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--> 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 Avenue, NW Washington, DC 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 Engineering, 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 Engineering 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 Engineering. 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. 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. Includes index. ISBN 0-309-06332-9 1. Mice—Infections. 2. Rats—Infections. 3. Laboratory animals—Infections. 4. Mice as laboratory animals. 5. Rats as laboratory animals. I. Institute of Laboratory Animal Resources (U.S.) Committee on Infectious Diseases of Mice and Rats. [DNLM: 1. Animals, Laboratory. 2. Communicable Diseases—veterinary. 3. Mice. 4. Rats. QY 60.R6 I43] SF996.5.I54 1990 636'.93233—dc20 DNLM/DLC for Library of Congress 90-6152 CIP Copyright © 1991 by the National Academy of Sciences 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 official use by the United States Government. Printed in the United States of America First Printing, May 1991 Second Printing, May 1997 Third Printing, November 1998
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--> COMMITTEE ON INFECTIOUS DISEASES OF MICE AND RATS J. Russell Lindsey, Department of Comparative Medicine, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama (Chairman) 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., Division of Animal Medicine, University of Washington, Seattle, Washington Joseph E. Wagner, Veterinary Medical Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri Staff Dorothy D. Greenhouse, Senior Program Officer Bernadette M. Marriott, Staff Officer Sybil A. Paige, Administrative Secretary Thomas L. Wolfle, Director 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, University of Texas Southwestern Medical Center, Dallas, Texas (Chairman) June R. Aprille, Department of Biology, Tufts University, Medford, Massachusetts Melvin W. Balk, Charles River Laboratories, Inc., Washington, Massachusetts Douglas M. Bowden, Washington Regional Primate Research Center, University of Washington, Seattle, Washington Lester M. Crawford, Food Safety and Inspection Service, U. S. Department of Agriculture, Washington, D.C. Thomas J. Gill III, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Alan M. Goldberg, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland Jon W. Gordon, Department of Obstetrics and Gynecology, Mt. Sinai School of Medicine, New York, New York Margaret Z. Jones, Department of Pathology, Michigan State University, E. Lansing, Michigan Michael D. Kastello, Merck Sharp & Dohme, Rahway, New Jersey Robert H. Purcell, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland J. Wesley Robb, School of Medicine, University of Southern California, Los Angeles, California John L. VandeBerg, Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas Staff Thomas L. Wolfle, Director
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--> COMMISSION ON LIFE SCIENCES Bruce M. Alberts, University of California, San Francisco, California (Chairman) Bruce N. Ames, University of California, Berkeley, California Francisco J. Ayala, University of California, Irvine, California J. Michael Bishop, University of California Medical Center, San Francisco, California Michael T. Clegg, University of California, Riverside, California Glenn A. Crosby, Washington State University, Pullman, Washington Freeman J. Dyson, The Institute for Advanced Study, Princeton, New Jersey Leroy E. Hood, California Institute of Technology, Pasadena, California Donald F. Hornig, Harvard University School of Public Health, Boston, Massachusetts Ernest G. Jaworski, Monsanto Company, St. Louis, Missouri Marian E. Koshland, University of California, Berkeley, California Richard E. Lenski, University of California, Riverside, California Steven P. Pakes, Southwestern Medical Center, Dallas, Texas Emil A. Pfitzer, Hoffman-LaRoche, Inc., Nutley, New Jersey Joseph E. Rall, National Institutes of Health, Bethesda, Maryland Richard D. Remington, University of Iowa, Iowa City, Iowa Paul G. Risser, University of New Mexico, Albuquerque, New Mexico 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
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--> PREFACE Progress in biomedical science leads inexorably to greater refinements in scientific methodologies. In recent years it has become apparent that further refinement is needed in the quality of laboratory mice and rats. The scientific community has increasingly recognized that infectious diseases in these species significantly alter many research results. Unfortunately, the literature on this subject is voluminous, scattered, and often confusing, with the result that its practical application has been disappointing. Additional material on control of infections in immunodeficient rodents can be found in Immunodeficient Rodents: A Guide to Their Immunobiology, Husbandry, and Use, 1989, report of the Institute of Laboratory Animal Resources (ILAR) Committee on Immunologically Compromised Rodents (Washington, D.C.: National Academy Press. 246 pp.). This text is an expansion of the newly revised second edition of the Companion Guide to Infectious Diseases of Mice and Rats. It is intended to serve as a detailed reference of principles, methods, and facts to be applied by biomedical scientists in improving the quality of animals required in individual research settings. The expanded text is written for students of infectious disease and for investigators and veterinarians who want more detail than that contained in the companion guide. There are three main parts. Part I, "Principles of Rodent Disease Prevention," summarizes the basic concepts and practices of infectious disease exclusion and detection, and gives data on the prevalence of infectious agents in contemporary rodent populations. Part II, "Individual Disease Agents and Their Effects on
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--> Research," gives in a synoptic format the factual information deemed most pertinent to understanding the importance, epizootiology, pathogenesis, diagnosis, and control of natural infections due to each agent, complete with a listing of the known instances in which each agent has interfered with research. Part III, "Indexes to Diagnosis and Research Complications of Infectious Agents," contains tabular information intended for use as an aid to diagnostic problem solving. Many people have contributed to the compilation of the information in this report. The outlines in Part II were patterned after those in the first edition of the handbook, but have been extensively revised by one of us (J. R. L.) through many years of teaching a course on diseases of laboratory animals and have been further revised by this committee. The many contributions of the faculty and students in the Department of Comparative Medicine at the University of Alabama at Birmingham are gratefully acknowledged. In addition, the following gave invaluable advice on specific agents: Drs. Gail H. Cassell and Jerry K. Davis, University of Alabama at Birmingham (mycoplasmal infections); Dr. C. A. Bruggeman, Department of Medical Microbiology, State University of Limburg, Maastricht, The Netherlands (rat cytomegalovirus); Dr. Steven W. Barthold, Yale University (mouse hepatitis virus); Dr. Steven L. Vonderfecht, Johns Hopkins University (rat rotavirus-like agent); Dr. James R. Ganaway, National Institutes of Health, Bethesda, Md. (Bacillus piliformis); Dr. Anton M. Allen, National Institutes of Health, Bethesda, Md. (mousepox); and Dr. Lizbeth M. Kraft, National Aeronautics and Space Administration/Ames Research Center, Moffett Field, Calif. (poxviruses of rats). Dr. Kenneth Boschert, formerly a postdoctoral fellow at the University of Alabama at Birmingham, assisted with compiling information for the diagnostic indexes in Part III. Drs. Fred Quimby and Melvin Balk provided review at each stage of preparation for the ILAR Council. Special gratitude is due Ms. Doris Whatley and Ms. Audrey Farrow, who typed the manuscript through numerous revisions.
