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Histoplasma capsulatum and Histoplasmosis

Histoplasma capsulatum and Histoplasmosis. Brandon Hang. Outline. Characteristics Pathogenesis Histoplasmosis Pulmonary Disseminated Treatment Future challenges. Characteristics. Member of the phylum Ascomycota Worldwide distribution Naturally found in fecal-contaminated soils

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Histoplasma capsulatum and Histoplasmosis

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  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) • Globosecleistothecia (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 shockphenomenon • Restimulation ofcellular 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 immunocompetentindividuals

  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 • Fibrosingmediastinitis • 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.) • Fibrosingmediastinitis • 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 • 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 fibrosingmediastinitis Amphotericin B Itraconazole

  17. Future Challenges • Treatment of fibrosingmediastinitis 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?

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