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Contents
Preface xi 15
Viruses of Diarrhea 283
16 Arthropod-Borne and
Other Zoonotic Viruses 295
PART I
17 Rabies 319
Infection 1
L. Barth Reller, Megan E. Reller, and Kenneth J. Ryan 18
Retroviruses: Human T-Lymphotropic Virus,
Human Immunodeficiency Virus,
1 Infection—Basic Concepts 3 and Acquired Immunodeficiency
2 Immune Response to Infection 19 Syndrome 327
vii
30
Neisseria 567 46 The Opportunistic Fungi: Candida,
Aspergillus, the Zygomycetes, and
31
Haemophilus and Bordetella 583 Pneumocystis 771
32 Vibrio, Campylobacter, and Helicobacter 599 47 The Systemic Fungal Pathogens:
33 613
Enterobacteriaceae Cryptococcus, Histoplasma, Blastomyces,
787
Coccidioides, Paracoccidioides
34 645
Legionella and Coxiella
36
Plague and Other Bacterial
Pathogenic Parasites 803
Zoonotic Diseases 665 Paul Pottinger and Charles R. Sterling
AUTHORS
NAFEES AHMAD, PhD L. BARTH RELLER, MD
Professor of Immunobiology Professor of Pathology and Medicine
Director, Immunity and Infection Duke University School of Medicine
University of Arizona College of Medicine Durham, North Carolina
Tucson, Arizona
MEGAN E. RELLER, MD, PhD, MPH
J. ANDREW ALSPAUGH, MD Associate Professor of Medicine
Professor of Medicine, Molecular Genetics Duke University School of Medicine
and Microbiology Durham, North Carolina
Duke University School of Medicine
Durham, North Carolina CHARLES R. STERLING, PhD
Professor Emeritus
W. LAWRENCE DREW, MD, PhD School of Animal and Comparative
Emeritus Professor of Laboratory Biomedical Sciences
Medicine and Medicine University of Arizona
University of California, San Francisco Tucson, Arizona
School of Medicine
Mount Zion Medical Center SCOTT WEISSMAN, MD
San Francisco, California Associate Professor of Pediatrics
University of Washington School of
MICHAEL LAGUNOFF, PhD Medicine
Professor of Microbiology Seattle Children’s
University of Washington School of Seattle, Washington
Medicine
Seattle, Washington
PAUL POTTINGER, MD
Associate Professor of Medicine
Division of Allergy and Infectious Diseases
University of Washington School of
Medicine
Seattle, Washington
W
ith this seventh edition, Sherris Medical Microbiology will complete its fourth
decade. We are pleased to welcome new authors, Andy Alspaugh (mycology)
and Megan Reller (epidemiology) from Duke and Scott Weissman (bacteriology)
from the University of Washington. Sadly, George Ray a founding author and coeditor of the
last three editions is no longer with us (see Dedication). John Sherris, the founding editor,
continues to act as an inspiration to all of us.
BOOK STRUCTURE
The goal of Sherris 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 biol-
ogy, 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 Medi-
cal Microbiology, the emphasis is on the text narrative, which is designed to be read com-
prehensively, 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.
The back of the book includes two more review tools. Infectious Diseases: Syndromes
and Etiologies is a set of tables that brings together the infectious agents (viruses, bacteria,
fungi, parasites) discussed separately in Parts II through V as probable causes of the major
infection syndromes (pneumonia, arthritis, diarrhea, etc.). It is hoped these will be of value
when the student prepares for case discussion exercises or sees patients. The 100 Practice
Questions are in USMLE format and in addition to the ones at the end of earlier chapters.
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 sixth 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 a 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. Newspaper headlines now carry not only the new names of
emerging threats like Zika virus but also the antigenic formulas of more familiar pathogens
like E coli and influenza virus. Resistance to antimicrobial agents and the havoc created by
antivaccine movements are regular topics on the evening news. I1t is not all bad news. We
sense a new optimism that deeper scientific understanding of worldwide scourges like 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
Infection—Basic Concepts C H A P T ER 1
Immune Response to Infection C H A P T ER 2
Sterilization, Disinfection, and Infection Control C H A P T ER 3
Principles of Laboratory Diagnosis of Infectious Diseases C H A P T ER 4
Emerging and Reemerging Infectious Diseases: Emergence and Global Spread of Infection C H A P T ER 5
W
hen 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 vac-
cines and antimicrobial agents changed this (Figure 1–1), but only for the nations that could
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 sur-
passed infection as causes of premature death and those in which infection is still the leader.
