1. Histoplasma capsulatum
Dipendra Shrestha KDCH

2. 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

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

6. 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

7. 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. 

8. Pulmonary Histoplasmosis

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 sputum
reactivation or reinfection
Mediastinal granulomatosis and fibrosis
Fibrosis, occlusion of mediastinal structure

11. Pulmonary Histoplasmosis
Chronic fibrocavitary histoplasmosis

12. Mediastinal granulomatosis

14. 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

16. Disseminated Histoplasmosis (cont.)

17. Disseminated Histoplasmosis (cont.)

18. 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)

19. Oral histoplasmosis

20. 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

21. Blood Thin smear

22. Calcofluor stain x400
Narrow-neck bud

23. H&E mouth biopsy
Yeast in macrophages

24. Giemsa staining of lung biopsy

25. 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

26. Microscopic morphology

27. Microscopic morphology
macroconidia and microconidia

28. Hyphal to yeast conversion at 37ºC
Yeast cells
Yeast-like colonies

29. Diagnosis (cont.) Histoplasmin Skin test Serology
Culture filtrate (histoplasmin) is inoculated to observe cell mediated immunity.
Serology
Complement fixation test
Precipitation and agglutination

30. 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