Fusarium spp.

Fusarium spp. on gypsum boardFusarium spp. on EM agarFusarium spp. on RB agarFusarium spp. - Microscopy (EM Culture)

Basics

As well as being common contaminants and well-known plant pathogens, Fusarium spp. may cause various infections in humans and are one of the emerging causes of opportunistic mycoses. They are mostly known for their production of potent mycotoxins.

Taxonomy

Kingdom Fungi Order Hypocreales
Phylum Ascomycota Family Hypocreaceae
Class Euascomycetes Genus Fusarium

The genus Fusarium may contain hundreds of species, depending on the consulted registry; currently the genus contains 68 named species registered with the Universal Protein Resource (UniProt) agency {3318};  there are over 1300 species and strains registered with the International Mycological Association data bank (IMA- MycoBank) {3971}; these strains have been described and their specific characteristics often lie within minute differences {4275}. Fusarium roseum is the type taxon.

Many species of Fusarium have known teleomorph forms mostly included in the genera Gibberella; Gibberella fujikuroi is the perfect form of Fusarium moniliforme {3842}.

Fusarium solani is the most common Fusarium species recovered in humans and animals; F. culmorum, F. moniliforme(syn. F. proliferatum or F. verticillioides), F. napiforme have also been reported associated with infections in man.

Fusarium has often been reported with health problems associated with environmental outdoor and indoor exposure; in these cases Fusarium is mostly reported as Fusarium sp.

Habitat/Ecology

Fusarium species are ubiquitous and may be found in the soil, air and on plants {2972}. They are mostly known as associated with cereal crops and grain dust {2982}, rye, barley, corn, oats and buckwheat {1182}. Certain Fusarium, such asF. solani, are often associated with cereal and other specific cultures; consequently these Fusarium species are more often found in rural areas than in other settings {2964}. 

However, many Fusarium species can be found both in outdoor and indoor air {2079; 1584; 706}; the highest levels of airborne spores are found in summer, both in urban and sub-urban areas as well as coastal and inland areas {1584; 689}; occurrence may vary according to outdoor environmental factors in the immediate surroundings and levels of indoor contamination.

Fusarium species are also associated with water sources {2959; 2978}.  

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Fusarium species have been recovered from water system samples and their aerosolisation has been documented after running the showers {2959}.  Fusarium spp. may also be the most common taxon isolated from surfaces inside swimming pool facilities {1578}.

Aerobiological records over the different continents show that Fusarium species are regularly present in outdoor air samples even if, in most community settings, they are not observed in high concentrations {1788; 638; 2971}.  Airborne concentrations vary seasonally and constitute a small proportion of the natural aerosolised fungal flora in northern climates; although present year-round, the highest numbers of airborne Fusarium are recorded during summer {1788; 2999}. Outdoor air concentrations of Fusarium seem to be at their highest during the rainy summer season {343}. The mode of dissemination of Fusarium spores is by wet spores and water splashes, or by insects and wind once the growth has dried out.

Growth requirements

Fusarium is best known for growing on cereal crops (grain, straw, hay); many species can occasionally be found on a variety of substrates. Species of Fusarium can adapt to many nutritional circumstances although in turn, their morphological characteristics may vary greatly depending on environmental parameters {4277}. Fusarium requires wet conditions: it even grows in contaminated stagnant water such as humidifier pans. Most Fusarium species encountered in the indoor environment are slightly xerophilic and have a minimum Aw in the  0.86 to 0.91 range {3729}.

Water Activity :         F. moniliforme           Aw =87-91
F. solani :                   Aw = 87-90

Growth on building materials or indoor environment

Fusarium can be found in a small proportion of dwellings, growing on contaminated building materials {2991} and in contaminated air conditioning systems {1584}.

The occurrence of Fusarium in a dwelling is proof of humidity in the environment {1814}.

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In an environmental survey, positive findings of Fusarium spp. were made in 2–6% of examined US homes {2256}, with even higher values recorded in other geographical areas of North America and Europe, such as in South California (25%, with 4.5 -47 CFU/m3) {1824}, Scotland (10% of homes) {4274}, the Netherlands (9% of homes) {4314} and in 1 of the 16 homes investigated in Toronto, Canada {1817}.

