New insights into a disfiguring fungal disease, eumycetoma

Human mycetoma is a mutilating disease of the cutaneous and subcutaneous tissues with a potential to invade deeper structures like muscles and bones. The disease commonly affects the limbs, and in tropical areas, where mycetoma is endemic it is a major cause of disability. The distinctive and unique clinical feature of this infection is the presence of subcutaneous granules which are oozed via fistulas on the skin; the grains are micro-colonies of the causative agent. When this agent is a fungus the disease is known as eumycetoma, while the bacterial type is known as actinomycetoma. Eumycetoma is more troublesome in terms of diagnosis and treatment, and in many cases the infection ends up with amputation. The diagnosis primarily relies on the identification of the causative agent, which may be difficult because eumycetoma can be caused by large number of fungal species that have thus far poorly been characterized. Therefore, the first part of the thesis is devoted to description and classification of the common agents of the disease in the kingdom of fungi. After taxonomic characterization of the species, further reliable criteria for identification of these species were selected. In the second part of the thesis the focus is on development and evaluation of rapid and simple identification tools aiming to improve diagnosis in endemic areas. In an effort to improve the challenging treatment of the disease, the third part of the thesis is focused on antifungal susceptibility of the causative agents and on new treatment options.

[1]  S. Dolatabadi,et al.  Implantation phaeohyphomycosis caused by a non-sporulating Chaetomium species. , 2014, Journal de mycologie medicale.

[2]  Alexandros Stamatakis,et al.  RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies , 2014, Bioinform..

[3]  L. Cai,et al.  Phylogenetic assessment of Chaetomium indicum and allied species, with the introduction of three new species and epitypification of C. funicola and C. indicum , 2014, Mycological Progress.

[4]  J. Killen,et al.  Non-candidal Fungal Peritonitis in Far North Queensland: A Case Series , 2013, Peritoneal Dialysis International.

[5]  B. Stielow,et al.  Phylogenetic Findings Suggest Possible New Habitat and Routes of Infection of Human Eumyctoma , 2013, PLoS neglected tropical diseases.

[6]  A. Al-Salem,et al.  Chaetomium peritonitis in an immunocompetent patient simulating tuberculous peritonitis: A case report and review of the literature , 2013 .

[7]  A. Colombo,et al.  Molecular Identification of Melanised Non-Sporulating Moulds: A Useful Tool for Studying the Epidemiology of Phaeohyphomycosis , 2013, Mycopathologia.

[8]  A. Casadevall Fungi and the Rise of Mammals , 2012, PLoS pathogens.

[9]  W. V. D. van de Sande Phylogenetic Analysis of the Complete Mitochondrial Genome of Madurella mycetomatis Confirms Its Taxonomic Position within the Order Sordariales , 2012, PloS one.

[10]  G. S. de Hoog,et al.  Identification problems with sterile fungi, illustrated by a keratitis due to a non-sporulating Chaetomium-like species. , 2012, Medical mycology.

[11]  P. Thomas,et al.  Keratitis due to Chaetomium sp. , 2012, Case reports in ophthalmological medicine.

[12]  G. S. de Hoog,et al.  New Species of Madurella, Causative Agents of Black-Grain Mycetoma , 2011, Journal of Clinical Microbiology.

[13]  M. Nei,et al.  MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. , 2011, Molecular biology and evolution.

[14]  V. Hubka,et al.  Phaeohyphomycosis and onychomycosis due to Chaetomium spp., including the first report of Chaetomium brasiliense infection. , 2011, Medical mycology.

[15]  John W. Taylor,et al.  One Fungus = One Name: DNA and fungal nomenclature twenty years after PCR , 2011, IMA fungus.

[16]  R. Zare,et al.  The genus Chaetomium in Iran, a phylogenetic study including six new species , 2011, Mycologia.

[17]  H. Badali,et al.  Fatal Cerebral Phaeohyphomycosis in an Immunocompetent Individual Due to Thielavia subthermophila , 2011, Journal of Clinical Microbiology.

