Histoplasma capsulatum and HistoplasmosisBrandon Hang

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Outline

• Characteristics• Pathogenesis• Histoplasmosis• Pulmonary• Disseminated

• Treatment• Future challenges

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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

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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)

4A

C E F

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)

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A B

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 process1. Heat shock

phenomenon2. Restimulation of

cellular respiration3. Increase of RNA

& protein synthesis6

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

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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

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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

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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

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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

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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

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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

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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

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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

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Treatment• Treatment is not required in most cases• Itraconazole and/or amphotericin B in more serious cases• No effective treatment for fibrosing mediastinitis

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Itraconazole

Amphotericin B

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

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Questions?

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