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 ~  Abstract
 ~ Introduction
 ~  Epidemiology of ...
 ~  Fusarium-...
 ~  Fusarium-...
 ~  Host Response to...
 ~ Diagnosis
 ~ Treatment
 ~ Prevention
 ~ Conclusion
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 ~  Susceptibility P...
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  Table of Contents  
REVIEW ARTICLE
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 8-17
 

Fusarium: The versatile pathogen


Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Sri Ramachandra University, Porur, Chennai, Tamil Nadu, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Anupma Jyoti Kindo
Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Porur, Chennai - 600 016, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_16_24

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 ~ Abstract 

Fusarium is an emerging human opportunistic pathogen of growing importance, especially among immunosuppressed haematology patients due to an increased incidence of disseminated infections over the past two decades. This trend is expected only to continue due to the advances in medical and surgical technologies that will prolong the lives of the severely ill, making these patients susceptible to rare opportunistic infections. Production of mycotoxins, enzymes such as proteases, angio-invasive property and an intrinsically resistant nature, makes this genus very difficult to treat. Fusarium is frequently isolated from the cornea and less commonly from nail, skin, blood, tissue, Continuous Ambulatory Peritoneal Dialysis (CAPD) fluid, urine and pleural fluid. Conventional microscopy establishes the genus, but accurate speciation requires multilocus sequence typing with housekeeping genes such as internal transcribed spacer, translation elongation factor-1α and RPB1 and 2 (largest and second largest subunits of RNA polymerase), for which expansive internet databases exist. Identifying pathogenic species is of epidemiological significance, and the treatment includes immune reconstitution by granulocyte–colony-stimulating factor, granulocyte macrophage–colony-stimulating factor and a combination of the most active species – specific antifungals, typically liposomal amphotericin-B and voriconazole. However, patient outcome is difficult to predict even with in vitro susceptibility with these drugs. Therefore, prevention methods and antifungal prophylaxis have to be taken seriously for these vulnerable patients by vigilant healthcare workers. The current available literature on PubMed and Google Scholar using search terms 'Fusarium', 'opportunistic invasive fungi' and 'invasive fusariosis' was summarised for this review.


Keywords: Amphotericin B, Fusarium, keratitis, multilocus sequence typing, opportunistic fungi, voriconazole


How to cite this article:
Tupaki-Sreepurna A, Kindo AJ. Fusarium: The versatile pathogen. Indian J Med Microbiol 2018;36:8-17

How to cite this URL:
Tupaki-Sreepurna A, Kindo AJ. Fusarium: The versatile pathogen. Indian J Med Microbiol [serial online] 2018 [cited 2018 Sep 21];36:8-17. Available from: http://www.ijmm.org/text.asp?2018/36/1/8/231655



 ~ Introduction Top


Fusarium sp. are hyaline filamentous fungi found everywhere – in air, water, soil, on plants and organic substrates. This widespread distribution of Fusarium is due to its ability to withstand a wide range of conditions and to grow on a broad range of substrates and their efficient mechanisms for dispersal. Often regarded as soil-borne fungi, because of their abundance in soil and frequent association with plant roots, they are also present in water as components of water biofilms.[1] Being common colonisers of aerial plant parts, they form either part of the normal mycoflora or act as plant pathogens on horticultural crops and cereal grains, rendering these unfit for consumption – causing huge economic losses to the agricultural industry aside from posing a threat to human and animal health.[2],[3],[4]Fusarium sp. have recently been implicated in the low hatch success of endangered sea turtles.[5] The incurable Panama disease (Fusarium wilt) of banana caused the Gros Michel cultivar variety of the Cavendish banana to perish in the 1950s.[6]

Conventionally, Fusarium has been more of an agronomic threat than a medical one, but over the last three decades, owing to a variety of contributing factors, this scenario has undergone a radical change, with Fusarium sp. emerging as major opportunistic human pathogens, causing an expansive range of superficial and systemic infections with high morbidity in the former and extreme mortality in the latter.[4],[7] The current available literature on PubMed and Google Scholar using search terms 'Fusarium', 'opportunistic invasive fungi' and 'invasive fusariosis' was summarised for this review.


 ~ Epidemiology of Human Disease Top


Fusarium causes a wide spectrum of infections in humans, termed fusarioses, including superficial (keratitis, onychomycosis), locally invasive (cellulitis, intertrigo, sinusitis), deep or disseminated infections, the last occurring almost exclusively in severely immunocompromised patients.[2] With the utilization of fluconazole prophylaxis in transplant recipients and other immune suppressed patients came a change in the epidemiology of fungal infections – incidence of candidiasis reduced and by contrast, invasive mould infections increased, especially in patients receiving large doses of corticosteroids and who had prolonged or profound neutropenia and/or severe T-cell immunodeficiency. Fusariosis is now the third most common cause of mould infections after aspergillosis and zygomycosis, with an increasing incidence in patients with haematological malignancies and haematopoietic stem cell transplantation (HSCT). Persistent or profound neutropenia has been proven to be the single most predisposing factor towards disseminated Fusarium infections.[4],[8]Fusarium from soil or water gains entry inside the body through contact with minute breaks in the skin or mucous membranes, causing onychomycosis or locally invasive skin infections (cellulitis, paronychia and interdigital intertrigo), the latter seen more commonly in diabetics. These sites serve these organisms as cutaneous portals of systemic entry during periods of immunosuppression, allowing for dissemination of infection.[9] Infection may occur as a result of extensive skin breakdown, such as in burns and wounds, wherein even air-borne conidia may be the source [10] or due to presence of foreign bodies, such as keratitis in contact lens wearers or peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD). Fusarium sp. have been isolated from public swimming pools, shower drains and hospital water systems.[11],[12],[13],[14],[15]Fusarium keratoplasticum, a member of the Fusarium solani species complex (FSSC), is recognised as a plumbing inhabiting pathogen.[16] Outbreaks and pseudo-outbreaks of fusariosis have occurred in the hospital as well as in the community, due to contamination of a common source such as water or disinfecting solutions.[17]Fusarium sp. may cause allergic diseases (e.g. sinusitis) in immunocompetent individuals.[18] The distinct mycotoxins (secondary metabolites) produced by some species are associated with a variety of human and animal health problems. Fusarium mycotoxins include trichothecenes, fumonisins, moniliformins and the fungal oestrogen, zearalenone. Mycotoxicosis is seen in humans and animals following ingestion of food contaminated by mycotoxin-producing Fusarium spp. (Fusarium langsethiae, Fusarium sporotrichioides, Fusarium poae, Fusarium avenaceum, Fusarium tricinctum, Fusarium graminearum and Fusarium culmorum).[2],[19] Mycoproteins derived from a soil-inhabiting Fusarium sp. (Fusarium venenatum) are commercially manufactured as high-protein meat-substitute foods and marketed by the brand name 'Quorn', which have been proven to cause severe allergic reactions in sensitive individuals.[20]

