PULMONARY FUNGAL PULMONARY FUNGAL DISEASESDISEASES

DR. ZIAD ELNASSERDR. ZIAD ELNASSER

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

STRUCTURESTRUCTURE

No peptidoglycan, glycerol, LPS, or No peptidoglycan, glycerol, LPS, or teichoic acids.teichoic acids.

Cell wall is formed of Polysaccharides, Cell wall is formed of Polysaccharides, Mannan, Glucan, and Chitin.Mannan, Glucan, and Chitin.

Determinants of serologic specificity.Determinants of serologic specificity.Chitin is similar to crab shells or cellulose Chitin is similar to crab shells or cellulose

of plansts.of plansts.

METABOLISMMETABOLISM

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

Conidia vs Spores.Conidia vs Spores.

GROWTH AND MORPHOLOGYGROWTH AND MORPHOLOGY

Size 2 - 4 µ up to visible structures.Size 2 - 4 µ up to visible structures.Two courses Two courses YEASTYEAST and or and or MOLD.MOLD.Yeasts buds produce blastoconidia.Yeasts buds produce blastoconidia.Colonies.Colonies.Molds formMolds form Hyphae Hyphae then then MyceliumMycelium, ,

SeptaSepta..Aerial, or Rhizoids.Aerial, or Rhizoids.Pseudohyphae.Pseudohyphae.

GROWTH AND MORPHOLOGYGROWTH AND MORPHOLOGY

Conidia on a condiophore.Conidia on a condiophore.Macroconidia, Microconidia.Macroconidia, Microconidia.Chlamydoconidia.Chlamydoconidia.ArthroconidiaArthroconidiaAscosporesAscospores

DimorphicDimorphic fungi. fungi.

CLASSIFICATIONCLASSIFICATION

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

CLASSIFICATIONCLASSIFICATION

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

OPPORTUNISTIC FUNGIOPPORTUNISTIC 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.

CANDIDACANDIDA

Candida albicansCandida albicans are the most seen. are the most seen.Normal flora GIT, and female vagina.Normal flora GIT, and female vagina.Budding yeast, can form pseudohyphae Budding yeast, can form pseudohyphae

and chlamydoconidia.and chlamydoconidia.Germ tube formation is diagnostic.Germ tube formation is diagnostic.

CANDIDIASISCANDIDIASIS Endogenous flora, Sexual intercouse, Endogenous flora, Sexual intercouse,

Nosocomial, and invasive procedures.Nosocomial, and invasive procedures. Adherence Adherence associated with the hyphal form.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 Antibiotics abuse, Leukopenia, indwelling

devices.devices. Diabetes meletisDiabetes meletis..

IMMUNITYIMMUNITY

Humoral and CMI.Humoral and CMI. Neutrophiles.Neutrophiles. Binding to iC3b receptors and Binding to iC3b receptors and

phagocytosis.phagocytosis. Mannan down regulate CMI.Mannan down regulate CMI. Cytokines play a positive role.Cytokines play a positive role.

CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONS

Plaques, oral thrush.Plaques, oral thrush.Vagina: Thick discharge, itching, 5% Vagina: Thick discharge, itching, 5%

recurrent infections.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 DIAGNOSISLABORATORY 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.

TREATMENTTREATMENT

Amphotericin B.Amphotericin B.Nystatin.Nystatin.Flucytosine.Flucytosine.Azoles.Azoles.Amphotericin B and FluconazoleAmphotericin B and FluconazoleRemove catheters.Remove catheters.Control Diabetes.Control Diabetes.

ASPERGILLUSASPERGILLUS

Rapid growers, Septate hyphae, fluffy Rapid growers, Septate hyphae, fluffy colonies.colonies.

Aspergillus fumigatus, A. flavusAspergillus fumigatus, A. flavus, , A. nigerA. niger.. Environmental disruption, building Environmental disruption, building

remodeling, Nosocomial.remodeling, Nosocomial. Immunocomromized, inhalation.Immunocomromized, inhalation. Interference with opsonophagocytosis.Interference with opsonophagocytosis. Neutrophile killing is crucial.Neutrophile killing is crucial.

