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DEDICATION
John C. Sherris, M.D., 1921–2021
(Reproduced, with permission, from McAdam AJ. John C. Sherris, M.D, JClinMicrobiol 2012 Nov;50(11):3416–3417.)
John Sherris was one of the most respected and admired microbiologists of his time. Trained in London and Oxford he was recruited by the University of Washington School of Medicine in 1959 to develop clinical microbiology laboratories, research, and the first clinical microbiology postdoctoral training program (PhDs and MDs) outside the Center for Disease Control and Prevention (CDC). John’s best-known research accomplishment was leading the development and standardization of accurate yet practical antimicrobial susceptibility testing methods for pathogenic bacteria. The single disk diffusion technique was the most celebrated of these, but equally important were the underlying principles of interpreting individual bacterial strain results in relation to known pharmacologic and clinical data. These have turned out to be enduring. Even automated instruments, which now turn out results by the hundreds in a matter of hours, follow John’s rules. An excellent teacher, John’s motivation in developing this book was to strictly limit the text to material relevant to students of medicine and other health professions, and to explain it well. Stepping down as editor after the
second edition he remained involved until literally weeks before his death. John Sherris’ work and leadership have been recognized worldwide including presidency of the American Society for Microbiology, chair of the American Board of Medical Microbiology, and an honorary doctorate from Sweden’s Karolinska Institute (see reference below the portrait above for many more). Amid all this success John Sherris and his wife Elizabeth were the most kind, witty, and downright enjoyable people one could ever hope to know.
Kenneth J. Ryan
Contents
Contributors
Preface
PART I • Infection
L. Barth Reller , Megan E. Reller , Kenneth J. Ryan, and Gayatri Vedantam
1 Infection—Basic Concepts
2 Immune Response to Infection
3 Sterilization, Disinfection, and Infection Control
4 Principles of Laboratory Diagnosis of Infectious Diseases
5 Emerging and Reemerging Infectious Diseases: Emergence and Global Spread of Infection
PART II • Pathogenic Viruses
NafeesAhmadandW.LawrenceDrew
6 Viruses—Basic Concepts
7 Pathogenesis of Viral Infection
8 Antiviral Agents and Resistance
9 Respiratory Viruses
10 Viruses of Mumps, Measles, Rubella, and Other Childhood Exanthems
11 Poxviruses
12 Enteroviruses
13 Hepatitis Viruses
14 Herpesviruses
15 Viruses of Diarrhea
16 Arthropod-Borne and Other Zoonotic Viruses
17 Rabies
18 Human Retroviruses: HTLV, HIV, and AIDS
19 Papilloma and Polyoma Viruses
20 Persistent Viral Infections of the Central Nervous System
35 Pseudomonas and Other Opportunistic Gram-negative Bacilli
36 Plague and Other Bacterial Zoonotic Diseases
37 Spirochetes
38 Mycoplasma
39 Chlamydia
40 Rickettsia, Orientia, Ehrlichia, Anaplasma, and Bartonella
41 Dental and Periodontal Infections
PART IV • Pathogenic Fungi
J.AndrewAlspaughandJulieM.Steinbrink
42 Fungi—Basic Concepts
43 Pathogenesis and Diagnosis of Fungal Infections
44 Antifungal Agents and Resistance
45 The Superficial and Subcutaneous Fungi: Dermatophytes, Malassezia, Sporothrix, and Pigmented Molds
46 The Opportunistic Fungi: Candida, Aspergillus, the Zygomycetes, and Pneumocystis
47 The Systemic Fungal Pathogens: Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Paracoccidioides
PART V • Pathogenic Parasites
PaulPottingerandCharlesR.Sterling
48 Parasites—Basic Concepts
49 Pathogenesis and Diagnosis of Parasitic Infection
50 Antiparasitic Agents and Resistance
51 Apicomplexa and Microsporidia
52 Sarcomastigophora—The Amebas
53 Sarcomastigophora—The Flagellates
54 Intestinal Nematodes
55 Tissue Nematodes
56 Cestodes
57 Trematodes
PracticeQuestionsinUSMLEFormat
Index
Contributors
Editor
KENNETH J. RYAN, MD
Emeritus Professor of Pathology and Microbiology
University of Arizona College of Medicine
Tucson, Arizona
AUTHORS
NAFEES AHMAD, PhD
Professor of Immunobiology
Director, Immunity and Infection
University of Arizona College of Medicine
Tucson, Arizona
J. ANDREW ALSPAUGH, MD