Taxonomy

Genus Fusarium is classified as belonging to the Order Hypocreales of Phylum Ascomycota.[21] The taxonomy of Fusarium species has been controversial. Earlier work on Fusarium systematics was done before pleomorphism and variation in fungi were recognised, which led to the naming of numerous separate species based on superficial observations. The necessity for a precise and reliable system of classification became clear when it became evident that Fusarium species cause serious diseases. The name Fusarium had been used to denote the asexual ('anamorph') stage of the fungus, and the rarely encountered sexual ('teleomorph') stage was recognised by the names Gibberella, Nectria, Neocosmospora and Haematonectria. However, under the new nomenclatural rules and for taxonomic stability (one fungus one name, 2013),[22]Fusarium is to be preferred above all other names for the genus. This effort is to simplify the already complicated taxonomy of Fusarium and greatly improve the state of the molecular databases such as GenBank, MycoBank and Fusarium-ID that are currently available, wherein the confused state of Dual Nomenclature associated with Fusarium is reflected plainly. At present, GenBank accessions from the FSSC are deposited under four different genus names (i.e., Fusarium, Nectria, Neocosmospora and its later synonym Haematonectria).[22],[23] The genus Fusarium currently comprises at least 200 species, grouped into approximately 10 phylogenetic species complexes.[24]Fusarium was one of the first fungal groups where the term 'species complex' was commonly used for closely related species. Most of the identified opportunistic Fusarium pathogens belong to FSSC, (F. keratoplasticum, Fusarium falciforme, Fusarium lichenicola and Fusarium petroliphilum); Fusarium oxysporum species complex (FOSC) and Fusarium fujikuroi (previously Gibberella fujikuroi) species complex (FFSC, Fusarium napiforme, Fusarium temperatum, Fusarium guttiforme, Fusarium verticillioides, Fusarium thapsinum, Fusarium nygamai, Fusarium acutatum, F. fujikuroi, Fusarium proliferatum, Fusarium sacchari, Fusarium ananatum and Fusarium subglutinans). Less frequently observed are members of Fusarium incarnatum-equiseti species complex (Fusarium lacertarum, Fusarium scirpi, Fusarium equiseti, i.e. haplotypes 1–14, Fusarium incarnatum or Fusarium semitectum); Fusarium dimerum species complex (FDSC, Fusarium delphinoides, Fusarium penzigii, F. dimerum); Fusarium chlamydosporum species complex; Fusarium sambucinum species complex (including F. sporotrichioides) and F. tricinctum species complex.[3],[21],[25]Fusarium moniliforme has now been renamed F. verticillioides. Some members of the species-rich FSSC have now been named: F. petroliphilum (FSSC 1), F. keratoplasticum (FSSC 2) and F. falciforme (FSSC 3 + 4).[26]


 ~ Fusarium-Culture Top


Typically, the genus is rapidly growing in culture media without cycloheximide although some species within FDSC and FFSC are slow growing.[3] They vary in colour and many yield a diffusible violaceous pigment (e.g. FSSC). In potato dextrose agar, Fusarium colonies grow with a velvety or cottony surface and are white, yellow, pink, purple, salmon or grey on the surface, with a pale, red, violet, brown or sometimes blue reverse.[4] The pionnotal type (moist and slimy) may mislead identification.[27] Microscopically, they may produce different types of spores called macroconidia, microconidia, mesoconidia and chlamydospores. The macroconidia are produced on monophialides and polyphialides in the aerial mycelium [2] or in specialised structures called sporodochia in which the spore mass is supported by a superficial cushion-like mass of short monophialides bearing the macroconidia. The shape of these conidiophores (the specialised hyphae from which conidia arise) may differ between species and aid genus-level identification.[21] Macroconidia are hyaline, formed holoblastically and singly, banana/canoe-shaped, multicellular/multiseptate with a foot cell at the base and differ among genus/species.[2] Morphological keys for species recognition are available in published literature.[28],[29] Species identification however is difficult, requires expert training and use of standardised media and may require molecular methods. [Table 1] summarises the morphological features of a few common clinical Fusarium species.
Table 1: Macroscopic and microscopic morphology of some common clinical Fusarium species

Click here to view



 ~ Fusarium-Genome Top


Polymerase chain reaction (PCR) followed by DNA sequencing allows unambiguous identification of Fusarium sp. However, the most often used pan-fungal molecular marker the internal transcribed spacer region of fungal rDNA has considerable overlap among the various Fusarium species and is not recommended as a target for DNA sequencing and molecular identification. Partial regions of translation elongation factor 1 alpha gene and the second largest subunit of RNA polymerase II gene (RPB2) genes have been found to be better discriminatory and are useful in determining the species and also for phylogenetic analysis of isolates (e.g. multilocus sequence typing [MLST]).[26]Fusarium-specific primers targeting these regions for both PCR and DNA sequencing are available in the literature.[24],[30] Species identification requires matching the DNA sequences using Basic Local Alignment and Search Tool (BLAST) in the Fusarium-ID (http://isolate.fusariumdb.org/blast.php),[31] NCBI GenBank (http://blast.ncbi.nlm.nih.gov/Blast.cgi) and CBS-KNAW (http://www.cbs.knaw.nl/fusarium/) databases. Using curated databases that accept only verified sequences gives accurate results and minimises errors and misidentification. The Fusarium-ID and CBS-KNAW are growing databases which contain only vouchered sequences attached to publicly available cultures. During BLAST analysis, looking specifically for matches with reference strains will give better and more accurate results.


 ~ Fusarium and Human Disease Top


Ocular infection

Keratitis

FSSC members are now proven to be the most common etiologic agent of fungal keratitis.[32],[33],[34] Most commonly occurring agents within this complex are F. keratoplasticum and F. falciforme.[16] In tropical countries such as Tanzania, the incidence of Fusarium keratitis is 75%.[34] Predisposing factors to fungal keratitis include ocular trauma (injury by vegetative matter/nail/flying insect/cow tail/soil/dirty water leading to fungal inoculation), topical antibiotic and corticosteroid use, diabetes mellitus, exposure keratitis, tear insufficiency, nasolacrimal duct blockage and contact lens use.[2],[32],[35] Local trauma such as foreign body trauma or surgery helps fungal spores or mycelial fragments to overcome the natural skin or the mucosal barrier.[36] Farmers suffering vegetative trauma and contact lens wearers, who are otherwise immunocompetent, form majority of those affected.[2],[37]

2005–2006 outbreak

In 2005–2006, an unprecedented outbreak of contact lens-associated Fusarium keratitis occurred with >250 cases reported worldwide including countries such as India, China, United States,[38] Hong Kong and Singapore.[39] Cases were primarily soft hydrophilic contact lens wearers who used Bausch and Lomb ReNu with MoistureLoc and Bausch and Lomb ReNu MultiPlus multipurpose contact lens disinfecting solutions which contained the antimicrobial agent alexidine dihydrochloride (0.00045%), a new ingredient in the contact lens solution market at the time. At least 10 different Fusarium species were identified among the isolates, including F. solani, comprising 19 unique multilocus genotypes.[40] It was proven that the lack of temperature control during storage of lens solution bottles in closed shelves of retail shops allowed alexidine to permeate into the walls of the containing plastic bottles by heat acceleration, thus decreasing the effective concentration of the biocide and resulting in an unusual mechanism of drug failure, which allowed Fusarium introduced by the user from the environment while lens handling to multiply and infect the wearers.[41] The manufacturing company Bausch and Lomb was cited by the Food and Drug Administration for inadequate temperature control of their products and ReNu with MoistureLoc was ultimately withdrawn from the world market on 15 May 2006.[40]

Ophthalmitis

Resistant Fusarium keratitis progressing to endophthalmitis has been recorded,[42],[43] and failure of treatment with topical, intravitreal and systemic antifungals necessitates enucleation of affected eye. Exogenous Fusarium post-surgical endophthalmitis can complicate cataract surgery and has poor patient outcome.[44]

Onychomycosis

Fusarium is the major non-dermatophyte mould causing nail infections, leading to onychomycosis with highly characteristic milky lesions or onychogryphosis,[2] almost always involving the great toenails (very rarely, the fingernails), especially those affected by traumatic and dystrophic abnormalities, and/or nails already infected by dermatophytes. Increasing age, male gender, close contact with soil, trauma, poor peripheral circulation (due to smoking or peripheral vascular disease), pre-existing tinea pedis, the habit of walking barefoot/wearing sandals or the habit of frequenting swimming pools are predisposing factors to the development of onychomycosis and intertrigo due to Fusarium.[21],[45],[46],[47] Among diabetics, onychomycosis represents an independent and important predictor for the development of diabetic foot syndrome and foot ulcer.[48] Although usual presentation is of a localised infection in immunocompetent individuals, these infections require more attention because of the angio-invasive potential of Fusarium, which can manifest when host immune responses are impaired.[49],[50],[51],[52]

