DOCSLIB.ORG

Molecular Diagnosis of Invasive Fungal Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Molecular Diagnosis of Invasive Fungal Disease Molecular Diagnosis of Invasive Fungal Disease Rebecca Louise Gorton UCL Infection and Immunity I, Rebecca Louise Gorton, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 1 Acknowledgments Firstly, I would like to express my sincere gratitude to my Ph.D. supervisors Prof. Christopher Kibbler and Prof. Tim McHugh for their continuous support throughout my Ph.D. Thank you for the many years of patience, motivation, and guidance. Your commitment to my Ph.D. was ever present throughout my research and the last months whilst writing my thesis. Without your support this would not have been possible. I would like to thank Dr Lewis White, who throughout my Ph.D. was a source of collaboration and inspiration as an expert in the field of molecular mycology. To Dr Emmanuel Wey, thank you for believing in me over last few years of collaborative service development. I am looking forward to many more exciting years of research. My sincere thanks also go to Shila Seaton who was my laboratory trainer in Mycology and inspired me every day to be a Mycologist. I would also like to thank my fellow laboratory colleagues from the NHS laboratory and UCL Infection and Immunity research group. Thank you for the stimulating discussions, for the sleepless nights working together before deadlines, and for all the fun we have had in the last eight years. There are too many of you to name but I hope all of you know how grateful I am to you. Last but not the least, I would like to thank my best friend and my family: to Janet and Philip for whom words will never be able to express just how grateful and lucky I am to have you as my parents. To my sisters, brother, sisters-in-law, brothers-in law, nieces and nephews, you have all allowed me to be away from home for so many years pursuing my career as a Mycologist. Without your continued love and support I could not have achieved so much. To Michelle Cairns who travelled along the Ph.D. pathway with me and was an inspiration and my close friend throughout, I’m sure we will look back on this and smile in years to come. Finally to my partner Michael, for the endless cups of tea whilst writing my chapters through to sitting with me in the final hours before my submission deadline willing me to complete this thesis. You have all been my inspiration and compass throughout. 2 Abstract Background Invasive fungal infections (IFI) are opportunistic infections caused by yeast or filamentous fungi, typically presenting in immunocompromised patients (haemato- oncology, intensive care, HIV, solid organ transplant settings). This research aims to comprehensively evaluate molecular diagnostics to address the current shortfall in IFI diagnosis and, where appropriate, embed molecular methods into routine clinical service. Methods Molecular methodologies, including PCR, MALDI-TOF MS and PNA-FISH, were evaluated on clinical sample cohorts from the Royal Free Hospital NHS Foundation Trust. Each method was critically appraised for: statistical performance, clinical utility and suitability for service adoption. Results MALDI-TOF MS improved yeast agar culture identification, demonstrating 97.4% (185/190) concordance with ITS rRNA sequencing, and time to identification was significantly reduced (p<0.01, 24 hrs. v’s 15 mins). Lower identification rates of 66% (33/50) were observed when applying MALDI-TOF MS directly to blood culture for yeast identification. In contrast PNA-FISH identified 98.5% (93/96, CI: 91.2, 98.9) of yeasts direct from blood culture within 30 minutes. Using PCP PCR a 60% (3/5) increase in the detection of PCP from BAL in non-HIV patients was demonstrated compared with GMS staining. Overall sensitivity was 100% (95% CI: 56.6, 100) and specificity was 97.9% (95% CI: 88.9, 99.6) for the diagnosis of PCP. Aspergillus PCR demonstrated a sensitivity of 100% (95% CI: 34.2, 100) and specificity of 93.8% (95% CI: 86.4, 97.3) for the diagnosis of IA but a low PPV of 28.6% (95% CI: 8.2, 64.1). Conclusions Molecular diagnostic assays can improve the diagnosis of IFI through improved accuracy of identification and increased detection of fungal pathogens from specimens. Results must be interpreted alongside clinical presentation, as false positivity occurs utilising highly sensitive molecular assays. Dual biomarker strategies may improve the performance of molecular diagnostics but the associated impact on healthcare economics must also be considered 3 Table of contents Acknowledgments ............................................................................................... 2 Abstract ............................................................................................................... 3 Table of contents ................................................................................................. 4 Abbreviations .................................................................................................... 11 Table of figures .................................................................................................. 13 1. Chapter 1 Introduction ............................................................................. 18 1.1 Global incidence and mortality of invasive fungal disease .................................... 