Professor of Medicine, Molecular Genetics and Microbiology
Duke University School of Medicine
Durham, North Carolina
W. LAWRENCE DREW, MD, PhD
Emeritus Professor of Laboratory Medicine and Medicine
University of California, San Francisco School of Medicine
Mount Zion Medical Center
San Francisco, California
PAUL POTTINGER, MD
Associate Professor of Medicine
Division of Allergy and Infectious Diseases
University of Washington School of Medicine
Seattle, Washington
L. BARTH RELLER, MD
Professor of Pathology and Medicine
Duke University School of Medicine
Durham, North Carolina
MEGAN E. RELLER, MD, PhD, MPH
Associate Professor of Medicine
Duke University School of Medicine
Durham, North Carolina
JULIE M. STEINBRINK, MD
Assistant Professor of Medicine
Duke University School of Medicine
Durham, North Carolina
CHARLES R. STERLING, PhD
Professor Emeritus
School of Animal and Comparative Biomedical Sciences
University of Arizona
Tucson, Arizona
GAYATRI VEDANTAM, PhD
Professor
School of Animal and Comparative Biomedical Sciences
University of Arizona
Research Career Scientist, US Department of Veterans Affairs
Tucson, Arizona
SCOTT WEISSMAN, MD
Associate Professor of Pediatrics
University of Washington School of Medicine
Seattle Children’s
Seattle, Washington
Preface
With this eighth edition, SherrisMedicalMicrobiologywill enter its fifth decade as Sherris & Ryan’s Medical Microbiology. We are pleased to welcome new authors Julie M. Steinbrink and Gayatri Vedantam from Duke University and the University of Arizona. John Sherris, the founding editor, continues to act as an inspiration to all of us (see Dedication).
BOOK STRUCTURE
The goal of Sherris & Ryan’s Medical Microbiology remains unchanged from that of the first edition (1984). This book is intended to be the primary text for students of medicine and medical science who are encountering microbiology and infectious diseases for the first time. Part I opens with a chapter that explains the nature of infection and the infectious agents at the level of a general reader. The following four chapters give more detail on the immunologic, diagnostic, and epidemiologic nature of infection with minimal detail about the agents themselves. Parts II through V form the core of the text with chapters on the major viral, bacterial, fungal, and parasitic diseases, and each begins with its own chapters on basic biology, pathogenesis, and antimicrobial agents.
CHAPTER STRUCTURE
In the specific organism/disease chapters, the same presentation sequence is maintained throughout the book. First, features of the Organism (structure, metabolism, genetics, etc.) are described; then mechanisms of the Disease (epidemiology, pathogenesis, immunity) the organism causes are explained; the sequence concludes with the Clinical Aspects (manifestations, diagnosis, treatment, prevention) of these diseases. A clinical Case Study followed by questions in USMLE format concludes each of these chapters. In Sherris & Ryan’s Medical Microbiology, the emphasis is on the text narrative, which is designed to be read comprehensively, not as a reference work. Considerable effort has been made to supplement this text with other learning aids such as the above-
mentioned cases and questions as well as tables, photographs, and illustrations.
STUDENT-DRIVEN STUDY AIDS
This edition continues a number of new study aids first seen in the seventh edition. These were the product of a Student Advisory Group conceived and led by Laura Bricklin, MD then a second-year medical student at the University of Arizona College of Medicine. They include a boxed narrative OVERVIEW opening each diseaseoriented chapter or major section, highlighted MARGINAL NOTES judged to be “high yield” for USMLE Step 1 preparation, and bulleted lists of KEY CONCLUSIONS at the end of major sections. A THINK
→ APPLY feature randomly inserts thought-provoking questions into the body of the text, which are answered at the bottom of the page. These new features are explained in detail and illustrated on pages iv and v. Practice Questions in USMLE format are also included. In the online version of this book the case-based, and other USMLE type questions are presented independent of the narrative text.
