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COMPANION GUIDE TO INFECTIOUS DISEASES OF MICE AND RATS Committee on Infectious Diseases of Mice and Rats Institute of Laboratory Animal Resources Commission on Life Sciences National Research Council NATIONAL ACADEMY PRESS Washington, D. C. 1991

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NATIONAL ACADEMY PRESS 2101 CONSTITUTION AVE., N.W. WASHINGTON, D.C. 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, National Academy of Engineenng, and Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences. National Academy of Engineering, and Institute of Medicine. The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Frank Press is president of the National Academy of Sciences. The National Academy of Engineenng was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Robert M. White is president of the National Academy of Engineenng. The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and upon its own initiative to identify issues of medical care, research, and education. Dr. Samuel O. Thier is president of the Institute of Medicine. The National Research Council was established by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy's purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and National Academy of Engineering in the conduct of their services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Frank Press and Dr. Robert M. White are chairman and vice-chairman, respectively, of the National Research Council. This project was supported by the National Cancer Institute, National Institutes of Health, under contracts NO1-CM-57644 and NO1-CM-07316, administered by the Division of Cancer Treatment. Library of Congress Cataloging-in-Publication Data Companion guide to infectious diseases of mice and rats / Committee on Infectious Diseases of Mice and Rats, Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. p. cm. Includes bibliographical references. ISBN 0-309-04283-6 1. Mice-Infections. 2. Rats-Infections. 3. Laboratory animals-Infections. 4. Mice as laboratory animals. 5. Rats as laboratory animals. 1. Institute of Laboratory Animal Resources (U. S.). Committee on Infectious Diseases of Mice and Rats. II. Infectious diseases of mice and rats. SF996.5.C65 199 1 636'.93233-dc20 Copyright (D 1991 by the National Academy of Sciences 91- 10495 CIP No part of this book may be reproduced by any mechanical, photographic, or electronic process, or in the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher, except for the purposes of the official use of the U.S. government. Printed in the United States of America First Printing, May 1991 Second Printing, June 1991 Third Printing, November 1997

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COMMITTEE ON INFECTIOUS DISEASES OF MICE AND RATS J. Russell Lindsey (Chairman), Department of Comparative Medicine, Schools of Medicine and Dentistry, University of Alabama at Birmingham, and Birmingham Veterans Administration Medical Center Gary A. Boorman, Chemical Pathology Branch, Toxicological Research and Testing Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina Michael J. Collins, Jr., Animal Health Diagnostic Laboratory, NCI-Frederick Cancer Research Facility, Frederick, Maryland Chao-Kuang Hsu, Smith Kline Animal Health Products, West Chester, Pennsylvania Gerald L. Van Hoosier, Jr., Department of Comparative Medicine, University of Washington, Seattle Joseph E. Wagner, Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri-Columbia Staff Dorothy D. Greenhouse, Senior Program Officer The Institute of Laboratory Animal Resources (ILAR) was founded in 1952 under the auspices of the National Research Council. Its mission is to provide expert counsel to the federal government, the biomedical research community, and the public on the scientific, technological, and ethical use of laboratory animals within the context of the interests and mission of the National Academy of Sciences. ILAR "promotes the high-quality humane care of laboratory animals; the appropriate use of laboratory animals; and the exploration of alternatives in research, testing, and teaching.

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INSTITUTE OF LABORATORY ANIMAL RESOURCES COUNCIL Steven P. Pakes (Chairman), The University of Texas Southwestern Medical Center, Dallas June R. Aprille, Tufts University, Medford, Massachusetts Melvin W. Bank, Charles River Laboratories, Inc., Wilmington, Massachusetts Douglas M. Bowden, University of Washington, Seattle Lester M. Crawford, U.S. Department of Agriculture, Washington, D.C. Thomas J. Gill III, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Alan M. Goldberg, The Johns Hopkins University, Baltimore, Maryland Jon W. Gordon, Mt. Sinai School of Medicine, New York, New York Margaret Z. Jones, Michigan State University, East Lansing Michael D. Kastello, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey Robert H. Purcell, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland J. Wesley Robb, School of Medicine, University of Southern California, Los Angeles John L. VandeBerg, Southwest Foundation for Biomedical Research, San Antonio, Texas Staff Thomas L. Wolfle, Director COMMISSION ON LIFE SCIENCES Bruce M. Alberts (Chairman), University of California, San Francisco Bruce N. Ames, University of California, Berkeley Francisco J. Ayala, University of California, Irvine J. Michael Bishop, University of California Medical Center, San Francisco Michael T. Clegg, University of California, Riverside Glenn A. Crosby, Washington State University, Pullman Freeman J. Dyson, The Institute for Advanced Study, Princeton, New Jersey Leroy E. Hood, California Institute of Technology, Pasadena Donald F. Hornig, Harvard University School of Public Health, Boston, Massachusetts Marian E. Koshland, University of California, Berkeley Richard E. Lenski, University of California, Irvine Steven P. Fakes, The University of Texas Southwestern Medical Center, Dallas IV

