Dimorphic Fungal Infections

Dimorphic fungi basics Dr.T.V.Rao MD: 

Dimorphic fungi basics Dr.T.V.Rao MD Dr.T.V.Rao MD 1 10/22/2011

Dimorphic fungus cause Systemic Mycosis: 

Dimorphic fungus cause Systemic Mycosis Deep seated fungal infections Inhalation of air borne spores produced by casual moulds Present as saprophytes in soil and on plant material They are caused by Dimorphic fungi Occurs mainly American continent. Dr.T.V.Rao MD 2 10/22/2011

Important Fungi in Systemic Mycosis: 

Important Fungi in Systemic Mycosis Coccidioidomycosis. Histoplasmosis Blast mycosis Paracoccidioidomycosis. Others can also manifest with systemic infection ( Not Dimorphic ) Aspergillus,Candida,Cryptococcus spp Dr.T.V.Rao MD 3 10/22/2011

Dimorphic Fungi: 

4 Dimorphic Fungi Histoplasmosis Blastomycosis Coccidiodomycosis Paracoccidiodomycosis Sporotrichosis

Dimorphic Fungi: 

Dimorphic Fungi There are five genera of dimorphic fungi: Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Paracoccidioides braziliensis Sporothrix schenckii Subcutaneous Systemic

Dimorphic Fungi: 

Dimorphic Fungi Dimorphic fungi grow in natural environments as saprobic molds When they gain entrance into the human body and cause an infection they grow as yeast, or in the case of C. immitis , as a spherule (round structure resembling a sporangium without sporangiophores within which spores develop

Dimorphic Fungi: 

Dimorphic Fungi These fungal pathogens can generally overcome the physiological and cellular defenses of the normal human host by changing their morphological form.  They are geographically or occupationally restricted. Human infections of the four most common systemic dimorphic is by inhalation of conidia from environmental saprobes Primary disease is in the lung but all can disseminate throughout the body to any organ system (i.e. systemic)

Over view of diagnosis of dimorphic fungus: 

Over view of diagnosis of dimorphic fungus 10/22/2011 Dr.T.V.Rao MD 8

Dimorphic Fungi: 

Dimorphic Fungi Lab confirmation requires three (or four) steps: 1 . Detect and presumptively identify the “tissue” form (yeast?) in clinical specimens 2. Culture the mold form on primary media and identifying characteristic hyphae and conidia

Dimorphic Fungi: 

Dimorphic Fungi Lab confirmation requires three (or four) steps: 3. Convert the mold form to “tissue” form (yeast) in vitro using rich media (usually containing blood and glucose) incubated at body temperature C. immitis requires a special medium incubated at 42 o C in CO 2 )

Dimorphic Fungi: 

Dimorphic Fungi Lab confirmation requires three (or four) steps: If the first three steps fail to definitively identify the organism, an exoantigen test can be done Many hospital labs send isolates to reference labs for this test It involves extracting water soluble antigens from young mold cultures

Dimorphic Fungi: 

Dimorphic Fungi Exoantigen test This is an example of a “precipitin test” in which a visible opaque “lattice” forms at the “zone-of-equivalence.” Monoclonal Ab is added and the lattice occurs where the concentration Ag and Ab are equal. An Ouchterlony type double Immunodiffusion procedure is usually used on a commercially available product. Ouchterlony can be ran in this manner or can be ran using patients serum & bottled Ag in an attempt to detect Abs in a patients serum.

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Histoplasmosis and Coccidioidomycosis: 

Histoplasmosis and Coccidioidomycosis Histoplasmosis and Coccidioidomycosis are similar fungal organisms that both produce a disease that resembles tuberculosis .  Both are caused by fungi that grow as spore producing hyphae at environmental temperatures, but as yeasts (spherules or ellipses) at body temperature within the lungs. Dr.T.V.Rao MD 14 10/22/2011

Coccidioidomycosis: 

Coccidioidomycosis Coccidioidomycosis is initially, a respiratory infection, resulting from the inhalation of conidia, that typically resolves rapidly leaving the patient with a strong specific immunity to re-infection. However, in some individuals the disease may progress to a chronic pulmonary condition or to a systemic disease involving the meninges, bones, joints and subcutaneous and cutaneous tissues . Dr.T.V.Rao MD 15 10/22/2011

