Dipendra ShresthaKDCH

Histoplasma capsulatum

CHARACTERISTICS (CONT.)

Dimorphic fungus Mycelium at 25-30º C - Sexual multi-cellular

saprophyte, septate, form microconidia and macroconidia

Yeast at 37º C - Asexual unicellular intracellular parasite, white, thin walled, oval

Mycelial form is most commonly found in the environment

Reservoir is soil enriched with droppings of birds or bats

Human, many domestic animals, bats are infected by ingestion of spores 2

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PATHOGENESIS

Infection begins with inhalation of microconidia or hyphal fragments

Mycelial form transforms into yeast form Triggered by elevated temperatures and

increased cysteine levels

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PATHOGENESIS (CONT.)

Yeast cells are phagocytized by host immune system

H. capsulatum is able to survive phagocytosis Apoptosis of infected macrophages allow H.

capsulatum to spread Infection is usually self-limiting in

immunocompetent individuals, Cell mediated immunity arises in 15 days

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HISTOPLASMOSIS 2 major forms of histoplasmosis

Pulmonary and disseminated

Pulmonary histoplasmosis Conidia or mycelial fragments are inhaled and

lodge on the mucous membranes of the respiratory tree or in the alveoli of the lungs, where they encounter macrophages and are phagocytosed.

Form lesions in lungs nodes The patient may feel fever, chest pains, a

general ill feeling, and a dry cough. Distinct patterns may be seen on a chest x-ray. Chronic lung disease resembles tuberculosis and

can worsen over months or years. 

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PULMONARY HISTOPLASMOSIS

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PULMONARY HISTOPLASMOSIS

Chronic pulmonary histoplasmosis (1/100,000)pre-existing structural lung

defect, i.e. COPD, emphysema (damage of alveoli resulting less O2 supply)

chronic pneumonia or infection in cavities, increased sputum

reactivation or reinfectionMediastinal granulomatosis and fibrosis

Fibrosis, occlusion of mediastinal structure

PULMONARY HISTOPLASMOSIS

Chronic fibrocavitary histoplasmosis

MEDIASTINAL GRANULOMATOSIS

DISSEMINATED HISTOPLASMOSIS

Occurs primarily in immunocompromised individuals where H. capsulatum is able to spread from the lungs into other organs

Patients display fever, malaise, and occasionally petechiae or skin lesions (cutaneous histoplasmosis)

Tests often reveal mucous membrane ulcerations, simultaneous enlargement of the liver and spleen, and enlarged lymph nodes

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DISSEMINATED HISTOPLASMOSIS (CONT.)

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DISSEMINATED HISTOPLASMOSIS (CONT.)

Defects in host immunity Infants, immuncompromised, HIV

Acute, subacute, chronicFailure of macrophages to kill fungusDiffuse spread throughout MPS

Oropharyngeal ulcers Hepatosplenomegaly Adrenal GI Endocarditis Meningitis Brain abscess Lymphadenopathy Coagulopathy Bone marrow suppression (pancytopenia)

PROGRESSIVE DISSEMINATED HISTOPLASMOSIS

ORAL HISTOPLASMOSIS

DIAGNOSIS

1. Obtain appropriate specimenssputum bone marrowblood lesion scrapingsurine biopsy specimens

2. Direct Examination Tissue Specimens

stains for fungi – Giemsa, Wrightroutine histology - H & E- small yeast (2-4 ) intracellular in

macrophages- Sputum - KOH or calcofluor

BLOOD THIN SMEAR

CALCOFLUOR STAIN X400

Narrow-neck bud

H&E MOUTH BIOPSY

Yeast in macrophages

GIEMSA STAINING OF LUNG BIOPSY

HISTOPLASMOSIS (DIAGNOSIS CONT.)

3. CultureSabouraud’s agar with cycloheximide and cholramphenicol, 25º C for 2-6 weeks give white cottony mycelium

White - brown mould

Typical microscopic morphology

Mould at RT in SDA

MICROSCOPIC MORPHOLOGY

MICROSCOPIC MORPHOLOGY

macroconidia and microconidia

HYPHAL TO YEAST CONVERSION AT 37ºC

Yeast-like colonies

Yeast cells

DIAGNOSIS (CONT.)

Histoplasmin Skin testCulture filtrate (histoplasmin) is inoculated

to observe cell mediated immunity. Serology

Complement fixation test Precipitation and agglutination

TREATMENT

Treatment is not required in most cases Itraconazole and/or amphotericin B in more

serious cases No effective treatment for fibrosing

mediastinitis

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Itraconazole

Amphotericin B