Skin and soft tissue infections

Localised primary skin infections present as paronychia, interdigital intertrigo [53] or cellulitis and can occur in immunocompetent patients with a pre-existing onychomycosis, recent history of skin breakdown from local trauma, plant puncture [54] or insect bite. Diabetes mellitus,[55],[56],[57] burns and excessive moisture are other predisposing factors.[58] Some patients present with ulcerated lesions resembling chromoblastomycosis. Fusarium also causes mycetoma [59],[60] and haemodialysis graft rejection.[61] These localised lesions need aggressive treatment as they are ports of systemic entry for angio-invasive Fusarium during periods of immunosuppression.[50],[62],[63],[64] Chronic infection may mimic lupus vulgaris and escape detection.[65]

Development of papules, nodules or characteristic 'target' lesions (rarely bullae or vesicles) is sometimes the only diagnostic sign of disseminated multi-organ Fusarium infection in the immunosuppressed individuals.[66],[67] Most commonly involved body sites are the extremities, but lesions can occur at any site and evolve rapidly over a few days. Multiple lesions at different stages of evolution can exist in one patient at a single time. Skin biopsy is indicated and can be used for rapid molecular diagnosis. Material from skin lesions are valuable clinical specimen and grow Fusarium in culture.[68]

Sinusitis

Fusarium sinusitis may present as allergic,[18] chronic, non-invasive [69] (with symptoms of nasal obstruction/discharge) or even invasive type in the immunocompetent,[70] whereas in the immunocompromised (largely acute myeloid leukaemia patients), it is always of the invasive type, accompanied by mucosal necrosis (characteristic of the angio-invasive nature of Fusarium), periorbital/paranasal cellulitis and serves as portal for systemic dissemination.[71]

Deep systemic and invasive disseminated fusariosis

Fusarium osteomyelitis,[72] septic arthritis,[73],[74] pneumonia,[75] brain [76],[77],[78],[79] and vertebral [72] abscesses are documented with the occasional positive outcome. Route of Fusarium entry in these cases was traumatic inoculation or inhalation. Disseminated infection, first reported in 1973, is characterised by persistent fever refractory to broad-spectrum antibiotic treatment and by skin lesions with a central necrosis.[3] In contrast to other fungi such as Aspergillus, disseminated Fusarium infections yield higher number of positive blood cultures. Multiple organ systems can be involved. Source of infection is often Fusarium from the external environment (soil, indoor plants, shower drains) or nosocomial sources such as water.[4],[8] Thus, infection can be community acquired or hospital acquired. Conidia enter through minute breaks in the skin and mucous membranes or inhalation (rare). Endogenous sources include pre-existing localised infections (sinusitis/onychomycosis/cellulitis/interdigital intertrigo/abscess) spreading systemically due to Fusarium angio-invasion during prolonged or even short [80] periods of neutropenia.[3],[62],[63],[81],[82],[83],[84] Disseminated fusariosis is commonly observed in patients with haematologic malignancies and HSCTs,[27],[85],[86],[87],[88],[89],[90],[91] including autologous transplants,[80] and rarely even in HIV-patients [92] and solid organ transplant recipients including liver,[93] lung [94],[95] and kidney.[96] Their true incidence may very well be underestimated and invasive fusariosis needs to be ruled out in all cases of febrile neutropenia.

Foreign body-associated Fusarium infection

Soft contact lenses with high water content can be Fusarium colonised.[97] Their proficiency to adhere, infiltrate and thrive within the interior lens matrix can cause fungal keratitis.[98] The ability of Fusarium species to adhere and invade the silastic wall of CAPD catheters and occlude them has been demonstrated by electron microscopy.[99]Fusarium peritonitis following CAPD has been reported on several occasions and outcome of the cases was uniformly good after removal of the catheter alone or in combination with antifungal therapy.[99],[100] An electron microscopic picture of the central venous catheter in case of catheter-associated fusaremia reveals plugging of the catheter with masses of fungal hyphae and invasive destruction of the catheter wall. Recovery may follow catheter removal alone, but bloodstream infections require antifungal chemotherapy.[101] In these examples of foreign body-associated Fusarium infections, favourable outcomes may be due to the presence of a removable focus of infection. A point of note is that there are no reports so far of infections of implants made of hard materials (titanium and platinum).[2]

Fusarium mycotoxicoses

Consumption of food prepared from overwintered cereals colonised by T-2 toxin producing F. sporotrichioides and F. poae leads to alimentary toxic aleukia affecting the haematopoietic system. The disease occurs in three progressively worse clinical stages and is more severe in the malnourished and fatal if diagnosed late. Historically, it was observed on a big scale in USSR in the immediate post WW2 era when 100,000 people died from being forced to consume infected grain due to severe food shortage.[102] Kashin–Beck disease is a chronic dystrophic osteoarthritis of the peripheral joints and spine which starts in childhood and worsens to severe disability, occurring endemically in regions of Siberia (Urov River Valley), China and North Korea where climatic factors are conducive to high level of Fusarium infection in harvested grains. Another example of human mycotoxicosis are the sporadic epidemics of akakabi-byo (red mould disease/ scab) that occur in Japan, caused by contamination of cereal grains with mycotoxins produced by F. graminearum and F. sporotrichioides.[2]


 ~ Virulence Factors of Fusarium Top


Fusarium sp. possess several virulence factors, including the ability to produce mycotoxins, such as trichothecenes, which suppress humoral and cellular immunity and aided by production of adventitious yeast-like propagules, cause tissue breakdown and angio-invasion.[2] They have the capacity to adhere to prosthetic material and produce proteases and collagenases.[103] Proteases produced by species such as FSSC might have a role in the pathogenesis of Fusarium keratitis, and FSSC are the most virulent species as shown in a murine model of fusariosis in immunocompetent animals.[4] A fungal transcriptional regulator PacC was found to allow fungal adaptation to the ocular surface, promoting hyphal penetration of the cornea in FOSC.[104] Morphological changes in vivo with thickening of cell walls may protect Fusarium from the neutrophil assault. Keratitis-associated fusaria form robust biofilms as compared to wild-type strains.


 ~ Host Response to Fusarium Top


Innate immunity plays a major role in resisting mould infections. Toll-like receptors,[105] T-cell defences [8] and phagocytes [106] play crucial roles in progression of invasive fusariosis. The occurrence of disseminated Fusarium in non-neutropenic HSCT recipients having severe T-cell immunodeficiency (caused by multiple therapies for their underlying disease and for graft-versus-host disease) and the major adverse impact of corticosteroid therapy on the outcome of fusariosis [82] support the importance of T-cell immunity. Macrophages and neutrophils damage Fusarium hyphae, and their effect is primed by √-interferon, granulocyte–colony-stimulating factor, granulocyte macrophage–colony-stimulating factor [107] and interleukin-15.[108] The effect of interleukin-15 is mediated by the release of interleukin-8 and by direct stimulation of hyphal damage.[4] There is a strong relationship between immune reconstitution and patient outcome which highlights the importance of the immune response in the pathogenesis of Fusarium infection [82],[109] [Figure 1].
Figure 1: The innate immune response in Fusarium infection

Click here to view



 ~ Diagnosis Top


Culture is the gold standard for diagnosis, but morphology-based identification has severe limitations for Fusarium species and cannot be used successfully without other approaches.

