Legionella Human Health Criteria Document

Total Page:16

File Type:pdf, Size:1020Kb

Legionella Human Health Criteria Document United States Office of Science and Technology EPA-822-R-99-001 Environmental Protection Office of Water November 1999 Agency Washington, DC 20460 www.epa.gov Legionella: Human Health Criteria Document ACKNOWLEDGMENTS This document was prepared for the U. S. Environmental Protection Agency, Office of Ground Water and Drinking Water (OGWDW) by the Office of Science and Technology (OST) under contract with ICF Consulting Group (Contract No. 68-C6-0029). Overall planning and management for the preparation of this document was provided by Latisha S. Parker, MS of OST. EPA acknowledges the valuable contributions of those who reviewed this document. They include Lisa Almodovar MPH, Robin Oshiro, MS and Stephen Schaub, Ph.D. of the U.S. EPA. EPA also recognizess the following external peer reviewers for their excellent review and valuable comments on the draft document: Janette E. Stout Ph.D. and Paul H. Eldelstein M.D. TABLE OF CONTENTS I. Summary ............................................................................ I-1 II. General Information and Properties .......................................................II-1 A. History .......................................................................II-1 B. Taxonomy .....................................................................II-2 C. Microbiology, Morphology, and Ecology ............................................II-6 D. Symbiosis in Microorganisms .....................................................II-7 III. Occurrence ........................................................................ III-1 A. Worldwide Distribution ......................................................... III-1 B. Occurrence in Water ............................................................ III-9 1. Natural Surface Water ..................................................... III-9 2. Groundwater ........................................................... III-10 3. Man-Made Waters ...................................................... III-11 C. Occurrence in Soil ............................................................ III-19 D. Occurrence in Air ............................................................. III-20 E. Specific Disease Outbreaks ..................................................... III-21 1. Nosocomial Outbreaks ................................................... III-22 2. Outbreaks Among Travelers ............................................... III-22 3. Community Outbreaks ................................................... III-32 F. Environmental Factors Affecting Legionella Survival ................................. III-32 1. Symbiotic Microorganisms ................................................ III-32 2. Water Temperature ...................................................... III-35 3. Other Factors ........................................................... III-36 G. Summary ................................................................... III-37 IV. Health Effects in Animals .............................................................IV-1 A. Laboratory Studies .............................................................IV-1 B. Summary ....................................................................IV-4 V. Health Effects in Humans ............................................................. V-1 A. Symptoms and Clinical Manifestations ............................................. V-1 B. Clinical Laboratory Findings ..................................................... V-5 C. Mechanism of Action ........................................................... V-6 D. Immunity .................................................................... V-9 E. Chronic Conditions ............................................................ V-11 F. Treatment ................................................................... V-11 G. Summary ................................................................... V-14 VI. Risk Assessment ....................................................................VI-1 A. Hazard Identification ...........................................................VI-1 B. Dose-Response Information ......................................................VI-2 C. Potential for Human Exposure to Legionella .........................................VI-3 1. Prevalence of Legionella in the Environment ...................................VI-3 2. Mode of Transmission to Humans ...........................................VI-3 i D. Risk Factors ..................................................................VI-6 E. Quantification of Potential Health Effects ...........................................VI-9 F. Minimizing Risk ..............................................................VI-10 G. Summary ...................................................................VI-12 VII. Analysis and Treatment ............................................................. VII-1 A. Analysis of Samples ........................................................... VII-1 1. Collection of Legionella .................................................. VII-1 2. Detection of Legionella in Environmental and Biological Samples ................. VII-3 B. Disinfection as a Water Treatment Practice ......................................... VII-8 C. Summary .................................................................. VII-13 VIII. Research Requirements ............................................................VIII-1 IX. References .........................................................................IX-1 ii LIST OF FIGURES Figure III-1. Summary of Reported Cases of Legionellosis in the United States, 1984-1996 ..................................................... III-4 LIST OF TABLES Table II-1. Approved Legionella Species ..................................................II-3 Table III-1. Summary of Reported Cases of Legionellosis in the United States, 1984-1996 ..................................................... III-3 Table III-2. Legionnaires’ Disease in 24 European Countries in 1996 ............................ III-7 Table III-3. Occurrence of Legionella Bacteria in Potable Water Supplies and Distribution Systems ....................................................... III-12 Table III-4. Occurrence of Legionella Bacteria in Cooling Towers ............................. III-16 Table III-5. Occurrence of Legionellosis Outbreaks ......................................... III-23 Table V-1. Frequency of Symptoms of Legionnaires’ Disease ................................. V-3 Table V-2. Extrapulmonary Sites of Legionella Infection ..................................... V-4 Table V-3. Common Clinical Laboratory Findings in Patients with Legionnaires’ Disease ....................................................... V-5 Table V-4. Recommendations for Antibiotic Treatment of Legionnaires’ Disease ................. V-13 iii (this page intentionally left blank) iv I. Summary This document was prepared to update information in the Environmental Protection Agency’s (EPA) Drinking Water Criteria Document on Legionella (EPA 1985) and is intended to serve as an addendum to that report. Where appropriate, a summary of relevant information from the 1985 document is presented in each chapter of this addendum. For a more detailed description of information published before 1986, please refer to the 1985 document. This chapter presents a summary of the information contained in Chapters II through VII. Chapter VIII contains a discussion of research recommendations and Chapter IX lists references. Legionella bacteria are aerobic gram-negative rods associated with respiratory infections. Legionella pneumophila was first recognized as a disease entity from a pneumonia outbreak at a 1976 Convention of the American Legion in Philadelphia. Of the 42 known species of Legionella, 18 have been linked to pneumonia infections in humans. The species L. pneumophila (particularly serogroups 1-6) has been accepted as the principal cause of human outbreaks of legionellosis, which includes both legionnaires’ disease and Pontiac fever. Legionella are ubiquitous in natural aquatic environments, capable of existing in waters with varied temperatures, pH levels, and nutrient and oxygen contents. They can be found in groundwater as well as fresh and marine surface waters. Their widespread survival in nature can be attributed to their relationships with other microorganisms in the environment. Symbiotic existence with algae and other bacteria, particularly in biofilms, increases the availability of nutrients. They also are able to infect protozoans and subsequently reproduce within these organisms. These relationships provide protection against adverse environmental conditions, including standard water disinfection techniques. Consequently, Legionella are also prevalent in anthropogenic waters such as potable water, cooling tower reservoirs, and whirlpools. Aerosol-generating systems such as faucets, showerheads, cooling towers, and nebulizers aid in the transmission of Legionella from water to air. Human inhalation of contaminated aerosols leads to Legionella infections and disease outbreaks. Historically, many of the reported outbreaks were nosocomial (i.e., hospital- acquired), resulting from the adulteration of hospital potable water supplies, air conditioning systems, or cooling towers. Due to increased awareness of the disease, numerous community-acquired and travel-acquired outbreaks are now reported each year as well. However, most cases of legionnaires’ disease are sporadic (i.e., non-outbreak related) and are acquired
Recommended publications
  • Identification by 16S Ribosomal RNA Gene Sequencing of an Enterobacteriaceae Species from a Bone Marrow Transplant Recipient
    J Clin Pathol: Mol Pathol 2000;53:211–215 211 Identification by 16S ribosomal RNA gene sequencing of an Enterobacteriaceae species from Mol Path: first published as 10.1136/mp.53.4.211 on 1 August 2000. Downloaded from a bone marrow transplant recipient PCYWoo,PKLLeung, K W Leung, K Y Yuen Abstract with biochemical characteristics that do not fit Aims—To ascertain the clinical relevance into patterns of any known genus and species. of a strain of Enterobacteriaceae isolated Since the discovery of the polymerase chain from the stool of a bone marrow trans- reaction (PCR) and DNA sequencing, the plant recipient with diarrhoea. The isolate genomes of some bacteria have been se- could not be identified to the genus level quenced completely.1 A comparison of the by conventional phenotypic methods and genomic sequences of bacterial species showed required 16S ribosomal RNA (rRNA) gene that the 16S ribosomal RNA (rRNA) gene is sequencing for full identification. highly conserved within a species and among Methods—The isolate was investigated species of the same genus, and hence can be phenotypically by standard biochemical used as the new gold standard for the methods using conventional biochemical speciation of bacteria. Using this new standard, tests and two commercially available sys- phylogenetic trees based on base diVerences tems, the Vitek (GNI+) and API (20E) sys- between species are constructed; bacteria are tems. Genotypically, the 16S bacterial classified and re-classified into new genera;23 rRNA gene was amplified by the polymer- and classifications of non-cultivable micro- ase chain reaction (PCR) and sequenced.