For any textbook, dealing with the onslaught of new information is a major challenge. In this edition, much new material has been included, but to keep the student from being overwhelmed, older or less important information has been deleted to keep the size of this book no larger than of the seventh edition. As a rule of thumb, material on classic microbial structures, toxins, and the like in the Organism section has been trimmed unless its role is clearly explained in the Disease section. At the same time, we have tried not to eliminate detail to the point of becoming synoptic and uninteresting. Genetics is one of the greatest challenges in this regard. Without doubt this is where major progress is being made in understanding infectious diseases, but a coherent discussion may require using the names and abbreviations of genes, their products, and multiple regulators to tell the complete story. Whenever possible we have tried to tell the story without all the code language. We have also tried to fully describe the major genetic mechanisms in general chapters and then refer to them again when that mechanism is deployed by a pathogen. For example, Neisseria gonorrhoeae is
used to explain the genetic mechanisms for antigenic variation in a general chapter on bacterial pathogenesis (Chapter 22), but how it influences its disease, gonorrhea, is taken up with its genus Neisseria(Chapter 30).
A saving grace is that our topic is important, dynamic, and fascinating—not just to us but to the public at large. Newspapers, radio, television, and now social media reports of infectious diseases are now filled daily with details of the Covid-19 pandemic. Resistance to antimicrobial agents and the havoc created by antivaccine movements remain regular topics on the evening news. It is not all bad news. We sense a new optimism that deeper scientific understanding of worldwide scourges like Covid-19, HIV/AIDS, tuberculosis, and malaria will lead to their control. We are hopeful that the basis for understanding these changes is clearly laid out in the pages of this book.
Kenneth J. Ryan Editor
PART I Infection
L. Barth Reller • Megan E. Reller • Kenneth J. Ryan • Gayatri Vedantam
CHAPTER 1 Infection—Basic Concepts
CHAPTER 2 Immune Response to Infection
CHAPTER 3 Sterilization, Disinfection, and Infection Control
CHAPTER 4 Principles of Laboratory Diagnosis of Infectious Diseases
CHAPTER 5 Emerging and Reemerging Infectious Diseases: Emergence and Global Spread of Infection
When Sir William Osler, the great physician/humanist, wrote these words, fever (infection) was indeed the scourge of the world. Tuberculosis and other forms of pulmonary infection were the leading causes of premature death among the well-to-do and the less fortunate. The terror was due to the fact that, although some of the causes of infection were being discovered, little could be done to prevent or alter the course of disease. In the 20th century, advances in public sanitation and the development of vaccines and antimicrobial agents changed this (Figure 1–1), but only for the nations that can afford these interventions. As we move through the second decade of the 21st century, the world is divided into countries in which heart attacks, cancer, and stroke have surpassed infection as causes of premature death and those in which infection is still the leader. That is, unless there is a pandemic causing infection to again become the leading killer everywhere.
FIGURE 1–1. Death rates for infectious disease in the United States in the 20th century. Note the steady decline in death rates related to the introduction of public health, immunization, and antimicrobial interventions.
A new uneasiness that is part evolutionary, part discovery, and part diabolic has taken hold. Infectious agents once conquered have shown resistance to established therapy, such as multiresistant Mycobacterium tuberculosis, and diseases, such as acquired immunodeficiency syndrome (AIDS), have emerged. The spectrum of infection has widened, with discoveries that organisms earlier thought to be harmless can cause disease under certain circumstances. Who could have guessed that Helicobacterpylori, not even mentioned in the first edition of this book (1984), would be the major cause of gastric and duodenal ulcers and an officially declared carcinogen? Bioterrorist forces have unearthed two previously controlled infectious diseases—anthrax and smallpox and threatened their distribution as agents of biological warfare. Finally, our current COVID-19 pandemic caused by the emergence of a new member of the well-known Coronavirus genus threatens to become the leading killer, not just in a century but ever. For students of medicine,
understanding the fundamental basis of infectious diseases has more relevance than ever.