Scandinavian studies showed that products most vulnerable to mould attacks were aged, water-damaged organic materials containing cellulose, such as wooden materials, jute, wallpaper and cardboard. Studies have demonstrated that certain species of Fusarium spp. are able to grow on damp building materials such as beech wood, pinewood particle board and gypsum board (715; 594).

Indoor total airborne fungal concentrations depend on sources and extent of dampness as well as type of wall and floor coverings, aeration levels, overall cleaning frequency and presence of pets (624; 2747). Other important factors such as seasonal fluctuations and outdoor environment-linked levels also largely contribute to the variability of the baseline flora {3021}.

Laboratory section

Normal laboratory precautions should be exercised in handling cultures of this species within Biosafety Level 2 practices and containment facilities.

Fusarium species grow easily and rapidly on most media without cycloheximide.  
This genus lacks the large number of morphological characteristics that would allow to easily distinguish its numerous species. Recently, a commercially available PCR-based method was successfully tested with clinical isolates ofFusarium species and 5 ATCC isolates {3251}.

Colony, macroscopic morphology

On Sabouraud dextrose agar, at 25°C, Fusarium spp. grow rapidly 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. The reverse side of the colony may be colorless, tan, red, dark purple or brown.

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Sclerotia, (organized masses of hyphae that remain dormant during unfavourable conditions) may be observed macroscopically and are usually dark blue in color. On the other hand, sporodochia (a cushion-like mat of hyphae bearing conidiophores over its surface) are usually absent in culture. When present, they may be observed in cream to tan or orange colour, except for Fusarium solani, which gives rise to blue-green or blue sporodochia {2207; 2052}. 

On Czapek agar, at 25°C, Fusarium spp. colonies grow rapidly to 4-5 cm within 10 days. The colonies are flat, either velvety to cottony in texture, initially white or yellow often becoming pinkish or light grey in time; some species at maturity have a broad white mycelium margin and the reverse side often displays shades of pink rose to red.

Strains of Fusarium solani can grow at 37°C on Sabouraud, potato dextrose agar (PDA) and asparagine liquid media {2964}; this species can even survive at least 3 weeks in cultures at 40°C {2964}.

Microscopic morphology

The genus Fusarium can generally be identified by the typical production of hyaline, fusiform (banana-shaped), multicellular macroconidia with a foot cell at the base. In some cases, species identification is difficult and may require molecular methods (1596; 1596). Recently, a commercially available PCR-based method was tested with 21 clinical isolates ofFusarium species and 5 ATCC isolates: using sequencing identification as a gold standard, seven of nine different species were identified {3251}.

The basic elements of Fusarium spp. are hyaline septate hyphae, conidiophores, phialides, macroconidia and microconidia, observed microscopically. In addition to these basic elements, chlamydospores are also produced by some species (2207; 412; 2052).    

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These species are Fusarium chlamydosporumFusarium napiformeFusarium oxysporumFusarium semitectum,Fusarium solani and Fusarium sporotrichioides.

Phialides are cylindrical, with a small collaret, 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, 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 (2207; 412; 2052).

Specific metabolites

Organics compounds (including VOCs)

Fusarium spp. produce various hydrocarbons, alcohols, ketones, esters and terpenes (myrcenes) in nature as well as on building materials (715; 594; 2076). They also produce other metabolites such as pyrazines, methylfurans, benzenes, limonene and products known as KAUR-like {Sunesson, 1996 607 /id} .

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Toxigenic strains of Fusarium produce volatile sesquiterpene hydrocarbons such as trichodiene; each of these intermediate metabolites is particular to the mycotoxin end product {3258}.

A number of organic compounds, including volatile organic compounds (VOCs), have been identified in indoor air in damp buildings contaminated by fungi: these VOCs are thought to contribute to various indoor air problems. However, most of the identified metabolites are non-reactive and found in low concentration in the indoor air {594}. 

Some species have a defined microbial volatile organic compound (mVOC) profile; mVOC production is influenced by both growth substrate and species of Fusarium. For example, experimentally grown Fusarium species show a mVOC profile which may be subject to considerable modification in response to external factors such as cultivation on different substrata {715}. These differing substrata change both the number and concentration of mVOCs  {715; 2968; 2809; 1148}, whereas other volatiles are specific for a single species (2809; 129; 1149; 2809).