18 1.2 Overview of Invasive fungal infections in the United Kingdom ............................. 20 1.3 Overview of Antifungal drugs ............................................................................. 21 1.4 Guidelines for the definition, diagnosis and management of invasive fungal disease 24 1.5 Overview of Immunity to fungal infection ........................................................... 25 1.6 Invasive fungal infections ................................................................................... 27 1.7 Invasive Candidiasis ............................................................................................ 27 1.7.1 Epidemiology of invasive candidiasis................................................................... 28 1.7.2 Clinical presentation of invasive Candidiasis ....................................................... 31 1.7.3 Laboratory diagnosis of Invasive Candidiasis ...................................................... 32 1.8 Pneumocystis pneumonia (PCP) .......................................................................... 39 1.8.1 Epidemiology of P. jirovecii infection .................................................................. 40 1.8.2 Clinical presentation of PCP ................................................................................. 40 1.8.3 Radiological diagnosis of PCP .............................................................................. 41 1.8.4 Microscopy for the detection of P. jirovecii ........................................................ 42 1.8.5 Serological diagnosis of PCP – (1-3)-β-D-glucan .................................................. 45 1.8.6 PCR for the diagnosis of PCP ................................................................................ 45 1.8.7 Prophylaxis and treatment of PCP ....................................................................... 46 1.9 Invasive mould infection ..................................................................................... 47 1.10 Invasive Aspergillosis .......................................................................................... 48 1.10.1 Epidemiology of Invasive Aspergillosis ................................................................ 48 1.10.2 Clinical presentations of Invasive Aspergillosis ................................................... 49 1.10.3 Laboratory diagnosis of Invasive aspergillosis ..................................................... 50 1.10.4 Histopathology of tissue sections ........................................................................ 51 1.10.5 Microscopy and culture of Aspergillus sp from clinical specimens ..................... 52 1.10.6 Serological diagnosis of Aspergillosis .................................................................. 54 1.10.7 PCR for the diagnosis of Invasive Aspergillosis .................................................... 55 1.10.8 Prophylaxis and treatment of invasive aspergillosis ........................................... 56 1.11 Non-Aspergillus invasive mould infection ............................................................ 57 1.11.1 Epidemiology of non-Aspergillus invasive mould infection................................. 57 1.11.2 Clinical presentation of Non-Aspergillus invasive mould infection ..................... 59 1.11.3 Laboratory diagnosis of Non-Aspergillus invasive mould infection .................... 61 1.11.4 Microscopy for the detection of non-Aspergillus IFI ........................................... 61 1.11.5 Fungal culture ...................................................................................................... 61 1.11.6 PCR for the detection and identification of non-Aspergillus fungi ...................... 62 4 1.11.7 Antifungal therapy and management of non-Aspergillus invasive fungal infection 63 1.12 Molecular diagnostic tool box ............................................................................. 64 1.12.1 Parameters used to determine the performance of a diagnostic test ............... 64 1.12.2 Polymerase chain reaction (PCR) ........................................................................ 66 1.12.3 Matrix assisted laser desorption ionisation time
Load more

Recommended publications
  • Aspergillus Hydrophobins - Identification, Classification and Characterization
    Downloaded from orbit.dtu.dk on: Oct 09, 2021 Aspergillus hydrophobins - Identification, classification and characterization Jensen, Britt Guillaume Publication date: 2012 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Jensen, B. G. (2012). Aspergillus hydrophobins - Identification, classification and characterization. Department of Systems Biology, Technical University of Denmark. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Preface PhD Thesis Britt Guillaume Jensen I Aspergillus hydrophobins – Identification, classification and characterization Preface This thesis is submitted to the Technical University of Denmark and describes the results obtained during my PhD study. The work was carried out at the Center for Microbial Biotechnology (CMB) at the Department of Systems Biology from January 1st 2009 to March 1st 2012. The project was financed by the Technical University of Denmark. First and foremost, I would like to thank my main supervisor Kristian Fog Nielsen for excellent guidance, constructive criticism and interesting discussions.
