Fusarium oxysporum in Medical mycology
Fusarium
Taxonomy: The genus Fusarium is a filamentous fungus under the phylum Ascomycota, class
Ascomycetes, order Hypocreales, while the teleomorphs of Fusarium species are mostly classified in the genus Gibberella, and smaller number of
species are classified as Hemanectria
and Albonectria 1. According to Leslie and Summerell modern
taxonomy of Fusarium, there are 70 species within the genus 1.
Known as the most difficult species to distinguish by pathologists and
mycologists worldwide 2, the taxonomy of Fusarium is still a continuous debate. The members of this genus
are difficult to identify and require specialized media to induce conidia. However
positive identification can be achieved using PCR-sequencing of different genes
and comparisons with the FUSARIUM-ID database 3.
Habitat: Fusarium species are ubiquitous, found widely
distributed in soil, plant, organic substrates, water, and biofilms 4.
This distribution of Fusarium is
mainly attributed to its efficient mechanisms of dispersal and the ability to
grow on a wide range of substrates 4.
Fungal Structure and Culture
characteristics:
Fusarium has a distinctive canoe or banana shaped macroconidia, an asexual spore which is the hallmark character of this genus 5. Macroscopic features of Fusarium include a sclerotium or a sporodochium according to the growth conditions. During favourable conditions sclerotium, an organized mass of hyphae, is usually dark blue in color. The sporodochium, a cushion-like mat of hyphae bearing conidiophores over its surface, is usually absent in culture. If present, it may be cream to tan or orange color, with an exception for Fusarium solani, which gives blue-green or blue sporodochia. Microscopically, Fusarium consists of hyaline septate hyphae, conidiophores, phialides, macroconidia, and microconidia 6.
Fusarium has a distinctive canoe or banana shaped macroconidia, an asexual spore which is the hallmark character of this genus 5. Macroscopic features of Fusarium include a sclerotium or a sporodochium according to the growth conditions. During favourable conditions sclerotium, an organized mass of hyphae, is usually dark blue in color. The sporodochium, a cushion-like mat of hyphae bearing conidiophores over its surface, is usually absent in culture. If present, it may be cream to tan or orange color, with an exception for Fusarium solani, which gives blue-green or blue sporodochia. Microscopically, Fusarium consists of hyaline septate hyphae, conidiophores, phialides, macroconidia, and microconidia 6.
Diseases:
Fusarium genera is a well-known mycotoxin
producer 7 with about 50 species 4 that act as
opportunistic human and animal pathogens as well as a phytopathogenic genera of
microfungi 7. In humans, it is
known to cause a broad spectrum of infections, known as fusariosis, from
superficial, local to disseminated infections according to the immune status of
the host and the site of entry 4. Superficial and locally invasive
diseases 3, 4 like onychomycosis and keratitis are seen in
immunocompetent people as well as infections in people with serious burns or
those receiving peritoneal dialysis 3. In immunocompromised people,
it is responsible for diseases such as paronychia, invasive sinusitis and
pulmonary and extra pulmonary hematogenously disseminated disease with skin
lesions and fungemia3.
The biggest population at risk are people with prolonged
neutropenia and T-cell immunodeficiency, especially in hematopoietic stem cell
transplant recipients with severe graft-versus-host disease 4. Fusarium enters the body through inhalation.
Skin at site of tissue breakdown and the mucosal membranes are also other sites
of entry 4.
Disease Diagnosis: Disseminated fusariosis is
frequently identified as a combination of
characteristic cutaneous lesions and positive blood cultures while lung or sinus
involvement may or may not be seen 4. Invasive fusariosis is similar
to invasive asperigillosis and other invasive infections with similar high risk
patients including corticosteroids receiving and neutropenic patients4.
The diagnosis is difficult and is determined largely by the degree of
immunosuppression as well as extent of infection. Hundred percent death rate is
seen in persistently neutropenic patients with disseminated disease 4.
Fusarium
can be detected using colony morphology, microscopy, blood cultures and
FUSARIUM-ID.3
Treatment: Amphotericin B,
voriconazole, and posaconazole 4.
Fusarium oxysporum:
Habitat: Fusarium
oxysporum are ubiquitous soil and plant inhabiting microbes 8.
