Page 421 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART V Mycology
410
Histoplasma
of infected persons, especially infants and individuals with
reduced cell-mediated immunity, such as patients with
acquired immunodeficiency syndrome (AIDS). In AIDS
patients, pancytopenia and ulcerated lesions on the tongue

competent people, EN can occur (see description of EN in
earlier section on Coccidioides). EN is a sign that cell-
FIGURE 49–5 Histoplasma capsulatum. Yeasts are located are typical of disseminated histoplasmosis. In immuno-
mediated immunity is active and the organism will proba-
within the macrophage. (Reproduced with permission from Brooks GF et al.
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bly be contained.
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Medical Microbiology. 19th ed. Originally published by Appleton & Lange. Copyright
A skin test using histoplasmin (a mycelial extract)
1991 McGraw-Hill.)
becomes positive (i.e., shows at least 5 mm of induration)
In several tropical African countries, histoplasmosis
many years. However, because there are many false-positive
is caused by Histoplasma duboisii. The clinical picture is
reactions (due to cross-reactivity) and many false-negative
reactions (in disseminated disease), the skin test is not use-
different from that caused by H. capsulatum. A descrip-
ful for diagnosis. Furthermore, the skin test can stimulate
tion of the differences between African histoplasmosis
and that seen in the United States is beyond the scope of
an antibody response and confuse the serologic tests. The
skin test is useful for epidemiologic studies, and up to 90%
this book.
infection.
Pathogenesis & Clinical Findings
Inhaled spores are engulfed by macrophages and develop of individuals have positive results in areas of endemic
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into yeast forms. In tissues, H. capsulatum occurs as an oval
Laboratory Diagnosis
budding yeast inside macrophages (Figures 49–5 and
In tissue biopsy specimens or bone marrow aspirates, oval
49–6). The yeasts survive within the phagolysosome of the
macrophage by producing alkaline substances, such as
(see Figure 49–6). Cultures on Sabouraud’s agar show
bicarbonate and ammonia, which raise the pH and thereby
hyphae with tuberculate macroconidia when grown at low
inactivate the degradative enzymes of the phagolysosome.
temperature (e.g., 25°C) and yeasts when grown at 37°C.
The organisms spread widely throughout the body,
Tests that detect a Histoplasma polysaccharide antigen by
especially to the liver and spleen, but most infections
enzyme-linked immunosorbent assay (ELISA) and Histo-
remain asymptomatic, and the small granulomatous foci
plasma RNA with DNA probes are also useful. In immuno-
heal by calcification. With intense exposure (e.g., in a
compromised patients with disseminated disease, tests for
chicken house or bat-infested cave), pneumonia and cavi-
Histoplasma antigen in the urine are especially useful
tary lung lesions may become clinically manifest. Severe
because antibody tests may be negative.
Two serologic tests are useful for diagnosis: comple-
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ment fixation (CF) and immunodiffusion (ID). An anti-
body titer of 1:32 in the CF test with yeast phase antigens
is considered to be diagnostic. However, cross-reactions
fall when the disease becomes inactive and rise in dis-
seminated disease. The ID test detects precipitating anti-
bodies (precipitins) by forming two bands, M and H, in an
agar-gel diffusion assay. The ID test is more specific but
less sensitive than the CF test.
Treatment & Prevention
No therapy is needed in asymptomatic or mild primary
infections. With progressive lung lesions, oral itraconazole
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is effective. In disseminated disease, parenteral itraconazole
FIGURE 49–6
Histoplasma capsulatum—yeasts within mac-
(or amphotericin B) is the treatment of choice. Liposomal
rophages. Arrow points to a macrophage containing several
purple-stained yeasts in the cytoplasm. Yeasts within macro-
kidney damage. In meningitis, fluconazole is often used
phages can be seen in many macrophages in this specimen of
because it penetrates the spinal fluid well. Oral itraconazole
spleen. (Source: Dr. M. Hicklin, Public Health Image Library, Centers for Disease
is used for chronic suppression in patients with AIDS.
Control and Prevention.)
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