Mycotoxins

Many species of Fusariumare common contaminants on various organic materials and most are recognised potential mycotoxin producers. Among the best studied mycotoxins generated by Fusarium spp. are highly potent toxins such as deoxynivalenol (DON), nivalenol (NIV), moniliformin (MON) and ochratoxin A (OTA) {1180; 2982}; many strains also produce T-2 toxin, zearalenone (ZEN) {2986} and scirpentriol toxins {1633}. DON, NIV and OTA can be found both in grain and settled dust samples, with the latter exhibiting greater concentrations {2982} suggesting the importance of inhalation exposure to these mycotoxins in occupational settings.

Some Fusarium mycotoxins have also been studied in cases of indoor building contamination {1220; 16}.  

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Some of the mycotoxins associated with Fusarium such as citrinine, DAS, DON sterigmatocystin and ochratoxin have been found in building materials or dust contaminated with Fusarium and other fungi.

Fusarium moniliformeF. subglutinans and F. proliferatum, all important spoilers of maize, produce fumonisins among other toxins. These mycotoxins are responsible for several animal mycotoxicoses (leuko­encephalomalacia in horses and pulmonary oedema in swines) and possibly for oesophageal cancer in humans {3247}.

T-2 toxin is a mycotoxin of type A trichothecene produced by several Fusarium species: in cereals, it ranges from trace to high concentrations in the order of one microgram per kg {2986}. This mycotoxin can affect both cell mediated and humoral immune mechanisms.

Most Fusarium toxins are associated with food and grain spoilage. In these circumstances, variation in relative air-humidity appears to play a role on the incidence of Fusarium spp. both on the amounts of fungi and on the mycotoxin content in grain {2986}.

For example, it has been observed that weather conditions at harvesting contribute to an increase in the contents ofFusarium fungi and DON and ZEN mycotoxins produced these fungi in winter wheat grain {2986}.

In a study of settled and airborne grain dust by PCR assay, the presence of F. langsethiae was associated with HT-2 and T-2 toxins in settled dust: the trichothecene levels in grain dust toxin reached detectable levels even after short exposures of 10-60 minutes {1158}. DON, T-2 and HT-2 toxins were present in most settled dust samples at levels ranging from 20 to 50 µg/kg of dust; concentrations were slightly higher in settled dust samples than in air samples.

Unsupported allegations have suggested that Fusarium toxins have been used as biological weapons {4277}.

Adverse health reactions

Health risks associated with mould exposure in water damaged buildings are well established, especially for upper and lower respiratory tract symptoms. Although Fusarium contamination seldom occurs indoors, given the numerous severe adverse health effects reported in other circumstances, such contamination must be considered as a possible contributor to various indoor air problems.   

Irritation and inflammation

Generally speaking all moulds contain substances that are irritants and promote inflammation to some degree. Some VOCs produced by moulds on damp building materials in the indoor setting are thought to contribute to different health problems, such as eye irritation, irritation of the nose and throat, lethargy and headache {594}.   

In vitro and in vivo studies have demonstrated that Fusarium spores and spore extracts can experimentally produce eye irritation and erythema {2964}. In controlled experiments, inoculums of F. solani instilled in rabbit eyes produced a clinical reaction producing irritation and erythema {2964}.

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(1-->3)-Beta-D-glucans are non-specific and non-allergenic structural cell wall components present in most fungi: many authors have suggested that they play a causal role in the development of respiratory symptoms associated with indoor fungal exposure {1346}.

Allergic reactions

Airborne spores of Fusarium spp. are widespread but especially common in agricultural areas.  Fusarium airborne spores are considered common seasonal and perennial airborne allergens 2609  2971 linked to Type I allergies, hay fever and asthma {2342; 3095; 2971; 1180; 2018; 2774}.  Fusarium is among the most frequent positive dermal tests within mould allergen panels {638}.   

Fusarium solani is isolated repeatedly from patients diagnosed with allergic fungal sinusitis (AFS) {719; 1481}. Some species implicated in AFS are found to colonise the surfaces of indoor construction and finishing materials in the patients’ environments (1397; 1387).  Cases of Fusarium infectious sinusitis have also been reported in particular circumstances such as maxillary sinusitis {3272} and in transplant patients (3259). 