In keratitis, direct microscopy and culture of corneal scrapings are the usual method. Using a cost-effective assembly of smartphone and LED-integrated pocket magnifier was recently described, which can be useful in resource-limited or point-of-care settings.[110]In vivo confocal microscopy of infected eye is another rapid, non-invasive method.[111]

Blood tests are helpful in disseminated infections – the Aspergillus serum galactomannan tests cross-react with Fusarium infections due to similar cell wall structure. The Platelia Candida antigen detection enzyme immunoassay directed against mannan has been reported to give cross-reactions with F. verticillioides but not with F. solani or F. oxysporum[112] Enzyme immunoassay tests to detect mycotoxins produced by Fusarium also exist although these are used more in the field of phytopathology.[68] Radiological techniques such as early chest computed tomographic imaging can aid diagnosis. Histopathology, whenever viable, is highly recommended by experts.[113] Alternately, immunochemistry and in situ hybridisation methods are employed.[38],[114],[115]

DNA-based identification involves PCR assays that need adequate pure fungal DNA and procedures using whole-blood and tissue specimen have been described.[116] Furthermore, loop-mediated isothermal amplification assays have been established for Fusarium.[117] In the current era of genomics, DNA sequencing and use of MLST approach in combination with the genealogical concordance phylogenetic species recognition principle is a far better tool to recognise species and to sort out their relationships rather than relying alone on the phenotypic characters.[21] Genotyping in cases of outbreaks can be done by AFLP (Amplified Fragment Length Polymorphism) fingerprinting. Furthermore, progress is being made in peptide-based identification using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry [118],[119] systems.

Although a preliminary genus-level identification gives healthcare workers enough information to start patient treatment, it is immensely useful to further characterise these clinical Fusarium and understand the epidemiological significance of the strains causing human infections.


 ~ Susceptibility Profiles of Fusarium Species Top


Antifungal susceptibility testing is done following the broth microdilution method as per the CLSI M38-A2[120] or the EUCAST 9.3.1 guidelines (http://www.eucast.org/ast_of_fungi/methodsinantifungalsusceptibilitytesting/susceptibility_testing_of_moulds/). Fusarium sp. show typically high minimum inhibitory concentrations (MICs) on testing. Members of the FSSC are intrinsically resistant to fluconazole and show higher MICs to other azoles and amphotericin B,[121] whereas FOSC show lower MICs to voriconazole and posaconazole.[123] Susceptibility profiles differ within species complexes too – e.g. F. verticillioides[73] shows the lowest MICs and F. nygamai shows the highest MICs [122] within the FFSC. Espinel-Ingroff et al.[123] have gathered MIC distributions for the common human pathogens FSSC, FOSC and F. verticillioides with three triazoles and amphotericin B and proposed epidemiological cut-off value for them. E-test could be used as an alternative to broth microdilution for susceptibility testing of amphotericin B, voriconazole and posaconazole against clinical Fusarium isolates.


 ~ Treatment Top


Treatment of Fusarium infections is difficult owing to the intrinsic multidrug-resistant nature exhibited by members of the genus, some of them being pan resistant. Amphotericin B, natamycin and newer azoles such as voriconazole are the most active agents and can be used in combination. Posaconazole has been used for salvage therapy.[124] However, in vitro susceptibility or resistance to these agents may not predict the in vivo response in Fusarium infection. Antifungal susceptibility testing on individual strains allows for species-specific treatment and may result in considerable improvement in patient outcome. Topical 5% natamycin hourly is the treatment of choice for Fusarium keratitis along with systemic voriconazole and early keratectomy when indicated.[125] The new topical azole efinaconazole (10% solution) seems promising in the treatment of Fusarium onychomycosis.[126],[127],[128] Surgical debridement when required and prompt therapy with a combination of appropriate antifungals along with use of colony stimulating factors for immune reconstitution help improve outcome of invasive fusarioses.[7],[82],[109],[129],[130],[131]


 ~ Prevention Top


Prevention of contact lens-related keratitis includes avoidance of mouldy environments and of non-sterile or reusable-cleaning solutions. Hand washing before lens manipulation and frequent cleaning and sterilisation of the lens paraphernalia are recommended.[40],[132],[133] Agriculturists and outdoor workers are urged to use protective eye wear. Footwear should be worn when in damp public places; toenails should be kept clean and trimmed to avoid trauma; feet should be dried completely immediately after bathing; socks should be made of absorbent material (e.g., cotton) and changed immediately if wet.[134] Symptoms of tinea pedis should be addressed without delay. Immunosuppressed patients, especially in haematology, need primary or secondary voriconazole prophylaxis, hospital wards with high efficiency particulate arrestance filtered air and without indoor plants. They are advised boiled food over other diet and sponge baths over showers during their period of susceptibility. Aerosolised amphotericin B deoxycholate is recommended for lung-transplant recipients.[94]


 ~ Conclusion Top


Due to medical and surgical treatment advances taking place in this century, the susceptible patient pool for Fusarium is set to rise and its role as an opportunistic human pathogen will increase in prominence. There is an urgent need for increasing our knowledge base regarding this genus, for epidemiology and treatment. Owing to the difficulties in the management of established infection, prevention is deemed better than cure and demands the focus of healthcare workers.

Acknowledgement

The Indian Council of Medical Research (ICMR) has funded this study on Fusarium through the ICMR-TSS MD-PhD Fellowship awarded to Dr. Ananya Tupaki-Sreepurna.

Financial support and sponsorship

ICMR-TSS MD-PhD Fellowship.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

1.
Elvers KT, Leeming K, Moore CP, Lappin-Scott HM. Bacterial-fungal biofilms in flowing water photo-processing tanks. J Appl Microbiol 1998;84:607-18.  Back to cited text no. 1
    
2.
Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev 1994;7:479-504.  Back to cited text no. 2
    
3.
Guarro J. Fusariosis, a complex infection caused by a high diversity of fungal species refractory to treatment. Eur J Clin Microbiol Infect Dis 2013;32:1491-500.  Back to cited text no. 3
    
4.
Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev 2007;20:695-704.  Back to cited text no. 4
    
5.
Sarmiento-Ramírez JM, Abella-Pérez E, Phillott AD, Sim J, van West P, Martín MP, et al. Global distribution of two fungal pathogens threatening endangered sea turtles. PLoS One 2014;9:e85853.  Back to cited text no. 5
    
6.
O'Donnell K, Kistler HC, Cigelnik E, Ploetz RC. Multiple evolutionary origins of the fungus causing panama disease of banana: Concordant evidence from nuclear and mitochondrial gene genealogies. Proc Natl Acad Sci U S A 1998;95:2044-9.  Back to cited text no. 6
    
7.
Stempel JM, Hammond SP, Sutton DA, Weiser LM, Marty FM. Invasive fusariosis in the voriconazole era: Single-center 13-year experience. Open Forum Infect Dis 2015;2:ofv099.  Back to cited text no. 7
    
8.
Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, et al. Fusarium infection in hematopoietic stem cell transplant recipients. Clin Infect Dis 2004;38:1237-42.  Back to cited text no. 8
    
9.
Vennewald I, Wollina U. Cutaneous infections due to opportunistic molds: Uncommon presentations. Clin Dermatol 2005;23:565-71.  Back to cited text no. 9
    
10.
Łukaszuk CR, Kułak W. Effects of fungal air pollution on human health. Prog Health Sci 2011;1:156-64.  Back to cited text no. 10
    
11.
Williams MM, Armbruster CR, Arduino MJ. Plumbing of hospital premises is a reservoir for opportunistically pathogenic microorganisms: A review. Biofouling 2013;29:147-62.  Back to cited text no. 11
    
12.
Short DP, O'Donnell K, Zhang N, Juba JH, Geiser DM. Widespread occurrence of diverse human pathogenic types of the fungus Fusarium detected in plumbing drains. J Clin Microbiol 2011;49:4264-72.  Back to cited text no. 12
    
13.
Viegas C, Alves C, Carolino E, Pinheiro C, Rosado L, Silva Santos C. Assessment of fungal contamination in a group of Lisbon's gymnasiums with a swimming pool. Ital J Occup Environ Hyg 2011;2:15-20.  Back to cited text no. 13
    
