Description and Habitats
is a thermally dimorphic fungus found in nature. Soil contaminated with bird
droppings or excrements of bats is the common natural habitat for
Histoplasma. Although it is claimed to exist worldwide, tropical areas
are where this fungus is more frequently encountered. It is endemic in the
Tennessee-Ohio-Mississippi river basins
Based on the mycological
information found in www.doctorfungus.org, the genus Histoplasma contains one species,
Histoplasma capsulatum. Histoplasma capsulatum has two
varieties: Histoplasma capsulatum var. capsulatum and
Histoplasma capsulatum var. duboisii. It has a teleomorph
referred to as Ajellomyces capsulatus.
Histoplasmosis is a
systemic disease, mostly of the reticuloendothelial system, manifesting
itself in the bone marrow, lungs, liver, and the spleen. In fact,
hepatosplenomegaly is the primary sign in children, while in adults,
histoplasmosis more commonly appears as pulmonary disease. This is one of
the most common fungal infections, occurring frequently in South Carolina,
particularly the northwestern portion of the state.
The ecological niche of
H. capsulatum is in blackbird roosts, chicken houses and bat guano.
Typically, a patient will have spread chicken manure around his garden and 3
weeks later will develop pulmonary infection. There have been several
outbreaks in South Carolina where workers have cleared canebrakes which
served as blackbird roosts with bulldozers. All who were exposed, workers
and bystanders, contracted histoplasmosis. Histoplasmosis is a significant
occupational disease in bat caves in Mexico when workers harvest the guano
In the endemic area the majority of patients who develop
histoplasmosis (95%) are asymptomatic. The diagnosis is made from their
history, serologic testing or skin test. In the patients who are clinically
ill, histoplasmosis generally occurs in one of three forms: acute pulmonary,
chronic pulmonary or disseminated. There is generally complete recovery from
the acute pulmonary form (another "flu-like"
illness). However, if untreated, the disseminated form of disease is usually
fatal. Patients will first notice shortness of breath and a cough which
becomes productive. The sputum may be purulent or bloody. Patients will
become anorexic and lose weight. They have night sweats. This again sounds
like tuberculosis, and the lung x- ray also looks like tuberculosis, but
today radiologists can distinguish between these diseases on the chest film
(histoplasmosis usually appears as bilateral interstitial infiltrates).
Histoplasmosis is prevalent primarily in the eastern U.S. In S.C., a
histoplasmin skin test survey of lifetime, one county residents, white
males, 17 to 21 years old, was performed on Navy recruits. The greatest
number of positive skin tests appeared in the northwestern part of the
state. A similar study of medical students conducted at Medical University
of South Carolina, about 25 years ago, bore the same distribution (Goodman
and Ever, J.S.C.M.A. 67:53-55, 1971).The skin test is NOT used for
diagnostic purposes, because it interferes with serological tests. Skin
tests are used for epidemiological surveys.
Clinical specimens sent to the lab depend on the presentation of the
disease: Sputum or Bronchial alveolar lavage, if it is pulmonary disease, or
Biopsy material from the diseased organ. Bone marrow is an excellent source
of the fungus, which tends to grow in the reticulo-endothelial system.
Peripheral blood is also a source of visualizing the organism histologically.
The yeast is usually found in monocytes or in PMN's. Many times an astute
medical technologist performing a white blood cell count will be the first
one to make the diagnosis of histoplasmosis. In peripheral blood, H.
capsulatum appears as a small yeast about 5-6 microns in diameter. (Blastomyces
is 12 to 15 microns). Gastric washings are also a source of H. capsulatum
as people with pulmonary disease produce sputum and frequently swallow their
a thermally dimorphic fungus, Histoplasma capsulatum grows in mold
form at 25°C, and in yeast form at 37°C. Below are the macroscopic
characteristics at varying temperatures and for both varieties.
Colonies are slow growing and
granular to cottony in appearance. The color is white initially and
usually becomes buff brown with age. The colonies are not sensitive to cycloheximide in the culture media. From the reverse, a yellow or
yellowish orange color may be observed. While these features are best
observed on Sabouraud dextrose agar (SDA), brain heart infusion agar (BHIA)
enhances growth more efficiently.
Creamy, slowly growing, moist and
yeast-like colonies are formed. This phase is observed in infected tissues
and in vitro on enriched media, such as BHIA containing 5-10% blood.
For definitive identification of the
fungus, yeast-to-mold conversion should be demonstrated.
Hyphae are septate and hyaline. Histoplasma
capsulatum produces hyphae-like conidiophores which arise at right
angles to the parent hyphae. It has both macro- and microconidia.
Macroconidia are tuberculate, thick-walled, round, unicellular, hyaline,
large and often have fingerlike projections on the surface. These
macroconidia are also referred to as tuberculochlamydospores or
macroaleurioconidia. Microconidia (microaleurioconidia) are unicellular,
hyaline and round, with a smooth or rough wall.
Narrow-based, ovoid, budding yeast
cells are formed. Yeasts of var. capsulatum are smaller than (2-4
µm) those of var. duboisii (12-15 µm).
Cultures of H. capsulatum represent a severe biohazard
to laboratory personnel and must be handled with extreme caution in an
appropriate pathogen handling cabinet.
Data on in vitro activity of
Histoplasma capsulatum are yet limited. The NCCLS antifungal
susceptibility testing methods have not been standardized for testing the
activity of this fungus.
posaconazole in general yield relatively low MICs for Histoplasma
Fluconazole generally appears active, but resistance may develop. The
anidulafungin have relatively higher MICs, and one in vivo study found
caspofungin to have little activity.
Amphotericin B, itraconazole and
fluconazole are currently used in treatment of histoplasmosis. Fluconazole
is less active than itraconazoleand is a second-line agent. Ketoconazole is
also a second-line drug due to the availability of safer and more