    [Show full text]
  • NCTC) Bacterial Strain Equivalents to American Type Culture Collection (ATCC) Bacterial Strains
    This list shows National Collection of Type Cultures (NCTC) bacterial strain equivalents to American Type Culture Collection (ATCC) bacterial strains. NCTC Number CurrentName ATCC Number NCTC 7212 Acetobacter pasteurianus ATCC 23761 NCTC 10138 Acholeplasma axanthum ATCC 25176 NCTC 10171 Acholeplasma equifetale ATCC 29724 NCTC 10128 Acholeplasma granularum ATCC 19168 NCTC 10172 Acholeplasma hippikon ATCC 29725 NCTC 10116 Acholeplasma laidlawii ATCC 23206 NCTC 10134 Acholeplasma modicum ATCC 29102 NCTC 10188 Acholeplasma morum ATCC 33211 NCTC 10150 Acholeplasma oculi ATCC 27350 NCTC 10198 Acholeplasma parvum ATCC 29892 NCTC 8582 Achromobacter denitrificans ATCC 15173 NCTC 10309 Achromobacter metalcaligenes ATCC 17910 NCTC 10807 Achromobacter xylosoxidans subsp. xylosoxidans ATCC 27061 NCTC 10808 Achromobacter xylosoxidans subsp. xylosoxidans ATCC 17062 NCTC 10809 Achromobacter xylosoxidans subsp. xylosoxidans ATCC 27063 NCTC 12156 Acinetobacter baumannii ATCC 19606 NCTC 10303 Acinetobacter baumannii ATCC 17904 NCTC 7844 Acinetobacter calcoaceticus ATCC 15308 NCTC 12983 Acinetobacter calcoaceticus ATCC 23055 NCTC 8102 acinetobacter dna group 13 ATCC 17903 NCTC 10304 Acinetobacter genospecies 13 ATCC 17905 NCTC 10306 Acinetobacter haemolyticus ATCC 17907 NCTC 10305 Acinetobacter haemolyticus subsp haemolyticus ATCC 17906 NCTC 10308 Acinetobacter johnsonii ATCC 17909 NCTC 10307 Acinetobacter junii ATCC 17908 NCTC 5866 Acinetobacter lwoffii ATCC 15309 NCTC 12870 Actinobacillus delphinicola ATCC 700179 NCTC 8529 Actinobacillus equuli ATCC 19392
    [Show full text]
  • Legionella Shows a Diverse Secondary Metabolism Dependent on a Broad Spectrum Sfp-Type Phosphopantetheinyl Transferase
    Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase Nicholas J. Tobias1, Tilman Ahrendt1, Ursula Schell2, Melissa Miltenberger1, Hubert Hilbi2,3 and Helge B. Bode1,4 1 Fachbereich Biowissenschaften, Merck Stiftungsprofessur fu¨r Molekulare Biotechnologie, Goethe Universita¨t, Frankfurt am Main, Germany 2 Max von Pettenkofer Institute, Ludwig-Maximilians-Universita¨tMu¨nchen, Munich, Germany 3 Institute of Medical Microbiology, University of Zu¨rich, Zu¨rich, Switzerland 4 Buchmann Institute for Molecular Life Sciences, Goethe Universita¨t, Frankfurt am Main, Germany ABSTRACT Several members of the genus Legionella cause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella. Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs) that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis) and secondary metabolism (polyketide and non-ribosomal peptide synthesis). Using conserved active site motifs, we predict Submitted 29 June 2016 some novel compounds that are probably involved in cell-cell communication, Accepted 25 October 2016 Published 24 November 2016 differing to known communication systems.