CLINICAL MANIFESTAIONCLINICAL MANIFESTAION

Allergic aspergillosis.Allergic aspergillosis.Farmers lung syndrome.Farmers lung syndrome.Exacerbation of asthmatic attacks.Exacerbation of asthmatic attacks. Invasive aspergillosis, predisposing lesion Invasive aspergillosis, predisposing lesion

and pneumonia.and pneumonia.

DIAGNOSISDIAGNOSIS

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

TREATMENTTREATMENT

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

ZYGOMYCOSISZYGOMYCOSIS

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 MYCOSISSYSTEMIC MYCOSIS

Subclinical to progressive.Subclinical to progressive.Dimorphic.Dimorphic.Geographic habitat.Geographic habitat.None are transmitted from human to None are transmitted from human to

human.human.Cryptococcosis, Histoplasmosis, Cryptococcosis, Histoplasmosis,

Blastomycosis, Coccidiodomycosis, Blastomycosis, Coccidiodomycosis, Paracoccidiodomycosis.Paracoccidiodomycosis.

CRYPTOCOCCOSISCRYPTOCOCCOSIS

Cryptococcus neoformans.Cryptococcus neoformans.Yeast , large capsue unique, Yeast , large capsue unique,

polysaccharidepolysaccharideUrease 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.

PATHOGENESISPATHOGENESIS

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 MANIFESTATIONSCLINICAL MANIFESTATIONS

Meningitis, skin, pneumonia.Meningitis, skin, pneumonia.Slow insidious onset.Slow insidious onset.Headache, irritability, dizziness and Headache, irritability, dizziness and

behavioural changes.behavioural changes.Seizures, cranial nerves, papillidema, Seizures, cranial nerves, papillidema,

and dementia.and dementia. In AIDS 5 - 15% becomes infected.In AIDS 5 - 15% becomes infected.

DIAGNOSISDIAGNOSIS

CSF pleocytosis, lymphocytes CSF pleocytosis, lymphocytes predominance, Sugar, protein.predominance, Sugar, protein.

Microscopy, negative staining.Microscopy, negative staining.Culture, urease.Culture, urease.Serology.Serology.

TREATMENTTREATMENT

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

HISTOPLASMOSISHISTOPLASMOSIS

Histoplasma capsulatumHistoplasma capsulatum..Dimorphic, no capsule.Dimorphic, no capsule.Septate hyphae, Tuberculate Septate hyphae, Tuberculate

macroconidia.macroconidia.Soil in humid climates, bird or bat droppingSoil in humid climates, bird or bat droppingGeographical distribution.Geographical distribution.Disturbance of environment.Disturbance of environment.

PATHOGENESISPATHOGENESIS

Intracellular RES.Intracellular RES. Inhalation, phagocyte survival, Inhalation, phagocyte survival,

dissamination.dissamination.Granuloma formation.Granuloma formation.CMI , Histoplasmin positive long lasting.CMI , Histoplasmin positive long lasting.Fulminant in immunocompromised Fulminant in immunocompromised

patients.patients.

CLINICAL MANIFESTATIONCLINICAL 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.

DIAGNOSISDIAGNOSIS

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.

TREATMENTTREATMENT

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

BLASTOMYCOSISBLASTOMYCOSIS

Blastomyces dermatitidisBlastomyces 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.

PATHOGENESISPATHOGENESIS

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 MANIFESTATIONSCLINICAL 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.

DIAGNOSISDIAGNOSIS

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.

TREATMENTTREATMENT

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

COCCIDIODOMYCOSISCOCCIDIODOMYCOSIS

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

PATHOGENESISPATHOGENESIS

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,

DIAGNOSISDIAGNOSIS

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.

TREATMENTTREATMENT

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

PARACOCCIDIODOMYCOSISPARACOCCIDIODOMYCOSIS

Paracoccidiodes brasiliensisParacoccidiodes brasiliensis..South american blastomycosis.South american blastomycosis.Dimorphic fungus.Dimorphic fungus.Multiple blastoconidia.Multiple blastoconidia.Chronic mucocutaneous or cutaneous Chronic mucocutaneous or cutaneous

ulcersulcersSame pathogenesis, and treatment.Same pathogenesis, and treatment.