Emerging & Rare Fungal Infections in Solid Organ Transplant Recipients

Abstract

Newly emerging and rare fungal agents are increasingly reported as genuine pathogens in posttransplant fungal infections. The description ‘emerging’ has been coined for these fungal agents as they have not been traditionally implicated, recognized, or recovered as the etiological agents of fungal infections in immunocompromised patients. An increased understanding of the importance of these emerging and rare fungal pathogens has developed from infections reported in patients with hematological malignancies undergoing chemotherapeutic regimens and conditioning for bone marrow transplantation (1Wingard JR The changing face of invasive fungal infections in hematopoietic cell transplant recipients.Curr Opin Oncol. 2005; 17: 89-92Crossref PubMed Scopus (50) Google Scholar, 2Malani AN Kauffman CA Changing epidemiology of rare mould infections: implications for therapy.Drugs. 2007; 67: 1803-1812Crossref PubMed Scopus (111) Google Scholar, 3Richardson M Lass-Florl C Changing epidemiology of systemic fungal infections.Clin Microbiol Infect. 2008; 14: 5-24Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar, 4Kubak BM Pegues DA Holt CD Hwang AH Changing patterns of fungal infection in transplantation.Curr Opin Organ Transplant. 2000; 5: 176-191Crossref Google Scholar, 5Varkey JB Perfect JR Rare and emerging fungal pulmonary infections.Semin Respir Crit Care Med. 2008; 29: 121-131Crossref PubMed Scopus (25) Google Scholar, 6Barnes PD Marr KA Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients.Br J Haematol. 2007; 139: 519-531Crossref PubMed Scopus (134) Google Scholar). The ‘rare’ fungal agents have been increasingly reported in susceptible patients with unique risk factors including solid organ transplantation (7Stelzmueller I Lass-Floerl C Geltner C et al.Zygomycosis and other rare filamentous fungal infections in solid organ transplant recipients.Transpl Int. 2008; 21: 534-546Crossref PubMed Scopus (48) Google Scholar, 8Husain S Alexander BD Munoz P et al.Opportunistic mycelial fungal infections in organ transplant recipients: emerging importance of non-Aspergillus mycelial fungi.Clin Infect Dis. 2003; 37: 221-229Crossref PubMed Scopus (294) Google Scholar, 9Fungal infections.Am J Transplant. 2004; 4: 110-134PubMed Google Scholar, 10Grossi P Farina C Fiocchi R Dalla Gasperina D Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Italian Study Group of Fungal Infections in Thoracic Organ Transplant Recipients.Transplantation. 2000; 70: 112-116PubMed Google Scholar, 11Alexander BD Tapson VF Infectious complications of lung transplantation.Transpl Infect Dis. 2001; 3: 128-137Crossref PubMed Scopus (91) Google Scholar). The detection and isolation of these fungi correlates with the pathophysiology and clinical symptoms thereby confirming their causative role in disease. Although in many cases, the exposure source is unknown; immunocompetent and immunocompromised patients will come into contact with these emerging and rare potential pathogens as a result of environmental contact with soil and vegetation/plant material, contaminated and polluted water, sewage, wood, certain foods and decaying fruit. Several species are widely disseminated in air and presumably acquired by inhalation of fungal structures such as spores, conidia or actual hyphal elements. Specific modes of acquisition such as traumatic exposure or contamination of wounds or intravascular access sites are generally accepted. Many of these moulds and yeasts were originally considered nonpathogenic contaminants from clinical specimens (e.g. surveillance cultures of respiratory, sinus, skin, or wound sources) and might have been initially dismissed as the etiologic agent (s) of infection. Most patients infected with emerging and rare fungal agents have unique risk factors such as neutropenia, poorly controlled diabetes mellitus, malnutrition, renal failure, inherent disorders of immunity and anatomy, and receipt of chemotherapy or other immunosuppressive medications (1Wingard JR The changing face of invasive fungal infections in hematopoietic cell transplant recipients.Curr Opin Oncol. 2005; 17: 89-92Crossref PubMed Scopus (50) Google Scholar, 3Richardson M Lass-Florl C Changing epidemiology of systemic fungal infections.Clin Microbiol Infect. 2008; 14: 5-24Abstract Full Text Full Text PDF PubMed Scopus (356) Google Scholar, 6Barnes PD Marr KA Risks, diagnosis and outcomes of invasive fungal infections in haematopoietic stem cell transplant recipients.Br J Haematol. 