 80% of patients have large skin lesions; a large number also have granulomatous pulmonary lesions. • Risk Factors: Occupational contact with soil; owning a dog. Living in endemic area. • Diagnosis: based on clinical findings and microscopic detection of organisms in tissue specimens

10. Treatment • Amphotericin B is the drug of choice for rapidly progressive blastomycosis • Itraconazole or Ketoconazole for less severe cases