[18]  W. Meyer,et al.  Abundance of Pseudallescheria/Scedosporium species in the Australian urban environment suggests a possible source for scedosporiosis including the colonization of airways in cystic fibrosis. , 2010, Medical mycology.

[19]  S. Revankar,et al.  Melanized Fungi in Human Disease , 2010, Clinical Microbiology Reviews.

[20]  F. Prenafeta-Boldú,et al.  Isolation and Identification of Black Yeasts by Enrichment on Atmospheres of Monoaromatic Hydrocarbons , 2010, Microbial Ecology.

[21]  H. Badali,et al.  Cladophialophora saturnica sp. nov., a new opportunistic species of Chaetothyriales revealed using molecular data. , 2009, Medical mycology.

[22]  K. Pastirčáková,et al.  European record of Subramaniula thielavioides on opium poppy , 2009 .

[23]  S. A. Ghiasian,et al.  Isolation and Characterization of Medically Important Aerobic Actinomycetes in Soil of Iran (2006 - 2007) , 2009, The open microbiology journal.

[24]  J. Spatafora,et al.  Molecular systematics of the marine Dothideomycetes , 2009, Studies in mycology.

[25]  J. Rougemont,et al.  A rapid bootstrap algorithm for the RAxML Web servers. , 2008, Systematic biology.

[26]  A. Tsuneda,et al.  Evidence that the gemmae of Papulaspora sepedonioides are neotenous perithecia in the Melanosporales , 2008, Mycologia.

[27]  James C. Wilgenbusch,et al.  AWTY (are we there yet?): a system for graphical exploration of MCMC convergence in Bayesian phylogenetics , 2008, Bioinform..

[28]  Seonju Lee,et al.  Phylogenetic relationships of Chaetomium and similar genera based on ribosomal DNA sequences , 1999 .

[29]  A. Padhye,et al.  Occurrence of pathogenic fungi in soil of burrows of rats and of other sites in bamboo plantations in India and Nepal , 2007, Mycoses.

[30]  M. Piepenbring,et al.  Chromoblastomycosis caused by Chaetomium funicola: a case report from Western Panama , 2007, The British journal of dermatology.

[31]  Shu-wei Yang,et al.  Sch 213766, A Novel Chemokine Receptor CCR-5 Inhibitor from Chaetomium globosum , 2007, The Journal of Antibiotics.

[32]  M. Brandt,et al.  Discovering Potential Pathogens among Fungi Identified as Nonsporulating Molds , 2006, Journal of Clinical Microbiology.

[33]  J. Rogers,et al.  An overview of the systematics of the Sordariomycetes based on a four-gene phylogeny. , 2006, Mycologia.

[34]  Alexandros Stamatakis,et al.  RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models , 2006, Bioinform..

[35]  R. Watling An Illustrated Guide to the Coprophilous Ascomycetes of Australia, Ann Bell, CBS Biodiversity Series No. 3, Centraalbureau voor Schimmelcultures, PO Box 85167, 3508 AD Utrecht, The Netherlands, 2005, ISBN 90-70351-580, ISSN 1571-8859, Pp. 172, Price €55 (paperback, spiral bound). , 2006 .

[36]  M. Aribandi,et al.  Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium. , 2005, Australasian radiology.

[37]  Maria José Figueras,et al.  Atlas of clinical fungi. , 2005 .

[38]  T. Anke,et al.  Inhibition of inducible TNF-α expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale , 2004, Biological chemistry.

[39]  G. S. Hoog,et al.  Phylogeny and typification of Madurella mycetomatis, with a comparison of other agents of eumycetoma , 2004, Mycoses.

[40]  G. Sumbali,et al.  Production of extracellular keratinases by keratinophilic fungal species inhabiting feathers of living poultry birds (Gallus domesticus): A comparison , 1999, Mycopathologia.

[41]  J. Guarro,et al.  A new species of Achaetomium from Indian soil , 2004 .