2007; 139: 519-531Crossref PubMed Scopus (134) Google Scholar, 12Fleming RV Walsh TJ Anaissie EJ Emerging and less common fungal pathogens.Infect Dis Clin North Am. 2002; 16 (vi-vii): 915-933Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar). One established example of these rare fungal agents infecting patients with disordered immunity and anatomy occurs in end-stage lung disease due to cystic fibrosis or advanced pulmonary fibrosis and bronchiectasis (5Varkey JB Perfect JR Rare and emerging fungal pulmonary infections.Semin Respir Crit Care Med. 2008; 29: 121-131Crossref PubMed Scopus (25) Google Scholar). The underlying pulmonary architectural distortion and mucosal defects predispose these patients to colonization and infection with Scedosporium, Zygomycetes, and dematiaceous moulds. Such ‘colonization’ may result in posttransplant infection in a subgroup of lung transplant recipients (13Sole A Salavert M Fungal infections after lung transplantation.Transplant Rev (Orlando). 2008; 22: 89-104Crossref PubMed Scopus (71) Google Scholar, 14Symoens F Knoop C Schrooyen M et al.Disseminated Scedosporium apiospermum infection in a cystic fibrosis patient after double-lung transplantation.J Heart Lung Transplant. 2006; 25: 603-607Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). Disease presentations include pulmonary, dermatological, and central nervous system involvement as well as widely disseminated disease involving other less reported sites. The disease potential of the emerging moulds may depend on several specific and yet unrecognized fungal virulence factors. Reported factors include melanin (especially with the dematiaceous fungi), proteases, phospholipases, catalases, calcineurin, and lipid signaling molecules (15Gauwerky K Borelli C Korting HC Targeting virulence: A new paradigm for antifungals.Drug Discov Today. 2009; Crossref PubMed Scopus (139) Google Scholar). The milieu of post transplant immunosuppression, the intensity of rejection therapy, and graft dysfunction facilitate the acquisition of fungal spores and moulds leading to disease. Exposure to selective antifungal agents, specifically azole prophylaxis or therapy, may contribute to this shift in incidence of infection with the emerging fungi. Voriconazole usage has been associated with zygomycosis in hematopoietic stem-cell transplant (HSCT) recipients in some medical centers (16Kontoyiannis DP Lewis RE Invasive zygomycosis: update on pathogenesis, clinical manifestations, and management.Infect Dis Clin North Am. 2006; 20 (vi): 581-607Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 17Siwek GT Dodgson KJ De Magalhaes-Silverman M et al.Invasive zygomycosis in hematopoietic stem cell transplant recipients receiving voriconazole prophylaxis.Clin Infect Dis. 2004; 39: 584-587Crossref PubMed Scopus (261) Google Scholar, 18Marty FM Cosimi LA Baden LR Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants.N Engl J Med. 2004; 350: 950-952Crossref PubMed Scopus (371) Google Scholar). Multicenter controlled trials of risk factors, diagnostic approaches, and prophylaxis and treatment strategies for emerging fungal infections in organ transplant recipients are limited. Many of the clinical practices are evolving from small case series, anecdotal experiences, and joint center reviews. The following diseases will be discussed in this section: zygomycosis, hyalohyphomycosis, scedosporiosis (pseudoallescheriosis), phaeohyphomycosis, chromoblastomycosis, mycetoma, emerging yeast infections, and dermatophytosis. Specific agents and associated diseases are listed in Table 1.Table 1Emerging fungal pathogens listed by more common reported sites of infection and clinical syndromes.Sepsis/FungemiaPulmonaryGenitourinaryCentral Nervous SystemOcular (& Ear)Skin/SubcuatenousIntra-abdominalAcremoniumFusarium spp.Hasemula (Y)Malasseziaspp. (Y)PaecilomycesTrichodermaspp.Trichosporon (Y)Rhodotorula (Y)Fusarium spp.Malassezia spp. (Y)PaecilomycesPencillium marneffeiScedosporium spp.Scopulariopsis spp.Trichoderma spp.Trichosporon beigelii (Y)Zycomycoses (Rhizopus, Mucor, Apophysomyces, Cunninghamella)PhaeohyphomycosesBipolaris spp.Curvularia spp.CladophialophorabantianaDactylaria gallopava/constrictaScedosporiumprolificansMalassezia spp. (Y)Trichosporon (Y)Zycomycoses (Rhizopus, Absidia)Fusarium spp.PaecilomycesScedosporium spp.Trichosporon beigelii (Y)Trichoderma spp.Zycomycoses (Rhizopus, Mucor, Cunninghamella, Apophysomyces, Absidia)PhaeohyphomycosesBipolaris spp.Wangiella dermatitidisCladophialophorabantianiRamichloridiummackenzieiDactylaria gallopavaOnchroconis gallopavumRhinocerebralFusarium spp.PaecilomycesScedosporium spp.Trichoderma spp.Zycomycoses (Rhizopus, Mucor)PhaeohyphomycosesAlternaria alternataBipolaris spp.Curvularia spp.Exserohilum rostratumExophiala spp.Dactylaria gallopavaRamichloridiummackenziei(ear)Fusarium spp.Scedosporium spp.Trichosporon (Y)Zygomycoses (Rhizopus, Mucor, Cunninghamella, Apophysomyces)PhaeohyphomycosesAlternaria alternataCurvularia spp.Exserohilum rostratumExophiala spp.Phialophora spp.Wangiella dermati-tidisKeratitisFusarium spp.Scedosporium spp.Endopthalmitis UveitisAcremoniumFusarium spp.PaecilomycesRhodotorula (Y)Scedosporium spp.ScopulariopsisTrichosporon (Y)ZycomycosesFusarium spp.Malassezia spp. (Y)Penicillium marneffei Scedosporium spp.PaecilomycesTrichoderma spp.Zygomycoses (Rhizopus, Mucor)PhaeohyphomycosesAlternaria alternataBipolaris spp.Curvularia spp.ExserohilumrostratumExophiala spp.WangielladermatitidisPhialophora spp.ScedosporiumprolificansCladophialophorabantianaDactylaria gallopavaFusarium spp.PaecilomycesPenicillium marneffeiPhaeohyphomycosesTrichoderma spp.Trichosporonbeigelii (Y)ZycomycosesMusculoskeletalAngio-invasive/Thrombosis/InfarctionDisseminated diseaseFusarium spp.Scedosporium spp.Trichoderma spp.Penicillium marneffeiZygomycosesPhaeohyphomycosesAlternaria alternataCurvularia spp.ScedosporiumprolificansDactylaria gallopava/constrictaFusariumScedosporiumZygomycoses (Rhizopus,Mucor)PhaeohyphomycosesFusarium spp.Malassezia spp. (Y)Penicillium marneffeiScedosporium spp.Trichosporon (Y)Trichoderma spp.Zycomycoses (Rhizopus Mucor)PhaeohyphomycosesAlternaria alternataBipolaris spp.Curvularia spp.Phialophora spp.ScedosporiumprolificansCladophialophorabantianaY = Yeast, otherwise Mould form.Fusarium spp.: F. solani, F. oxysporum, F. moniliformePaecilomyces spp.: P. variotii, P. lilacinusTrichoderma spp.: T. longibrachiatum, T. viride, T. harzianumScedosporium spp: Pseudallescheria boydii (sexual state), Scedosporium apiospermum (asexual state)Scopulariopsis spp.: S. brumptii, S. brevicaulisMalassezia spp.: M. furfur; M. pachydermatisZygomycoses: Rhizopus oryzae, Rhizopus microsporus; Mucor spp.; Cunninghamella bertholletiae; Absidia corymbifera; Apophysomyces elegansPhaeohyphomycoses:Alternaria: A. alternaria. A. tenuissimaBipolaris: B. hawaiiensis, B. spiciferaCladophialophora bantiana: also known as Xylohyha bantiana and Cladosporium trichoidesCurvularia: C. lunata, C. geniculata, othersDactylaria: D. gallopava, D. constrictaExophiala: E. jeanselmei var jeanselmei, E. jeanselmei var lecanii-corni, E. spinifera, E. monliae, E. castellaniiPialophora: P. repens, P. richardsiae, P. verrucosa (chromoblastomycosis)Ramichloridium mackenzieiScedosporium: S. prolificans, formerly S. inflatum Open table in a new tab Y = Yeast, otherwise Mould form. Fusarium spp.: F. solani, F. oxysporum, F. moniliforme Paecilomyces spp.: P. variotii, P. lilacinus Trichoderma spp.: T. longibrachiatum, T. viride, T. harzianum Scedosporium spp: Pseudallescheria boydii (sexual state), Scedosporium apiospermum (asexual state) Scopulariopsis spp.: S. brumptii, S. brevicaulis Malassezia spp.: M. furfur; M. pachydermatis Zygomycoses: Rhizopus oryzae, Rhizopus microsporus; Mucor spp.; Cunninghamella bertholletiae; Absidia corymbifera; Apophysomyces elegans Phaeohyphomycoses: Alternaria: A. alternaria. A. tenuissima Bipolaris: B. hawaiiensis, B. spicifera Cladophialophora bantiana: also known as Xylohyha bantiana and Cladosporium trichoides Curvularia: C. lunata, C. geniculata, others Dactylaria: D. gallopava, D. constrictaExophiala: E. jeanselmei var jeanselmei, E. jeanselmei var lecanii-corni, E. spinifera, E. monliae, E. castellanii Pialophora: P. repens, P. richardsiae, P. verrucosa (chromoblastomycosis) Ramichloridium mackenziei Scedosporium: S. prolificans, formerly S. inflatum Zygomycosis is a collective term generally referring to infections caused by members of the Zygomycetes class, Mucorales order, including Absidia, Apophysomyces, Cunninghamella, Mucor, Rhizopus, and Rhizomucor. These moulds appear in tissue as broad hyphal structures that are ribbon-like, right angle or irregularly branched, and sparsely septated (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Hyalohyphomycosis is the general term for infections due to fungi with hyaline (i.e. non-pigmented or