2 Characteristics (cont.) Dimorphic fungusMycelium at 25-30º C - Sexual multi-cellular saprophyte, septate, form microconidia and macroconidiaYeast at 37º C - Asexual unicellular intracellular parasite, white, thin walled, ovalMycelial form is most commonly found in the environmentReservoir is soil enriched with droppings of birds or batsHuman, many domestic animals, bats are infected by ingestion of spores
5 PathogenesisInfection begins with inhalation of microconidia or hyphal fragmentsMycelial form transforms into yeast formTriggered by elevated temperatures and increased cysteine levels
6 Pathogenesis (cont.)Yeast cells are phagocytized by host immune systemH. capsulatum is able to survive phagocytosisApoptosis of infected macrophages allow H. capsulatum to spreadInfection is usually self-limiting in immunocompetent individuals, Cell mediated immunity arises in 15 days
7 Histoplasmosis 2 major forms of histoplasmosis Pulmonary and disseminatedPulmonary histoplasmosisConidia 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 nodesThe 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.
10 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 sputumreactivation or reinfectionMediastinal granulomatosis and fibrosisFibrosis, occlusion of mediastinal structure
14 Disseminated Histoplasmosis Occurs primarily in immunocompromised individuals where H. capsulatum is able to spread from the lungs into other organsPatients 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
25 Histoplasmosis (diagnosis cont.) 3. CultureSabouraud’s agar with cycloheximide and cholramphenicol, 25º C for 2-6 weeks give white cottony myceliumWhite - brown mouldTypical microscopic morphologyMould at RT in SDA