    [Show full text]
  • Fungal Infections in HIV-Positive Peruvian Patients: Could the Venezuelan Migration Cause a Health Warning Related-Infectious Diseases?
    Moya-Salazar J, Salazar-Hernández R, Rojas-Zumaran V, Quispe WC. Fungal Infections in HIV-positive Peruvian Patients: Could the Venezuelan Migration Cause a Health Warning Related-infectious Diseases?. J Infectiology. 2019; 2(2): 3-10 Journal of Infectiology Journal of Infectiology Research Article Open Access Fungal Infections in HIV-positive Peruvian Patients: Could the Venezuelan Migration Cause a Health Warning Related-infectious Diseases? Jeel Moya-Salazar1,2*, Richard Salazar-Hernández3, Victor Rojas-Zumaran2, Wanda C. Quispe3 1School of Medicine, Faculties of Health Science, Universidad Privada Norbert Wiener, Lima, Peru 2Pathology Department, Hospital Nacional Docente Madre Niño San Bartolomé, Lima, Peru 3Cytopathology and Genetics Service, Department of Pathology, Hospital Nacional Guillermo Almenara Irigoyen, Lima, Peru Article Info Abstract Article Notes In patients with human immunodeficiency virus (HIV), opportunistic Received: December 22, 2018 infections occur that could compromise the health of patients. In order to Accepted: March 7, 2019 determine the frequency of fungal opportunistic and superficial infections *Correspondence: in HIV-positive men-who-have-sex-with-men (MSM) patients at the Hospital Jeel Moya-Salazar, M.T, M.Sc., 957 Pacific Street, Urb. Sn Nacional Guillermo Almenara, we conducted a cross-sectional retrospective Felipe, 07 Lima, Lima 51001, Peru; Telephone No: +51 986- study. We include Peruvian patients >18 years-old, derived from infectious or 014-954; Email: [email protected]. gynecological offices, with or without antiretroviral treatment. © 2019 Moya-Salazar J. This article is distributed under the One hundred thirteen patients were enrolled (36.7±10, range: 21 to terms of the Creative Commons Attribution 4.0 International 68 years), which 46 (40.7%) has an opportunistic fungal infection, mainly License.
    [Show full text]
  • Histopathology of Important Fungal Infections
    Journal of Pathology of Nepal (2019) Vol. 9, 1490 - 1496 al Patholo Journal of linic gist C of of N n e o p ti a a l- u i 2 c 0 d o n s 1 s 0 a PATHOLOGY A m h t N a e K , p d of Nepal a l a M o R e d n i io ca it l A ib ss xh www.acpnepal.com oc g E iation Buildin Review Article Histopathology of important fungal infections – a summary Arnab Ghosh1, Dilasma Gharti Magar1, Sushma Thapa1, Niranjan Nayak2, OP Talwar1 1Department of Pathology, Manipal College of Medical Sciences, Pokhara, Nepal. 2Department of Microbiology, Manipal College of Medical Sciences , Pokhara, Nepal. ABSTRACT Keywords: Fungus; Fungal infections due to pathogenic or opportunistic fungi may be superficial, cutaneous, subcutaneous Mycosis; and systemic. With the upsurge of at risk population systemic fungal infections are increasingly common. Opportunistic; Diagnosis of fungal infections may include several modalities including histopathology of affected tissue Systemic which reveal the morphology of fungi and tissue reaction. Fungi can be in yeast and / or hyphae forms and tissue reactions may range from minimal to acute or chronic granulomatous inflammation. Different fungi should be differentiated from each other as well as bacteria on the basis of morphology and also clinical correlation. Special stains like GMS and PAS are helpful to identify fungi in tissue sections. INTRODUCTION Correspondence: Dr Arnab Ghosh, MD Fungal infections or mycoses may be caused by Department of Pathology, pathogenic fungi which infect healthy individuals or by Manipal College of Medical Sciences, Pokhara, Nepal.
