1. Histoplasma capsulatum and Histoplasmosis
Brandon Hang

2. Outline Characteristics Pathogenesis Histoplasmosis Pulmonary
Disseminated
Treatment
Future challenges

3. Characteristics Member of the phylum Ascomycota Worldwide distribution
Naturally found in fecal-contaminated soils
Birds and bats appear to be reservoirs
Etiologic agent of histoplasmosis

4. Characteristics (cont.)
Dimorphic fungus
Sexual multi-cellular saprophytic mycelia
Asexual single-celled parasitic yeast
Mycelial form is most commonly found in the environment
Heterothallic species
Tightly coiled septate hyphae (A)
Globose cleistothecia (C)
Pear-shaped asci (E)
Smooth, hyaline, spherical ascospores (F) A C E F

5. Characteristics (cont.)
Yeast form is the infectious agent in humans
Form asexual macro- and microconidia
Also borne by hyphae in the mycelial form (B)
Conidia germinate via non/polar budding
Yeast cells have white, thin-walled, oval bodies (A) A B

6. Pathogenesis
Infection begins with inhalation of microconidia or hyphal fragments
Mycelial form transforms into yeast form
Triggered by elevated temperatures and increased cysteine levels
3-stage process
Heat shock phenomenon
Restimulation of cellular respiration
Increase of RNA & protein synthesis

7. Pathogenesis (cont.)
Yeast cells are phagocytized by host immune system
M. capsulatum is able to survive phagocytosis
Calcium-binding protein, a cytoplasmic enzyme, a peroxisomal enzyme, and immunogenic M antigen are involved
Apoptosis of infected macrophages allow M. capsulatum to spread
Infection is usually self-limiting in immunocompetent individuals

8. Histoplasmosis 2 major forms of histoplasmosis
Pulmonary and disseminated
Pulmonary histoplasmosis occurs when microconidia or mycelial fragments are inhaled
Form lesions in the hilar and/or mediastinal nodes
Many types of pulmonary histoplasmosis
Asymptomatic pulmonary histoplasmosis
Acute pulmonary histoplasmosis
Mediastinal granuloma
Fibrosing mediastinitis
Chronic cavitary pulmonary histoplasmosis

9. Pulmonary Histoplasmosis
Asymptomatic pulmonary histoplasmosis
Low level exposure to H. capsulatum
99% of infected people display no symptoms
May display a mild “illness” not recognized as histoplasmosis
Diagnosed using radiography, CT scans, or biopsies

10. Pulmonary Histoplasmosis (cont.)
Acute pulmonary histoplasmosis
Higher level exposure to H. capsulatum
Patients display fever, malaise, headache, dyspnea, and other respiratory problems
Diagnosed using radiography, BAL, CF, or ID

11. Pulmonary Histoplasmosis (cont.)
Mediastinal granuloma
Substantial enlargement of a large number of mediastinal lymph nodes
Can impede airways or the superior vena cava
Often matted together and necrotic
Patients have severe chest pain when breathing
Diagnosed using radiography or CT scans

12. Pulmonary Histoplasmosis (cont.)
Fibrosing mediastinitis
Uncontrolled immune response to necrotizing nodes causes fibrosis around mediastinal lymph nodes
Patients display worsening dyspnea, cough, hemoptysis, and chest pain
Superior vena cava obstruction and heart failure can occur
Diagnosed using radiography and CT scans

13. Pulmonary Histoplasmosis (cont.)
Chronic cavitary pulmonary histoplasmosis
Exclusive to older patients with emphysema
H. capsulatum infection near emphysematous bullae form a cavity
The cavity progressively grows and spreads from lobe to lobe to form more cavities
Patients display fatigue, fever, anorexia, weight loss, hemoptysis, and dyspnea
Diagnosed using radiography and bronchoscopy

14. Disseminated Histoplasmosis
Occurs primarily in immunocompromised individuals
In healthy individuals, H. capsulatum is similar to tuberculosis
While the infection is usually resolved, the fungus is still present
Constantly kept in check by T lymphocytes
In immunocompromised individuals, 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

15. Disseminated Histoplasmosis (cont.)
Diagnosis is performed by demonstrating the presence of the fungus in extrapulmonary tissue
Blood cultures, bronchoscopy, BAL, ID, CF, and positive antigen tests are commonly performed
Elevated levels of lactate dehydrogenase and ferritin in AIDS patients

16. 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

17. Future Challenges
Treatment of fibrosing mediastinitis continues to be difficult and ineffective
Quick and accurate identification of H. capsulatum in infected patients needs to be addressed
Developing a broad spectrum vaccine may be a step in the right direction to address some of these concerns

18. Questions?

19. References
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