Coccidioidomycosis: 

Coccidioidomycosis Dimorphic fungi present in soil Coccidioides imitis, Prevalent in USA and Mexico Dark skinned and Agricultural workers, Dr.T.V.Rao MD 16 10/22/2011

Coccidioidomycosis : 

Coccidioidomycosis Dr.T.V.Rao MD 17 10/22/2011

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Culturing : 

Culturing In culture / Soil as molds Barrel shaped Arthoconida Disperses through wind. In the lungs arthoconida becomes spherules 30-60 microns Contains end spores. Dr.T.V.Rao MD 19 10/22/2011

Pathogenesis: 

Pathogenesis C.imitis can be asymptomatic or self limited. Pulmonary involvement. Fatal illness Pulmonary 7-28 days Skin rashes Chronic cavitation's, Pulmonary infection Local infection Dr.T.V.Rao MD 20 10/22/2011

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Devastating Lesions are produced: 

Devastating Lesions are produced Dr.T.V.Rao MD 22 10/22/2011

Pathogenesis ( cont ): 

Pathogenesis ( cont ) Generalized infection in immune suppressed. Organ transplant recipients Lymphoma patients AIDS CNS Skin, Joints, Poor prognosis in immune suppressed and Meningitis patients. Dr.T.V.Rao MD 23 10/22/2011

Laboratory Diagnosis : 

Laboratory Diagnosis Microscopy Sputum Pus, Biopsy, Mature spherules, Grown in test tube slopes at 25 -30 c 3 weeks Morphology thick walled Arthoconida Fine Septate hyphae. Arthoconida are highly infectious. Skin test with Coccid odes Dr.T.V.Rao MD 24 10/22/2011

Serology: 

Serology Precipitation test. Latex agglutination test. Complement fixation test. Dr.T.V.Rao MD 25 10/22/2011

Treatment: 

Treatment I V Amphotericin B Fluconazole, Itraconazole Dr.T.V.Rao MD 26 10/22/2011

Histoplasmosis : 

Histoplasmosis Histoplasmosis is an intracellular mycotic infection of the reticuloendothelial system caused by the inhalation of conidia from the fungus Histoplasma capsulatum . Histoplasmosis has a world wide distribution, however, the Mississippi-Ohio River Valley in the U.S.A. is recognized as a major endemic region. Africa, Australia and parts of East Asia, in particular India and Malaysia are also endemic regions Dr.T.V.Rao MD 27 10/22/2011

Histoplasmosis: 

Histoplasmosis Soil – Enriched with Bird droppings and Bat droppings, Spread through inhalation of spores Prevalent in Eastern USA – 95% Causative agent Histoplasma duboisii, Dr.T.V.Rao MD 28 10/22/2011

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Clinical manifestations: : 

Clinical manifestations: Approximately 95% of cases of Histoplasmosis are in apparent, subclinical or benign. Five percent of the cases have chronic progressive lung disease, chronic cutaneous or systemic disease or an acute fulminating fatal systemic disease. All stages of this disease may mimic tuberculosis . 10/22/2011 Dr.T.V.Rao MD 30

Lung involvement a Major Manifestation in Histoplasmosis: 

Lung involvement a Major Manifestation in Histoplasmosis 10/22/2011 Dr.T.V.Rao MD 31

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Culturing: 

Culturing Grows as mould at 25 – 30 c Animal tissues as Yeast and 37 c Grows in Blood agar, Enriched medium Sabouraud dextrose agar Mould looks fluffy, wheat brown colored. Produce Unicellular, asexual spores Tuberculate Microcondia 8-14 microns Dr.T.V.Rao MD 34 10/22/2011

Pathology: 

Pathology Active influenza like illness Calcified lesions in lungs, Lung cavities develop. Looks like Tuberculosis Wide spread infection in RES Disseminated infection in infants and old age. Aggregation in Neutropenia and Hematological malignancies, Dr.T.V.Rao MD 35 10/22/2011

Laboratory Diagnosis: 

Laboratory Diagnosis Microscopic appreance in sputum,pus, Giemsas staining Blood cultures, Liver and lung biopsy, Culturing on Sabouraud agar at 37 and 25-30 c 1-2 weeks Recognize Macrocondia and Micro conidia Dr.T.V.Rao MD 36 10/22/2011