lightly pigmented), septate, branched, or sometimes mycelial attributes. They can be subcutaneous, organ or tissue specific (with abscess formation) or widely disseminated. Agents include Acremonium, Arthrographis kalrae, Chyrsosporium, Fusarium, Paecilomyces, Penicillium marneffi, Scopulariopsis, and Trichoderma, among others (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Scedosporium spp. (Pseudallescheria) retains a unique place in the hierarchy of emerging fungal infections as it ranks closely behind Candida and Aspergillus infections in organ transplant recipients. Scedosporium apiospermum is the asexual form (anamorph) of Pseudallescheria boydii. Both are filamentous moulds causing hyalohyphomycosis. Historically the sexual form Pseudallescheria boydii has been reported under the heading pseudoallescheriosis (also monosporiosis) with the spectrum of diseases involving cases of mycetoma, localized skin infections from traumatic inoculation, pneumonia, and disseminated disease. The organism is a ubiquitous saprophyte isolated from soil, polluted water, compost material and manure, and decaying vegetation. The organism is often recovered in respiratory specimens from patients with cystic fibrosis and severe bronchiectasis (5Varkey JB Perfect JR Rare and emerging fungal pulmonary infections.Semin Respir Crit Care Med. 2008; 29: 121-131Crossref PubMed Scopus (25) Google Scholar, 14Symoens F Knoop C Schrooyen M et al.Disseminated Scedosporium apiospermum infection in a cystic fibrosis patient after double-lung transplantation.J Heart Lung Transplant. 2006; 25: 603-607Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). Scedosporium prolificans has no known sexual form and is typically classified as phaeohyphomycosis. The phaeohyphomycoses are a heterogeneous group of infections caused by dematiaceous fungi (Table 1). The dematiaceous fungi are characterized by the presence of pale brown-black pigment in the cell walls of their vegetative cells, conidial elements, or both (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). The pigment is usually melanin, specifically dihydroxynapthalene melanin. Mycotic infections caused by dematiaceous fungi include phaeohyphomycosis, chromoblastomycosis, mycetoma, and sprorotrichosis (discussed elsewhere). Dematiaceous fungi appear in tissue in any combination of hyphal, pseudohyphal, or yeast-like forms, lacking the cellular forms called muriform cells (sclerotic bodies). While many dematiaceous moulds are darkly pigmented in tissue, pathogens such as Alternaria, Bipolaris, and Curvularia have scanty melanin formation in infected tissues. Consequently, they have a hyaline appearance mimicking the agents causing hyalohyphomycosis, yet they are dematiaceous in culture and retain this association. Phaeohyphomycoses are classified as follows: 1) superficial, involving infection of the skin and hair; 2) cutaneous and corneal, involving keratinized tissues with greater invasion and tissue destruction; 3) subcutaneous, involving deeper implantation of the fungi resulting in cyst and/or abscess formation; 4) systemic, with the initial portal of entry usually via the lung resulting in sino-pulmonary infection and subsequent dissemination to extrapulmonary sites including the central nervous system, liver, spleen, pancreas and other sites (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). The primary pulmonary infection may not have been clincally recognized. Important pathogens in this group include Bipolaris, Exophiala, Exserohilum, Cladosporium, and Curvularia (see Table 1). Chromoblastomycosis refers to chronic cutaneous and subcutaneous lesions, resulting from traumatic implantation of one of several closely related dematiaceous fungi. The causative organisms are soil saprobes, commonly tropical or subtropical in origin but reported from every continent (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar). The disease hallmark is the presence of muriform cells, embedded in the granulomatous and suppurative tissue reaction (22Queiroz-Telles F Esterre P Perez-Blanco M Vitale RG Salgado CG Bonifaz A Chromoblastomycosis: an overview of clinical manifestations, diagnosis and treatment.Med Mycol. 