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H. capsulatum exhibits thermal dimorphism, developing as moulds at
relatively low temperatures, and as a budding yeast-like fungus at body
temperature (37ºC), growing in
living tissue, in soil or in culture agars.
On Sabouraud's
dextrose agar at 25C, colonies are slow growing, white or buff-brown,
suede-like to cottony with a pale yellow-brown reverse. Other colony
types are glabrous or verrucose, and a red pigmented strain has been
noted. Microscopic morphology shows the presence of characteristic large
(8-14 um in diameter), rounded, single-celled, tuberculate macroconidia
formed on short, hyaline, undifferentiated conidiophores. Microconidia,
if present, are small (2-4 um in diameter), round to pyriform and borne
on short branches or directly on the sides of the hyphae.
On brain heart
infusion (BHI) blood agar incubated at 37C, colonies are smooth, moist,
white and yeast-like. Microscopically, numerous small round to oval
budding yeast-like cells, 3-4 x 2-3 um in size are observed.
Species
Based on the mycological
information found in
Doctor Fungus, 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.
Three varieties of
H. capsulatum are recognized, depending on the clinical disease:
var. capsulatum is the common histoplasmosis, var. duboisii
is the African type and var. farciminosum causes lymphangitis in
horses. Histoplasma isolates may also resemble species of Sepedonium
and Chrysosporium. Traditionally, positive identification
required conversion of the mould form to the yeast phase by growth at
37C on enriched media, however culture identification by the exoantigen
test is now the method of choice.
Description and Habitats
Histoplasma
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.
Macroscopic
Features
Being
a thermally dimorphic fungus, Histoplasma capsulatum grows in mould
form at 25°C, and in yeast form at 37°C. Below are the macroscopic
characteristics at varying temperatures and for both varieties.
At 25°C
- Hyphal colonies (25-30°) appear nondescript, white or slightly
pink or brown on Sabouraud. dextrose agar, and cobweb-like.
- Mould colonies may be moist and white on brain heart infusion agar
(BHIA).
The color is white initially and usually becomes buff brown with age.
From the reverse, a yellow or yellowish orange color may be observed.
- Yeast colonies may be small and yellow on 5% sheep blood agar
- Colonies grow slowly
- Several generations of culture may be necessary to convert hyphal
form to yeast form
- Cyclohexamide inhibits the yeast form
- Tuberculate macroconidia and microconidia are observed
- Identification may be confused with Sepedonium species
At 37°C
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.
Health Effects
Mycosis:
HISTOPLASMOSIS
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
for fertilizer.
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
sputum.
(Source:
Mycology Online)
Microscopic
Features
At
25°C
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.
At 37°C
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)
Laboratory Precautions
Cultures of H. capsulatum represent a severe biohazard
to laboratory personnel and must be handled with extreme caution in an
appropriate pathogen handling cabinet.
Susceptibility
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.
Amphotericin B,
voriconazole,
itraconazole, and
posaconazole in general yield relatively low MICs for Histoplasma
capsulatum.
Fluconazole generally appears active, but resistance may develop. The
echinocandins,
caspofungin and
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
efficacious alternatives.
The mycological information gathered and organized in
this extensive research on the different Pathogenic Moulds was sourced
out from the list of websites below:
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