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Emil A. Pfitzer, Hoffmann-LaRoche, Inc., Nutley, New Jersey Thomas D. Pollard, The Johns Hopkins University, Baltimore, Maryland Joseph E. Rall, National Institutes of Health, Bethesda, Maryland Richard D. Remington, University of Iowa, Iowa City Paul G. Risser, University of New Mexico, Albuquerque Harold M. Schmeck, Jr., Armonk, New York Richard B. Setlow, Brookhaven National Laboratory, Upton, New York Carla J. Shatz, Stanford University School of Medicine, Stanford, California Torsten N. Wiesel, Rockefeller University, New York, New York Staff John E. Burris, Executive Director v

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Preface This handbook is a companion to the volume Infectious Diseases of Mice and Rats. It summarizes the information in the longer text and is intended to serve as a guide for biomedical scientists and for veterinarians and others associated with an animal resources program to assist them in identifying infectious agents of mice and rats and determining the effect of these agents on their research. Like Infectious Diseases of Mice and Rats, the handbook is comprised of three parts: Part I, Principles of Rodent Disease Prevention, summarizes basic concepts and practices for detecting and excluding infectious diseases from animal facilities; Part II, Disease Agents, provides pertinent information on the epizootiology, pathogenesis, diagnosis, and control of infectious agents and the effects of these agents on research; and Part III, Diagnostic Indexes, contains tabular information intended as an aid to diagnostic problem solving. The committee extends its thanks to the staff of the Institute of Laboratory Animal Resources, which worked with the committee to summarize the information in infectious Diseases of Mice and Rats to produce this guide. J. Russell Lindsey, Chairman Committee on Infectious Diseases of Mice and Rats . . V11

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Contents PART I: PRINCIPLES OF RODENT DISEASE PREVENTION 1 Scientific Objectives 1 Infection Versus Disease 1 Terminology of Microbial and Pathogen Status 2 Commitment to Maintaining Pathogen-Free Status of Rodents 2 Health Surveillance Programs 3 Rodent Diagnostic Laboratories 6 References 7 PART II: DISEASE AGENTS Bacteria, Fungi, and Viruses 9 Adenoviruses 9 Bacillus piliformis 10 Cilia-Associated Respiratory Bacillus 12 Citrobacter freundii Biotype 4280 13 Corynebacterium kutscheri 14 Cytomegalovirus, Mouse 15 Ectromelia Virus 16 Encephalitozoon cuniculi 18 Hantaviruses 20 Hepatitis Virus, Mouse 21 H-1 Virus 24 Kilham Rat Virus 25 Lactic Dehydrogenase-Elevating Virus 26 Leukemia Viruses, Murine 28 Lymphocytic Choriomeningitis Virus 30 1X 9

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x CONTENTS Mammary Tumor Virus, Mouse 32 Minute Virus of Mice 33 Mycoplasmoarthritidis 35 Mycoplasma pulmonis 36 Pasteurella pneumotropica 38 Pneumocystis carinii 39 Pneumonia Virus of Mice 40 Polyomavirus 41 Pseudomonas aeruginosa 42 Reovirus-3 43 Rotavirus, Mouse 44 Salmonella enteritidis 45 Sendai Virus 47 Sialodacryoadenitis Virus 50 Staphylococcus aureus 51 Streptobacillus moniliformis 53 Streptococcus pneumoniae 54 Theiler's Murine Encephalomyelitis Virus 55 Thymic Virus, Mouse 56 Dermatophytes 57 Trichophyton spp. and Microsporum spp. 57 Common Ectoparasites 58 Myobia musculi 58 Myocoptes musculinus and Radfordia affinis 60 Other Ectoparasites 60 Endoparasites 61 Aspicularis tetraptera (Mouse Pinworm) 61 Entamoebamuris 61 Giardia muris 62 Hymenolepis nana 64 Spironucleus muris 65 Syphacia obvelata (Mouse Pinworm) and Syphacia muris (Rat Pinworm) 66 Trichomonas muris 67 Other Endoparasites 68 PART III: INDEXES TO DIAGNOSIS AND RESEARCH COMPLICATIONS OF INFECTIOUS AGENTS Introduction 70 Clinical Signs 71 Pathology 76 Research Complications 84 INDEX 70 87