2009; 47: 3-15Crossref PubMed Scopus (228) Google Scholar). This appearance may be confused with squamous cell carcinoma. In the histopathology literature, muriform cells have been referred to as sclerotic cells, copper pennies, or as fumagoid, chromo or Medlar bodies. Texts may still retain these older descriptions. The identification of these appearances in infected tissues with a specialist in pathological mycology is essential for their exact diagnosis. Members include Cladosporium, Fonsecaea, and Phialophora (see Table 1). Mycetoma is a chronic inflammatory process characterized by swelling and tumefacation of an affected body part with associated destruction of adjacent subcutaneous tissue, muscle, and bone (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Sinus tract formation draining onto the skin is a component of this infection; usually the causative organism in visible aggregates is contained in the sinus material. Common agents include Pseudallescheria boydii, Madurella mycetomatis, Acremonium spp., and Exophiala spp. among other very rare agents. These agents are most commonly seen in tropical areas, but may be detected in parts of the southern United States. Trichosporonosis is caused by the geophilic yeast and the occasional human commensal Trichosporon beigelii (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Trichosporon species belong to the Cryptococcacaeae family and are ubiquitous yeasts found in soil and water. The clinical spectrum of trichosporonosis may range from the harmless hair disease white piedra to serious systemic infections. Trichosporon species are characterized by hyphae with rectangular arthrospores, true hyphae, pseudohyphae, and budding yeast. Malessezia species also belong to the Cryptococcacaeae family and appear as budding yeast cells in pityriasis veriscolor or as both budding yeast cells and hyphae in its pathogenic form, tinea versicolor. Rhodotorula are round to oval-shaped, multilateral budding yeasts that are normal inhabitants of moist skin. Rhodotorula share many similar morphologic and physiologic characteristics with Cryptococcus but are less pathogenic. Dermatophytes are classified according to macroconidial characteristics as well as their natural habitats. Anthropophilic species exclusively parasitize humans, zoophilic prefer lower animals, and geophilic species are soil-dwelling saprophytes. All three groups are capable of producing human disease (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar, 21Patterson TF Advances and challenges in management of invasive mycoses.Lancet. 2005; 366: 1013-1025Abstract Full Text Full Text PDF PubMed Scopus (199) Google Scholar). Colonization with yeasts and moulds occurs frequently in transplant candidates with end-stage organ disease and in recipients after transplantation (5Varkey JB Perfect JR Rare and emerging fungal pulmonary infections.Semin Respir Crit Care Med. 2008; 29: 121-131Crossref PubMed Scopus (25) Google Scholar). Transplant candidates may harbor fungal organisms as a consequence of receiving broad-spectrum antibiotics or immunosuppression. Chronic corticosteroid usage for end-stage lung disease commonly predisposes patients to filamentous mould colonization before transplant (14Symoens F Knoop C Schrooyen M et al.Disseminated Scedosporium apiospermum infection in a cystic fibrosis patient after double-lung transplantation.J Heart Lung Transplant. 2006; 25: 603-607Abstract Full Text Full Text PDF PubMed Scopus (104) Google Scholar). In transplant candidates with end-stage bronchiectasis, pulmonary fibrosis, or cystic fibrosis, fungal organisms can be isolated with frequency due to underlying parenchymal disease, dysfunctional clearance mechanisms, and altered immunological responses with and without signs of invasive disease (23Logan PM Primack SL Miller RR Muller NL Invasive aspergillosis of the airways: radiographic, CT, and pathologic findings.Radiology. 1994; 193: 383-388Crossref PubMed Scopus (155) Google Scholar). Invasive pulmonary or sinus disease with mycelial fungi or yeasts is considered a contraindication for transplantation until such processes are ameliorated or resolved. Scedosporium and Zygomycetes have contributed to morbidity and mortality in these patients. Pretransplant mortality in cystic fibrosis patients with invasive Scedosporium has been reported. The presence of preoperative respiratory fungi such as Fusarium, Scedosporium, or dematiaceous moulds may result in invasive disease after intensive immunosuppression and transplant. Evidence demonstrating a direct correlation to posttransplant fungal infection has varied among transplant centers (24Cimon B Carrere J Vinatier JF Chazalette JP Chabasse D Bouchara JP Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis.Eur J Clin Microbiol Infect Dis. 2000; 19: 53-56Crossref PubMed Scopus (220) Google Scholar, 25Kanj SS Welty-Wolf K Madden J et al.Fungal infections in lung and heart-lung transplant recipients. Report of 9 cases and review of the literature.Medicine (Baltimore). 