PULMONARY FUNGAL DISEASES DR. ZIAD ELNASSER

FUNGI More than 200,000 species. More than 200,000 species. Eucaryotes. Eucaryotes. Chronic diseases. Chronic diseases.

STRUCTURE No peptidoglycan, glycerol, LPS, or teichoic acids. No peptidoglycan, glycerol, LPS, or teichoic acids. Cell wall is formed of Polysaccharides, Mannan, Glucan, and Chitin. Cell wall is formed of Polysaccharides, Mannan, Glucan, and Chitin. Determinants of serologic specificity. Determinants of serologic specificity. Chitin is similar to crab shells or cellulose of plansts. Chitin is similar to crab shells or cellulose of plansts.

METABOLISM Heterotrophic, decaying organic matter. Heterotrophic, decaying organic matter. Strict aerobes, some are anaerobes. Strict aerobes, some are anaerobes. Asexual vs Sexual reproduction, Conidia vs Spores. Asexual vs Sexual reproduction, Conidia vs Spores.

GROWTH AND MORPHOLOGY Size µ up to visible structures. Size µ up to visible structures. Two courses YEAST and or MOLD. Two courses YEAST and or MOLD. Yeasts buds produce blastoconidia. Yeasts buds produce blastoconidia. Colonies. Colonies. Molds form Hyphae then Mycelium, Septa. Molds form Hyphae then Mycelium, Septa. Aerial, or Rhizoids. Aerial, or Rhizoids. Pseudohyphae. Pseudohyphae.

GROWTH AND MORPHOLOGY Conidia on a condiophore. Conidia on a condiophore. Macroconidia, Microconidia. Macroconidia, Microconidia. Chlamydoconidia. Chlamydoconidia. Arthroconidia Arthroconidia Ascospores Ascospores Dimorphic fungi. Dimorphic fungi.

CLASSIFICATION Depends on spores, septation. Depends on spores, septation. Zygomycetes. Zygomycetes. Ascomycetes. Ascomycetes. Basidiomycetes. Basidiomycetes. Deuteromycetes (Fungi imperfecta). Deuteromycetes (Fungi imperfecta).

CLASSIFICATION Superficial Mycosis. Superficial Mycosis. Subcutaneous Mycosis. Subcutaneous Mycosis. Opportunistic Fungi. Opportunistic Fungi. Systemic Mycosis. Systemic Mycosis.

OPPORTUNISTIC FUNGI Candida, Aspergillus, and others. Candida, Aspergillus, and others. Normal flora, or environmental. Normal flora, or environmental. Superficial to systemic infections. Superficial to systemic infections. Associated with low CMI status. Associated with low CMI status.

CANDIDA Candida albicans are the most seen. Candida albicans are the most seen. Normal flora GIT, and female vagina. Normal flora GIT, and female vagina. Budding yeast, can form pseudohyphae and chlamydoconidia. Budding yeast, can form pseudohyphae and chlamydoconidia. Germ tube formation is diagnostic. Germ tube formation is diagnostic.

CANDIDIASIS Endogenous flora, Sexual intercouse, Nosocomial, and invasive procedures. Endogenous flora, Sexual intercouse, Nosocomial, and invasive procedures. Adherence associated with the hyphal form. Adherence associated with the hyphal form. Binding to the extra cellular matrix. Binding to the extra cellular matrix. Proteinase activity. Proteinase activity. Antibiotics abuse, Leukopenia, indwelling devices. Antibiotics abuse, Leukopenia, indwelling devices. Diabetes meletis. Diabetes meletis.

IMMUNITY Humoral and CMI. Humoral and CMI. Neutrophiles. Neutrophiles. Binding to iC3b receptors and phagocytosis. Binding to iC3b receptors and phagocytosis. Mannan down regulate CMI. Mannan down regulate CMI. Cytokines play a positive role. Cytokines play a positive role.

CLINICAL MANIFESTATIONS Plaques, oral thrush. Plaques, oral thrush. Vagina: Thick discharge, itching, 5% recurrent infections. Vagina: Thick discharge, itching, 5% recurrent infections. Diaper rash, skin folds. Diaper rash, skin folds. Chronic mucocutaneous candidiasis. Chronic mucocutaneous candidiasis. Eosophigitis, gastritis, enteritis, ulcers. Eosophigitis, gastritis, enteritis, ulcers. UTI, systemic, endophthalmitis. UTI, systemic, endophthalmitis.

LABORATORY DIAGNOSIS Microscopy. Microscopy. Direct aspirate, Biobsy, and BAL. Direct aspirate, Biobsy, and BAL. Arterial vs venous blood for culture. Arterial vs venous blood for culture. Blood plates, SAB. Blood plates, SAB. Germ tube test. Germ tube test. Serology. Serology.