BACKGROUND
The science of medical microbiology dates back to the pioneering studies of Pasteur and Koch, who isolated specific agents and proved that they could cause disease by introducing the experimental method. The methods they developed lead to the first golden age of microbiology (1875-1910), when many bacterial diseases and the organisms responsible for them were defined. These efforts, combined with epidemiologic work begun by Semmelweis and Lister, which showed how these diseases spread, led to the great advances in public health that initiated the decline in disease and death. In the first half of the 20th century, scientists studied the structure, physiology, and genetics of microbes in detail and began to answer questions relating to the links between specific microbial properties and disease. By the end of the 20th century, the sciences of molecular biology, genetics, genomics, and proteomics extended these insights to the molecular level. Genetic advances have reached the point at which it is possible to know not only the genes involved but also to understand how they are regulated and mutated. The discoveries of penicillin by Fleming in 1929 and of sulfonamides by Domagk in 1935 opened the way to great developments in chemotherapy. These gradually extended from bacterial diseases to fungal, parasitic, and finally viral infections. Almost as quickly, virtually all categories of infectious agents developed resistance to all categories of antimicrobial agents to counter these chemotherapeutic agents.
• INFECTIOUS AGENTS: THE MICROBIAL WORLD
Microbes are small
Microbiology is a science defined by smallness. Its creation was made possible by the invention of the microscope (Gr. micro, small + skop, to look, see), which allowed visualization of structures too small to see with the naked eye. This definition of microbiology as the study of microscopic living forms still holds if one can accept that some organisms can reproduce only within other cells (eg, all viruses and some bacteria)
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Lowell, P., 174
Luck, rays of, 190
Lumber (in world building), 235, 243
Macroscopic survey, 154, 227, 299, 304
Man, 169, 178
Man-years, 180
Mars, 172
Mass, increase with velocity, 39, 50, 59
Mathematician, 161, 209, 337, 347
Matrix, 208
Matter, 1, 31, 156, 203, 248, 262
Maxwell, J. C., 8, 60, 156, 237
Measures of structure, 234, 268
Mechanical models, 209
Mechanics and Geometry, 137
Mendelian theory, 250
Mental state, 279
Metric, 142, 153
Metrical and non-metrical properties, 275
Michelson-Morley experiment, 5, 11
Microscopic analysis, reaction from, 103
Milky Way, 163
Miller, D. C., 5
Mind and matter, 259, 268, 278; selection by mind, 239, 243, 264
Mind-stuff, 276
Minkowski, H., 34, 53
Mirror, distortion by moving, 11
Models, 198, 209, 344
Molecular bombardment, 113, 131
Momentum, 153, 208, 223, 239, 262
Monomarks, 231
Moon, origin of, 171
Morley, E. W., 5
Motion, law of, 123
Multiplicationist, 86
Multiplicity of space and time frames, 20, 35, 61
Myself, 42, 53
Mysticism, defence of, 323; religious, 338
Nautical Almanac, 150
Nebulae, 165
Nebular observers, 9, 12
Neptune, 49
Neutral stuff, 280
Neutral wedge, 48
New quantum theory, 206
Newton, 111, 122, 201; quotation from, 111
Newtonian scheme, 4, 18, 125
Non-empty space, 127, 153, 238
Non-Euclidean geometry, 157
Nonsense, problem of, 344
Now-lines, 42, 47, 49, 184
Nucleus of atom, 3
Objectivity of “becoming”, 94; of a picture, 107
Observer, attributes of, 15, 337
Odds, 301, 303
