BOOK
Mims' Medical Microbiology
Richard Goering | Hazel Dockrell | Mark Zuckerman | Ivan Roitt | Peter L. Chiodini
(2012)
Additional Information
Book Details
Abstract
Mims’ Microbiology makes it easy for you to learn the microbiology and basic immunology concepts you need to know for your courses and USMLE. Using a clinically relevant, systems-based approach, this popular medical textbook accessibly explains the microbiology of the agents that cause diseases and the diseases that affect individual organ systems. With lavish illustrations and straightforward, accessible explanations, Mims’ Microbiology makes this complex subject simple to understand and remember.
- Learn about infections in the context of major body systems and understand why these are environments in which microbes can establish themselves, flourish, and give rise to pathologic changes. This systems-based approach to microbiology employs integrated and case-based teaching that places the "bug parade" into a clinical context.
- Grasp and retain vital concepts easily thanks to a user-friendly color-coded format, succinct text, key concept boxes, and dynamic illustrations.
- Effectively review for problem-based courses with the help of chapter introductions and "Lessons in Microbiology" text boxes that highlight the clinical relevance of the material, offer easy access to key concepts, and provide valuable review tools.
- Approach microbiology by body system or by pathogen through an extensively cross-referenced "Pathogen Review" section.
- Access the complete contents online at studentconsult.com, along with downloadable illustrations…150 multiple choice review questions... "Pathogen Parade"...and many other features to enhance learning and retention.
- Enhance your learning and absorb complex information in an interactive, dynamic way with Pathogen Parade – a quickly searchable online glossary of viruses, bacteria, and fungi.
- Deepen your understanding of epidemiology and the important role it plays in providing evidence-based identification of key risk factors for disease and targets for preventive medicine. A completely re-written chapter on this topic keeps abreast of the very latest findings.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Mims’ Microbiology Medical | iii | ||
| Copyright | iv | ||
| Preface | v | ||
| Acknowledgements | vi | ||
| Contributors | vi | ||
| Student Consultants | vii | ||
| Contents | viii | ||
| A contemporary approach to microbiology | xi | ||
| Introduction | xi | ||
| Microbes and parasites | xi | ||
| The conventional distinction between ‘microbes’ and ‘parasites’ is essentially arbitrary | xi | ||
| The context for contemporary medical microbiology | xi | ||
| Host response is the outcome of the complex interplay between host and parasite | xi | ||
| Emerging or re-emerging diseases continue to pose new microbiologic problems | xi | ||
| Microbiology Past, Present and Future | xii | ||
| Infectious diseases are still killers in the resource-rich world | xii | ||
| Infectious diseases are a major problem in the resource-poor world, particularly in children | xii | ||
| Infections continue to emerge or re-emerge | xiii | ||
| Modern lifestyles and technical developments facilitate transmission of disease | xiii | ||
| What of the future? | xiii | ||
| The Approach Adopted in this Book | xiv | ||
| Section 1: The adversaries – microbes | 1 | ||
| Chapter 1: Microbes as parasites | 3 | ||
| The varieties of microbes | 3 | ||
| Prokaryotes and eukaryotes | 3 | ||
| All organisms other than viruses and prions are made up of cells | 3 | ||
| Bacteria are prokaryotes, all other organisms are eukaryotes | 3 | ||
| Gram-negative bacteria have an outer lipopolysaccharide-rich layer | 4 | ||
| Microparasites and macroparasites | 4 | ||
| Microparasites replicate within the host | 4 | ||
| Organisms that are small enough can live inside cells | 4 | ||
| Living inside or outside cells | 4 | ||
| Pathogens within cells are protected from many of the host's defence mechanisms | 4 | ||
| Living outside cells provides opportunities for growth, reproduction and dissemination | 4 | ||
| Systems of classification | 5 | ||
| Classification of bacteria and viruses | 5 | ||
| Correct identification of bacteria below the species level is often vital to differentiate pathogenic and non-pathogenic f ... | 5 | ||
| Classification of viruses departs even further from the binomial system | 6 | ||
| Classification assists diagnosis and the understanding of pathogenicity | 6 | ||
| Chapter 2: The bacteria | 7 | ||
| Structure | 7 | ||
| Bacteria are ‘prokaryotes’ and have a characteristic cellular organization | 7 | ||
| Bacteria are classified according to their cell wall as Gram-positive or Gram-negative | 7 | ||
| Many bacteria possess flagella | 8 | ||
| Pili are another form of bacterial surface projection | 8 | ||
| Nutrition | 9 | ||
| Bacteria obtain nutrients mainly by taking up smallmolecules across the cell wall | 9 | ||
| All pathogenic bacteria are heterotrophic | 9 | ||
| Growth and division | 10 | ||
| A bacterial cell must duplicate its genomic DNA before it can divide | 11 | ||
| Replication must be accurate | 11 | ||
| Cell division is preceded by genome segregation and septum formation | 11 | ||
| Bacterial growth and division are important targets for antimicrobial agents | 11 | ||
| Gene expression | 11 | ||
| Most genes are transcribed into messenger RNA (mRNA) | 12 | ||
| Transcription | 12 | ||
| Transcription is initiated at promoters | 12 | ||
| Transcription usually terminates at specific termination sites | 12 | ||
| mRNA transcripts often encode more than one protein in bacteria | 12 | ||
| Translation | 12 | ||
| Translation begins with formation of an initiation complex and terminates at a STOP codon | 12 | ||
| Transcription and translation are important targets for antimicrobial agents | 13 | ||
| Regulation of gene expression | 13 | ||
| Bacteria adapt to their environment by controlling gene expression | 13 | ||
| Expression of many virulence determinants by pathogenic bacteria is highly regulated | 13 | ||
| The most common way of altering gene expression is to change the amount of mRNA transcription | 13 | ||
| The principles of gene regulation in bacteria can be illustrated by the regulation of genes involved in sugar metabolism | 13 | ||
| Expression of bacterial virulence genes is often controlled by regulatory proteins | 13 | ||
| Many bacterial virulence genes are subject to positive regulation by ‘two-component regulators’ | 14 | ||
| Regulation of virulence genes often involves a cascade of activators | 15 | ||
| In some instances the pathogenic activity of bacteria specifically begins when cell numbers reach a certain threshold | 15 | ||
| Survival under adverse conditions | 16 | ||