14.
Buot G, Toutous-Trellu L, Hennequin C. Swimming pool deck as environmental reservoir of Fusarium. Med Mycol 2010;48:780-4.  Back to cited text no. 14
    
15.
Rasti S, Assadi MA, Iranshahi L, Saffari M, Gilasi HR, Pourbabaee M. Assessment of microbial contamination and physicochemical condition of public swimming pools in Kashan, Iran. Jundishapur J Microbiol 2012;5:450-5.  Back to cited text no. 15
    
16.
Short DP, O'Donnell K, Geiser DM. Clonality, recombination, and hybridization in the plumbing-inhabiting human pathogen Fusarium keratoplasticum inferred from multilocus sequence typing. BMC Evol Biol 2014;14:91.  Back to cited text no. 16
    
17.
Sharma P, Kumar N, Jain S. Fungal contaminants in cytopathology specimens. Biomed J 2014;37:31-2.  Back to cited text no. 17
[PUBMED]  [Full text]  
18.
Wickern GM. Fusarium allergic fungal sinusitis. J Allergy Clin Immunol 1993;92:624-5.  Back to cited text no. 18
    
19.
Kokkonen M, Ojala L, Parikka P, Jestoi M. Mycotoxin production of selected Fusarium species at different culture conditions. Int J Food Microbiol 2010;143:17-25.  Back to cited text no. 19
    
20.
Hoff M, Trueb RM, Ballmer-Weber BK, Vieths S, Wuethrich B. Immediate-type hypersensitivity reaction to ingestion of mycoprotein (Quorn) in a patient allergic to molds caused by acidic ribosomal protein P2. J Allergy Clin Immunol 2003;111:1106-10.  Back to cited text no. 20
    
21.
van Diepeningen AD, Al-Hatmi AM, Brankovics B, de Hoog GS. Taxonomy and clinical spectra of Fusarium species: Where do we stand in 2014? Curr Clin Microbiol Rep 2014;1:10-8.  Back to cited text no. 21
    
22.
Geiser DM, Aoki T, Bacon CW, Baker SE, Bhattacharyya MK, Brandt ME, et al. One fungus, one name: Defining the genus Fusarium in a scientifically robust way that preserves longstanding use. Phytopathology 2013;103:400-8.  Back to cited text no. 22
    
23.
Wingfield MJ, De Beer ZW, Slippers B, Wingfield BD, Groenewald JZ, Lombard L, et al. One fungus, one name promotes progressive plant pathology. Mol Plant Pathol 2012;13:604-13.  Back to cited text no. 23
    
24.
O'Donnell K, Sutton DA, Rinaldi MG, Sarver BA, Balajee SA, Schroers HJ, et al. Internet-accessible DNA sequence database for identifying fusaria from human and animal infections. J Clin Microbiol 2010;48:3708-18.  Back to cited text no. 24
    
25.
Al-Hatmi AM, Bonifaz A, de Hoog GS, Vazquez-Maya L, Garcia-Carmona K, Meis JF, et al. Keratitis by Fusarium temperatum, a novel opportunist. BMC Infect Dis 2014;14:588.  Back to cited text no. 25
    
26.
Short DP, O'Donnell K, Thrane U, Nielsen KF, Zhang N, Juba JH, et al. Phylogenetic relationships among members of the Fusarium solani species complex in human infections and the descriptions of F. keratoplasticum sp. nov. and F. petroliphilum stat. nov. Fungal Genet Biol 2013;53:59-70.  Back to cited text no. 26
    
27.
Ersal T, Al-Hatmi AS, Cilo BD, Curfs-Breuker I, Meis JF, Özkalemkaş F, et al. Fatal disseminated infection with Fusarium petroliphilum. Mycopathologia 2015;179:119-24.  Back to cited text no. 27
    
28.
Azor M, Gene J, Cano J, Manikandan P, Venkatapathy N, Guarro J. Less-frequent Fusarium species of clinical interest : Correlation between morphological and molecular identification and antifungal susceptibility. J Clin Microbiol 2009;47:1463-8.  Back to cited text no. 28
    
29.
Taylor JW, Jacobson DJ, Kroken S, Kasuga T, Geiser DM, Hibbett DS, et al. Phylogenetic species recognition and species concepts in fungi. Fungal Genet Biol 2000;31:21-32.  Back to cited text no. 29
    
30.
Oechsler RA, Feilmeier MR, Ledee DR, Miller D, Diaz MR, Fini ME, et al. Utility of molecular sequence analysis of the ITS rRNA region for identification of Fusarium spp. From ocular sources. Invest Ophthalmol Vis Sci 2009;50:2230-6.  Back to cited text no. 30
    
31.
Geiser DM, Jiménez-Gasco MD, Kang S, Makalowska I, Veeraraghavan N, Ward TJ, et al. FUSARIUM-ID v. 1.0: A DNA sequence database for identifying Fusarium. Eur J Plant Pathol 2004;110:473-9.  Back to cited text no. 31
    
32.
Nath R, Baruah S, Saikia L, Devi B, Borthakur AK, Mahanta J, et al. Mycotic corneal ulcers in upper Assam. Indian J Ophthalmol 2011;59:367-71.  Back to cited text no. 32
[PUBMED]  [Full text]  
33.
Oechsler RA, Yamanaka TM, Bispo PJ, Sartori J, Yu MC, Melo AS, et al. Fusarium keratitis in Brazil: Genotyping, in vitro susceptibilities, and clinical outcomes. Clin Ophthalmol 2013;7:1693-701.  Back to cited text no. 33
    
34.
Doczi I, Gyetvai T, Kredics L, Nagy E. Involvement of Fusarium spp. in Fungal Keratitis. Clinical Microbiology and Infection : The Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. France; 2004. p. 773-6.  Back to cited text no. 34
    
35.
Homa M, Shobana CS, Singh YR, Manikandan P, Selvam KP, Kredics L, et al. Fusarium keratitis in South India: Causative agents, their antifungal susceptibilities and a rapid identification method for the Fusarium solani species complex. Mycoses 2013;56:501-11.  Back to cited text no. 35
    
36.
Sarma SS, Pennagaram S. Microbial keratitis – A prospective study. J Pharm Biomed Sci 2014;4:818-24.  Back to cited text no. 36
    
37.
Bharathi MJ, Ramakrishnan R, Vasu S, Meenakshi R, Palaniappan R. Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A three-year study. Indian J Ophthalmol 2003;51:315-21.  Back to cited text no. 37
[PUBMED]  [Full text]  
38.
O'Donnell K, Sarver BA, Brandt M, Chang DC, Noble-Wang J, Park BJ, et al. Phylogenetic diversity and microsphere array-based genotyping of human pathogenic fusaria, including isolates from the multistate contact lens-associated U.S. keratitis outbreaks of 2005 and 2006. J Clin Microbiol 2007;45:2235-48.  Back to cited text no. 38
    
39.
Jureen R, Koh TH, Wang G, Chai LY, Tan AL, Chai T, et al. Use of multiple methods for genotyping Fusarium during an outbreak of contact lens associated fungal keratitis in Singapore. BMC Infect Dis 2008;8:92.  Back to cited text no. 39
    
40.
Epstein AB. In the aftermath of the Fusarium keratitis outbreak: What have we learned? Clin Ophthalmol 2007;1:355-66.  Back to cited text no. 40
    
41.
Bullock JD, Elder BL, Warwar RE, Snyder SA, Sizemore IE. Mechanism of drug failure in Fusarium keratitis, 2004-2006. N Engl J Med 2014;370:88-9.  Back to cited text no. 41
    
