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Pathogenicity and
Health Effects
Aspergillus
species are recognized to play a significant role in three different
clinical settings in man namely, in opportunistic infections, allergic
conditions, and in toxicoses. The major factor which led to the emergence
of opportunistic infections is immunosuppression. Opportunistic infections
are generally called aspergillosis. The most common forms of aspergillosis
in humans are pulmonary in nature; on the other hand, other deep infections
are also encountered particularly among immunocompromised patients. Among
all filamentous fungi, Aspergillus is generally the most recovered
one in invasive infections and is second to Candida as the most
frequently isolated fungus in opportunistic mycoses.
Cerebral, cutaneous,
hepatosplenic,
pulmonary, and
disseminated aspergillosis,
endocarditis,
endophthalmitis,
meningitis,
myocarditis,
onychomycosis,
osteomyelitis,
otomycosis,
sinusitis, and as well as Aspergillus
fungemia may
develop as almost any organ or system in the human body may be involved once
Aspergillus - induced infection sets in.
Furthermore, there
are numerous outbreaks of disseminated aspergillosis cases that have been
recorded in neutropenic patients in concurrence with construction /
renovation projects in hospital environments.
Aspergillus
species may colonize lung
cavities which may have previously been developed due to
tuberculosis,
sarcoidosis,
bronchiectasis,
pneumonia,
ankylosing spondylitis or neoplasms. This whole distinct clinical identity is referred to as
aspergilloma. Kidneys may also be targeted by aspergilloma.
Some Aspergillus species
produce various mycotoxins which have proven to possess carcinogenic
potential particularly in animals and these are acquired through chronic
ingestion. Aspergillus flavus produces aflatoxin which is a well – known
mycotoxin. Aflatoxin may induce
hepatocellular carcinoma and it contaminates
foodstuffs such as peanuts and grains. Ingestion of high amounts of
aflatoxin may induce toxic effects in poultry animals fed with aflatoxin –
contaminated grain.
Aspergillus
species are known as occasional causative agent of respiratory infection in
birds and
mycotic abortion in certain animals, particularly cattle and
sheep.
Aspergillus
species are also encountered as common laboratory contaminants due to being
ubiquitous in nature.
Other Health
Effects of Aspergillus mold
Aspergillosis. Although metabolites of species of Aspergillus
(Hyphomycetes) cause other health problems, such as acute and chronic
aflatoxin poisoning, we are concerned here only with diseases caused by
the growth of the fungus itself somewhere in the body.
(1)
Bronchopulmonary aspergillosis is usually caused by Aspergillus
fumigatus, which colonizes mucus within the bronchi, evoking a severe
allergic reaction.
(2) In
Aspergilloma, the fungus forms a mycelial ball in a lung cavity
produced by an earlier attack of tuberculosis. The wall of the cavity may
erode, causing the patient to spit blood, and necessitating surgical
intervention.
(3) Invasive
aspergillosis is found only in patients who are severely debilitated,
or are immunosuppressed, as in AIDS. The fungus grows outward from the
lung, invading blood vessels and spreading to other organs through the
bloodstream. This insidious disease is usually fatal, and is often
diagnosed only when an autopsy is performed. [from Bryce Kendrick's The
Fifth Kingdom]
Macroscopic Features
Ø
The
major macroscopic characteristics that are essential in Aspergillus
species identification are the growth rate, colony color and thermo –
tolerance;
Ø
Texture of colonies varies from being downy to powdery;
Ø
The
growth rate varies from slow to rapid depending on the species with diameter
size ranging from 0.5 to 1 cm and 1 to 9 cm for Aspergillus species
with slow growth and with moderately to rapid growth, respectively, after
seven days of incubation at 25°C on Czapek – Dox agar;
Ø
Surface colony color may also vary depending on the species while the
reverse is mostly uncolored to pale yellow, however, some strains of
Aspergillus nidulans may be purple or olive while it is orange to purple
in Aspergillus versicolor;
Ø
The
only thermo – tolerant Aspergillus which can grow at temperature
range of 20°C to 50°C is Aspergillus fumigatus.