TREATMENT Amphotericin B. Amphotericin B. Nystatin. Nystatin. Flucytosine. Flucytosine. Azoles. Azoles. Amphotericin B and Fluconazole Amphotericin B and Fluconazole Remove catheters. Remove catheters. Control Diabetes. Control Diabetes.

ASPERGILLUS Rapid growers, Septate hyphae, fluffy colonies. Rapid growers, Septate hyphae, fluffy colonies. Aspergillus fumigatus, A. flavus, A. niger. Aspergillus fumigatus, A. flavus, A. niger. Environmental disruption, building remodeling, Nosocomial. Environmental disruption, building remodeling, Nosocomial. Immunocomromized, inhalation. Immunocomromized, inhalation. Interference with opsonophagocytosis. Interference with opsonophagocytosis. Neutrophile killing is crucial. Neutrophile killing is crucial.

CLINICAL MANIFESTAION Allergic aspergillosis. Allergic aspergillosis. Farmers lung syndrome. Farmers lung syndrome. Exacerbation of asthmatic attacks. Exacerbation of asthmatic attacks. Invasive aspergillosis, predisposing lesion and pneumonia. Invasive aspergillosis, predisposing lesion and pneumonia.

DIAGNOSIS Common contaminant. Common contaminant. Lung aspiration, Biobsy, BAL. Lung aspiration, Biobsy, BAL. Braching septate hyphae. Braching septate hyphae. Fruiting bodies. Fruiting bodies. Serology. Serology.

TREATMENT Amphotericin B. Amphotericin B. Itraconazole. Itraconazole. Flucytosine + Amphotericin B. Flucytosine + Amphotericin B. Surgical intervension. Surgical intervension.

ZYGOMYCOSIS Mucor mycosis, Rhizopus, and Absidia. Mucor mycosis, Rhizopus, and Absidia. Soil is the source, common contaminants. Soil is the source, common contaminants. Sever immunocompromized, Diabetes. Sever immunocompromized, Diabetes. Pulmonary, Rhinocerebral. Pulmonary, Rhinocerebral. Large aseptate hyphae in tissues. Large aseptate hyphae in tissues. Amphotericin B, Surgery. Amphotericin B, Surgery.

SYSTEMIC MYCOSIS Subclinical to progressive. Subclinical to progressive. Dimorphic. Dimorphic. Geographic habitat. Geographic habitat. None are transmitted from human to human. None are transmitted from human to human. Cryptococcosis, Histoplasmosis, Blastomycosis, Coccidiodomycosis, Paracoccidiodomycosis. Cryptococcosis, Histoplasmosis, Blastomycosis, Coccidiodomycosis, Paracoccidiodomycosis.

CRYPTOCOCCOSIS Cryptococcus neoformans. Cryptococcus neoformans. Yeast, large capsue unique, polysaccharide Yeast, large capsue unique, polysaccharide Urease positive. Urease positive. Bacterial like colonies. Bacterial like colonies. Pigeon and birds droppings in soil. Pigeon and birds droppings in soil. No human to human transmission. No human to human transmission.

PATHOGENESIS Inhalation of yeast or conidia. Inhalation of yeast or conidia. Minimal signs and symptoms. Minimal signs and symptoms. CNS is the primary target. CNS is the primary target. Common complication of AIDS. Common complication of AIDS. Phagocytosis? Phagocytosis? Humoral and CMI role. Humoral and CMI role.

CLINICAL MANIFESTATIONS Meningitis, skin, pneumonia. Meningitis, skin, pneumonia. Slow insidious onset. Slow insidious onset. Headache, irritability, dizziness and behavioural changes. Headache, irritability, dizziness and behavioural changes. Seizures, cranial nerves, papillidema, and dementia. Seizures, cranial nerves, papillidema, and dementia. In AIDS % becomes infected. In AIDS % becomes infected.

DIAGNOSIS CSF pleocytosis, lymphocytes predominance, Sugar, protein. CSF pleocytosis, lymphocytes predominance, Sugar, protein. Microscopy, negative staining. Microscopy, negative staining. Culture, urease. Culture, urease. Serology. Serology.

TREATMENT Amphotericin B + Flucytosine. Amphotericin B + Flucytosine. Fluconazole. Fluconazole. Relapse is a problem, chronic. Relapse is a problem, chronic. Residual neurological damage. Residual neurological damage.

HISTOPLASMOSIS Histoplasma capsulatum. Histoplasma capsulatum. Dimorphic, no capsule. Dimorphic, no capsule. Septate hyphae, Tuberculate macroconidia. Septate hyphae, Tuberculate macroconidia. Soil in humid climates, bird or bat dropping Soil in humid climates, bird or bat dropping Geographical distribution. Geographical distribution. Disturbance of environment. Disturbance of environment.