| Some bacteria form endospores | 16 | ||
| Mobile genetic elements | 16 | ||
| Many bacteria possess small, independently replicating (extrachromosomal) nucleic acid molecules termed plasmids and bacte ... | 16 | ||
| Widespread use of antimicrobials has applied a strong selection pressure in favour of bacteria able to resist them | 16 | ||
| Plasmids can carry virulence genes | 16 | ||
| Plasmids are valuable tools for cloning and manipulating genes | 16 | ||
| Bacteriophages are bacterial viruses that can survive outside as well as inside the bacterial cell | 17 | ||
| Transposition | 17 | ||
| Insertion sequences are the smallest and simplest ‘jumping genes’ | 18 | ||
| Transposons are larger, more complex elements, which encode multiple genes | 18 | ||
| Mobile genetic elements promote a variety of DNA rearrangements which may have important clinical consequences | 20 | ||
| Other mobile elements also behave as portable cassettes of genetic information | 20 | ||
| Mutation and gene transfer | 20 | ||
| Mutation | 20 | ||
| Changes in the nucleotide sequence of DNA can occur spontaneously or under the influence of external agents | 20 | ||
| Bacterial cells are not defenceless against genetic damage | 21 | ||
| Bacterial DNA repair has provided a model for understanding similar, more complex processes in humans | 22 | ||
| Gene transfer and recombination | 22 | ||
| Transformation | 22 | ||
| Some bacteria can be transformed by DNA present in their environment | 22 | ||
| Transduction | 22 | ||
| Transduction involves the transfer of genetic material by infection with a bacteriophage | 22 | ||
| Conjugation | 22 | ||
| Conjugation is a type of bacterial ‘mating’ in which DNA is transferred from one bacterium to another | 22 | ||
| The genomics of medically important bacteria | 23 | ||
| Application of genomics facilitates identification | 24 | ||
| Various approaches to the detection and utilization of genomic sequence information exist | 24 | ||
| DNA microarrays provide a means for the ‘parallel processing’ of genomic information | 25 | ||
| At present, DNA microarrays are finding use in two main applications: identification of mutations and studies on gene expr ... | 25 | ||
| Major groups of bacteria | 26 | ||
| Chapter 3: The viruses | 27 | ||
| Viruses share some common structural features | 27 | ||
| The outer surface of the virus particle is the part that first makes contact with the membrane of the host cell | 27 | ||
| Infection of host cells | 27 | ||
| Virus particles enter the body of the host in many ways | 28 | ||
| Viruses show host specificity and usually infect only one or a restricted range of host species. The initial basis of spec ... | 28 | ||
| Once in the host's cytoplasm the virus is no longer infective | 28 | ||
| Replication | 29 | ||
| Viruses must first synthesize messenger RNA (mRNA) | 29 | ||
| RNA viruses produce mRNA by several different routes | 29 | ||
| Viral mRNA is then translated in the host cytoplasm to produce viral proteins | 29 | ||
| Viruses must also replicate their nucleic acid | 30 | ||
| Replication of viral DNA occurs in the host nucleus – except for poxviruses, where it takes place in the cytoplasm | 31 | ||
| The final stage of replication is assembly and release of new virus particles | 31 | ||
| Outcome of viral infection | 31 | ||
| Viral infections may cause cell lysis or be persistentor latent | 31 | ||
| Some viruses can ‘transform’ the host cell into a tumour or cancer cell | 31 | ||
| Tumour formation as a result of viral infection: direct and indirect mechanisms | 33 | ||
| Viral oncogenes have probably arisen from incorporation of host oncogenes into the viral genome during viral replication | 33 | ||
| Major groups of viruses | 33 | ||
| Chapter 4: The fungi | 37 | ||
| Major groups of disease-causing fungi | 37 | ||
| Importance of fungi in causing disease | 37 | ||
| Fungal pathogens can be classified on the basis of their growth forms or the type of infection they cause | 37 | ||
| Control of fungal infection | 38 | ||
| Chapter 5: The protozoa | 41 | ||
| Protozoa can infect all the major tissues and organs of the body | 41 | ||
| Protozoa have evolved many sophisticated strategies to avoid host responses | 41 | ||
| Protozoa use a variety of routes to infect humans | 41 | ||
| Chapter 6: The helminths and arthropods | 43 | ||
| The helminths | 43 | ||
| Transmission of helminths occurs in four distinct ways | 43 | ||
| The outer surfaces of helminths provide the primary host–parasite interface | 43 | ||
| Life cycles | 44 | ||
| Many helminths have complex life cycles | 44 | ||
| The larvae of flukes and tapeworms must pass through one or more intermediate hosts, but those of nematodes can develop to ... | 44 | ||
| Helminths and disease | 44 | ||
| Adult tapeworms are acquired by eating undercooked or raw meat containing larval stages | 44 | ||
| The most important flukes are those causing schistosomiasis | 44 | ||
| Certain nematodes that infect humans are highly specific; others are zoonoses | 45 | ||
| Survival of helminths in their hosts | 45 | ||
| The arthropods | 46 | ||
| Many arthropods feed on human blood and tissue fluids | 46 | ||
| Arthropod infestation carries the additional hazard of disease transmission | 46 | ||
| Chapter 7: Prions | 49 | ||
| ‘Rogue protein’ pathogenesis | 49 | ||
| Section 2: The adversaries–host defences | 65 | ||
| Chapter 9: The innate defences of the body | 67 | ||
| The body has both ‘innate’ and ‘adaptive’ immune defences | 67 | ||
| Defences against entry into the body | 67 | ||
| A variety of biochemical and physical barriers operate at the body surfaces | 67 | ||
| Defences once the microorganism penetrates the body | 68 | ||
| Two types of professional phagocyte | 68 | ||
| Macrophages are widespread throughout the tissues | 68 | ||
| Polymorphs possess a variety of enzyme-containing granules | 69 | ||
| Phagocytosis and killing | 71 | ||
| Phagocytes recognize pathogen-associated molecular patterns (PAMPs) | 71 | ||
| The phagocyte is activated through PAMP recognition | 71 | ||
| The internalized microbe is the target for a fearsome array of killing mechanisms | 71 | ||
| Phagocytes are mobilized and targeted onto the microorganism by chemotaxis | 73 | ||
| Activation of the complement system | 73 | ||
| Complement synergizes with phagocytic cells to produce an acute inflammatory response | 74 | ||
| C9 molecules form the ‘membrane attack complex’, which is involved in cell lysis | 74 | ||
| Acute phase proteins | 75 | ||
| Other extracellular antimicrobial factors | 77 | ||
| Interferons are a family of broad spectrum antiviral molecules | 77 | ||
| Extracellular killing | 78 | ||
| Natural killer cells attach to virally infected cells, allowing them to be differentiated from normal cells | 78 | ||