    [Show full text]
  • A Review on Recent Diseases Caused by Microbes
    Journal of Applied & Environmental Microbiology, 2014, Vol. 2, No. 4, 106-115 Available online at http://pubs.sciepub.com/jaem/2/4/4 © Science and Education Publishing DOI:10.12691/jaem-2-4-4 A Review on Recent Diseases Caused by Microbes Smruti Ranjan Singh, Krishnamurthy N.B., Blessy Baby Mathew* Department of Biotechnology, Sapthagiri College of Engineering, Bangalore, India *Corresponding author: [email protected] Received May 03, 2014; Revised May 15, 2014; Accepted May 15, 2014 Abstract Microbes are called disease-causing microbes and can make humans, animals and plants sick by causing infection and disease. Disease-causing microbes can also be called pathogens, germs or bugs and are responsible for causing infectious diseases. Microorganisms are very diverse. They include all of the prokaryotes, namely the bacteria and archaea and various forms of eukaryotes, comprising the protozoa, fungi, algae, microscopic plants (green algae), and animals such as rotifers and planarians. Some microbiologists also classify viruses as microorganisms, but others consider these as nonliving. This review deals with the current status of disease causing microbes and the recent diseases which mostly went unnoticed. Keywords: microbes, disease causing microorganisms, algae, fungi Cite This Article: Smruti Ranjan Singh, Krishnamurthy N.B., and Blessy Baby Mathew, “A Review on Recent Diseases Caused by Microbes.” Journal of Applied & Environmental Microbiology, vol. 2, no. 4 (2014): 106-115. doi: 10.12691/jaem-2-4-4. microscopic organisms are found in both plants and animals as well as in the human body [2,3]. Mainly these 1. Introduction microbes cause different types of infectious diseases [2,4].
    [Show full text]
  • Recent Discovery of Heterocyclic Alkaloids from Marine-Derived Aspergillus Species
    marine drugs Review Recent Discovery of Heterocyclic Alkaloids from Marine-Derived Aspergillus Species Kuo Xu 1 , Xiao-Long Yuan 1, Chen Li 2,3 and Xiao-Dong Li 2,3,* 1 Tobacco Research Institute of Chinese Academy of Agricultural Sciences, Qingdao 266101, China; [email protected] (K.X.); [email protected] (X.-L.Y.) 2 Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; [email protected] 3 Key Laboratory of marine biotechnology in Universities of Shandong (Ludong University), School of Life Sciences, Ludong University, Yantai 264025, China * Correspondence: [email protected]; Tel.: +86-535-210-9018 Received: 27 December 2019; Accepted: 11 January 2020; Published: 14 January 2020 Abstract: Nitrogen heterocycles have drawn considerable attention due to of their significant biological activities. The marine fungi residing in extreme environments are among the richest sources of these basic nitrogen-containing secondary metabolites. As one of the most well-known universal groups of filamentous fungi, marine-derived Aspergillus species produce a large number of structurally unique heterocyclic alkaloids. This review attempts to provide a comprehensive summary of the structural diversity and biological activities of heterocyclic alkaloids that are produced by marine-derived Aspergillus species. Herein, a total of 130 such structures that were reported from the beginning of 2014 through the end of 2018 are included, and 75 references are cited in this review, which will benefit future drug development and innovation. Keywords: Aspergillus; metabolite; marine; alkaloid; biological activity 1. Introduction Heterocyclic alkaloids are one of the most challenging natural product classes to characterize, not only because of their structurally unique skeletons that arise from distinct amino acids, but also because of their potential bioactivities.
