Histoplasma capsulatum Dipendra Shrestha KDCH

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

Pathogenesis Infection begins with inhalation of microconidia or hyphal fragments Mycelial form transforms into yeast form Triggered by elevated temperatures and increased cysteine levels

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

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. 

Pulmonary Histoplasmosis

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 reinfection Mediastinal 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

Disseminated Histoplasmosis (cont.)

Disseminated Histoplasmosis (cont.)

Progressive disseminated histoplasmosis Defects in host immunity Infants, immuncompromised, HIV Acute, subacute, chronic Failure of macrophages to kill fungus Diffuse spread throughout MPS Oropharyngeal ulcers Hepatosplenomegaly Adrenal GI Endocarditis Meningitis Brain abscess Lymphadenopathy Coagulopathy Bone marrow suppression (pancytopenia)

Oral histoplasmosis

Diagnosis 1. Obtain appropriate specimens sputum bone marrow blood lesion scrapings urine biopsy specimens 2. Direct Examination Tissue Specimens stains for fungi – Giemsa, Wright routine 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. Culture Sabouraud’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 cells Yeast-like colonies

Diagnosis (cont.) Histoplasmin Skin test Serology Culture 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 Amphotericin B Itraconazole