Allergic components and mechanism

Many extracts from species of Fusarium have been studied experimentally by various serological assays in an attempt to characterise specific fractions {2285}. In one study, up to 38 antigenic fractions were isolated and 21 were IgE binding. However these fractions are currently not available for routine testing.

In the diagnosis of Fusarium allergy, as for certain other fungi, available allergen panels for radioallergosorbent testing (RAST) {1875} seem unlikely to produce false-positive responses due to cross-reactivity because of the observed frequent significant variance in test scores from mould to mould within the same patient {1977}.

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Nevertheless, some components of Curvularia have been identified to cross-react with  F. solani but show negligible IgE binding properties to F. solani in Curvularia-sensitised patients {2973}. Consequently, positive reactions to Fusarium are unlikely due to Curvularia sensitisation.  Some allergenic components of spores from Fusarium vasinfectum have been shown to cross-react with raw mushroom allergens by immunoblot assay: in one case, both the skin test and the IgE test cross reacted in a patient with oral allergy symptoms to raw, but not cooked, mushrooms {2965}. 

Hypersensitivity pneumonitis

Type III hypersensitivity pneumonitis due to Fusarium is not often reported except in occupational settings related to the handling of grain or hay.  A few cases of hypersensitivity pneumonitis (HP) have been attributed to indoor contamination due to mouldy building materials {716} and contaminated air conditioners {277}. 

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In one study, specific IgG antibodies against fungal antigens present in a contaminated air conditioner were estimated in serum of exposed symptomatic patients: anti-Fusarium antibodies were found in 26% of these cases {277}.  In another report, a case of hypersensitivity pneumonitis (HP) caused by Fusarium napiforme found in the home environment was reported in a 17-year-old male student {716}. This case was diagnosed according to history, chest radiograph, spirometry, high-resolution chest CT and transbronchial lung biopsy.

Toxic effects (mycotoxicosis)

Many strains of Fusarium are active producers of toxins under given sets of growth conditions. These fusarial toxic metabolites can cause mycotoxicosis not only in animals but also in humans following repeated ingestion of food colonised by the fungal organism {2972}. 

Fusarium toxicoses have been associated to both acute and chronic exposure to contaminated material.

Toxic effects due to ingested Fusarium include cytotoxic, nephrotoxic and tremorgenic effects as well as immunosuppressive and carcinogenic effects. These pathologies are well known to occur in man, livestock and other animals {3182; 3184; 3185}.  Consequently, concentrations of some of these toxins in livestock feed as well as in food for human consumption are strictly regulated (3189; 3190; 3191) {3191; 3190; 3189}.

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Immunosuppression and carcinogenetic effects have been linked to Fusarium toxins.  In fact, in vitro and in vivo studies results suggest that T-2 toxin, even at low concentrations, can induce the secretion of IL-12, TNF-alpha and IFN-gamma and may be used as a positive immuno­modulator in the human model {2958}.  

Laboratory studies have described the carcinogenicity of fumonisin B1 (FB1) in rodents and epidemiological evidence suggests an association between FB1 and cancer in humans {2963; 2305}. 

Many mycotoxicosis due to Fusarium species have been identified in veterinarian medicine including  facial eczema in sheep {2316}; alimentary toxic aleukia, has also been well studied and attributed to Fusarium mycotoxins {130}. 

Fusarium moniliformeF. subglutinans and F. proliferatum, all important spoilers of maize, produce fumonisins among other toxins. These mycotoxins are responsible for several animal mycotoxicoses (leuko­encephalomalacia in horses and pulmonary oedema in swines) and possibly for oesophageal cancer in humans {3247}.

For certain toxins, the precise mechanisms of Fusarium toxicity have been well documented at the cellular level. Such is the case of the effects of T-2 toxin on cytokine production by mice peritoneal macrophages and lymph node T-cells. T-2 toxin significantly reduces IL-1beta release in a concentration dependent manner (p<0.005, p<0.001). Conversely, Interleukin-12 and TNF-alpha production are significantly increased in response to 0.1 ng/ml, 0.01 ng/ml and even to doses as low as 0.001 ng/ml of T-2 toxin (p<0.001). However, T-2 toxin, at higher concentrations ranging from 1 ng/ml to 100 ng/ml, reduces both IL-12 (p<0.001) and TNF-alpha production (p<0.005, p<0.05). The effects of T-2 toxin on lymph node T cells also show a decrease in IL-4 and IL-10 release in a concentration-dependent manner (all with p<0.01). Lastly, T-2 toxin at concentrations between 1 ng/ml and 100 ng/ml reduces the release of both IL-2 and IFN-gamma {2958}.