| Eosinophils act against large parasites | 79 | ||
| Chapter 10: Adaptive responses provide a ‘quantum leap’ in effective defence | 83 | ||
| The role of antibodies | 83 | ||
| The acute inflammatory response | 83 | ||
| Antibodies act as adaptors to focus acute inflammatory reactions | 83 | ||
| Antibody complexed with antigen activates complement through the ‘classical’ pathway | 85 | ||
| The acute inflammatory reaction can also be initiated by antibody bound to mast cells | 86 | ||
| Activation of phagocytic cells | 86 | ||
| Antigen–antibody complexes activate phagocytic cells | 86 | ||
| Blocking microbial reactions | 86 | ||
| Antibodies block microbial interactions by combining with one of the reacting molecules | 86 | ||
| The role of T lymphocytes | 86 | ||
| Defence against intracellular organisms | 86 | ||
| Most T lymphocytes bind to peptide derived from intracellular organisms complexed with major histocompatibility complex | 87 | ||
| T lymphocytes help macrophages kill intracellular parasites | 87 | ||
| Extracellular attack on large infectious agents | 89 | ||
| Defensive cells attack the antibody-coated surfaces of parasites | 89 | ||
| Local defences at mucosal surfaces | 90 | ||
| Larger parasites, such as nematodes, within the lumen of the gut pose special problems | 91 | ||
| A subset of T cells bearing γδ receptors dominates the mucosal epithelium | 91 | ||
| Chapter 11: The cellular basis of adaptive immune responses | 95 | ||
| B- and T-cell receptors | 98 | ||
| B and T cells can be distinguished by their surface markers | 98 | ||
| Each lymphocyte expresses an antigen receptor of unique specificity on its surface | 98 | ||
| Clonal expansion of lymphocytes | 98 | ||
| The role of memory cells | 99 | ||
| Vaccination depends upon secondary immune responses being bigger and brisker than primary responses | 99 | ||
| Stimulation of lymphocytes | 101 | ||
| T lymphocytes are activated by antigen presented on specialized cells | 101 | ||
| Some antigens stimulate B cells without the need for intervention by T lymphocytes | 101 | ||
| Antibody production frequently requires T-cell help | 102 | ||
| Cytokines | 102 | ||
| Cytokines are soluble intercellular communication factors in the immune response | 102 | ||
| Cytokine production helps to define T-helper subsets (cf. Table 10.2) | 102 | ||
| Regulatory mechanisms | 105 | ||
| Unlimited expansion of clones must be checked by regulatory mechanisms | 105 | ||
| Antibody itself has feedback potential | 106 | ||
| Immune responses can be controlled by regulatory T cells | 106 | ||
| Tolerance mechanisms | 106 | ||
| Tolerance mechanisms prevent immunologic self-reactivity | 106 | ||
| T cells are more readily tolerized than B cells at a given antigen concentration | 106 | ||
| Section 3: The conflicts | 109 | ||
| Chapter 12: Background to the infectious diseases | 111 | ||
| Microbes rapidly evolve characteristics that enable them to overcome the host's defences | 111 | ||
| Host–parasite relationships | 111 | ||
| The speed with which host adaptive responses can be mobilized is crucial | 111 | ||
| Adaptation by both host and parasite leads to a more stable balanced relationship | 114 | ||
| Causes of infectious diseases | 115 | ||
| More than 100 microbes commonly cause infection | 115 | ||
| Koch's postulates to identify the microbial causes of specific diseases | 116 | ||
| Conclusions about causation are now reached using enlightened common sense | 116 | ||
| Possible problems in assigning disease aetiology | 117 | ||
| The biologic response gradient | 117 | ||
| It is uncommon for a microbe to cause exactly the same disease in all infected individuals | 117 | ||
| Chapter 13: Entry, exit and transmission | 119 | ||
| Receptor molecules | 119 | ||
| Exit from the body | 119 | ||
| Sites of entry | 119 | ||
| Skin | 119 | ||
| Microorganisms gaining entry via the skin may cause a skin infection or infection elsewhere | 119 | ||
| Biting arthropods | 120 | ||
| The conjunctiva | 120 | ||
| Respiratory tract | 120 | ||
| Some microorganisms can overcome the respiratory tract's cleansing mechanisms | 120 | ||
| Interfering with cleansing mechanisms | 121 | ||
| Avoiding destruction by alveolar macrophages | 121 | ||
| Gastrointestinal tract | 121 | ||
| Some microorganisms can survive the intestine's defences of acid, mucus and enzymes | 121 | ||
| Crude mechanical devices for attachment | 123 | ||
| Mechanisms to counteract mucus, acids, enzymes and bile | 123 | ||
| Successful intestinal microbes must counteract or resist mucus, acids, enzymes and bile | 123 | ||
| Microbial exotoxin, endotoxin and protein absorption | 123 | ||
| Urogenital tract | 124 | ||
| Microorganisms gaining entry via the urogenital tract can spread easily from one part of the tract to another | 124 | ||
| Vaginal defences | 124 | ||
| Urethral and bladder defences | 124 | ||
| Mechanism of urinary tract invasion | 124 | ||
| Oropharynx | 125 | ||
| Microorganisms can invade the oropharynx when mucosal resistance is reduced | 125 | ||
| Oropharyngeal defences | 125 | ||
| Mechanisms of oropharyngeal invasion | 125 | ||
| Exit and transmission | 125 | ||
| Microorganisms have a variety of mechanisms toensure exit from the host and transmission | 125 | ||
| Number of microorganisms shed | 126 | ||
| Stability in the environment | 126 | ||
| Number of microorganisms required to infect a fresh host | 127 | ||
| Other factors affecting transmission | 127 | ||
| Types of transmission between humans | 127 | ||
| Transmission from the respiratory tract | 127 | ||
| Respiratory infections spread rapidly when people are crowded together indoors | 127 | ||
| Transmission from the gastrointestinal tract | 129 | ||
| Intestinal infection spreads easily if public health and hygiene are poor | 129 | ||
| Transmission from the urogenital tract | 129 | ||
| Urogenital tract infections are often sexually transmitted | 129 | ||
| Sexually transmitted infections (STIs) | 130 | ||
| Semen as a source of infection | 130 | ||
| Perinatal transmission | 130 | ||
| Transmission from the oropharynx | 130 | ||
| Oropharyngeal infections are often spread in saliva | 130 | ||
| Transmission from the skin | 131 | ||
| Skin can spread infection by shedding or direct contact | 131 | ||
| Shedding to the environment | 131 | ||
| Transmission in milk | 131 | ||
| Transmission from blood | 131 | ||
| Blood can spread infection via arthropods or needles | 131 | ||
| Vertical and horizontal transmission | 132 | ||
| Vertical transmission takes place between parents and their offspring | 132 | ||
| Transmission from animals | 132 | ||
| Humans and animals share a common susceptibility to certain pathogens | 132 | ||
| Invertebrate vectors | 133 | ||
| Insects, ticks and mites – the bloodsuckers – are the most important vectors spreading infection | 133 | ||