    [Show full text]
  • Which Organisms Are Used for Anti-Biofouling Studies
    Table S1. Semi-systematic review raw data answering: Which organisms are used for anti-biofouling studies? Antifoulant Method Organism(s) Model Bacteria Type of Biofilm Source (Y if mentioned) Detection Method composite membranes E. coli ATCC25922 Y LIVE/DEAD baclight [1] stain S. aureus ATCC255923 composite membranes E. coli ATCC25922 Y colony counting [2] S. aureus RSKK 1009 graphene oxide Saccharomycetes colony counting [3] methyl p-hydroxybenzoate L. monocytogenes [4] potassium sorbate P. putida Y. enterocolitica A. hydrophila composite membranes E. coli Y FESEM [5] (unspecified/unique sample type) S. aureus (unspecified/unique sample type) K. pneumonia ATCC13883 P. aeruginosa BAA-1744 composite membranes E. coli Y SEM [6] (unspecified/unique sample type) S. aureus (unspecified/unique sample type) graphene oxide E. coli ATCC25922 Y colony counting [7] S. aureus ATCC9144 P. aeruginosa ATCCPAO1 composite membranes E. coli Y measuring flux [8] (unspecified/unique sample type) graphene oxide E. coli Y colony counting [9] (unspecified/unique SEM sample type) LIVE/DEAD baclight S. aureus stain (unspecified/unique sample type) modified membrane P. aeruginosa P60 Y DAPI [10] Bacillus sp. G-84 LIVE/DEAD baclight stain bacteriophages E. coli (K12) Y measuring flux [11] ATCC11303-B4 quorum quenching P. aeruginosa KCTC LIVE/DEAD baclight [12] 2513 stain modified membrane E. coli colony counting [13] (unspecified/unique colony counting sample type) measuring flux S. aureus (unspecified/unique sample type) modified membrane E. coli BW26437 Y measuring flux [14] graphene oxide Klebsiella colony counting [15] (unspecified/unique sample type) P. aeruginosa (unspecified/unique sample type) graphene oxide P. aeruginosa measuring flux [16] (unspecified/unique sample type) composite membranes E.
    [Show full text]
  • The Risk to Human Health from Free-Living Amoebae Interaction with Legionella in Drinking and Recycled Water Systems
    THE RISK TO HUMAN HEALTH FROM FREE-LIVING AMOEBAE INTERACTION WITH LEGIONELLA IN DRINKING AND RECYCLED WATER SYSTEMS Dissertation submitted by JACQUELINE MARIE THOMAS BACHELOR OF SCIENCE (HONOURS) AND BACHELOR OF ARTS, UNSW In partial fulfillment of the requirements for the award of DOCTOR OF PHILOSOPHY in ENVIRONMENTAL ENGINEERING SCHOOL OF CIVIL AND ENVIRONMENTAL ENGINEERING FACULTY OF ENGINEERING MAY 2012 SUPERVISORS Professor Nicholas Ashbolt Office of Research and Development United States Environmental Protection Agency Cincinnati, Ohio USA and School of Civil and Environmental Engineering Faculty of Engineering The University of New South Wales Sydney, Australia Professor Richard Stuetz School of Civil and Environmental Engineering Faculty of Engineering The University of New South Wales Sydney, Australia Doctor Torsten Thomas School of Biotechnology and Biomolecular Sciences Faculty of Science The University of New South Wales Sydney, Australia ORIGINALITY STATEMENT '1 hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom 1 have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged.' Signed ~ ............................