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 immunode-
ficiency 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 Helicobacter pylori, 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? Finally, bioterrorist forces have unearthed two
previously controlled infectious diseases—anthrax and smallpox—and threatened their
distribution as agents of biological warfare. 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 introduc-
ing 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 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
*
Osler W. JAMA. 1896;26:999.
Public health
departments
1000
established Influenza pandemic
600
Diphtheria immunization (1940)
Chlorination
Penicillin usage (1945)
400 of water
Polio vaccine
Haemophllus influenzae
200 conjugate vaccine (1990)
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. 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 antimi-
crobial agents to counter these chemotherapeutic agents.
Microscopic
protozoa and
fungi, 4–10 µm
Classes of
organisms Bacteria
0.1–10 µm
Viruses
0.03–0.3 µm
The major classes of microorganisms in terms of ascending size and complexity are
viruses, bacteria, fungi, and parasites. Parasites exist as single or multicellular structures
with the same compartmentalized eukaryotic cell plan of our own cells including a nucleus
and cytoplasmic organelles like mitochondria. Fungi are also eukaryotic, but have a rigid
Increasing complexity: viruses →
external wall that makes them seem more like plants than animals. Bacteria also have a cell
bacteria → fungi → parasites
wall, but with a cell plan called “prokaryotic” that lacks the organelles of eukaryotic cells.
Viruses are not cells at all. They have a genome and some structural elements, but must take
over the machinery of another living cell (eukaryotic or prokaryotic) to replicate. The four
classes of infectious agents are summarized in Table 1–1, and generic examples of each are
shown in Figure 1–3.
VIRUSES
Viruses are strict intracellular parasites of other living cells, not only of mammalian and
plant cells, but also of simple unicellular organisms, including bacteria (the bacteriophages).
Viruses are simple forms of replicating, biologically active particles that carry genetic infor-
mation in either DNA or RNA molecules. Most mature viruses have a protein coat over Viruses contain little more than
their nucleic acid and, sometimes, a lipid surface membrane derived from the cell they DNA or RNA
infect. Because viruses lack the protein-synthesizing enzymes and structural apparatus nec-
essary for their own replication, they bear essentially no resemblance to a true eukaryotic
or prokaryotic cell.
Viruses replicate by using their own genes to direct the metabolic activities of the cell
they infect to bring about the synthesis and reassembly of their component parts. A cell
infected with a single viral particle may, thus, yield thousands of viral particles, which can
a
Parasitic cysts have cell walls.
b
A few bacteria grow only within cells.
c
The life cycle of some parasites includes intracellular multiplication.
Envelope
Spike
Capsid
Capsid
Nucleic acid
Nucleic acid
A
Plasma
Capsule Ribosomes Cell wall membrane
Nucleoid
Flagellum
Bud scar
Ribosomes
Mitochondrion
Endoplasmic
reticulum
Nucleus
Pellicle
Nucleolus
Cell wall
Cell membrane
Golgi apparatus
Water vacuole
Storage vacuole
Centrioles Centrioles
be assembled almost simultaneously under the direction of the viral nucleic acid. Infec-
tion of other cells by the newly formed viruses occurs either by seeding from or lysis of the Replication is by control of the
infected cells. Sometimes, viral and cell reproduction proceed simultaneously without cell host cell metabolic machinery
death, although cell physiology may be affected. The close association of the virus with the
cell sometimes results in the integration of viral nucleic acid into the functional nucleic Some integrate into the genome
acid of the cell, producing a latent infection that can be transmitted intact to the progeny
of the cell.