| Passive carriage | 133 | ||
| Biologic transmission | 133 | ||
| Other invertebrate vectors spread infection either passively or by acting as an intermediate host | 134 | ||
| Transmission from vertebrates | 134 | ||
| Many pathogens are transmitted directly to humans from vertebrate animals | 134 | ||
| Domestic pets or pests? | 135 | ||
| Chapter 14: Immune defences in action | 137 | ||
| Antimicrobial peptides protect the skin against invading bacteria | 137 | ||
| Complement | 137 | ||
| The alternative pathway and lectin binding pathways of complement activation are part of the early defence system | 137 | ||
| Acute phase proteins and pattern recognition receptors | 137 | ||
| C-reactive protein is an antibacterial agent produced by liver cells in response to cytokines | 137 | ||
| Macrophages can recognize bacteria as foreign using Toll-like receptors | 138 | ||
| Collectins and ficolins | 138 | ||
| Fever | 139 | ||
| It is probably unwise to generalize about the benefit or otherwise of fever | 139 | ||
| Natural killer cells | 139 | ||
| Natural killer cells are a rapid but non-specific means of controlling viral and other intracellular infections | 139 | ||
| Phagocytosis | 139 | ||
| Phagocytes engulf, kill and digest would-be parasites | 139 | ||
| Intracellular killing by phagocytes | 140 | ||
| Phagocytes kill organisms using either an oxidative or a non-oxidative mechanism | 140 | ||
| Oxidative killing | 140 | ||
| Oxidative killing involves the use of ROIs | 140 | ||
| The way in which ROIs actually kill microorganisms is controversial | 140 | ||
| Cytotoxic lipids prolong the activity of ROIs | 141 | ||
| Non-oxidative killing | 141 | ||
| Non-oxidative killing involves the use of the phagocyte's cytotoxic granules | 141 | ||
| Nitric oxide | 141 | ||
| Cytokines | 142 | ||
| Cytokines contribute to both infection control andinfection pathology | 142 | ||
| Interferons | 142 | ||
| IFNα and IFNβ constitute a major part of the early response to viruses | 143 | ||
| Other cytokines | 143 | ||
| TNFα production can be good or bad | 143 | ||
| Antibody-mediated immunity | 144 | ||
| Speed, amount and duration | 144 | ||
| Affinity | 145 | ||
| Antibody classes and subclasses (isotypes) | 145 | ||
| Blocking and neutralizing effects of antibody | 145 | ||
| Immobilization and agglutination | 145 | ||
| Lysis | 145 | ||
| Opsonization | 146 | ||
| Antibody-dependent cellular cytotoxicity | 146 | ||
| Cell-mediated immunity | 146 | ||
| T-cell immunity correlates with control of bacterial growth in leprosy | 146 | ||
| Further evidence for the protective effects of IFN γ | 146 | ||
| Cytokine signatures | 147 | ||
| Th17 T cells | 147 | ||
| Is a positive delayed-type hypersensitivity skin test an indicator of immunity? | 148 | ||
| Cytotoxic T lymphocytes kill by inducing ‘leaks’ in the target cell | 149 | ||
| Recovery from infection | 149 | ||
| Nutrition may have more subtle effects on immunity to infection | 151 | ||
| Chapter 15: Spread and replication | 153 | ||
| Features of surface and systemic infections | 154 | ||
| A variety of factors determine whether an infection is a surface or a systemic infection | 154 | ||
| In systemic infections, there is a stepwise invasion of different tissues of the body | 154 | ||
| Rapid replication is essential for surface infections | 155 | ||
| Mechanisms of spread through the body | 155 | ||
| Spread to lymph and blood | 155 | ||
| Invading microbes encounter a variety of defences on entering the body | 155 | ||
| Spread from blood | 156 | ||
| The fate of microorganisms in the blood depends upon whether they are free or associated with circulating cells | 156 | ||
| Each circulating microorganism invades characteristic target organs and tissues | 156 | ||
| Spread via nerves | 156 | ||
| Certain viruses spread via peripheral nerves from peripheral parts of the body to the central nervous system and vice versa | 156 | ||
| Spread via cerebrospinal fluid | 157 | ||
| Once microorganisms have crossed the blood–cerebrospinal barrier, they spread rapidly in the cerebrospinal fluid spaces | 157 | ||
| Spread via other routes | 157 | ||
| Rapid spread from one visceral organ to another can take place via the pleural or peritoneal cavity | 157 | ||
| Genetic determinants of spread and replication | 158 | ||
| The pathogenicity of a microorganism is determined by the interplay of a variety of factors | 158 | ||
| Genetic determinants in the host | 158 | ||
| The ability of a microorganism to infect and cause disease in a given host is influenced by the genetic constitution of the ... | 158 | ||
| Susceptibility often operates at the level of the immune response | 158 | ||
| Genetic determinants in the microbe | 158 | ||
| Virulence is often coded for by more than one microbial gene | 158 | ||
| Other factors affecting spread and replication | 159 | ||
| The brain can influence immune responses | 159 | ||
| Chapter 16: Parasite survival strategies and persistent infections | 163 | ||
| Strategies to evade natural non-adaptive defences such as the phagocyte | 163 | ||
| Strategies to evade adaptive defences | 163 | ||
| Strategies to evade adaptive defences are more sophisticated than those for evading innate defences | 163 | ||
| Parasite survival strategies | 164 | ||
| Viruses are particularly good at thwarting immune defences | 164 | ||
| Some microbes are able to persist in the host | 164 | ||
| Strategies for evading host defences cause a rapid ‘hit-and-run’ infection | 164 | ||
| Concealment of antigens | 165 | ||
| Remaining inside cells without their antigens being displayed on the surface prevents recognition | 165 | ||
| Colonizing privileged sites keeps the microbe out of reach of circulating lymphocytes | 165 | ||
| Mimicry sounds like a useful strategy, but does not prevent the host from making an antimicrobial response | 167 | ||
| Microbes can conceal themselves by taking up host molecules to cover their surface | 167 | ||
| Immune modulation | 167 | ||
| Infection during early embryonic life | 168 | ||
| Production of large quantities of microbial antigen or antigen–antibody complexes | 168 | ||
| Exploiting ‘gaps’ in the host's immune repertoire | 168 | ||
| Upsetting the balance between Th1 and Th2 responses | 168 | ||
| Regulatory T cells | 168 | ||
| Antigenic variation | 169 | ||
| The best known example of mutation is the influenza virus | 169 | ||
| The classic example of recombination involves influenza A virus | 169 | ||
| Gene switching was first demonstrated in African trypanosomes | 169 | ||
| Gene switching is thought to result in the relapsing persistent course of certain infections | 170 | ||
| Immunosuppression | 170 | ||
| Many virus infections cause a general temporary immunosuppression | 170 | ||
