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Identification of
Fusarium species is often difficult due to the variability
between isolates (e.g. in shape and size of conidia and colony color) and
because features that are required are not always well developed (eg. the
absence of macroconidia in some isolates after subculture). The important
characteristics used in the identification of Fusarium
species are as follows. Note, sporulation may need to be induced in some
isolates and a good slide culture is essential.
1. A pure culture, obtained if possible from a single
conidium or hyphal tip isolation.
2. Colony growth diameters on potato dextrose agar
and/or potato sucrose agar after incubation in the dark for 4 days at 25C.
3. Culture pigmentation on potato dextrose agar
and/or potato sucrose agar after incubation for 10-14 days with a daily
exposure to light.
4. Microscopic morphology including shape of the macroconidia; presence or
absence of microconidia; shape and mode of formation of microconidia;
nature of the conidiogenous cell bearing microconidia; and presence or
absence of chlamydoconidia.
Description
and Natural Habitats
Fusarium is a filamentous fungus widely distributed on plants and
in the soil. It is found in normal mycoflora of commodities, such as rice,
bean, soybean, and other crops. While most species are more common at
tropical and subtropical areas, some inhabit in soil in cold climates.
Some Fusarium species have a teleomorphic state.
As well as
being a common contaminant and a well-known plant pathogen, Fusarium
species may cause various infections in humans. Fusarium is
one of the emerging causes of opportunistic mycoses.
Species
The genus Fusarium currently contains over 20 species. The most
common of these are Fusarium solani, Fusarium oxysporum, and
Fusarium chlamydosporum. Please refer to the table of synonyms for
a much more complete list of the currently recognized Fusarium species.
Most
Fusarium species are soil fungi and have a world-wide distribution.
Some are plant pathogens causing root and stem rot, vascular wilt or fruit
rot. Other species cause storage rot and are important mycotoxin
producers. Several species, notably F. oxysporum, F. solani and F.
moniliforme, are recognized as being pathogenic to man and animals
causing mycotic keratitis, onychomycosis and hyalohyphomycosis, especially
in burn victims and bone marrow transplant patients.
Pathogenicity and Clinical Significance
As
well as being common plant pathogens, Fusarium species. are
causative agents of superficial and systemic infections in humans.
Infections due to Fusarium spp. are collectively referred to as
fusariosis. The most virulent Fusarium spp. is Fusarium solani.
Trauma is the major predisposing factor for development of cutaneous
infections due to Fusarium strains. Disseminated opportunistic
infections, on the other hand, develop in immunosuppressed hosts,
particularly in neutropenic and transplant patients. Fusarium
infections following solid organ transplantation tend to remain local and
have a better outcome compared to those that develop in patients with
hematological malignancies and bone marrow transplantation patients.
Keratitis, endophthalmitis, otitis media, onychomycosis, cutaneous
infections particularly of burn wounds, mycetoma, sinusitis, pulmonary
infections, endocarditis, peritonitis, central venous catheter infections,
septic arthritis, disseminated infections, and fungemia due to Fusarium
spp. have been reported.
Outbreaks of nosocomial fusariosis have also been reported. Existence of Fusarium
in hospital water distribution systems may result in disseminated
fusariosis in immunosuppressed patients. Fusarium may also exist in
soil of potted plants in hospitals. These plants constitute a hazardous
mycotic reservoir for nosocomial fusariosis.
Fusarium
species produce mycotoxins. Ingestion of grains contaminated with
these toxins may give rise to allergic symptoms or be carcinogenic in
long-term consumption. Fumonisins are the mycotoxins produced by Fusarium
moniliforme and Fusarium proliferatum in maize. They may cause
oesophageal cancer. Another group of mycotoxins, zearalenones, may also be
produced by some Fusarium spp. growing in grains. Studies on
reduction or elimination of Fusarium mycotoxins from contaminated
agricultural and food commodities are in progress.
Clinical manifestations of hyalohyphomycosis caused by Fusarium;
include cutaneous and subcutaneous infections, endophthalmitis,
osteomyelitis, and arthritis following traumatic implantation. Peritonitis
has also been reported in patients on continuous ambulatory peritoneal
dialysis (CAPD). Disseminated infections are similar to disseminated
aspergillosis, however fungemia and ulcerated skin lesions are often more
pronounced. The typical patient is granulocytopenic and receiving
broad-spectrum antibiotics for unexplained fever.