Microscopic
Features
Ø
Hyphae are
septate and hyaline; and
Ø
Conidiophores arise from the basal foot cell found at the supporting hyphae
and terminate in a vesicle at the tip;
Ø
Vesicle is the typically formation for the genus Aspergillus;
Ø
Phialides are flask – shaped, may either cover the surface of the vesicle
entirely called as “radiate head,” or partially at the upper surface only
termed as “columnar head,” and may either be uniseriate – directly attached
to the vesicle, or biseriate – attached to the vesicle via a supporting
cell, metula;
Ø
Conidia are found over the phialides forming radial chains and with diameter
size of 2 to 5 µm.
Ø
Other
microscopic structures of the genus Aspergillus are:
a.
Aleuriconidia – observed with a truncated base and carries remnants of the
lysed supporting cell; a type of conidium produced by lysis of the cell that
supports it;
b.
Cleistothecia – produced during the sexual production of some
Aspergillus species, are round and closed structures which enclose the
ascospore – containing asci wherein the asci are distributed into the
surrounding upon the bursting of cleistothecia;
c.
Hülle
cells - are large sterile cell bearing a small lumen; and
d.
Sclerotia - are compact or hard masses of mycelium.
Table 1.
Morphological Characteristics of Aspergillus species
|
Aspergillus
species |
Colony
Color |
Conidial
Head |
Conidiophore |
Phialides |
Other
Characteristics |
|
Surface |
Reverse |
|
Aspergillus flavus |
Yellow-green |
Yellow, brownish |
Mostly radiate, some becoming columnar at maturity |
Rough, colorless |
Uniseriate and biseriate |
Sclerotia occasionally present |
|
A. fumigatus |
Gray green, blue green |
yellowish |
Columnar |
Smooth, colorless or greenish |
Uniseriate |
Good growth at 480C |
|
A. glaucus
group |
Green and yellow |
Yellowish, brown |
Radiate to loosely columnar |
Smooth, colorless |
Uniseriate |
Yellow to orange cleistothecia present |
|
A. nidulans |
Green, buff |
Purplish red, olive |
Short columnar |
Smooth, brown |
Biseriate |
Round hülle cells and red cleistothecia usually present |
|
A.
niger |
Black |
White, yellowish |
Radiate, however, becoming loosely columnar at maturity |
Smooth, colorless or brown |
Biseriate |
- |
|
A. terreus |
Brown, cinnamon |
Yellowish brown |
Columnar |
Smooth, colorless |
Biseriate |
Round, solitary, aleurioconidia
produced directly on hyphae |
|
A. versicolor |
White, buff, yellow, pink, pale green |
White, yellow, purplish red |
Radiate |
Smooth, colorless |
Biseriate |
Round hülle cells occasionally present |
Laboratory Precautions
General laboratory
precautions are required, no special safety measures needed.
Susceptibility
Most of
Aspergillus isolates yield acceptably low MICs for amphotericin B,
itraconazole and voriconazole, however, a number of isolates show high
MICs which indicates potential prediction of resistance. Such as the few
isolates of Aspergillus fumigatus which are itraconazole –
resistant and Aspergillus terreus resistant to amphotericin B.
Fortunately, voriconazole appears effective in vitro against
itraconazole – resistant Aspergillus fumigatus.
Treatment of
invasive aspergillosis is still troublesome with high rate of mortality.
The clinical success rate of both amphotericin B and itraconazole are still
unsatisfactory due to low efficacy and / or high toxicity of the drugs and
existence of adverse immune status of the host.
The novel azoles
which include voriconazole, posaconazole or ravuconazole, glucan inhibitors
such as caspofungin and V - echinocandins, and liposomal nystatin are active
in vitro against Aspergillus and remain promising for future
therapy treatment of aspergillosis.
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