| Different microbes have different immunosuppressive effects | 171 | ||
| Certain microbe toxins are immunomodulators | 171 | ||
| Successful microbes often interfere with signalling between immune cells, with cytotoxic T-cell recognition or with host a ... | 172 | ||
| Some microbes interfere with the local expression of the immune response in tissues | 172 | ||
| Persistent infections | 173 | ||
| Persistent infections represent a failure of host defences | 173 | ||
| Latent infections can become patent | 174 | ||
| Reactivation of latent infections | 175 | ||
| Reactivation is clinically important in immunosuppressed individuals | 175 | ||
| It is useful to distinguish two stages in reactivation | 175 | ||
| Chapter 17: Pathologic consequences of infection | 179 | ||
| Pathology caused directly by microorganism | 179 | ||
| Direct effects may result from cell rupture, organ blockage or pressure effects | 179 | ||
| Exotoxins are a common cause of serious tissue damage, especially in bacterial infection | 179 | ||
| Inactivation of toxins without altering antigenicity results in successful vaccines | 180 | ||
| Mode of action of toxins and consequences | 180 | ||
| Bacteria may produce enzymes to promote their survival or spread | 182 | ||
| Toxins may damage or destroy cells and are then known as haemolysins | 182 | ||
| Toxins may enter cells and actively alter some of the metabolic machinery | 183 | ||
| Diphtheria toxin blocks protein synthesis | 183 | ||
| Cholera toxin results in massive loss of water from intestinal epithelial cells | 183 | ||
| Tetanus and botulinum toxins are among the most potent affecting nerve impulses | 183 | ||
| Toxins as magic bullets | 183 | ||
| Diarrhea | 183 | ||
| Diarrhea is an almost invariable result of intestinal infections | 183 | ||
| Pathologic activation of natural immune mechanisms | 183 | ||
| Overactivity can damage host tissues | 183 | ||
| Endotoxins are typically lipopolysaccharides | 184 | ||
| Endotoxin shock is usually associated with systemic spread of organisms | 185 | ||
| The cytokine most closely linked to disease is TNF | 186 | ||
| Complement is involved in several tissue-damaging reactions | 186 | ||
| Disseminated intravascular coagulation is a rare but serious feature of bacterial septicaemia | 187 | ||
| Mast cell degranulation in response to LPS is usually secondary to IgE antibody formation | 187 | ||
| Pathologic consequences of the immune response | 187 | ||
| Overreaction of the immune system is known as ‘hypersensitivity’ | 187 | ||
| Each of the four main types of hypersensitivity can be of microbial or non-microbial origin | 187 | ||
| Type I hypersensitivity | 187 | ||
| Allergic reactions are a feature of worm infections | 187 | ||
| Type II hypersensitivity | 187 | ||
| Type II reactions are mediated by antibodies to the infectious organism or autoantibodies | 187 | ||
| In blood-stage malaria, microbial antigens attach themselves to host cells | 187 | ||
| Antimyocardial antibody of group A β -haemolytic streptococcal infection is the classic autoantibody triggered by infectio ... | 187 | ||
| Type III hypersensitivity | 188 | ||
| Immune complexes cause disease when they become lodged in tissues or blood vessels | 188 | ||
| Occupational diseases associated with inhalation of fungi are the classic examples of immune complex deposition in the tis ... | 189 | ||
| Another well-known model of immune complex disease is serum sickness | 189 | ||
| Type IV hypersensitivity | 189 | ||
| Cell-mediated immune responses invariably cause some tissue destruction, which may be permanent | 189 | ||
| From the medical viewpoint, granuloma formation is the most important type IV response | 189 | ||
| The clinical features of schistosomiasis are produced by cell-mediated immunity | 190 | ||
| Antibodies can also cause enhancement of pathology, as in dengue | 191 | ||
| Skin Rashes | 191 | ||
| A variety of skin rashes have an immunologic origin | 191 | ||
| The SARS coronavirus caused lung immunopathology and T-cell loss | 191 | ||
| The hygiene hypothesis – are we too clean? | 192 | ||
| Viruses and cancer | 192 | ||
| Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukaemia/lymphoma | 192 | ||
| Epstein–Barr virus (EBV) is associated with nasopharyngeal carcinoma and lymphoma including post-transplant lymphoprolifer ... | 193 | ||
| Epstein–Barr virus is associated with Burkitt's lymphoma | 193 | ||
| Epstein–Barr virus is also associated with Hodgkin's lymphoma and lymphomas in immunosuppressed individuals | 193 | ||
| Certain human papillomavirus infections are associated with cervical cancer | 193 | ||
| Human papillomavirus infection is associated with squamous cell carcinoma of the skin | 194 | ||
| Hepatitis B and hepatitis C viruses are major causes of hepatocellular carcinoma | 194 | ||
| Several DNA viruses can transform cells in which they are unable to replicate | 194 | ||
| Kaposi's sarcoma is caused by HHV-8 | 195 | ||
| Bacteria associated with cancer | 195 | ||
| Section 4: Clinical manifestation and diagnosis of infections by body system | 197 | ||
| The Clinical Manifestations of Infection | 197 | ||
| Chapter 18: Upper respiratory tract infections | 199 | ||
| The upper and lower respiratory tracts form a continuum for infectious agents | 199 | ||
| Two useful generalizations can be made about upper and lower respiratory tract infections: | 199 | ||
| Rhinitis | 199 | ||
| Rhinoviruses and coronaviruses together cause more than 50% of colds | 199 | ||
| Common cold virus infections are diagnosed by clinical appearance | 199 | ||
| Treatment of the common cold is symptomatic | 200 | ||
| Pharyngitis and tonsillitis | 200 | ||
| About 70% of acute sore throats are caused by viruses | 200 | ||
| Cytomegalovirus infection | 201 | ||
| Cytomegalovirus can be transmitted by saliva, urine, blood, semen and cervical secretions | 201 | ||
| Cytomegalovirus infection is often asymptomatic, but can reactivate and cause disease when cell-mediated immunity (CMI) de ... | 201 | ||
| Cytomegalovirus infection can cause fetal malformations and pneumonia in immunodeficient patients | 204 | ||
| Antiviral treatment options in CMV infection | 204 | ||
| Prevention of CMV infection | 204 | ||
| Epstein–Barr virus infection | 204 | ||
| Epstein–Barr virus is transmitted in saliva | 204 | ||
| The clinical features of EBV infection are immunologically mediated | 205 | ||
| Epstein–Barr virus remains latent in a small proportion of B lymphocytes | 206 | ||
| Laboratory tests for diagnosing infectious mononucleosis should include viral capsid antigen IgM detection | 206 | ||
| Treatment of EBV infection is limited | 206 | ||
| Cancers associated with EBV | 206 | ||
| Epstein–Barr virus is closely associated with Burkitt's lymphoma in African children | 206 | ||