42.
Dursun D, Fernandez V, Miller D, Alfonso EC. Advanced Fusarium keratitis progressing to endophthalmitis. Cornea 2003;22:300-3.  Back to cited text no. 42
    
43.
Edelstein SL, Akduman L, Durham BH, Fothergill AW, Hsu HY. Resistant Fusarium keratitis progressing to endophthalmitis. Eye Contact Lens 2012;38:331-5.  Back to cited text no. 43
    
44.
Ferrer C, Alio J, Rodriguez A, Andreu M, Colom F. Endophthalmitis caused by Fusarium proliferatum. J Clin Microbiol 2005;43:5372-5.  Back to cited text no. 44
    
45.
Chan HH, Wong ET, Yeung CK. Psychosocial perception of adults with onychomycosis: A blinded, controlled comparison of 1,017 adult Hong Kong residents with or without onychomycosis. Biopsychosoc Med 2014;8:15.  Back to cited text no. 45
    
46.
Singal A, Khanna D. Onychomycosis: Diagnosis and management. Indian J Dermatol Venereol Leprol 2011;77:659-72.  Back to cited text no. 46
[PUBMED]  [Full text]  
47.
Ghannoum M, Isham N. Fungal nail infections (onychomycosis): A never-ending story? PLoS Pathog 2014;10:e1004105.  Back to cited text no. 47
    
48.
Nenoff P, Ginter-Hanselmayer G, Tietz HJ. Fungal nail infections – An update: Part 1 – Prevalence, epidemiology, predisposing conditions, and differential diagnosis. Hautarzt 2012;63:30-8.  Back to cited text no. 48
    
49.
Godoy P, Nunes E, Silva V, Tomimori-Yamashita J, Zaror L, Fischman O. Onychomycosis caused by Fusarium solani and Fusarium oxysporum in São Paulo, Brazil. Mycopathologia 2004;157:287-90.  Back to cited text no. 49
    
50.
Bourgeois GP, Cafardi JA, Sellheyer K, Andea AA. Disseminated Fusarium infection originating from paronychia in a neutropenic patient: A case report and review of the literature. Cutis 2010;85:191-4.  Back to cited text no. 50
    
51.
Hay RJ. Fusarium infections of the skin. Curr Opin Infect Dis 2007;20:115-7.  Back to cited text no. 51
    
52.
Romano C, Gianni C, Difonzo EM. Retrospective study of onychomycosis in Italy: 1985–2000. Mycoses 2005;48:42-4.  Back to cited text no. 52
    
53.
Romano C, Presenti L, Massai L. Interdigital intertrigo of the feet due to therapy-resistant Fusarium solani. Dermatology 1999;199:177-9.  Back to cited text no. 53
    
54.
Palmore TN, Shea YR, Childs RW, Sherry RM, Walsh TJ. Fusarium proliferatum soft tissue infection at the site of a puncture by a plant: Recovery, isolation, and direct molecular identification. J Clin Microbiol 2010;48:338-42.  Back to cited text no. 54
    
55.
Mustafa O, Nurittin A, Kadir T, Senol Y, Oguz O, Ugur D, et al. The isolation of Fusarium sporotrichioides from a diabetic foot wound sample and identification. Marmara Med J 2008;21:68-72.  Back to cited text no. 55
    
56.
Taj-Aldeen SJ, Gene J, Al Bozom I, Buzina W, Cano JF, Guarro J, et al. Gangrenous necrosis of the diabetic foot caused by Fusarium acutatum. Med Mycol 2006;44:547-52.  Back to cited text no. 56
    
57.
Poradzka A, Jasik M, Karnafel W, Fiedor P. Clinical aspects of fungal infections in diabetes. Acta Pol Pharm 2013;70:587-96.  Back to cited text no. 57
    
58.
Kindo AJ, Rana NS, Rekha A, Kalyani J. Fungal infections in the soft tissue: A study from a tertiary care center. Indian J Med Microbiol 2010;28:164-6.  Back to cited text no. 58
[PUBMED]  [Full text]  
59.
Yera H, Bougnoux ME, Jeanrot C, Baixench MT, De Pinieux G, Dupouy-Camet J. Mycetoma of the foot caused by Fusarium solani: Identification of the etiologic agent by DNA sequencing. J Clin Microbiol 2003;41:1805-8.  Back to cited text no. 59
    
60.
Tomimori-Yamashita J, Ogawa MM, Hirata SH, Fischman O, Michalany NS, Yamashita HK, et al. Mycetoma caused by Fusarium solani with osteolytic lesions on the hand: Case report. Mycopathologia 2002;153:11-4.  Back to cited text no. 60
    
61.
Riddell J 4th, Woodside KJ, Leavitt MA, Newton DW, Punch JD. Fusarium incarnatum/equiseti hemodialysis graft infection. Infect Dis Rep 2010;2:e14.  Back to cited text no. 61
    
62.
Nucci M, Varon AG, Garnica M, Akiti T, Barreiros G, Trope BM, et al. Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil. Emerg Infect Dis 2013;19:1567-72.  Back to cited text no. 62
    
63.
Varon AG, Nouer SA, Barreiros G, Trope BM, Magalhães F, Akiti T, et al. Superficial skin lesions positive for Fusarium are associated with subsequent development of invasive fusariosis. J Infect 2014;68:85-9.  Back to cited text no. 63
    
64.
Cocuroccia B, Gaido J, Gubinelli E, Annessi G, Girolomoni G. Localized cutaneous hyalohyphomycosis caused by a Fusarium species infection in a renal transplant patient. J Clin Microbiol 2003;41:905-7.  Back to cited text no. 64
    
65.
Pereiro M Jr., Abalde MT, Zulaica A, Caeiro JL, Flórez A, Peteiro C, et al. Chronic infection due to Fusarium oxysporum mimicking lupus vulgaris: Case report and review of cutaneous involvement in fusariosis. Acta Derm Venereol 2001;81:51-3.  Back to cited text no. 65
    
66.
Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: Implications for diagnosis and management. Clin Infect Dis 2002;35:909-20.  Back to cited text no. 66
    
67.
Collado C, Medina L, Zorraquino A, Baeza T, Ferrer C, Plazas J, et al. Cutaneous fusariosis by a species of the Fusarium dimerum species complex in a patient with acute myeloblastic leukemia. Rev Iberoam Micol 2013;30:119-21.  Back to cited text no. 67
    
68.
van Diepeningen AD, Brankovics B, Iltes J, van der Lee TA, Waalwijk C. Diagnosis of Fusarium infections: Approaches to identification by the clinical mycology laboratory. Curr Fungal Infect Rep 2015;9:135-43.  Back to cited text no. 68
    
69.
Stammberger H. Endoscopic surgery for mycotic and chronic recurring sinusitis. Ann Otol Rhinol Laryngol Suppl 1985;119:1-1.  Back to cited text no. 69
    
70.
Kurien M, Anandi V, Raman R, Brahmadathan KN. Maxillary sinus fusariosis in immunocompetent hosts. J Laryngol Otol 1992;106:733-6.  Back to cited text no. 70
    
71.
Segal BH, Walsh TJ, Liu JM, Wilson JD, Kwon-Chung KJ. Invasive infection with Fusarium chlamydosporum in a patient with aplastic anemia. J Clin Microbiol 1998;36:1772-6.  Back to cited text no. 71
    
72.
Edupuganti S, Rouphael N, Mehta A, Eaton M, Heller JG, Bressler A, et al. Fusarium falciforme vertebral abscess and osteomyelitis: Case report and molecular classification. J Clin Microbiol 2011;49:2350-3.  Back to cited text no. 72
    
73.
Gradon JD, Lerman A, Lutwick LI. Septic arthritis due to Fusarium moniliforme. Rev Infect Dis 1990;12:716-7.  Back to cited text no. 73
    