PATHOGENESIS Intracellular RES. Intracellular RES. Inhalation, phagocyte survival, dissamination. Inhalation, phagocyte survival, dissamination. Granuloma formation. Granuloma formation. CMI, Histoplasmin positive long lasting. CMI, Histoplasmin positive long lasting. Fulminant in immunocompromised patients. Fulminant in immunocompromised patients.

CLINICAL MANIFESTATION Most are asymptomatic, subclinical. Most are asymptomatic, subclinical. Mediastinal Lymphadenopathy. Mediastinal Lymphadenopathy. Slight pulmonary infiltrate. Slight pulmonary infiltrate. Positive histoplasmin skin test in 3weeks. Positive histoplasmin skin test in 3weeks. Chronic course resemble TB. Chronic course resemble TB. Systemic, depends on the organ involved. Systemic, depends on the organ involved.

DIAGNOSIS Yield from sputum is very low. Yield from sputum is very low. Blood culture, Biopsy of lymph nodes. Blood culture, Biopsy of lymph nodes. Bone marrow culture is the best. Bone marrow culture is the best. Special silver stain. Special silver stain. Typical conidia and dimorphism. Typical conidia and dimorphism. Serology, cross react with Blastomyces. Serology, cross react with Blastomyces. Skin testing. Skin testing.

TREATMENT Amphotericin B. Amphotericin B. Ketoconazole. Ketoconazole. Fluconazole. Fluconazole. Itraconazole. Itraconazole. Localized lung infection…No treatment. Localized lung infection…No treatment.

BLASTOMYCOSIS Blastomyces dermatitidis. Blastomyces dermatitidis. Dimorphic, similar to histoplasma. Dimorphic, similar to histoplasma. Yeast is larger, broad base buds. Yeast is larger, broad base buds. Septate hyphae, yeast is different. Septate hyphae, yeast is different. Geographic distribution. Geographic distribution. No skin testing. No skin testing.

PATHOGENESIS Not much is knows compared to others. Not much is knows compared to others. Inhalation of spores from soil. Inhalation of spores from soil. Mixed inflamatory response. Mixed inflamatory response. Organism spread to the skin causes ulcers. Organism spread to the skin causes ulcers. Activated macrophages kills. Activated macrophages kills. Antigenic cross reactivity. Antigenic cross reactivity.

CLINICAL MANIFESTATIONS Pulmonary symptoms. Pulmonary symptoms. Hilar lymphadenopathy. Hilar lymphadenopathy. Resemles TB, Tumour, other mycosis. Resemles TB, Tumour, other mycosis. Skin lesions. Skin lesions. Other systemic sites. Other systemic sites.

DIAGNOSIS Microscopy of broad based bud yeast. Microscopy of broad based bud yeast. Biobsy. Biobsy. Culture takes 4 weeks. Culture takes 4 weeks. Dimorphism. Dimorphism. Serology, negative in 50% of cases. Serology, negative in 50% of cases. Skin testing of no value. Skin testing of no value.

TREATMENT Amphotericin B. Amphotericin B. Response is slow and relapse is common. Response is slow and relapse is common. Ketoconazole. Ketoconazole. Fluconazole. Fluconazole. Itraconazole. Itraconazole.

COCCIDIODOMYCOSIS Coccidiodes immitis. Coccidiodes immitis. Dimorphic but no yeast. Dimorphic but no yeast. Spherule is pathognomonic. Spherule is pathognomonic. Hyphae has arthroconidia. Hyphae has arthroconidia. Semiarid climates. Semiarid climates. Not transmissible from person to person. Not transmissible from person to person.

PATHOGENESIS Inhalation of arthroconidia. Inhalation of arthroconidia. Spherule formation. Spherule formation. Rupture then dissamination. Rupture then dissamination. Granuloma formation. Granuloma formation. Positive skin test. Positive skin test. CMI, PMNs, CMI, PMNs,

DIAGNOSIS Spherule in sputum, or tissues. Spherule in sputum, or tissues. Culture, tease prep, Arthroconidia. Culture, tease prep, Arthroconidia. Coccidiodin test is positive is 4 weeks. Coccidiodin test is positive is 4 weeks. Serology. Serology.

TREATMENT Self limiting. Self limiting. Amophotericin B for dissaminated cases. Amophotericin B for dissaminated cases. Ketoconazole. Ketoconazole. Fluconazole and Itraconazole. Fluconazole and Itraconazole.

PARACOCCIDIODOMYCOSIS Paracoccidiodes brasiliensis. Paracoccidiodes brasiliensis. South american blastomycosis. South american blastomycosis. Dimorphic fungus. Dimorphic fungus. Multiple blastoconidia. Multiple blastoconidia. Chronic mucocutaneous or cutaneous ulcers Chronic mucocutaneous or cutaneous ulcers Same pathogenesis, and treatment. Same pathogenesis, and treatment.