| Epstein–Barr virus is closely associated with other B-cell lymphomas in immunodeficient patients | 206 | ||
| Epstein–Barr virus infection is also closely associated with nasopharyngeal carcinoma | 207 | ||
| Bacterial infections | 207 | ||
| Complications of Strep. pyogenes infection | 207 | ||
| Complications of Strep. pyogenes throat infection include quinsy, scarlet fever, rheumatic fever, rheumatic heart disease ... | 207 | ||
| Diagnosis | 208 | ||
| A laboratory diagnosis is not generally necessary for pharyngitis and tonsillitis | 208 | ||
| Parotitis | 208 | ||
| Mumps virus is spread by airborne droplets and infects the salivary glands | 208 | ||
| Treatment and prevention | 208 | ||
| Otitis and sinusitis | 209 | ||
| Otitis and sinusitis can be caused by many viruses and a range of secondary bacterial invaders | 209 | ||
| Acute otitis media | 209 | ||
| Common causes of acute otitis media are viruses, Strep. pneumoniae and H. influenzae | 209 | ||
| Otitis externa | 209 | ||
| Causes of otitis externa are Staph. aureus , Candida albicans and Gram-negative opportunists | 209 | ||
| Acute sinusitis | 210 | ||
| Acute epiglottitis | 210 | ||
| Acute epiglottitis is generally due to H. influenzae capsular type B infection | 210 | ||
| Acute epiglottitis is an emergency and necessitates intubation and treatment with antibiotics | 210 | ||
| Oral cavity infections | 210 | ||
| Saliva flushes the mouth and contains a variety of antibacterial substances | 210 | ||
| Oral candidiasis | 211 | ||
| Changes in the oral flora produced by broad-spectrum antibiotics and impaired immunity predispose to thrush | 211 | ||
| Caries | 211 | ||
| In the USA and Western Europe, 80–90% of people are colonized by Streptococcus mutans , which causes dental caries | 211 | ||
| Periodontal disease | 211 | ||
| Actinomyces viscosus , Actinobacillus and Bacteroides spp. are commonly involved in periodontal disease | 211 | ||
| Chapter 19: Lower respiratory tract infections | 213 | ||
| Laryngitis and tracheitis | 213 | ||
| Parainfluenza viruses are common causes of laryngitis | 213 | ||
| Diphtheria | 213 | ||
| Diphtheria is caused by toxin-producing strains of Corynebacterium diphtheriae and can cause lifethreatening respiratory o ... | 213 | ||
| Diphtheria toxin can cause fatal heart failure and a polyneuritis | 213 | ||
| Diphtheria is managed by immediate treatment with antitoxin and antibiotic | 214 | ||
| Contacts may need chemoprophylaxis or immunization | 214 | ||
| Diphtheria is prevented by immunization | 214 | ||
| Whooping cough | 214 | ||
| Whooping cough is caused by the bacterium Bordetella pertussis | 214 | ||
| B. pertussis infection is associated with the production of a variety of toxic factors | 214 | ||
| Whooping cough is managed with supportive care and erythromycin | 215 | ||
| Whooping cough can be prevented by active immunization | 215 | ||
| Acute bronchitis | 215 | ||
| Acute bronchitis is an inflammatory condition of the tracheobronchial tree, usually due to infection | 215 | ||
| Acute exacerbations of chronic bronchitis | 216 | ||
| Infection is only one component of chronic bronchitis | 216 | ||
| Bronchiolitis | 216 | ||
| Around 75% of bronchiolitis presentations are caused by respiratory syncytial virus infection | 216 | ||
| Respiratory syncytial virus infection | 216 | ||
| Respiratory syncytial virus is the most important cause of bronchiolitis and pneumonia in infants | 216 | ||
| Respiratory syncytial virus infection can be particularly severe in young infants | 216 | ||
| The manifestations of RSV infection appear to have an immunopathologic basis | 216 | ||
| Respiratory syncytial virus RNA is detectable in throat swab specimens, and ribavirin is indicated for severe disease | 217 | ||
| Hantavirus pulmonary syndrome (HPS) | 217 | ||
| Pneumonia | 217 | ||
| Microorganisms reach the lungs by inhalation, aspiration or via the blood | 217 | ||
| The respiratory tract has a limited number of ways in which it can respond to infection | 217 | ||
| A wide range of microorganisms can cause pneumonia | 218 | ||
| Bacterial pneumonia | 218 | ||
| Streptococcus pneumoniae is the classic bacterial cause of acute community-acquired pneumonia | 218 | ||
| A variety of bacteria cause primary atypical pneumonia | 219 | ||
| Patients with pneumonia usually present feeling unwell and with a fever | 220 | ||
| Patients with pneumonia usually have shadows in one or more areas of the lung | 220 | ||
| Pneumonia is the most common cause of death from infection in the elderly | 220 | ||
| Sputum samples are best collected in the morning and before breakfast | 220 | ||
| The usual laboratory procedures on sputum specimens from patients with pneumonia are Gram stain and culture | 220 | ||
| Microbiologic diagnosis of atypical pneumonia is usually confirmed by serology | 221 | ||
| Pneumonia is treated with appropriate antimicrobial therapy | 221 | ||
| Prevention of pneumonia involves measures to minimize exposure, and pneumococcal immunization post-splenectomy and for tho ... | 221 | ||
| Viral pneumonia | 221 | ||
| Viruses can invade the lung from the bloodstream as well as directly from the respiratory tract | 221 | ||
| Parainfluenza virus infection | 221 | ||
| There are four types of parainfluenza viruses with differing clinical effects | 222 | ||
| Adenovirus infection | 223 | ||
| Adenoviruses cause about 5% of acute respiratory tract illness overall | 223 | ||
| Human metapneumovirus | 223 | ||
| Human bocavirus | 223 | ||
| Influenza virus infection | 223 | ||
| Influenza viruses are classic respiratory viruses and cause endemic, epidemic and pandemic influenza | 223 | ||
| There are three types of influenza virus: A, B and C | 223 | ||
| The influenza virus envelope has haemagglutinin and neuraminidase spikes | 223 | ||
| Influenza viruses undergo genetic change as they spread through the host species | 223 | ||
| Transmission of influenza is by droplet inhalation | 226 | ||
| Influenzal damage to the respiratory epithelium predisposes to secondary bacterial infection | 227 | ||
| Rarely, influenza causes CNS complications | 227 | ||
| During influenza epidemics a diagnosis can generally be made clinically | 227 | ||
| Vaccines and antiviral agents can be used to prevent influenza | 228 | ||
| Severe acute respiratory syndrome-associated coronavirus infection | 228 | ||
| Measles | 229 | ||
| Secondary bacterial pneumonia is a frequent complication of measles in developing countries | 229 | ||
| Antibiotics are needed for secondary bacterial complications of measles, but the disease can be prevented by immunization | 229 | ||
| Cytomegalovirus infection | 230 | ||
| Cytomegalovirus (CMV) infection can cause an interstitial pneumonitis in immunocompromised patients | 230 | ||
| Tuberculosis | 230 | ||