74.
Jakle C, Leek JC, Olson DA, Robbins DL. Septic arthritis due to Fusarium solani. J Rheumatol 1983;10:151-3.  Back to cited text no. 74
    
75.
Gorman SR, Magiorakos AP, Zimmerman SK, Craven DE. Fusarium oxysporum pneumonia in an immunocompetent host. South Med J 2006;99:613-6.  Back to cited text no. 75
    
76.
Garcia RR, Min Z, Narasimhan S, Bhanot N. Fusarium brain abscess: Case report and literature review. Mycoses 2015;58:22-6.  Back to cited text no. 76
    
77.
Kleinschmidt-Demasters BK. Disseminated Fusarium infection with brain abscesses in a lung transplant recipient. Clin Neuropathol 2009;28:417-21.  Back to cited text no. 77
    
78.
Lortholary O, Obenga G, Biswas P, Caillot D, Chachaty E, Bienvenu AL, et al. International retrospective analysis of 73 cases of invasive fusariosis treated with voriconazole. Antimicrob Agents Chemother 2010;54:4446-50.  Back to cited text no. 78
    
79.
Steinberg GK, Britt RH, Enzmann DR, Finlay JL, Arvin AM. Fusarium brain abscess. Case report. J Neurosurg 1983;58:598-601.  Back to cited text no. 79
    
80.
Avelino-Silva VI, Ramos JF, Leal FE, Testagrossa L, Novis YS. Disseminated Fusarium infection in autologous stem cell transplant recipient. Braz J Infect Dis 2015;19:90-3.  Back to cited text no. 80
    
81.
Nucci M, Cunha CA, Silla L, Bittencourt H, Souza CA, Capellanno P, et al. Multicenter Survey of Invasive Fungal Infections in Patient with Hematologic Malignancies and Hematopoietic Stem Cell Transplant Recipients in Brazil. 48th Annual ICAAC/46th Annual IDSA, M-731; 2008.  Back to cited text no. 81
    
82.
Nucci M, Anaissie EJ, Queiroz-Telles F, Martins CA, Trabasso P, Solza C, et al. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer 2003;98:315-9.  Back to cited text no. 82
    
83.
Nir-Paz R, Strahilevitz J, Shapiro M, Keller N, Goldschmied-Reouven A, Yarden O, et al. Clinical and epidemiological aspects of infections caused by Fusarium species : A collaborative study from Israel. J Clin Microbiol 2004;42:3456-61.  Back to cited text no. 83
    
84.
Lionakis MS, Kontoyiannis DP. Fusarium infections in critically ill patients. Semin Respir Crit Care Med 2004;25:159-69.  Back to cited text no. 84
    
85.
Fanci R, Pini G, Bartolesi AM, Pecile P. Refractory disseminated fusariosis by Fusarium verticillioides in a patient with acute myeloid leukaemia relapsed after allogeneic hematopoietic stem cell transplantation: A case report and literature review. Rev Iberoam Micol 2013;30:51-3.  Back to cited text no. 85
    
86.
Liu YS, Wang NC, Ye RH, Kao WY. Disseminated Fusarium infection in a patient with acute lymphoblastic leukemia: A case report and review of the literature. Oncol Lett 2014;7:334-6.  Back to cited text no. 86
    
87.
Pereira GH, de Angelis DA, Brasil RA, dos Anjos Martins M, de Matos Castro e Silva D, Szeszs MW, et al. Disseminated amphotericin-resistant fusariosis in acute leukemia patients: Report of two cases. Mycopathologia 2013;175:107-14.  Back to cited text no. 87
    
88.
Vagace JM, Sanz-Rodriguez C, Casado MS, Alonso N, Garcia-Dominguez M, de la Llana FG, et al. Resolution of disseminated fusariosis in a child with acute leukemia treated with combined antifungal therapy: A case report. BMC Infect Dis 2007;7:40.  Back to cited text no. 88
    
89.
Kebabcı N, van Diepeningen AD, Ener B, Ersal T, Meijer M, Al-Hatmi AM, et al. Fatal breakthrough infection with Fusarium andiyazi: New multi-resistant aetiological agent cross-reacting with Aspergillus galactomannan enzyme immunoassay. Mycoses 2014;57:249-55.  Back to cited text no. 89
    
90.
Wu CH, Lu PL, Hsiao HH, Liu TC, Lin SF, Chang CS, et al. Breakthrough Fusarium solani infection in a patient with acute myeloid leukemia receiving posaconazole prophylaxis. Ann Hematol 2014;93:1079-81.  Back to cited text no. 90
    
91.
Kim MS, Lee HM, Sung HS, Won CH, Chang SE, Lee MW, et al. Breakthrough disseminated fusariosis in an immunocompromised patient on voriconazole therapy. Int J Dermatol 2012;51:621-3.  Back to cited text no. 91
    
92.
Inês I, Nogueira F, Neves RP, De Queiroz LA, Maria O, Magalhães C, et al. Fusarium lateritium(NEES) as an agent of fungemia in a patient infected with the human immunodeficiency virus (HIV). Braz J Microbiol 2007;38:285-6.  Back to cited text no. 92
    
93.
Halpern M, Balbi E, Carius L, Roma J, Gonzalez AC, Agoglia L, et al. Cellulitis and nodular skin lesions due to Fusarium spp in liver transplant: Case report. Transplant Proc 2010;42:599-600.  Back to cited text no. 93
    
94.
Carneiro HA, Coleman JJ, Restrepo A, Mylonakis E. Fusarium infection in lung transplant patients: Report of 6 cases and review of the literature. Medicine (Baltimore) 2011;90:69-80.  Back to cited text no. 94
    
95.
Terasaki JM, Shah SK, Schnadig VJ, Valentine VG. Airway complication contributing to disseminated fusariosis after lung transplantation. Transpl Infect Dis 2014;16:621-4.  Back to cited text no. 95
    
96.
Garbino J, Uckay I, Rohner P, Lew D, Van Delden C. Fusarium peritonitis concomitant to kidney transplantation successfully managed with voriconazole: Case report and review of the literature. Transpl Int 2005;18:613-8.  Back to cited text no. 96
    
97.
Ruben M. Preliminary observations of soft 9(hydrophilic) contact lenses. Proc R Soc Med 1966;59:531-2.  Back to cited text no. 97
    
98.
Yamaguchi T, Hubbard A, Fukushima A, Kimura T, Kaufman HE. Fungus growth on soft contact lenses with different water contents. Eye Contact Lens 1984;10:166-70.  Back to cited text no. 98
    
99.
Mcneely DJ, Vas SI, Dombros N, Oreopoulos DG. Fusarium peritonitis : An uncommon complication of continuous ambulatory peritoneal dialysis. Perit Dial Int 1981;1:94-6.  Back to cited text no. 99
    
100.
Khan FY, Elsayed M, Anand D, Abu Khattab M, Sanjay D. Fungal peritonitis in patients undergoing continuous ambulatory peritoneal dialysis in Qatar. J Infect Dev Ctries 2011;5:646-51.  Back to cited text no. 100
    
101.
Raad I, Hachem R. Treatment of central venous catheter-related fungemia due to Fusarium oxysporum. Clin Infect Dis 1995;20:709-11.  Back to cited text no. 101
    
102.
Marasas W, Nelson P, Toussoun T. Toxigenic Fusarium species: Identity and Mycotoxicology. Pennsylvania, USA: Pennsylvania State University Press; 1984. p. 328.  Back to cited text no. 102
    
103.
Krátká J, Kováciková E. The effect of temperature and age of strains of Fusarium oxysporum on its enzymatic activity. Zentralbl Bakteriol Naturwiss 1979;134:154-8.  Back to cited text no. 103
    
104.
Hua X, Yuan X, Di Pietro A, Wilhelmus KR. The molecular pathogenicity of Fusarium keratitis: A fungal transcriptional regulator promotes hyphal penetration of the cornea. Cornea 2010;29:1440-4.  Back to cited text no. 104
    