Fungal structure and Culture
Characteristics: With
production of three types of asexual spores, microconidia, macroconidia, and
chlamydospores, the fungus has the ability to survive as mycelium or as any one
of these spores. Microconidia are one or two celled and are the spores produced
most abundantly and frequently by the fungus under all conditions, even in
infected plants. Macroconidia are three to five celled, gradually pointed and
curved toward the ends and are commonly found on the surface of plants killed
by this pathogen as well as in sporodochia like groups. Chlamydospores of F. oxysporum
are either one or two celled and possess a two-layered wall, the outer layer
representing the original hyphal wall and the inner secondary layer formed
during maturation of the chlamydospore 9. These are produced either
terminally or intercalary on older mycelium or in macroconidia8. The
cells of hyphae of F. oxysporum are
uninucleate with only the nucleus in the apical compartment being mitotically
active (Acropetal nuclear pedigree) 10. The top of the colonies start with white aerial mycelium, become purple, with discrete orange
sporodochia present in some strain while the reverse hyaline are dark blue or dark purple. Conidiophores
are short, single, lateral monophialides in the aerial mycelium, later arranged
in densely branched clusters 11.
Diseases: With lack of good epidemiology
studies, the real frequency of this pathogen is unknown and apart from
keratitis, it is known as an infrequent cause of fungal infections. In the Fusarium genus, Fusarium oxysporum isthe
second most frequent species to cause human infection, with F. solani being the most frequent one 12.
Multistate US and international outbreaks of keratitis with use of soft contact
lenses related to Fusarium oxysporum biofilm production was seen during
2005-20063. Endophthalmitis,
onychomycosis, cutaneous and subcutaneous infections, arthritis and mycetoma
and sinusitis have been associated with F.
oxysporum. Mortality close to 100% has been associated with disseminated
infections in immunosuppressed patients (mainly haematological)12.
Disease Diagnosis: Colony morphology (fast growing
fungus), microscopic morphology and blood cultures 3.
Treatment: Amphotericin
B. It is resistant to azoles (except for Voriconazole) and echinocandins12.
Case study:
1. Cutaneous disease by Fusarium oxysporum 13
A
67-year-old female with a 20 year old-lesion in the right ear was referred to
the hospital in 2000. She had a history of type II diabetes (treated orally).
Upon asking the patient, she didn’t recall any previous traumatic injury in the
affected area. According to the patient history, in 1980 she was diagnosed with
infectious granuloma caused by fungi or mycobacteria. All the complementary tests for
mycobacteriosis were negative at that time and no mycological cultures were done.
She received treatment with rifampicin, isoniazid and ethambutol for 2 months
on the basis of clinical and histological findings followed by rifampicin and
isoniazid for 7 months. She received tentative cryotherapy in 1982 and in 1990,
she was diagnosed with cutaneous mycosis due to the presence fungal elements in
biopsy specimens. She received a treatment of itraconazole 200 mg/day for 6
months followed by terbinane® 250 mg/day for 2 months, yet the lesions were no
cured.
Her
lesions resembled lupus vulgaris (chronic,
postprimary, paucibacillary cutaneous tuberculosis)
Routine
tests were normal and a standard multi-test for cellular immunity was also
normal. PCR detection as well as cultures for mycobacteria was negative. When
biopsy specimen was stained with Hematoxylin-eosin, a chronic inflammatory
response by epithelioid cells, eosinophils and numerous giant foreign body
cells was seen. Pale structure resembling fungal hyphae were seen in the foreign
body cells. Numerous hyphae sparsely distributed in the dermis and also inside
giant cells were seen after Periodic acid-Schiff (PAS) staining.
When the
biopsy sample was cultured in chloramphenicol, gentamicin, SDA agar and SDA
with cyclohexamide at 25 and 37OC, the former showed velvety
colonies, white to pale gray in color at 25oC and orange at 37oC.
With time the cultures
developed violet areas at both temperature. When Subcultures and slide cultures
were prepared for species identification using oatmeal agar, potato sucrose and
PDA, “wide vegetative aerial mycelium, with septate, branched hyphae, scarce
fusiform, 3 to 5-celled, slightly curved, macroconidia, pointed at the tip,
numerous, single-celled, oval/ellipsoid, non-chain microconidia developed on
short lateral conidiophores and intercalary, single or paired, hyaline,
smoothwalled chlamydospores” were seen. On the basis of these data, the colony
was identified as F. oxysporum. The patient
was treated with oral Flucanazole for 3 months during which the
patient showed a marked improvement.
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