| Tuberculosis is one of the most serious infectious diseases of the resource-poor world | 230 | ||
| Tuberculosis is caused by Mycobacterium tuberculosis | 230 | ||
| The pathogenesis of tuberculosis depends upon the history of previous exposure to the organism | 231 | ||
| The CMI response helps to curb further spread of Mycobacterium tuberculosis | 231 | ||
| Tuberculosis illustrates the dual role of the immune response in infectious disease | 231 | ||
| Primary tuberculosis is often asymptomatic | 232 | ||
| Complications of Mycobacterium tuberculosis infection arise from local spread or dissemination | 232 | ||
| The Ziehl–Neelsen stain of sputum can provide a diagnosis of tuberculosis within 1 h, whereas culture can take 6 weeks | 232 | ||
| Specific antituberculosis drugs and prolonged therapy are needed to treat tuberculosis | 232 | ||
| Tuberculosis is prevented by improved social conditions, immunization and chemoprophylaxis | 233 | ||
| Cystic fibrosis | 233 | ||
| Individuals with cystic fibrosis are predisposed to develop lower respiratory tract infections | 233 | ||
| P. aeruginosa colonizes the lungs of almost all 15–20-year-olds with cystic fibrosis | 233 | ||
| Lung abscess | 233 | ||
| Lung abscesses usually contain a mixture of bacteria including anaerobes | 233 | ||
| Treatment of lung abscess should include an anti-anaerobic drug and last 2–4 months | 234 | ||
| Pleural effusion and empyema | 234 | ||
| Up to 50% of patients with pneumonia have a pleural effusion | 234 | ||
| Fungal infections | 234 | ||
| Aspergillus | 234 | ||
| Aspergillus can cause allergic bronchopulmonary aspergillosis, aspergilloma or disseminated aspergillosis | 234 | ||
| Pneumocystis jirovecii (formerly P. carinii) | 235 | ||
| Pneumocystis pneumonia is an important opportunistic infection in AIDS | 235 | ||
| Parasitic infections | 235 | ||
| A variety of parasites localize to the lung or involve the lung at some stage in their development | 235 | ||
| Chapter 20: Urinary tract infections | 237 | ||
| Acquisition and etiology | 237 | ||
| Bacterial infection is usually acquired by the ascending route from the urethra to the bladder | 237 | ||
| The Gram-negative rod Escherichia coli is the commonest cause of ascending UTI | 237 | ||
| Viral causes of UTI appear to be rare, although there are associations with haemorrhagic cystitis and other renal syndromes | 237 | ||
| Very few parasites cause UTIs | 238 | ||
| Pathogenesis | 238 | ||
| A variety of mechanical factors predispose to UTI | 238 | ||
| Pregnancy, prostatic hypertrophy, renal calculi, tumours and strictures are the main causes of obstruction to complete bla ... | 238 | ||
| Catheterization is a major predisposing factor for UTI | 239 | ||
| A variety of virulence factors are present in the causative organisms | 239 | ||
| The healthy urinary tract is resistant to bacterial colonization | 240 | ||
| Clinical features and complications | 240 | ||
| Acute lower UTIs cause dysuria, urgency and frequency | 240 | ||
| Acute bacterial prostatitis causes systemic symptoms (fever) and local symptoms (perineal and low back pain, dysuria and f ... | 240 | ||
| Upper UTIs | 240 | ||
| Pyelonephritis causes a fever and lower urinary tract symptoms | 240 | ||
| Laboratory diagnosis | 241 | ||
| Infection can be distinguished from contamination by quantitative culture methods | 241 | ||
| The usual urine specimen for microbiologic examination is an MSU sample | 241 | ||
| For patients with a catheter, a catheter specimen of urine is used for microbiologic examination | 241 | ||
| Special urine samples are required to detect M. tuberculosis and Schistosoma haematobium | 241 | ||
| Laboratory investigations | 242 | ||
| Microscopic examination of urine allows a rapid preliminary report | 242 | ||
| A laboratory diagnosis of significant bacteriuria requires quantification of the bacteria | 242 | ||
| Interpretation of the significance of bacterial culture results depends upon a variety of factors | 242 | ||
| Treatment | 242 | ||
| Depending on clinical evaluation of the patient and local antimicrobial resistance trends, uncomplicated UTI | 242 | ||
| Complicated UTI (pyelonephritis) should be treated with a systemic antibacterial agent | 243 | ||
| Prevention | 243 | ||
| Many of the features of the pathogenesis of UTI and host predispositions are not clearly understood | 243 | ||
| Chapter 21: Sexually transmitted infections | 245 | ||
| The incidence of most STIs is increasing | 245 | ||
| STIs and sexual behaviour | 245 | ||
| The spread of STIs is inextricably linked with sexual behaviour | 245 | ||
| Various host factors influence the risk of acquiring an STI | 245 | ||
| Syphilis | 245 | ||
| Syphilis is caused by the spirochete Treponema pallidum | 245 | ||
| Classically, T. pallidum infection is divided into three stages | 247 | ||
| An infected woman can transmit T. pallidum to her baby in utero | 247 | ||
| Laboratory diagnosis of syphilis | 247 | ||
| Microscopy | 247 | ||
| Serology | 247 | ||
| Non-specific tests (non-treponemal tests) for syphilis are the VDRL and RPR tests | 248 | ||
| Commonly used specific tests for syphilis are the treponemal antibody test, FTA-ABS test and the MHA-TP | 249 | ||
| Confirmation of a diagnosis of syphilis depends upon several serologic tests | 249 | ||
| Treatment | 249 | ||
| Penicillin is the drug of choice for treating people with syphilis and their contacts | 249 | ||
| Gonorrhoea | 249 | ||
| Gonorrhoea is caused by the Gram-negative coccus Neisseria gonorrhoeae (the ‘gonococcus’) | 249 | ||
| The gonococcus has special mechanisms to attach itself to mucosal cells | 249 | ||
| Host damage in gonorrhoea results from gonococcal-induced inflammatory responses | 249 | ||
| Gonorrhoea is initially asymptomatic in many women, but can later cause infertility | 250 | ||
| A diagnosis of gonorrhoea is made from microscopy and culture of appropriate specimens | 251 | ||
| Antibacterials used to treat gonorrhoea are cefixime or ceftriaxone | 251 | ||
| Chlamydial infection | 251 | ||
| C. trachomatis serotypes D–K cause sexually transmitted genital infections | 251 | ||
| Chlamydiae enter the host through minute abrasions in the mucosal surface | 252 | ||
| The clinical effects of C. trachomatis infection appear to result from cell destruction and the host's inflammatory respon ... | 252 | ||
| Laboratory tests are essential to diagnose chlamydial urethritis and cervicitis | 253 | ||
| C. trachomatis can be detected directly on microscopy using the direct fluorescent antibody test | 253 | ||
| A variety of nucleic acid-based tests are commercially available for chlamydial detection | 253 | ||
| Chlamydial infection is treated or prevented with doxycycline or azithromycin | 253 | ||
| Other causes of inguinal lymphadenopathy | 253 | ||
