Histoplasma capsulatum

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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
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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)
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A
C E F
Yeast form is the infectious agent in
humans
Form asexual macro- and micro
conidia
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
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
1. Heat shock
phenomenon
2. Restimulation of
cellular respiration
3. Increase of RNA
& protein synthesis
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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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2 major forms of histoplasmosis
Pulmonary and disseminated
Pulmonary histplasmosis occurs when micro conidia 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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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
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 extra pulmonary 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 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
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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