1. ENDEMIC MYCOSES
Sevtap Arikan, MD

2. TRUE SYSTEMIC (ENDEMIC) MYCOSES
Coccidioidomycosis
Histoplasmosis
Blastomycosis
Paracoccidioidomycosis

3. TRUE SYSTEMIC MYCOSES General features
Causative agents: thermally dimorphic fungi that exist in nature, soil
Geographic distribution varies
Inhalation pulmonary inf.  dissemination
No evidence of transmission among humans or animals
Otherwise healthy individuals are infected

4. COCCIDIOIDOMYCOSIS Etio: Coccidioides immitis
Location: Confined to southwestern US, northern Mexico, Central and South America
Micr.: Tissue (37°C): Spherules filled with endospores
25°C: hyphae, barrel-shaped arthroconidia

5. COCCIDIOIDOMYCOSIS Pathogenesis
Inhalation of the infectious particle, arthroconidia and spherule formation in vivo
Engulfment within phagosomes by alveolar MQs
Activation of macrophages ---phagosome-lysosome fusion ---killing
Immune complex formation
deposition leading to local inflammatory rx.s
immunosupression resulting from the binding of complexes to cells bearing Fc receptors

6. COCCIDIOIDOMYCOSIS Clinical findings
PRIMARY INF.
Asymptomatic in most
Fever, chest pain, cough, weight loss
Nodular lesions in lungs
SECONDARY (DISSEMINATED) INF. (1%)
Chronic / fulminant
Infection of lungs, meninges, bones and skin

7. COCCIDIOIDOMYCOSIS Diagnosis-I
Samples: Sputum, tissue
1. Direct examination (KOH; H&E) Spherule
2. Culture
SDA: Mould colonies at 25 °C Spherule production in vitro by incubation in an enriched medium at 40°C, 20% CO2

8. COCCIDIOIDOMYCOSIS Diagnosis-II
3. Serology
Tube precipitin (IgM) test
Complement fixation
Skin test (coccidioidin and spheruline antigens) Negative result may rule out the diagnosis

9. COCCIDIOIDOMYCOSIS Treatment
Symptomatic treatment only (primary infection)
Amphotericin B
Itraconazole
Fluconazole(particularly for meningitis)

10. HISTOPLASMOSIS Etio: Histoplasma capsulatum
Natural reservoir: soil, bat and avian habitats
Location: May be prevalent all over the world, but the incidence varies widely (most endemic in Ohio, Mississipi, Kentucky)
Micr. Yeast cell in tissue (37°C)
Hyphae, microconidia and macroconidia (tuberculate chlamydospore) at 25 °C

11. HISTOPLASMOSIS Pathogenesis
Inhalation of microconidia / primary cutaneous inoculation
Conversion to budding yeast cells
Phagocytosis by alveolar macrophages
Restriction of growth or dissemination to RES by bloodstream
Supression of cell-mediated immunity

12. HISTOPLASMOSIS Clinical findings
PULMONARY INF.
Asymptomatic (%95) / mild / moderate / severe/ chronic cavitary
DISSEMINATED INF.
RES (liver, spleen, lymph nodes, bone marrow), mucocutaneous inf.
PRIMARY CUTANEOUS INF.

13. HISTOPLASMOSIS Diagnosis-I
Samples: Sputum, tissue, bone marrow, CSF, blood
1. Direct examination: Giemsa / Wright
Intra- and extracellular yeast cells
2. Culture: Mould at 25°C
Conversion to yeast on an enriched medium at 37°C

14. HISTOPLASMOSIS Diagnosis-II
3. Serology: Complement fixation...
Skin test (Histoplasmin antigen): Limited diagnostic value

15. AFRICAN HISTOPLASMOSIS
Etio: Histoplasma capsulatum var. duboisii
Differentiation from classical histoplasmosis
Larger, thick-walled yeast cells
Pronounced giant cell formation in infected tissue
Diminished pulmonary involvement
Greater frequency of skin and bone lesions

16. HISTOPLASMOSIS Treatment
Not required for several cases
Amphotericin B
Itraconazole
Surgical resection of pulmonary lesions

17. BLASTOMYCOSIS Etio: Blastomyces dermatitidis
Location: America, Africa, Asia
Micr.: Yeasts at 37°C--bud is attached to the parent cell by a broad base
Hyphae and conidia at 25 °C

18. BLASTOMYCOSIS Pathogenesis
Inhalation of infectious particles
Primary cutaneous inoculation
Infiltration of macrophages and neutrophils and granuloma formation
Oxidative killing mechanisms of neutrophils and fungicidal activity of macrophages

19. BLASTOMYCOSIS Clinical findings
ASYMPTOMATIC INF.
PULMONARY INF.
CHRONIC CUTANEOUS INF. Subcutaneous nodule, ulceration
DISSEMINATED INF.
Skin, bone, GUT, CNS, spleen
PRIMARY CUTANEOUS INF.

20. BLASTOMYCOSIS Diagnosis-I
Samples: Sputum, tissue
1. Direct micr.ic exam: KOH, H&E
Yeast cells; bud is attached to the parent cell by a broad base
2. Culture: Mould at 25°C
Conversion to yeast on an enriched medium at 37°C

21. BLASTOMYCOSIS Diagnosis-II
3. Serology: Immunodiffusion test
ELISA to detect antibodies to exoantigen A
Skin test (Blastomycin antigen) Limited/no diagnostic value

22. BLASTOMYCOSIS Treatment
Amphotericin B
Itraconazole
Fluconazole
Corrective surgery

23. PARACOCCIDIOIDOMYCOSIS
Etio: Paracoccidioides brasiliensis
Location: Central and South America
Pathogenesis: Inhalation of conidia
*The inf. is more common in males
Micr.: At 37°C (in tissue ): multiply budding yeasts; the buds are attached to the parent cell by a narrow base
At 25 °C: hyphae and conidia

24. PARACOCCIDIOIDOMYCOSIS Determinants of pathogenicity
The fungus has a protein in its cytoplasm which binds only to estrogen but not to testosterone; this binding prevents conversion to yeast form at 37°C.
Yeast cell wall polysaccharides (alpha-glucan) stimulate granuloma formation.

25. PARACOCCIDIOIDOMYCOSIS Clinical findings
ASYMPTOMATIC INF.
LATENT FORM (duration variable)
SYMPTOMATIC INF.
Noduler lesions in lungs
Dissemination to other organs (rare)

26. PARACOCCIDIOIDOMYCOSIS Diagnosis-I
Samples: Sputum, tissue
1. Direct micr.ic exam.: KOH, H&E
multiply budding yeasts; the buds are attached to the parent cell by a narrow base
2. Culture: Mould at 25°C
Conversion to yeast on an enriched medium at 37°C

27. PARACOCCIDIOIDOMYCOSIS Diagnosis-II
3. Serology: Immunodiffusion
Complement fixation

28. PARACOCCIDIOIDOMYCOSIS Treatment
Amphotericin B
Ketoconazole
Itraconazole
Sulfonamides