Infections and colonisations

Fusarium species are saprophytic moulds and important plant pathogens. Human infections by Fusarium spp. are rare although they are increasingly recognised as agents of human mycosis in localised, focally invasive or disseminated infections. The infection is mostly superficial; deep tissue infection may occur as an opportunistic hyalohypho­mycosis, and wide dissemination can occur in immunocompromised hosts (2988; 2972). 
Infection of immunocompetent persons is rarely reported {2972}.

Fusarium is an aetiologic agent in keratitis, endophthalmitis, cutaneous infections, burn patients, mycetoma, onychomycosis, sinusitis, pulmonary disease, endocarditis, catheter infections and septic arthritis.

The clinical form of fusariosis depends largely on the immune status of the host and the portal of entry, with superficial and localised disease occurring mostly in immunocompromised subjects {1596}. The prognosis is poor and is largely determined by the degree of immunosuppression and extent of infection; there is virtually a 100% death rate among persistently neutropenic patients with disseminated disease. 

Up to 11 species of Fusarium have been documented as aetiologic agents of human infection; taxonomic identification is difficult however, as some isolates, especially the slow maturing ones, may have been attributed to the wrong species {2988}. Fusarium species frequently implicated in human infections include F. solani, F. oxysporum and F. moniliforme also termed F. verticillioides {2966; 2972}; more recently, cases of F. napiforme {2988} and F. proliferatum {730} have also been reported.   

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Superficial fusariosis

Onychomycosis is most commonly due to F. oxysporum or F. solani {2972; 2973} and corneal ulcers have been attributed to F. solani {2964}.  

Localised cutaneous Fusarium hyalohyphomycoses have been reported, and cutaneous manifestations of disseminated infections have also been described at later stages {3682}{1647; 1617}. These fatal infections usually occur in the setting of prolonged neutropenia.  

Among immunocompetent patients, tissue breakdown (such as caused by trauma, severe burns or foreign body) is the principle risk factor for fusariosis. Infections include keratitis, onycho­mycosis and occasionally peritonitis and cellulitis {2966}.  Localised infections also include septic arthritis, endophthalmitis, osteomyelitis, cystitis and brain abscesses {2972; 3248}. Typical skin lesions may be painful red or violaceous nodules, the center of which often becomes ulcerated and covered by a black eschar. Multiple necrotising lesions are often observed on the trunk and the extremities.

Deep-sited or disseminated fusariosis

Among immunocompromised patients, deep-sited or disseminated fusariosis are found mainly in patients with haematological malignancies: in these cases, Fusarium spp. are the second most common pathogenic mould {2966; 2972}. Risk factors for disseminated fusariosis include severe immunosuppression (neutropenia, lymphopenia, graft-versus-host disease and corticosteroids), colonisation and tissue damage. One study reported a systemic infection in a child with acute lympho­blastic leukemia caused by Fusarium proliferatum.

Most cases of disseminated infection due to Fusarium species are fatal, with mortality rates reaching 70 %.

Virulence factors

The fact that F. solani is able to grow at 37°C could represent a virulence factor.

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The high rate of dissemination in immunosupressed patients has been associated with the fact that some Fusariumspecies produce yeast-like structures (adventitious sporulation) which could facilitate their dissemination and growth in the blood {4280; 4281}.

Specific settings

Nosocomial infections

Fusarium spp. infections have not been thoroughly documented as true nosocomial infections. Environmental sampling in hospital settings has revealed the presence of Fusarium among the predominant fungal contamination {2409; 2978; 2987}.    Nevertheless, Fusarium is rarely isolated as a colonising or an invading fungi in nosocomial infections {2409; 1747}. In the rare instances where fusariosis appears to have been acquired in the hospital, its presence was associated with environmental exposure to Fusarium via air and water {2966} or introduced by indwelling devices.