    [Show full text]
  • Fungal Infections (Mycoses): Dermatophytoses (Tinea, Ringworm)
    Editorial | Journal of Gandaki Medical College-Nepal Fungal Infections (Mycoses): Dermatophytoses (Tinea, Ringworm) Reddy KR Professor & Head Microbiology Department Gandaki Medical College & Teaching Hospital, Pokhara, Nepal Medical Mycology, a study of fungal epidemiology, ecology, pathogenesis, diagnosis, prevention and treatment in human beings, is a newly recognized discipline of biomedical sciences, advancing rapidly. Earlier, the fungi were believed to be mere contaminants, commensals or nonpathogenic agents but now these are commonly recognized as medically relevant organisms causing potentially fatal diseases. The discipline of medical mycology attained recognition as an independent medical speciality in the world sciences in 1910 when French dermatologist Journal of Raymond Jacques Adrien Sabouraud (1864 - 1936) published his seminal treatise Les Teignes. This monumental work was a comprehensive account of most of then GANDAKI known dermatophytes, which is still being referred by the mycologists. Thus he MEDICAL referred as the “Father of Medical Mycology”. COLLEGE- has laid down the foundation of the field of Medical Mycology. He has been aptly There are significant developments in treatment modalities of fungal infections NEPAL antifungal agent available. Nystatin was discovered in 1951 and subsequently and we have achieved new prospects. However, till 1950s there was no specific (J-GMC-N) amphotericin B was introduced in 1957 and was sanctioned for treatment of human beings. In the 1970s, the field was dominated by the azole derivatives. J-GMC-N | Volume 10 | Issue 01 developed to treat fungal infections. By the end of the 20th century, the fungi have Now this is the most active field of interest, where potential drugs are being January-June 2017 been reported to be developing drug resistance, especially among yeasts.
    [Show full text]
  • Lists of Names in Aspergillus and Teleomorphs As Proposed by Pitt and Taylor, Mycologia, 106: 1051-1062, 2014 (Doi: 10.3852/14-0
    Lists of names in Aspergillus and teleomorphs as proposed by Pitt and Taylor, Mycologia, 106: 1051-1062, 2014 (doi: 10.3852/14-060), based on retypification of Aspergillus with A. niger as type species John I. Pitt and John W. Taylor, CSIRO Food and Nutrition, North Ryde, NSW 2113, Australia and Dept of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA Preamble The lists below set out the nomenclature of Aspergillus and its teleomorphs as they would become on acceptance of a proposal published by Pitt and Taylor (2014) to change the type species of Aspergillus from A. glaucus to A. niger. The central points of the proposal by Pitt and Taylor (2014) are that retypification of Aspergillus on A. niger will make the classification of fungi with Aspergillus anamorphs: i) reflect the great phenotypic diversity in sexual morphology, physiology and ecology of the clades whose species have Aspergillus anamorphs; ii) respect the phylogenetic relationship of these clades to each other and to Penicillium; and iii) preserve the name Aspergillus for the clade that contains the greatest number of economically important species. Specifically, of the 11 teleomorph genera associated with Aspergillus anamorphs, the proposal of Pitt and Taylor (2014) maintains the three major teleomorph genera – Eurotium, Neosartorya and Emericella – together with Chaetosartorya, Hemicarpenteles, Sclerocleista and Warcupiella. Aspergillus is maintained for the important species used industrially and for manufacture of fermented foods, together with all species producing major mycotoxins. The teleomorph genera Fennellia, Petromyces, Neocarpenteles and Neopetromyces are synonymised with Aspergillus. The lists below are based on the List of “Names in Current Use” developed by Pitt and Samson (1993) and those listed in MycoBank (www.MycoBank.org), plus extensive scrutiny of papers publishing new species of Aspergillus and associated teleomorph genera as collected in Index of Fungi (1992-2104).