    [Show full text]
  • Diplomarbeit
    DIPLOMARBEIT Titel der Diplomarbeit Influence of wastewater composition and operational mode on the community structure of nitrifying bacteria in wastewater treatment plants angestrebter akademischer Grad Magister/Magistra der Naturwissenschaften (Mag. rer.nat.) Verfasserin / Verfasser: Anneliese Müller Matrikel-Nummer: 0107262 Studienrichtung (lt. Ökologie Studienblatt): Betreuerin / Betreuer: Univ.-Prof. Mag. Dr. Michael Wagner Wien, am 10.11.2008 Table of contents A. Introduction 1 A.1. Wastewater treatment plants and ecological theory 1 A.2. The global nitrogen cycle 1 A.2.1. Ammonia-oxidizing bacteria 3 A.2.2. Ammonia-oxidizing archaea 6 A.2.3. Nitrite-oxidizing bacteria 7 A.2.4. Anaerobic ammonia-oxidizing bacteria 9 A.3. Biological nitrogen removal during wastewater treatment 10 A.3.1. Different design of wastewater treatment plants 11 A.3.1.1. Conventional full-scale treatment plants 11 A.3.1.2. Sequencing Batch Reactors 12 A.3.1.3. Fixed / Fluidized bed reactors 12 A.3.1.4. Membrane bioreactors 13 A.3.2. Different operating strategies 13 A.3.3. Wastewater composition 16 A.3.4. The concept of diversity and stability 17 A.4. Aims of the study 19 B. Materials and Methods 20 B.1. Investigated wastewater treatment plants 20 B.1.1. Conventional full-scale wastewater treatment plants 21 B.1.1.1. Plattling 21 B.1.1.2. Kraftisried 21 B.1.1.3 Oberding 23 B.1.1.4. GZM TBA Lyss 23 B.1.1.5. ARA Lyss 24 B.1.2. Sequencing batch reactors 24 B.1.3.DIC-Sequencing Batch Reactors 25 B.2.
    [Show full text]
  • List of the Pathogens Intended to Be Controlled Under Section 18 B.E
    (Unofficial Translation) NOTIFICATION OF THE MINISTRY OF PUBLIC HEALTH RE: LIST OF THE PATHOGENS INTENDED TO BE CONTROLLED UNDER SECTION 18 B.E. 2561 (2018) By virtue of the provision pursuant to Section 5 paragraph one, Section 6 (1) and Section 18 of Pathogens and Animal Toxins Act, B.E. 2558 (2015), the Minister of Public Health, with the advice of the Pathogens and Animal Toxins Committee, has therefore issued this notification as follows: Clause 1 This notification is called “Notification of the Ministry of Public Health Re: list of the pathogens intended to be controlled under Section 18, B.E. 2561 (2018).” Clause 2 This Notification shall come into force as from the following date of its publication in the Government Gazette. Clause 3 The Notification of Ministry of Public Health Re: list of the pathogens intended to be controlled under Section 18, B.E. 2560 (2017) shall be cancelled. Clause 4 Define the pathogens codes and such codes shall have the following sequences: (1) English alphabets that used for indicating the type of pathogens are as follows: B stands for Bacteria F stands for fungus V stands for Virus P stands for Parasites T stands for Biological substances that are not Prion R stands for Prion (2) Pathogen risk group (3) Number indicating the sequence of each type of pathogens Clause 5 Pathogens intended to be controlled under Section 18, shall proceed as follows: (1) In the case of being the pathogens that are utilized and subjected to other law, such law shall be complied. (2) Apart from (1), the law on pathogens and animal toxin shall be complied.