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Existence of Fusariumin hospital water distribution systems may result in disseminated fusariosis in immunosuppressed patients {Squier, 2000 4282 /id}. Fusarium may also exist in soil of potted plants in hospitals. These plants constitute a hazardous mycotic reservoir for nosocomial fusariosis {396}.

In one epidemiological study conducted on 70 cases of cancer patients with fusariosis,  results failed to link the infections to the hospital environment and concluded that the most likely source of fusariosis was the external environment, such as water, rather than nosocomial sources {343}.

A second group of invasive fusariosis in immunocompromised patients with haematological malignancy treated at a same cancer center were also studied {3249}. Forty patients with disseminated and three patients with invasive lung infections were included in the analysis. All patients were immunocompromised, including three patients infected following bone marrow transplantation. In this group of patients, Fusarium was probably introduced through the subcutaneous route (33%), the sino-pulmonary route (30%) or through an unknown route (37%).

In another epidemiological investigation, invasive organ infection was documented by both culture of organ samples and histopathological examination of the affected organ {2959, Anaissie, E.J., 2001}. Eight of 20 patients with F. solaniinfections had isolates with a molecular match with either an environmental isolate or another patient isolate.

Environmental cultures yielded Fusarium sporotrichioides as well as F. solani and F. oxysporum, the latter two strains being the most frequent.    
Aerosolisation of Fusarium species was notably documented after running the showers. The hospital water distribution system was also identified as a reservoir for Fusarium species  {2959} {2978}. 
Environmental cultures yielded Fusarium sporotrichioides as well as F. solani, F. oxysporum, with the latter two strains being the most frequent. 
A total of 38 patients were identified.  The risk factors for fusariosis included relapsing underlying disease (38 patients), neutropenia (36 patients), acute myelogenous leukemia (AML) (30 patients) or therapy with adrenal corticosteroids.

The role of central venous catheters as potential portals of entry for Fusarium is possibly underestimated {3250}. One recent report confirmed an iatrogenic infection by Fusarium for which both blood cultures and catheter tip cultures grew a mould identified as  Fusarium sp. {3268}.

Occupational diseases

Type III hypersensitivity pneumonites and organic dust toxic syndrome (ODTS) (see Mycotoxicosis section) associated withFusarium spp. are known in occupational settings such as farming and grain handling. In fact, Fusarium strains may be isolated in over half of grain samples collected at different stages of grain processing {2982; 1182}. Farmers and nearby residents are hence exposed to high levels of organic dust and bioaerosols which are generally high in Fusarium spore concentration (105 -106 CFU/m³) during the wheat harvesting season. This may cause health problems in exposed individuals based on toxic or allergic reactions {2974; 1180}. Inhalation of immunomodulating mycotoxins produced byFusarium spp. commonly found in grain dust may imply health risks for grain farmers {1158; 2385}.

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Considerable occupational risk among farmers engaged in grain threshing due to inhalation of allergenic species of filamentous fungi and mycotoxins {1180} has been associated with the presence of Fusarium. The potential risk of mycotoxicoses to agricultural workers exposed to grain dust is particularly high when handling wheat during threshing, unloading, shuffling and other farm occupations {2984; 1181}. Thus, Fusarium spp. are among fungi that can play a significant role in allergic and non-allergic diseases in modern working environments in alimentary industries and dairy farms as well as other similar circumstances {2989}.

Such is the case of cotton and hemp processing plants {2967}: dust and Fusarium spore concentrations, among a few other moulds, have been measured as being above norm, suggesting possible occupational exposure to mycotoxic and allergenic moulds.

In one instance, Fusarium has also been linked to a significant occupational exposure in an archive storage setting {2774}.

Diagnostic tools

The diagnosis of Fusarium infection may be established from histopathological examinations, direct examination of stained clinical specimens or their culture, blood cultures or serology tests {2972}.

The characteristic clinical signs of these infections are disseminated skin nodules, fungemia and multiorgan involvement. Frequently, myalgia is also present. Skin involvement occurs in over 80% of cases of disseminated infections. These lesions are proven to be important in the early diagnosis of fusariosis as they are readily accessible for biopsy and culture {2196; 1755}.