Macroscopic Features
Fusarium species grow rapidly on Sabouraud dextrose agar at 25°C and
produce woolly to cottony, flat, spreading colonies. The only slow-growing
species is Fusarium dimerum. From the front, the color of the
colony may be white, cream, tan, salmon, cinnamon, yellow, red, violet,
pink, or purple. From the reverse, it may be colorless, tan, red, dark
purple, or brown.
A sclerotium,
which is the organized mass of hyphae that remains dormant during
unfavorable conditions, may be observed macroscopically and is usually
dark blue in color. On the other hand, sporodochium, the cushion-like mat
of hyphae bearing conidiophores over its surface, is usually absent in
culture. When present, it may be observed in cream to tan or orange color,
except for Fusarium solani, which gives rise to blue-green or blue
sporodochia.
Microscopic Features
Hyaline septate hyphae, conidiophores, phialides, macroconidia, and
microconidia are observed microscopically. In addition to these basic
elements, chlamydospores are also produced by Fusarium chlamydosporum,
Fusarium napiforme, Fusarium oxysporum, Fusarium
semitectum, Fusarium solani, and Fusarium sporotrichoides.
Phialides are
cylindrical, with a small collarette, solitary or produced as a component
of a complex branching system. Monophialides and polyphialides (in heads
or in chains) may be observed. Macroconidia (3-8 x 11-70 µm) are produced
from phialides on unbranched or branched conidiophores. They are 2- or
more celled, thick-walled, smooth, and cylindrical or sickle-
(canoe-)shaped. Macroconidia have a distinct basal foot cell and pointed
distal ends. They tend to accumulate in balls or rafts. Microconidia (2-4
x4-8 µm), on the other hand, are formed on long or short simple
conidiophores. They are 1-celled (occasionally 2- or 3-celled), smooth,
hyaline, ovoid to cylindrical, and arranged in balls (occasionally
occurring in chains). Chlamydospores, when present, are sparse, in pairs,
clumps or chains. They are thick-walled, hyaline, intercalary or terminal.
Macroscopic and
microscopic features, such as, color of the colony, length and shape of
the macroconidia, the number, shape and arrangement of microconidia, and
presence or absence of chlamydospores are key features for the
differentiation of Fusarium species. Molecular methods, such as 28S
rRNA gene sequencing, may be used for rapid identification of Fusarium
strains to species level.
Laboratory Precautions
No special
precautions other than general laboratory precautions are required.
Susceptibility
Fusarium is one of the most drug-resistant fungi. Among the Fusarium
spp., Fusarium solani in general tends to be most resistant of all.
Fusarium strains yield quite high MICs for flucytosine,
ketoconazole, miconazole, fluconazole, itraconazole, and posaconazole.
The novel triazole, Syn-2869, has no activity against Fusarium. Fusarium
spp. are intrinsically resistant to the novel glucan synthesis
inhibitors, caspofungin, anidulafungin, and micafungin.
Despite the lack of its activity alone, the combination of caspofungin with
amphotericin B appears synergistic against some Fusarium isolates.
The only
antifungal drugs that yield relatively low MICs for Fusarium are
amphotericin B, voriconazole, and natamycin. Compared to
itraconazole, voriconazole yields notably lower MIC. Terbinafine
may show good in vitro activity against some isolates.
Fusarium
infections are difficult to treat and the invasive forms are often fatal.
Amphotericin B alone or in combination with flucytosine or rifampin is the
most commonly used antifungal drug for treatment of systemic fusariosis.
Lipid formulations of amphotericin B, such as liposomal amphotericin B
and amphotericin B lipid complex are also used. However, most cases
remain resistant and fail to respond to amphotericin B treatment.
Granulocyte and GM-CSF transfusions concommitant to amphotericin B therapy
may be life-saving in some immunosuppressed patients with disseminated
fusariosis. Despite its limited in vitro activity, posaconazole appears
effective in murine fusariosis. Human data are awaited for verification of
this finding. Topical natamycin is used for treatment of keratitis due to Fusarium. In
addition to antifungal therapy, keratoplasty is required for several
patients. Patients with mycetoma due to Fusarium may respond to
itraconazole. Onychomycosis due to Fusarium, on the other hand, may
be treated with itraconazole and cycloprox nail lacquer. |