105.
Romani L. Immunity to fungal infections. Nat Rev Immunol 2004;4:1-23.  Back to cited text no. 105
    
106.
Shoham S, Levitz SM. The immune response to fungal infections. Br J Haematol 2005;129:569-82.  Back to cited text no. 106
    
107.
Gaviria JM, van Burik JA, Dale DC, Root RK, Liles WC. Comparison of interferon-gamma, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor for priming leukocyte-mediated hyphal damage of opportunistic fungal pathogens. J Infect Dis 1999;179:1038-41.  Back to cited text no. 107
    
108.
Winn RM, Gil-Lamaignere C, Roilides E, Simitsopoulou M, Lyman CA, Maloukou A, et al. Effects of interleukin-15 on antifungal responses of human polymorphonuclear leukocytes against Fusarium spp. and Scedosporium spp. Cytokine 2005;31:1-8.  Back to cited text no. 108
    
109.
Lima TS, Ribeiro B, Godinho MM, Akiti T, Sodré CT, Ramos-E-Silva M. Fusariosis : five cases in immunodepressed patients. Virol Mycol 2015;4:2-6.  Back to cited text no. 109
    
110.
Agarwal T, Bandivadekar P, Satpathy G, Sharma N, Titiyal JS. Detection of fungal hyphae using smartphone and pocket magnifier: Going cellular. Cornea 2015;34:355-7.  Back to cited text no. 110
    
111.
Labbé A, Gabison E, Cochereau I, Baudouin C. Diagnosis of fungal keratitis by in vivo confocal microscopy: A case report. Eye (Lond) 2011;25:956-8.  Back to cited text no. 111
    
112.
Rimek D, Singh J, Kappe R. Cross-reactivity of the PLATELIA CANDIDA antigen detection enzyme immunoassay with fungal antigen extracts. J Clin Microbiol 2003;41:3395-8.  Back to cited text no. 112
    
113.
Tortorano AM, Richardson M, Roilides E, van Diepeningen A, Caira M, Munoz P, et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp. Scedosporium spp. and others. Clin Microbiol Infect 2014;20 Suppl 3:27-46.  Back to cited text no. 113
    
114.
Shinozaki M, Okubo Y, Sasai D, Nakayama H, Murayama SY, Ide T, et al. Identification of Fusarium species in formalin-fixed and paraffin-embedded sections by in situ hybridization using peptide nucleic acid probes. J Clin Microbiol 2011;49:808-13.  Back to cited text no. 114
    
115.
Hayden RT, Isotalo PA, Parrett T, Wolk DM, Qian X, Roberts GD, et al. In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Mol Pathol 2003;12:21-6.  Back to cited text no. 115
    
116.
Hue FX, Huerre M, Rouffault MA, de Bievre C. Specific detection of Fusarium species in blood and tissues by a PCR technique. J Clin Microbiol 1999;37:2434-8.  Back to cited text no. 116
    
117.
Ferdousi A, Shahhossein MH, Bayat M, Hashemi SJ, Ghahri M. Comparison of polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) for diagnosis of Fusarium solani in human immunodeficiency virus (HIV) positive patients. Afr J Biotechnol 2014;13:1496-502.  Back to cited text no. 117
    
118.
Marinach-Patrice C, Lethuillier A, Marly A, Brossas JY, Gené J, Symoens F, et al. Use of mass spectrometry to identify clinical Fusarium isolates. Clin Microbiol Infect 2009;15:634-42.  Back to cited text no. 118
    
119.
Al-Hatmi AM, Normand AC, van Diepeningen AD, Hendrickx M, de Hoog GS, Piarroux R, et al. Rapid identification of clinical members of Fusarium fujikuroi complex using MALDI-TOF MS. Future Microbiol 2015;10:1939-52.  Back to cited text no. 119
    
120.
CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Filamentous Fungi; Approved Standard – CLSI Document M38-A2. Pennsylvania, USA: Clinical and Laboratory Standards Institute (CLSI); 2008. p. 52.  Back to cited text no. 120
    
121.
Tupaki-Sreepurna A, Al-Hatmi AM, Kindo AJ, Sundaram M, de Hoog GS. Multidrug-resistant Fusarium in keratitis: A clinico-mycological study of keratitis infections in Chennai, India. Mycoses 2017;60:230-3.  Back to cited text no. 121
    
122.
Al-Hatmi AM, van Diepeningen AD, Curfs-Breuker I, de Hoog GS, Meis JF. Specific antifungal susceptibility profiles of opportunists in the Fusarium fujikuroi complex. J Antimicrob Chemother 2015;70:1068-71.  Back to cited text no. 122
    
123.
Espinel-Ingroff A, Colombo AL, Cordoba S, Dufresne PJ, Fuller J, Ghannoum M, et al. International evaluation of MIC distributions and epidemiological cutoff value (ECV) definitions for Fusarium species identified by molecular methods for the CLSI broth microdilution method. Antimicrob Agents Chemother 2016;60:1079-84.  Back to cited text no. 123
    
124.
Raad II, Hachem RY, Herbrecht R, Graybill JR, Hare R, Corcoran G, et al. Posaconazole as salvage treatment for invasive fusariosis in patients with underlying hematologic malignancy and other conditions. Clin Infect Dis 2006;42:1398-403.  Back to cited text no. 124
    
125.
Lin HC, Lin JL, Lin-Tan DT, Ma HK, Chen HC. Early keratectomy in the treatment of moderate Fusarium keratitis. PLoS One 2012;7:e42126.  Back to cited text no. 125
    
126.
Queller JN, Bhatia N. The dermatologist's approach to onychomycosis. J Fungi (Basel) 2015;1:173-84.  Back to cited text no. 126
    
127.
Iwata A, Watanabe Y, Kumagai N, Katafuchi-Nagashima M, Sugiura K, Pillai R, et al. In vitro and in vivo assessment of dermatophyte acquired resistance to efinaconazole, a novel triazole antifungal. Antimicrob Agents Chemother 2014;58:4920-2.  Back to cited text no. 127
    
128.
Jo Siu WJ, Tatsumi Y, Senda H, Pillai R, Nakamura T, Sone D, et al. Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob Agents Chemother 2013;57:1610-6.  Back to cited text no. 128
    
129.
Inano S, Kimura M, Iida J, Arima N. Combination therapy of voriconazole and terbinafine for disseminated fusariosis: Case report and literature review. J Infect Chemother 2013;19:1173-80.  Back to cited text no. 129
    
130.
Ho DY, Lee JD, Rosso F, Montoya JG. Treating disseminated fusariosis: Amphotericin B, voriconazole or both? Mycoses 2007;50:227-31.  Back to cited text no. 130
    
131.
Nucci M, Perfect JR. When primary antifungal therapy fails. Clin Infect Dis 2008;46:1426-33.  Back to cited text no. 131
    
132.
Hu S, Fan VC, Koonapareddy C, Du TT, Asbell PA. Contact lens-related Fusarium infection: Case series experience in New York city and review of fungal keratitis. Eye Contact Lens 2007;33:322-8.  Back to cited text no. 132
    
133.
Hume EB, Flanagan J, Masoudi S, Zhu H, Cole N, Willcox MD, et al. Soft contact lens disinfection solution efficacy: Clinical Fusarium isolates vs. ATCC 36031. Optom Vis Sci 2009;86:415-9.  Back to cited text no. 133
    
134.
Gupta AK, Baran R, Summerbell R. Onychomycosis: Strategies to improve efficacy and reduce recurrence. J Eur Acad Dermatol Venereol 2002;16:579-86.  Back to cited text no. 134
    


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2004 - Indian Journal of Medical Microbiology
Published by Wolters Kluwer - Medknow

Online since April 2001, new site since 1st August '04