BACTERIA
Bacteria are the smallest (0.1-10 μm) independently living cells. They have a cytoplasmic
membrane surrounded by a cell wall; a unique interwoven polymer called peptidoglycan
makes the wall rigid. The simple prokaryotic cell plan includes no mitochondria, lysosomes,
endoplasmic reticulum, or other organelles (Table 1–2). In fact, most bacteria are approxi-
mately the size of mitochondria. Their cytoplasm contains only ribosomes and a single,
Smallest living cells
double-stranded DNA chromosome. Bacteria have no nucleus, but all the chemical ele-
ments of nucleic acid and protein synthesis are present. Although their nutritional require-
Prokaryotic cell plan lacks
ments vary greatly, most bacteria are free living if given an appropriate energy source. Tiny
nucleus and organelles
metabolic factories, they divide by binary fission and can be grown in artificial culture,
often in less than 1 day. The Archaea are similar to bacteria but evolutionarily distinct. They
are prokaryotic, but differ in the chemical structure of their cell walls and other features.
The Archaea (archebacteria) can live in environments humans consider hostile (eg, hot
springs, high salt areas) but are not associated with disease.
FUNGI
Fungi exist in either yeast or mold forms. The smallest of yeasts are similar in size to
bacteria, but most are larger (2-12 μm) and multiply by budding. Molds form tubular
extensions called hyphae, which, when linked together in a branched network, form
the fuzzy structure seen on neglected bread slices. Fungi are eukaryotic, and both yeasts Yeasts and molds are surrounded
and molds have a rigid external cell wall composed of their own unique polymers, by cell wall
called glucan, mannan, and chitin. Their genome may exist in a diploid or haploid state
and replicate by meiosis or simple mitosis. Most fungi are free living and widely distrib-
uted in nature. Generally, fungi grow more slowly than bacteria, although their growth
rates sometimes overlap.
PARASITES
Parasites are the most diverse of all microorganisms. They range from unicellular
amoebas of 10 to 12 μm to multicellular tapeworms 1 m long. The individual cell plan
is eukaryotic, but organisms such as worms are highly differentiated and have their own
Range from tiny amoebas to organ systems. Most worms have a microscopic egg or larval stage, and part of their life
meter-long worms cycle may involve multiple vertebrate and invertebrate hosts. Most parasites are free liv-
ing, but some depend on combinations of animal, arthropod, or crustacean hosts for their
survival.
Language: Finnish
Kirj.
Kaarlo Hemmo
Piimälasku ja kokkelpiimee.
Kosto kortinpelloojille.
Ku on nousuluonto.
Herrastuomar Pohata uus turkki.
Joka toeselle kuoppoo kaevaa — se siihe ite lankioo.
Herrastuomar Pohata emännän nimipäevät.
Ku nenästä vettää…
Ku emäntä ja isäntä virkoja vaehto.
"Lassilline arvo".
Suu soattaa suven rittaa, kielj kärpän nakkii —
Sitä mukkoo kuokitaa, ku ruokitaa.
Sumujärven pappi hammasleäkärinä.
Varotushuuto naemattomille ja leskmiehille karkausvuonna.
Ku lautamies tuomittii.
Kauppias Riston erreys.
Silli poes haesemasta.
Mattiina.
Ku kukoestus kuorestaa puhkes…
Sielun viholline pötk pakkoo…
Matkalla Ametriikkii…
Hermovikako vae "Vanha-Oatam"?
Myyränmäkeläeset sähkössä.
Ku minä ite — varastin.
Rotta, rotta — voe herra siunatkoo!…
Ku suutarjmestärj pelekäs — tulovaasa varkaaks.
Lukkari viisautta…
Hoppeeheät ja — vallankummous.
Syksyilla vietto vanahaa aekaa.
Ite pilas…
Mite kuokkavieraelle liehka annettii.
Kepakkala Rietu.
Parturi purk kauppasa.
"Liikemiehe" sotamuistelmija.
Ku kasvoja pitj laettoo.
Yöjalakalaeste vaennooja.
Läskine talv.
PIIMÄLASKU JA KOKKELPIIMEE.