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--> CONTENTS I. Principles Of Rodent Disease Prevention 1.Objectives, Terminology, and Overview of Pathogen Status 3 Scientific Objectives 3 Infection Versus Disease 3 Terminology of Microbial and Pathogen Status 4 Pathogen Status of Contemporary Rodents 9 2.Breeding, Transportation, and Use of Pathogen-Free Rodents 13 3.Barrier Programs 17 Barrier Facilities 18 Barrier Rooms 18 Isolators as Barriers 19 Airflow Systems as Barriers 19 Barrier Cages 20 4.Health Surveillance Programs 21 Scientific Objectives 21 Agent Detection Objectives 22 Test Procedures 22 Sampling Strategies 25 Test Frequency 26 Sentinel Animals 27 Rodent Diagnostic Laboratories 27 II. Individual Disease Agents and Their Effects on Research 5.Introduction 31
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--> 6.Respiratory System 33 Overview 33 Sendai Virus 35 Mycoplasma pulmonis 42 Cilia-Associated Respiratory Bacillus 48 Streptococcus pneumoniae 50 Corynebacterium kutscheri 54 Rat Coronavirus 58 Pneumonia Virus of Mice 59 Mycobacterium avium-intracellulare 62 Pneumocystis carinii 64 Chlamydia trachomatis 69 Chlamydia psittaci 71 Klebsiella pneumoniae 72 Streptococcus pyogenes 75 Mycoplasma neurolyticum 77 Mycoplasma collis 80 K Virus 81 7.Digestive System 85 Overview 85 Mouse Cytomegalovirus 87 Rat Cytomegalovirus 91 Mouse Thymic Virus 94 Sialodacryoadenitis Virus 97 Mouse Hepatitis Virus 102 Mouse Rotavirus 111 Rat Rotavirus-Like Agent 116 Reovirus-3 118 Adenoviruses 123 Bacillus piliformis 126 Salmonella enteritidis 132 Citrobacter freundii (Biotype 4280) 139 Pseudomonas aeruginosa 141 Common Endoparasites 145 Spironucleus muris 146 Giardia muris 151 Hymenolepis nana (Dwarf Tapeworm) 154 Syphacia obvelata (Mouse Pinworm) and Syphacia muris (Rat Pinworm) 156 Aspicularis tetraptera 159 Entamoeba muris 160 Tritrichomonas muris 162 Other Endoparasites 163 8.Skin and Joints 164 Overview 164 Ectromelia Virus 165 Poxvirus(es) in Rats 171 Mycoplasma arthritidis 173 Streptobacillus moniliformis 176 Common Ectoparasites 179 Myobia musculi 179 Myocoptes musculinus and Radfordia affinis 182 Other Ectoparasites 182 Staphylococcus aureus 182 Dermatophytes 185 Pasteurella pneumotropica 187 Mouse Papule Virus 190 Mouse Mammary Tumor Virus 192 Self-Mutilation Associated with Otitis Media 195 Noninfectious Skin Conditions Important in Differential Diagnosis 195 Bite Wounds in Adult Mice and Rats 195 Bite Wounds in Weanling Mice 195 "Whisker Trimming," "Hair Nibbling," and "Barbering" 196 Muzzle Alopecia 197 Hair Growth Cycling Arrest 197 "Ringtail" 197 9.Hemopoietic System 198 Overview 198 Lymphocytic Choriomeningitis Virus 199 Lactic Dehydrogenase-Elevating Virus 205 Haemobartonella muris 211 Eperythrozoon coccoides 214 Murine Leukemia Viruses 217
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--> 10.Central Nervous System 222 Overview 222 Theiler's Virus 222 Encephalitozoon cuniculi 226 11.Genitourinary System 231 Overview 231 Leptospira interrogans serovar ballum 231 Mycoplasma muris 234 12.Multiple Systems 236 Overview 236 Kilham Rat Virus 236 H-1 Virus 240 Minute Virus of Mice 243 Polyoma Virus 247 Hantaviruses 251 III. Indexes to Diagnosis and Research Complications of Infectious Agents Introduction 259 Clinical Signs 260 Pathology 266 Research Complications 275 References 277 Index 387
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