    [Show full text]
  • Essential Oils of Lamiaceae Family Plants As Antifungals
    biomolecules Review Essential Oils of Lamiaceae Family Plants as Antifungals Tomasz M. Karpi ´nski Department of Medical Microbiology, Pozna´nUniversity of Medical Sciences, Wieniawskiego 3, 61-712 Pozna´n,Poland; [email protected] or [email protected]; Tel.: +48-61-854-61-38 Received: 3 December 2019; Accepted: 6 January 2020; Published: 7 January 2020 Abstract: The incidence of fungal infections has been steadily increasing in recent years. Systemic mycoses are characterized by the highest mortality. At the same time, the frequency of infections caused by drug-resistant strains and new pathogens e.g., Candida auris increases. An alternative to medicines may be essential oils, which can have a broad antimicrobial spectrum. Rich in the essential oils are plants from the Lamiaceae family. In this review are presented antifungal activities of essential oils from 72 Lamiaceae plants. More than half of these have good activity (minimum inhibitory concentrations (MICs) < 1000 µg/mL) against fungi. The best activity (MICs < 100) have essential oils from some species of the genera Clinopodium, Lavandula, Mentha, Thymbra, and Thymus. In some cases were observed significant discrepancies between different studies. In the review are also shown the most important compounds of described essential oils. To the chemical components most commonly found as the main ingredients include β-caryophyllene (41 plants), linalool (27 plants), limonene (26), β-pinene (25), 1,8-cineole (22), carvacrol (21), α-pinene (21), p-cymene (20), γ-terpinene (20), and thymol (20). Keywords: Labiatae; fungi; Aspergillus; Cryptococcus; Penicillium; dermatophytes; β-caryophyllene; sesquiterpene; monoterpenes; minimal inhibitory concentration (MIC) 1. Introduction Fungal infections belong to the most often diseases of humans.
    [Show full text]
  • 207-219 44(4) 01.홍승범R.Fm
    한국균학회지 The Korean Journal of Mycology Review 일균일명 체계에 의한 국내 보고 Aspergillus, Penicillium, Talaromyces 속의 종 목록 정리 김현정 1† · 김정선 1† · 천규호 1 · 김대호 2 · 석순자 1 · 홍승범 1* 1국립농업과학원 농업미생물과 미생물은행(KACC), 2강원대학교 산림환경과학대학 산림환경보호학과 Species List of Aspergillus, Penicillium and Talaromyces in Korea, Based on ‘One Fungus One Name’ System 1† 1† 1 2 1 1 Hyeon-Jeong Kim , Jeong-Seon Kim , Kyu-Ho Cheon , Dae-Ho Kim , Soon-Ja Seok and Seung-Beom Hong * 1 Korean Agricultural Culture Collection, Agricultural Microbiology Division National Institute of Agricultural Science, Wanju 55365, Korea 2 Tree Pathology and Mycology Laboratory, Department of Forestry and Environmental Systems, Kangwon National University, Chun- cheon 24341, Korea ABSTRACT : Aspergillus, Penicillium, and their teleomorphic genera have a worldwide distribution and large economic impacts on human life. The names of species in the genera that have been reported in Korea are listed in this study. Fourteen species of Aspergillus, 4 of Eurotium, 8 of Neosartorya, 47 of Penicillium, and 5 of Talaromyces were included in the National List of Species of Korea, Ascomycota in 2015. Based on the taxonomic system of single name nomenclature on ICN (International Code of Nomenclature for algae, fungi, and plants), Aspergillus and its teleomorphic genera such as Neosartorya, Eurotium, and Emericella were named as Aspergillus and Penicillium, and its teleomorphic genera such as Eupenicillium and Talaromyces were named as Penicillium (subgenera Aspergilloides, Furcatum, and Penicillium) and Talaromyces (subgenus Biverticillium) in this study. In total, 77 species were added and the revised list contains 55 spp. of Aspergillus, 82 of Penicillium, and 18 of Talaromyces.