Taloväe evväät olj iha toesta sorttia, uiinku entise paakari pullat
uunissa. Niillä olj suuressa vakkasessa voeta, isoja leipiä, jokkuu
kalakukko, pitkiä muekkuvutkakkeita, parissa piimälaskussa
kokkelpiimee ja vielä lisäks tattarjauhoja. Ja se piimä vasta ollii
piimee! Ei se tahtonna laskusta mahtuva tuoppii juoksemaa ilima
ettei puukolla söhinnä kokkelia pienemmiks. Ei ollunna ihme, että
sitä ryypätessä kuulu tavato ryssäys ja silimät tahto revetä. Ku siitä
ruvettii rueppoo tekemää, niin siinä käv semmoene rutkitus, ku
monella kirnulla oes yhtaekoo kirnuttu. Kyllä sitte passas täyvvellä
mahalla pitkällee heitäätyvä ja nukkuva tuhnahtoo ruuvva peälle!
Eikä pitkiä aekoja kulunakkaa, ennenku koko heinäväk kilipoo
kuorsas, niinku oes pellavia silivitty taekka liinoja roahnattu. Oljko
Suehkos-Antissa katteutta, sitä ei kukkaa tiijjä, voan erityisest se
eukkosa kansa näytti kahtoo tillistävä talon työväe herkkuja ja
syöntiä. Ja ku oma syömine peätty ja Antti rupes mahallee
pötköttämmää ja vetel savuja piipustaa, ei sitä unj ruvenna niin
imeläst paenamaa, ku toesia heinämiehiä. Ja jos koettas arvata,
mittee Antti siinä tuumail ja mietti, tekköö mielj arvelemmaa, että
jottae tämänlaesta sen aevokopassa kiertel:
— Niettu ponimaijjutsa.
— Suupaa naataa.
— Niettu, niettu.
Sillon yks puotmies läks sukkelana ku orava juoksemaa
kellarkerroksee sekä tuuvva roahas sieltä mahottoma suure
peällyksettömä lammasnahkase turkkirutmeijja. Tulos olj kuetennii
sama:
— Niettu, niettu.
Mut mittee pahhoo se suutarjpoeka sitte olj tehnä, että sille oekee
naesissa ja miehissä hammasta purtii? Lyhimmittäe sannoessa se tek
yöjalakalaesille kiusoo ja ilikeyttää — se tehtävä siihe olj männynnä
iha henkee ja verree. Ja sen keksimistaeto olj kerrassaa mittoomato.
Millon se laetto oven peälle vespyty semmoeste vehkeihe varraa,
että se yöjalakalaese ulostullessa kallistu ja kastel, niinku paemenet
kevväällä kastetaa, soattopa se pytty puota rumahtoo peähännii,
ikkääku satteevarjoks, vaekkei sitä kojetta ennee tarvinnakkaa, ku
kastumine olj jo tapahtunna. Märkänä ku uetettu koerra sae
yöjalakalaene tarsia kottiisa. Millon se toas, jos "vierustelijat" sattu
raskaast nukkuva tuhnahtammaa, ompel poekamiehe kenkäe
varresuut yhteen, niin että pitj paljae jaloe taekka sukkasillaa lähtee
lippaelemmaa ja vasta matkae peässä purkoo ompelukset varsista.
Ku toesen kerra kärsä käsk ja nenä neuvo, se ompel joko
peitevoattee tahikka tytön hammee poejja voatteisii kiin. Sen jäläkee
se nost ruminan, soahaksee yöjalakalaeset tavallista kiireemmäst
lähtemää. Sillon tietyst vieraat voatekappaleet tulj mukkaa ja jos
jonniimoesia kommelluksia synty. Ussei se myös salapas
yöjalakalaese tytön huoneesee, josta ei muehe peästämätä
peässynnä ies ätkähtämmää, ja sitte peästyvää sae häntä koepii
välissä luekkia tiehesä taekka kaeken muun hyvän peälle ottoo
potkut takapuolellee, mikä soapaskengästä annettuna ei ollenkaa
sokurille maestunna… Ja entäs tyttöparka? Sen pitj nörpällä nenin
tulla töehisä, jos ei sitä enne tehtynä käherryksiä hivuksii, ku
vanahempae tae isännän käs kävel karhuna sammalikossa: hattuutti
haevenista. Mut nämä tämmöeset vehkeelyt hankki suutarjpoejjalle
vihamiehiä ja niin paljo olj uhkauksia liikkeellä, ettei se uskaltanna
lähtee keskellä päeveekää ypöyksinää kylläe väliä kulukemaa.
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