The immediate assessment of any suspicious lesion, including a biopsy of the lesion for microbiological and histopathological examinations, will usually lead to the correct diagnosis {3253}. The diagnosis of infection by Fusarium sp. (p = 0.006) is strongly associated with a poor outcome {3254}.

Cultures

In contrast to disseminated aspergillosis, disseminated fusariosis can be diagnosed by blood cultures in up to 40% of patients {2966; 3268; 1596}. 

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Fusarium species grow readily and rapidly in most media without cycloheximide.  Although the genus Fusarium can be identified by its typical multicellular macroconidia , species identification is difficult and may require molecular methods (1596).  

In support of a confirmed infection is i) the isolation of several colonies from the same specimen or of the same fungus from different specimens (as opposed to isolating a single colony from only one biological sample), ii) a positive direct examination of the biological material and iii) most importantly, the site of isolation and the host. For example, culture of sinus aspirates or respiratory secretions in severely immunocompromised hosts should always be considered as diagnostic of fusarial infection, as opposed to isolating Fusarium spp. from skin scrapings in an immunocompetent host.

It is difficult to establish an accurate diagnosis when an immunosuppressed patient is infected with more than one fungal species, especially when the species are morphologically very similar {3252}.

Histopathology

Confirmatory diagnosis of fusariosis may require histopathology. In tissue, the hyphae are similar to those of Aspergillusspecies, with hyaline and septate filaments that typically dichotomise in acute and right angles. However, adventitious sporulation may be present in tissue, and the finding of hyphae and yeast-like structures together is highly suggestive of fusariosis in the high-risk population {Nucci, 2007 1596 /id}.

In the absence of microbial growth, distinguishing fusariosis from other hyalohyphomycoses may be difficult and requires the use of in situ hybridisation in paraffin-embedded tissue specimens {3255}

The histological presentation of a deep sited infection due to Fusarium is typically that of an opportunistic fungal hyphal infection with hyaline, septate, randomly branched hyphae. The hyphal contours are regular {816}. Deep sited fusariosis histopathology reveals hyaline acute-branching septate hyphae similar to those found in aspergillosis {2966}. Cases of respiratory infections, can manifest themselves as pulmonary nodules, including the presence of cavitation {3268}.

Immunodiagnosis

It has been possible to detect interspecies cross-reactivity of IgG and IgE within the genus Fusarium {760; 252}. However, serological tests may still be useful when used to study the sensitisation of atopic patients to Fusarium or to measureFusarium exposure in patients with hypersensitivity pneumonitis (HP).

In a study of atopic individuals, 24.5% (n = 69) of subjects had positive intradermal tests with saline extracts of F. solani.  Results showed a positive statistical correlation between responses to cutaneous skin tests and RAST immunoenzymatic test results {4283}.

In another study, researchers found elevated levels of IgG antibodies directed against Fusarium in patients suffering from farmer’s lung disease and asymptomatic farmers with high IgG levels against other agricultural fungi; antibody levels were significantly higher in these patients compared to the control group {760}.

Fusarium, as part perennial airborne allergens, may play an important role in the pathogenesis of nasal polyposis {2609; 1975}. Polyposis is related in one way or another to allergic phenomena. Fungal sensitisation to Fusarium can be measured by IgE in vitro tests or by intradermal tests. However, in one study, patients with a clinical picture of polyposis showed sensitisation to fungal allergens, without any apparent correlation between fungal nasal colonisation and actual diagnosis {4284}.

More details

Fusarium moniliforme allergen extracts {730} are commercially available for in vitro IgE testing {3730} while allergenic extracts of Fusarium vasinfectum are available for in vivo skin testing, either as single extracts or as pooled antigens{3284}

Allergenic extracts of Fusarium are part of the American Food and Drug Administration (FDA) surveillance program and of the «Biological Product Deviation Reporting Non-Blood Product Codes» mould list {3285}.

  • Fusarium sp.
  • Fusarium moniliforme
  • Fusarium oxysporum
  • Fusarium solani 
  • Fusarium vasinfectum
Test IgE IgG Antigens Other
Skin Tests X      
RAST-IgE X      
RAST-IgG   X    
ELISA-ELIFA   Experimental    
Immunodiffusion        
Immunofluorescence        
Complement fixation        
PCR     Experimental  
Other        

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