DIMORPHIC FUNGI

DR.T.V.RAO MD

BASICS

Dr.T.V.Rao MD

10/22/2011

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

10/22/2011

IMPORTANT FUNGI IN SYSTEMIC MYCOSIS

Coccidioidomycosis.
Histoplasmosis Blast mycosis Paracoccidioidomycosis. Others can also manifest with systemic infection ( Not Dimorphic )
10/22/2011

Dr.T.V.Rao MD

Aspergillus,Candida,Cryptococcus spp

DIMORPHIC FUNGI
HISTOPLASMOSIS
BLASTOMYCOSIS

COCCIDIODOMYCOSIS
PARACOCCIDIODOMYCOSIS

SPOROTRICHOSIS
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DIMORPHIC FUNGI
There are five genera of dimorphic fungi:

Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis Paracoccidioides braziliensis Sporothrix schenckii

Systemic

Subcutaneous

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
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

Dr.T.V.Rao MD

10/22/2011

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
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 42o C in CO2)

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

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 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.
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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.
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COCCIDIOIDOMYCOSIS
Dimorphic fungi present in soil
Coccidioides imitis,

Prevalent in USA and Mexico

Dark skinned and Agricultural workers,
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COCCIDIOIDOMYCOSIS

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CULTURING
In culture / Soil as molds Barrel shaped Arthoconida Disperses through wind. In the lungs arthoconida becomes spherules 3060 microns Contains end spores.
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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
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DEVASTATING LESIONS ARE PRODUCED

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PATHOGENESIS ( CONT )
Generalized infection in immune suppressed.

Organ transplant recipients

Lymphoma patients AIDS CNS Skin, Joints, Poor prognosis in immune suppressed and Meningitis patients.
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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
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SEROLOGY
Precipitation test.
Latex agglutination test. Complement fixation test.
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TREATMENT

IV
Amphotericin B

Fluconazole, Itraconazole

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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
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HISTOPLASMOSIS
Soil Enriched with Bird droppings and Bat droppings, Spread through inhalation of spores

Prevalent in Eastern USA 95%

Causative agent Histoplasma duboisii,
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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.
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LUNG INVOLVEMENT A MAJOR MANIFESTATION IN HISTOPLASMOSIS

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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 814 microns
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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,

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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
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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
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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.
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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
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MORPHOLOGY
Blastomycosis dermatitidisDimorphic fungus

Mould Septate mycelium 25 30 c

Asexual conidia

Conidia are 2-10 microns / Dumbbell shaped

Yeast at 37 c with broad based buds
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PATHOLOGY
Pulmonary forms Disseminated to other organs, X rays looks like Tuberculosis / Carcinoma Cutaneous lesions occur 80% patients with pulmonary infection
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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
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TREATMENT IV Amphotericin B

Itraconazole
Ketoconazole
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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
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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,
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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 230 microns, in diameter, with small buds attached by a narrow neck encircling the parent cells.
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PATHOGENESIS
Ulceration , Granulomatous infection of oral Nasal Mucosa Lymphatic system spleen, Intestines Liver involvement
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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
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TREATMENT
Amphotericin B

Oral Ketaconazole, Itraconazole.

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

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