Laboratory Diagnosis: 

Laboratory Diagnosis Culture at 37 c shows yeast phase Mold form at 25-30 c Skin test Histoplasmin Serology titers above 1in 8 > 32 CF test. Radio immunoassay ELISA Dr.T.V.Rao MD 37 10/22/2011

Blastomycosis : 

Blastomycosis Blast mycosis is a chronic granulomatous and suppurative disease having a primary pulmonary stage that is frequently followed by dissemination to other body sites, chiefly the skin and bone. Although the disease was long thought to be restricted to the North American continent, in recent years autochthonous cases have been diagnosed in Africa, Asia and Europe. Dr.T.V.Rao MD 38 10/22/2011

Blastomycosis: 

Blastomycosis Prevalent in USA and Canada Caused by Blastomycosis dermatitidis, Inhalation of spores, Men between 30 to 50 years are affected, Cool wet climate condition Dr.T.V.Rao MD 39 10/22/2011

Morphology: 

Morphology Blastomycosis dermatitidis- Dimorphic fungus Mould Septate mycelium 25 – 30 c Asexual conidia Conidia are 2-10 microns / Dumbbell shaped Yeast at 37 c with broad based buds Dr.T.V.Rao MD 40 10/22/2011

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Pathology: 

Pathology Pulmonary forms Disseminated to other organs, X rays looks like Tuberculosis / Carcinoma Cutaneous lesions occur 80% patients with pulmonary infection Dr.T.V.Rao MD 42 10/22/2011

Laboratory Diagnosis: 

Laboratory Diagnosis Microscopy – pus Scrapping from the lesions sputum Thick walled yeast cells 8- 15 microns Buds on broad base. PAS / Methenamine silver stain, Sabouraud dextrose agar – Blood agar, Retained for 6 weeks Grow in test tubes, ELISA test Dr.T.V.Rao MD 43 10/22/2011

Treatment: 

Treatment I V Amphotericin B Itraconazole Ketoconazole Dr.T.V.Rao MD 44 10/22/2011

Paracoccidioidomycosis : 

Paracoccidioidomycosis Paracoccidioidomycosis is a chronic granulomatous disease that characteristically produces a primary pulmonary infection, often in apparent, and then disseminates to form ulcerative granulomata of the buccal, nasal and occasionally the gastrointestinal mucosa.. The only etiological agent, Paracoccidioides brasiliensis is geographically restricted to areas of South and Central America Dr.T.V.Rao MD 45 10/22/2011

Parcoccodiomycosis: 

Parcoccodiomycosis Chronic granulomatus infection Paracoccodioides brasilensis, Lungs- Mucosa – Skin – Lymphatic vessels Enter through the lungs Saprophytic in nature, Humid forests of South and Central Common in 20 – 40 years, Dr.T.V.Rao MD 46 10/22/2011

Morphology: 

Morphology Mycelium at 25 – 30 c Yeast forms at 37 c Conversion from mycelial forms to yeast. The yeast forms consists of Oval or globose cells 2- 30 microns, in diameter, with small buds attached by a narrow neck encircling the parent cells. Dr.T.V.Rao MD 47 10/22/2011

Pathogenesis: 

Pathogenesis Ulceration , Granulomatous infection of oral Nasal Mucosa Lymphatic system spleen, Intestines Liver involvement Dr.T.V.Rao MD 48 10/22/2011

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Laboratory Diagnosis: 

Laboratory Diagnosis Microscopy – Sputum , Pus, Biopsy of glaucomatous lesions Presence of Numerous multipolar budding cells is diagnostic Staining with PAS / Silver methenamine Cultures kept for 6 weeks 25 c moulds 37 c yeasts Serology Precipitation tests, Complement fixation Dr.T.V.Rao MD 50 10/22/2011

Treatment : 

Treatment Amphotericin B Oral Ketaconazole, Itraconazole . Dr.T.V.Rao MD 51 10/22/2011

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Created by Dr.T.V.Rao MD for the Medical and Paramedical students in Developing world Email doctortvrao@gmail.com 10/22/2011 Dr.T.V.Rao MD 52