    [Show full text]
  • Genetic and Functional Studies of the Mip Protein of Legionella
    t1.ì. Genetic and Functional Studies of the Mip Protein of Legionella Rodney Mark Ratcliff, BSc (Hons)' MASM Infectious Diseases Laboratories Institute of Medical and Veterinary Science and Department of Microbiology and Immunology UniversitY of Adelaide. Adelaide, South Australia A thesis submitted to the University of Adelaide for the degree of I)octor of Philosophy 15'h March 2000 amended 14th June 2000 Colonies of several Legionella strains on charcoal yeast extract agar (CYE) after 4 days incubation at 37"C in air. Various magnifications show typical ground-glass opalescent appearance. Some pure strains exhibit pleomorphic growth or colour. The top two photographs demonstrate typical red (LH) and blue-white (RH) fluorescence exhibited by some species when illuminated by a Woods (IJV) Lamp. * t Table of Contents .1 Chapter One: Introduction .1 Background .............'. .2 Morphology and TaxonomY J Legionellosis ............. 5 Mode of transmission "..'....'. 7 Environmental habitat 8 Interactions between Legionella and phagocytic hosts 9 Attachment 11 Engulfment and internalisation.'.. 13 Intracellular processing 13 Intracellular replication of legionellae .. " "' " "' 15 Host cell death and bacterial release 18 Virulence (the Genetic factors involved with intracellular multiplication and host cell killing .20 icm/dot system) Legiolysin .25 Msp (Znn* metaloprotease) ...'..... .25 .28 Lipopolysaccharide .29 The association of flagella with disease.. .30 Type IV fimbriae.... .31 Major outer membrane proteins....'.......'. JJ Heat shock proteins'.'. .34 Macrophage infectivity potentiator (Mip) protein Virulenceiraits of Legionella species other than L. pneumophila..........' .39 phylogeny .41 Chapter One (continued): Introduction to bacterial classification and .41 Identificati on of Legionella...'.,..'.. .46 Phylogeny .52 Methods of phylogenetic analysis' .53 Parsimony methods.'.. .55 Distance methods UPGMA cluster analYsis.'.'...
    [Show full text]
  • Electronic Laboratory Reporting Use Case January 2011
    ILLINOIS HEALTH INFORMATION EXCHANGE Electronic Laboratory Reporting Use Case Electronic Laboratory Reporting and Health Information Exchange Illinois Health Information Exchange Public Health Work Group January 2011 Electronic Laboratory Reporting Use Case January 2011 Table of Contents 1.0 Executive Summary……………………………………………………………………….3 2.0 Introduction…………………………………………………………………...……………..5 3.0 Scope……………………………………..………………………………………………………5 4.0 Use Case Stakeholders…………………………………………………………….….....6 5.0 Issues and Obstacles……………………………………………………………………...8 6.0 Use Case Pre-Conditions .………………….…………………………………………...8 7.0 Use Case Post-Conditions.……………………………………………………………...9 8.0 Detailed Scenarios/Technical Specifications.………………………………10 9.0 Validation and Certification………………………………………………………...12 Appendix ………………………………………………………………………………………….....13 Page 2 Electronic Laboratory Reporting Use Case January 2011 1.0 Executive Summary This Use Case is a product of the Public Health Work Group (PHWG) of the Illinois Health Information Exchange (HIE) Advisory Committee. The Illinois HIE Advisory Committee was constituted as the diverse public healthcare stakeholder body providing input and recommendations on the creation of the Illinois Health Information Exchange Authority (“the Authority”) as the Illinois vehicle for designing and implementing electronic health information exchange in Illinois. The establishment of the Authority marks the formal transition of the work of the HIE Advisory Committee and the Work Groups into alignment with the provisions of Illinois
    [Show full text]
  • Supplementary Information For: “Co-Occurrence of Enzyme Domains Guides the Discovery of an Oxazolone Synthetase” Tristan De Rond, Julia E
    Supplementary Information For: “Co-Occurrence of Enzyme Domains Guides the Discovery of an Oxazolone Synthetase” Tristan de Rond, Julia E. Asay and Bradley S. Moore Contents This document includes: 1 Supplementary Figures ................................................................................................................................................... 4 1.1 Figure S1: CO-ED network for E. coli K12 ................................................................................................................ 4 1.2 Figure S2: CO-ED network for S. coelicolor A2(3).................................................................................................... 5 1.3 Figure S3: CO-ED network for S. tropica CNB-440 .................................................................................................. 6 1.4 Figure S4: CO-ED network for P. fluorescens Pf-5 ................................................................................................... 7 1.5 Figure S5: CO-ED network for P. rubra DSM 6842 .................................................................................................. 8 1.6 Figure S6: Phylogeny of organisms that harbor oxzB ............................................................................................. 9 1.7 Figure S7: Color properties of the metabolic products of oxzAB .......................................................................... 10 1.8 Figure S8: Degradation of the metabolic products of oxzAB ...............................................................................
