Page 111 - AIDSBK23C

Page 111

HISTOPLASMA CAPSULATUM INFECTIONS

Most cases of histoplasmosis are caused by Histoplasma capsulatum and are traditionally
seen in areas in which this particular fungus is endemic--mainly the Mississippi and Ohio River
valleys of the United States. Infections may also occur over a wider geographic area
encompassing the St. Lawrence River valley to the north, Florida, Central and South America,
and Africa. In the western and central regions of sub-Saharan Africa, H capsulatum coexists
with another species, H duboisii, which can also cause histoplasmosis (so-called “African
histoplasmosis”). Infections reported in non-endemic areas are probably the result of
reactivation of infections acquired earlier in endemic areas. HIV-infected persons who have
lived or traveled in endemic areas may have reactivation of long latent H capsulatum infection
with the onset of clinical AIDS.[478]
H capsulatum grows in a mycelial form in soils, particularly those enriched by bird or bat
excrement. Persons infected with HIV should avoid bird roosting sites (particularly chicken
coops) and caves in regions where H capsulatum is endemic. Inhalation of sporulating mycelial
fragments into lung is followed by rapid conversion to the yeast form. Histoplasmosis tends to
be a widely disseminated infection involving multiple organs, particularly reticuloendothelial
tissues (Table 5).[454]
Widespread organ involvement is seen in 95% of cases in patients with AIDS infected
with H capsulatum, and it results in protean manifestations. Fever, sepsis, hepatosplenomegaly,
lymphadenopathy, weight loss, skin lesions, and respiratory complaints including shortness of
breath and cough are common. Elevations in lactate dehydrogenase are common. Additional
frequent clinical findings include an interstitial pattern on chest x-ray, pancytopenia, and CD4
count <100/µL.[479,480]
There are several methods for diagnosis. Skin testing with histoplasmin is not predictive
of histoplasmosis, because of anergy in the majority of patients with HIV infection. The use of
complement fixation serologic testing for Histoplasma antigen may be useful in identifying
persons with histoplasmosis. False positives can occur with infection from other fungal agents,
particularly Blastomyces dermatitidis. There can be a false positive Aspergillus galactomannan
assay. Regardless of immune status, persons infected or reinfected with H capsulatum will
seroconvert within 4 weeks, with seroreversion within 5 years. A CD4 lymphocyte count
<300/µL also indicates an increased risk for infection. Cultures of bone marrow and blood are
positive in 70 to 90% of cases, but H capsulatum can be slow growing, requiring from 1 to 6
weeks for positive culture results. Serologic testing will demonstrate antibodies in 50 to 70% of
cases. Antigen can be detected in urine, serum, fluid from bronchoalveolar lavage, and in
cerebrospinal fluid in most cases.[454,481,482]
Infections with H capsulatum in AIDS typically involve multiple organs in a diffuse
pattern. There are no specific gross pathologic findings. Sometimes histoplasmosis will produce
visible granulomas that are variably sized, discrete, white to tan, firm, and indistinguishable from
those of other dimorphic fungi or Mycobacterium tuberculosis.
The organisms are small 2 to 4 micron yeasts that may show budding. The yeasts are
usually found within the cytoplasm of macrophages that tend to have irregular outlines with
indistinct cell membranes on hematoxylin-eosin staining. These macrophages may cluster to
form small granulomas that rarely have an accompanying pronounced or distinctive