    [Show full text]
  • Duke University Dissertation Template
    Systematics, Phylogeography and Ecology of Elaphomycetaceae by Hannah Theresa Reynolds Department of Biology Duke University Date:_______________________ Approved: ___________________________ Rytas Vilgalys, Supervisor ___________________________ Marc Cubeta ___________________________ Katia Koelle ___________________________ François Lutzoni ___________________________ Paul Manos Dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biology in the Graduate School of Duke University 2011 iv ABSTRACTU Systematics, Phylogeography and Ecology of Elaphomycetaceae by Hannah Theresa Reynolds Department of Biology Duke University Date:_______________________ Approved: ___________________________ Rytas Vilgalys, Supervisor ___________________________ Marc Cubeta ___________________________ Katia Koelle ___________________________ François Lutzoni ___________________________ Paul Manos An abstract of a dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Biology in the Graduate School of Duke University 2011 Copyright by Hannah Theresa Reynolds 2011 Abstract This dissertation is an investigation of the systematics, phylogeography, and ecology of a globally distributed fungal family, the Elaphomycetaceae. In Chapter 1, we assess the literature on fungal phylogeography, reviewing large-scale phylogenetics studies and performing a meta-data analysis of fungal population genetics. In particular, we examined
    [Show full text]
  • Neglected Fungal Zoonoses: Hidden Threats to Man and Animals
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW Neglected fungal zoonoses: hidden threats to man and animals S. Seyedmousavi1,2,3, J. Guillot4, A. Tolooe5, P. E. Verweij2 and G. S. de Hoog6,7,8,9,10 1) Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, 2) Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands, 3) Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran, 4) Department of Parasitology- Mycology, Dynamyic Research Group, EnvA, UPEC, UPE, École Nationale Vétérinaire d’Alfort, Maisons-Alfort, France, 5) Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran, 6) CBS-KNAW Fungal Biodiversity Centre, Utrecht, 7) Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, Amsterdam, The Netherlands, 8) Peking University Health Science Center, Research Center for Medical Mycology, Beijing, 9) Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and 10) King Abdullaziz University, Jeddah, Saudi Arabia Abstract Zoonotic fungi can be naturally transmitted between animals and humans, and in some cases cause significant public health problems. A number of mycoses associated with zoonotic transmission are among the group of the most common fungal diseases, worldwide. It is, however, notable that some fungal diseases with zoonotic potential have lacked adequate attention in international public health efforts, leading to insufficient attention on their preventive strategies. This review aims to highlight some mycoses whose zoonotic potential received less attention, including infections caused by Talaromyces (Penicillium) marneffei, Lacazia loboi, Emmonsia spp., Basidiobolus ranarum, Conidiobolus spp.
    [Show full text]
  • Activities of Sordarins in Experimental Models of Candidiasis
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Dec. 2000, p. 3389–3394 Vol. 44, No. 12 0066-4804/00/$04.00ϩ0 Copyright © 2000, American Society for Microbiology. All Rights Reserved. Activities of Sordarins in Experimental Models of Candidiasis, Aspergillosis, and Pneumocystosis ANTONIO MARTINEZ, PABLO AVILES, ELENA JIMENEZ, JESUS CABALLERO, AND DOMINGO GARGALLO-VIOLA* Research Department, Glaxo Wellcome S.A., 28760 Tres Cantos, Madrid, Spain Received 9 March 2000/Returned for modification 16 July 2000/Accepted 9 September 2000 Sordarin derivatives represent a new class of antifungal agents that act as potent inhibitors of fungal protein synthesis and possess a broad spectrum of activity. The in vivo activity of GM193663 and GM237354 was studied in mouse models of disseminated candidiasis and aspergillosis and in a rat model of pneumocystosis. The pharmacokinetic behavior of both sordarin derivatives was studied in mice and rats. In all studies, compounds were administered by the subcutaneous route. After a subcutaneous dose of 50 mg/kg of body weight to mice, the maximum level in serum, area under the concentration-time curve, half-life, and clearance for GM193663 and GM237354 were 51.8 and 23 ␮g/ml, 79.5 and 46 ␮g ⅐ h/ml, 0.8 and 0.85 h, and 21 and 25 ml/h, respectively. Systemic candidiasis and aspergillosis were established in CD-1 male mice infected with Candida albicans or Aspergillus fumigatus. For systemic candidiasis, compounds were given three times per day for seven consecutive days at 15, 30, 60, or 120 mg/kg/day. GM193663 and GM237354 showed dose-related Downloaded from efficacy against C. albicans, with 50% effective doses, 1 month after infection, of 25.2 and 10.7 mg/kg/dose, respectively.
    [Show full text]