    [Show full text]
  • WO 2016/188962 Al 1 December 2016 (01.12.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/188962 Al 1 December 2016 (01.12.2016) P O P C T (51) International Patent Classification: (74) Agents: GOODFELLOW, Hugh Robin et al; Carpmaels C12Q 1/68 (2006.01) & Ransford LLP, One Southampton Row, London WC1B 5HA (GB). (21) International Application Number: PCT/EP2016/061599 (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (22) Date: International Filing AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 23 May 20 16 (23.05.2016) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (25) Filing Language: English DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (26) Publication Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, (30) Priority Data: MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, 1508860.2 22 May 2015 (22.05.2015) GB PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (71) Applicant: NATIONAL UNIVERSITY OF IRELAND, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. GALWAY [IE/IE]; University Road, Galway (IE). (84) Designated States (unless otherwise indicated, for every (72) Inventors: REDDINGTON, Kate Mary; Deerpack East, kind of regional protection available): ARIPO (BW, GH, Newport Road, Westport, Co.
    [Show full text]
  • Legionella Pneumophila
    Open Research Online The Open University’s repository of research publications and other research outputs Environmental regulation of the growth, physiology and virulence of Legionella pneumophila Thesis How to cite: Mauchline, William Stuart (1996). Environmental regulation of the growth, physiology and virulence of Legionella pneumophila. PhD thesis The Open University. For guidance on citations see FAQs. c 1995 The Author https://creativecommons.org/licenses/by-nc-nd/4.0/ Version: Version of Record Link(s) to article on publisher’s website: http://dx.doi.org/doi:10.21954/ou.ro.0000e0d1 Copyright and Moral Rights for the articles on this site are retained by the individual authors and/or other copyright owners. For more information on Open Research Online’s data policy on reuse of materials please consult the policies page. oro.open.ac.uk ENVIRONMENTAL REGULATION OF THE GROWTH, PHYSIOLOGY AND VIRULENCE OF LEGIONELLA PNEUMOPHILA. WILLIAM STUART MAUCHLINE A thesis submitted in partial fulfilment of the requirements of the Open University for the Degree of Doctor of Philosophy. The research presented in this thesis was undertaken at the Centre for Applied Microbiology and Research, Porton Down, Salisbury. Thames Water Utilities plc was the collaborating establishment. December 1995 APPENDECIES NOT SCANNED AT THE REQUEST OF THE AWARDING UNIVERSITY ABSTRACT Members of the Legionellaceae cause respiratory infections in man; the most severe, pneumonic form is known as Legionnaires' disease. Of the 39 species described to date 16 have been associated with human disease, however the majority of reported cases of legionellosis are caused by Legionella pneumophila serogroup 1. A number of pathogenic bacteria regulate their virulence gene expression in response to environmental stimuli.
    [Show full text]