[42]  J. Guarro,et al.  Invasive Mycotic Infections Caused by Chaetomium perlucidum, a New Agent of Cerebral Phaeohyphomycosis , 2003, Journal of Clinical Microbiology.

[43]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[44]  A. van Belkum,et al.  Environmental Occurrence of Madurella mycetomatis, the Major Agent of Human Eumycetoma in Sudan , 2002, Journal of Clinical Microbiology.

[45]  M. Rinaldi,et al.  Disseminated phaeohyphomycosis: review of an emerging mycosis. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[46]  Hattori,et al.  Case Report. Onychomycosis due to Chaetomium globosum successfully treated with itraconazole , 2000, Mycoses.

[47]  P. Godoy,et al.  Contamination of peritoneal dialysis fluid by filamentous fungi. , 1999, Revista iberoamericana de micologia.

[48]  G. S. Hoog,et al.  Variability and molecular diagnostics of the neurotropic species Cladophialophora bantiana , 1999 .

[49]  T. A. Hall,et al.  BIOEDIT: A USER-FRIENDLY BIOLOGICAL SEQUENCE ALIGNMENT EDITOR AND ANALYSIS PROGRAM FOR WINDOWS 95/98/ NT , 1999 .

[50]  K. Guppy,et al.  Cerebral fungal infections in the immunocompromised host: a literature review and a new pathogen--Chaetomium atrobrunneum: case report. , 1998, Neurosurgery.

[51]  Shunqiang Gao,et al.  First Case of Phaeohyphomycosis Caused by Chaetomium Murorum in China , 1995 .

[52]  M. Rinaldi,et al.  Fatal cerebral mycoses caused by the ascomycete Chaetomium strumarium , 1995, Journal of clinical microbiology.

[53]  H. Sandermann,et al.  A simple and efficient protocol for isolation of high molecular weight DNA from filamentous fungi, fruit bodies, and infected plant tissues. , 1992, Nucleic acids research.

[54]  Tsuneo Watanabe New Species of Oedocephalum and Papulaspora from Japanese Soils , 1991 .

[55]  R. Vilgalys,et al.  Rapid genetic identification and mapping of enzymatically amplified ribosomal DNA from several Cryptococcus species , 1990, Journal of bacteriology.

[56]  T. White Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics , 1990 .

[57]  P. Cannon A revision of Achaetomium, Achaetomiella and Subramaniula, and some similar species of Chaetomium , 1986 .

[58]  J. Guarro,et al.  The Ascomycete genus Chaetomium , 1986 .

[59]  J. A. Arx,et al.  A revaluation of Chaetomium and the Chaetomiaceae , 1984 .

[60]  M. Rinaldi,et al.  Opportunistic mycotic infection caused by chaetomium in a patient with acute leukemia , 1983, Cancer.

[61]  A. Carter,et al.  New and interesting Chaetomium species from East Africa , 1982 .

[62]  J. A. Arx,et al.  A new coprophilous Ascomycete from India , 1978 .

[63]  L. K. Weresub,et al.  On Papulaspora and bulbilliferous basidiomycetes Burgoa and Minimedusa , 1971 .

[64]  F. Mariat,et al.  Recherches sur la présence d'agents de mycétomes dans le sol et sur les épineux du Sénégal et de la Mauritanie. , 1968 .

[65]  A. Padhye,et al.  Isolation of Madurella mycetomi from soil in India. , 1968, Hindustan antibiotics bulletin.

[66]  J. Stevenson,et al.  A monograph of the Chaetomiaceae. , 1963 .

[67]  W. Whiteside Morphological Studies in the Chaetomiaceae. I , 1962 .

[68]  P. Abbott Mycetoma in the Sudan. , 1956, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[69]  L. Ajello The isolation of Aliescheria boydii shear, an etiologic agent of mycetomas, from soil. , 1952, The American journal of tropical medicine and hygiene.

[70]  J. Hotson Notes on Bulbiferous Fungi with a Key to Described Species , 1917, Botanical Gazette.