1996; 75: 142-156Crossref PubMed Scopus (162) Google Scholar, 26Nunley DR Gal AA Vega JD Perlino C Smith P Lawrence EC Saprophytic fungal infections and complications involving the bronchial anastomosis following human lung transplantation.Chest. 2002; 122: 1185-1191Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 27Paradowski LJ Saprophytic fungal infections and lung transplantation–revisited.J Heart Lung Transplant. 1997; 16: 524-531PubMed Google Scholar, 28Silveira FP Kwak EJ Paterson DL Pilewski JM McCurry KR Husain S Post-transplant colonization with non-Aspergillus molds and risk of development of invasive fungal disease in lung transplant recipients.J Heart Lung Transplant. 2008; 27: 850-855Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar). Distinguishing fungal colonization from active infection prior to and after transplantation should be an essential component of the pre- and posttransplant evaluation (9Fungal infections.Am J Transplant. 2004; 4: 110-134PubMed Google Scholar, 29Sahi H Avery RK Minai OA et al.Scedosporium apiospermum (Pseudoallescheria boydii) infection in lung transplant recipients.J Heart Lung Transplant. 2007; 26: 350-356Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar). Donor-derived fungal infections have been observed with emerging fungal pathogens. Transmission of Monosporium (Scedosporium) from a cadaveric kidney was reported resulting in 50% mortality and 100% graft loss (30Rubin RH Young LS Clinical approach to infection in the compromised host. 4th ed.New York: Kluwer Academic/Plenum. 2002; Google Scholar). The possibilities exist for donor transmission of Zygomycetes or other filamentous moulds with unrecognized fungal acquisition of unusual fungi from nosocomial sources prior to death. Donors exposed to contaminated water such as near-drownings may have acquired unusual moulds in the lungs facilitating dissemination to other organs. Organ procurement agencies should exercise due diligence in reporting all fungal isolates from a donor to the recipient center, especially pending fungal cultures prior to harvesting. Due to the slow laboratory growth of some emerging fungal pathogens, preliminary fungal cultures may have been reported as ‘negative-preliminary’ in a donor evaluation. Many of the opportunistic fungi causing infection have worldwide geographic distribution. An assessment of pretransplant residence, travel, or exposure to areas of geographically-restricted mycoses is required. Tropical or subtropical travel or residency prior to or after organ transplant should be noted for possible exposure to agents of chromoblastomycoses, phaeohyphomycoses, and geographically restricted mycoses. Transplant tourism should be investigated in any organ transplant recipient returning from Southeast Asia, the Middle East, China, or India as geographically restricted moulds and yeasts may have been acquired in those areas (31Gill J Madhira BR Gjertson D et al.Transplant tourism in the United States: a single-center experience.Clin J Am Soc Nephrol. 2008; 3: 1820-1828Crossref PubMed Scopus (88) Google Scholar). Potential emerging fungi can include Penicillium marneffi (Southeast Asia), chromoblastomycotic agents (India, Middle East, Africa, China), dematiaceous moulds from all areas mentioned (e.g. Ramichloridium mackenzie from Egypt, Israel, Saudi Arabia), among other agents (19Murray PR American Society for Microbiology. Manual of clinical microbiology. 7th ed.Washington, D.C.: ASM Press. 1999; Google Scholar, 20Crissey JT Lang H Parish LC Manual of medical mycology.Cambridge, Mass, USA: Blackwell Scientific. 1995; Google Scholar). Transplant recipients with occupational exposure to emerging moulds should be closely monitored. These includes agricultural and greenhouse workers, carpenters, and workers exposed to soil, particulate, decaying vegetation, sewage and manure, compost material, and residential sites of mould habitation such as attics, crawlspaces, and garages. Workers and transplant recipients exposed to natural disaster cleanups (i.e. hurricanes, floods, and tsunamis) may become exposed to unusual moulds and yeast. Infection due to emerging moulds and yeasts can be difficult to diagnose. Advances