ENDEMIC MYCOSES

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. COCCIDIOIDOMYCOSISPathogenesis • 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. HISTOPLASMOSISPathogenesis • 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. HISTOPLASMOSISClinical 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. HISTOPLASMOSISTreatment 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. BLASTOMYCOSISPathogenesis • 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. PARACOCCIDIOIDOMYCOSISDeterminants 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. PARACOCCIDIOIDOMYCOSISClinical findings • ASYMPTOMATIC INF. • LATENT FORM (duration variable) • SYMPTOMATIC INF. • Noduler lesions in lungs • Dissemination to other organs (rare)

26. PARACOCCIDIOIDOMYCOSISDiagnosis-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. PARACOCCIDIOIDOMYCOSISDiagnosis-II 3. Serology:Immunodiffusion Complement fixation

28. PARACOCCIDIOIDOMYCOSISTreatment • Amphotericin B • Ketoconazole • Itraconazole • Sulfonamides