Official scientific attitude, 286, 334
Operator, 208
Orbit jumps of electron, 191, 196, 205, 215, 300, 312
Organisation, 68, 70, 104
Ought, 345
Oxygen and vegetation, 174
’s and ’s, 208, 223, 327
Pacific Ocean, 171
Particle, 202, 211, 218
Past, relative and absolute, 48
Pedantry, 340, 342
Permanence, 241
Personal aspect of spiritual world, 337
Phoenix complex, 85
Photoelectric effect, 187
Photon, 190
Physical time, 40
Picture and paint, 106
Picture of gravitation, 115, 138, 157
Plan, Nature’s, 27
Planck, M., 185
Plurality of worlds, 169
Pointer readings, 251
Ponderomotive force, 237
Porosity of matter, 1
Potential (gravitational), 261
Potential energy, 213
Potential gradient, 96
Pound sterling, relativity of, 26
Predestination, 293, 303
Predictability of events, 147, 228, 300, 307
Primary law, 66, 75, 98; insufficiency of, 107
Primary scheme of physics, 76, 129, 295
Principal curvature, 120, 139
Principia, 4
Principle of Correspondence, 196
Principle of detailed balancing, 80
Principle of indeterminacy, 220, 306
Probability, 216, 315
Proof and plausibility, 337
Proper-distance, 25
Proper-time, 37
Proportion, sense of, 341
Proton, 3
Psi ( ), 216, 305
Pure mathematician, 161, 337, 347
Purpose, 105
-numbers, 208, 270
Quantum, 184; size of, 200
Quantum laws, 193
Quantum numbers, 191, 205
Quest of the absolute, 26, 122; of science, 110, 287; of reality, 328
Quotations from Boswell, 326
Brooke, Rupert, 317
Clifford, W. K., 278
Dickens, 32
Einstein, A., 294
Hegel, 147
Huxley, T. H., 173
Kronecker, L., 246
Lamb, H., 316
Lewis Carroll, 28, 291, 344
Milton, 167
Newton, 111
Nursery Rhymes, 64, 70, 262
Omar Khayyam, 64, 293
O’Shaughnessy, A., 325
Russell, Bertrand, 160, 278
Quotations from (cont.)
Shakespeare, 21, 39, 83, 292, 330
Swift, 341
Whitehead, A. N., 145
Radiation pressure, 58
Random element, 64; measurement of, 74
Reality, meaning of, 282, 326
Really true, 34
Rectification of curves, 125
Rejuvenescence, theories of, 85, 169
Relata and relations, 230
Relativity of velocity, 10, 54, 59, 61; of space-frames, 21; of magnetic field, 22; of distance, 25; of pound sterling, 26; of Now (simultaneity), 46, 61; of acceleration, 129; of standard of length, 143
Time in physics, 36; time lived (proper-time), 40; dual recognition of, 51, 100; time’s arrow, 69; infinity of, 83; summary of conclusions, 101; time-triangles, 133; reality of, 275
Time-scale in astronomy, 167
Touch, sense of, 273
Track, longest, 125, 135, 148
Trade Union of matter, 126
Transcendental laws, 245
Traveller, time lived by, 39, 126, 135
Triangles in space and time, 133
Tug of gravitation, 115, 122
Undoing, 65
Unhappening, 94, 108
Uniformity, basis of, 145
Unknowable entities, 221, 308
Utopia, 265
Values, 243, 330
Vegetation on Mars, 173
Velocity, relativity of, 10; upper limit to, 56
Velocity through aether, 30, 32
Velocity of light, 46, 54
Venus, 170
Victorian physicist, ideals of, 209, 259
View-point, 92, 283
Void, 13, 137
Volition, 310
Watertight compartments, 194
Wave-group, 213, 217, 225
Wave-length, measurement of, 24
Wave-mechanics, 211
Wave-theory of matter, 202
Wavicle, 201
Wells, H. G., 67
White dwarfs, 203
Whitehead, A. N., 145, 249
Whittaker, E. T., 181
Winding up of universe, 83
World building, 230
World-lines, 253
Worm, four-dimensional, 42, 87, 92
Wright, W. H., 172
Wrong frames of reference, 116
X (Mr.), 262, 268
TRANSCRIBER’S NOTES
On page 32, the reference to Einstein has been replaced by Dickens as shown in the Index. This quote appears in “Martin Chuzzlewit” published in 1843.
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