| Lymphogranuloma venereum (LGV) | 253 | ||
| Lymphogranuloma venereum is caused by C. trachomatis serotypes L1, L2 and L3 | 253 | ||
| Lymphogranuloma venereum is a systemic infection involving lymphoid tissue and is treated with doxycycline or erythromycin | 254 | ||
| Chancroid (soft chancre) | 254 | ||
| Chancroid is caused by Haemophilus ducreyi and is characterized by painful genital ulcers | 254 | ||
| Chancroid is diagnosed by microscopy and culture and treated with azithromycin, ceftriaxone, erythromycin or ciprofloxacin | 254 | ||
| Donovanosis | 254 | ||
| Donovanosis is caused by Calymmatobacterium granulomatis and is characterized by genital nodules and ulcers | 254 | ||
| Donovanosis is diagnosed by microscopy and treated with doxycycline | 255 | ||
| Mycoplasmas and non-gonococcal urethritis | 255 | ||
| Mycoplasma hominis, M. genitalium, and Ureaplasma urealyticum may be causes of genital tract infection | 255 | ||
| Other causes of vaginitis and urethritis | 255 | ||
| Candida infection | 255 | ||
| Candida albicans causes a range of genital tract diseases, which are treated with oral or topical antifungals | 255 | ||
| Trichomonas infection | 255 | ||
| Trichomonas vaginalis is a protozoan parasite and causes vaginitis with copious discharge | 255 | ||
| Bacterial vaginosis | 256 | ||
| Bacterial vaginosis is associated with Gardnerella vaginalis plus anaerobic infection and a fishy-smelling vaginal dischar ... | 256 | ||
| Genital herpes | 256 | ||
| Genital herpes is characterized by ulcerating vesicles that can take up to 2 weeks to heal | 256 | ||
| Genital herpes is characterized by ulcerating vesiclesthat can take up to 2 weeks to heal | 256 | ||
| Genital herpes is generally diagnosed from the clinical appearance, and acyclovir can be used for treatment | 256 | ||
| Human papillomavirus infection | 257 | ||
| Many papillomavirus types are transmitted sexually and cause genital warts | 257 | ||
| Acquired immune deficiency syndrome (AIDS) was first recognized in 1981 in the USA | 258 | ||
| Human immunodeficiency virus, the causative virus of AIDS, was isolated from blood lymphocytes in 1983 | 258 | ||
| Human immunodeficiency virus infection probably started in Africa in the 1950s, and 35 million people worldwide were infec ... | 258 | ||
| Human immunodeficiency virus mainly infects cells bearing the CD4 cell surface antigen and also requires chemokine co-rece ... | 259 | ||
| At first the immune system fights back against HIV infection, but then begins to fail | 260 | ||
| The exact mechanism of the immunosuppression in HIV infection is still unclear | 261 | ||
| Routes of transmission | 261 | ||
| Heterosexual transmission has not so far been as important in resource-rich as in resource-poor countries | 261 | ||
| Development of disease | 263 | ||
| Primary HIV infection may be accompanied by a mild mononucleosis-type illness | 263 | ||
| Progression to AIDS | 263 | ||
| Treatment | 264 | ||
| Antiretroviral therapy results in a dramatic improvement in disease prognosis | 264 | ||
| Development of antiretroviral resistance and cross-resistance is a feature | 264 | ||
| Treatment of AIDS involves prophylaxis and treatment of opportunist infections as well as using antiretrovirals | 264 | ||
| Laboratory tests | 265 | ||
| Laboratory tests for HIV infection involve both serological and molecular analysis | 265 | ||
| Measures to control spread | 266 | ||
| Many resource-rich countries have taken measures to reduce the spread of HIV | 266 | ||
| Vaccination | 266 | ||
| There are a number of challenges in developing a successful vaccine against HIV infection | 266 | ||
| Opportunist STIs | 267 | ||
| Opportunist STIs include salmonellae, shigellae, hepatitis A, Giardia intestinalis and Entamoeba histolytica infections | 267 | ||
| Hepatitis B virus is often transmitted sexually | 267 | ||
| Arthropod infestations | 267 | ||
| Infection with the pubic or crab louse causes itching and is treated with permethrin shampoo | 267 | ||
| Genital scabies is also treated with permethrin cream | 267 | ||
| Chapter 22: Gastrointestinal tract infections | 269 | ||
| Food-associated infection versus food poisoning | 269 | ||
| Diarrheal diseases caused by bacterial or viral infection | 270 | ||
| Diarrhea is the most common outcome of gastrointestinal tract infection | 270 | ||
| In the resource-poor world, diarrheal disease is a major cause of mortality in children | 270 | ||
| Bacterial causes of diarrhea | 270 | ||
| Escherichia coli | 270 | ||
| There are six distinct groups of E. coli with different pathogenetic mechanisms | 271 | ||
| Enteropathogenic E. coli (EPEC) do not appear to make any toxins | 271 | ||
| Enterotoxigenic E. coli (ETEC) possess colonization factors (fimbrial adhesins) | 271 | ||
| Enterohaemorrhagic E. coli (EHEC) isolates produce a verotoxin | 272 | ||
| Enteroinvasive E. coli (EIEC) attach specifically to the mucosa of the large intestine | 272 | ||
| Enteroaggregative E. coli (EAEC) derive their name from their characteristic attachment pattern to tissue culture cells | 273 | ||
| Diffuse-aggregative E. coli (DAEC) produce an alpha haemolysin and cytotoxic necrotizing factor 1 | 273 | ||
| EPEC and ETEC are the most important contributors to global incidence of diarrhea, while EHEC is more important in resourc ... | 273 | ||
| Specific tests are needed to identify strains of pathogenic E. coli | 274 | ||
| Antibacterial therapy is not indicated for E. coli diarrhea | 274 | ||
| Salmonellae are the most common cause of food-associated diarrhea in many resource-rich countries | 274 | ||
| Salmonella | 274 | ||
| Salmonellae are almost always acquired orally in food or drink that is contaminated | 274 | ||
| Salmonella diarrhea can be diagnosed by culture on selective media | 275 | ||
| Fluid and electrolyte replacement may be needed for salmonella diarrhea | 275 | ||
| Salmonellae may be excreted in the faeces for several weeks after a salmonella infection | 275 | ||
| Campylobacter | 275 | ||
| Campylobacter infections are among the most common causes of diarrhea | 275 | ||
| Campylobacter diarrhea is clinically similar to that caused by other bacteria such as salmonella and shigella | 276 | ||
| Cultures for Campylobacter should be set up routinely in every investigation of a diarrheal illness | 276 | ||
| Erythromycin is used for severe Campylobacter diarrhea | 276 | ||
| Cholera | 276 | ||
| Cholera flourishes in communities with inadequate clean drinking water and sewage disposal | 276 | ||
| V. cholerae serotypes are based on somatic (O) antigens | 276 | ||
| The symptoms of cholera are caused by an enterotoxin | 277 | ||
| Culture is necessary to diagnose sporadic or imported cases of cholera and carriers | 277 | ||
| Prompt rehydration with fluids and electrolytes is central to the treatment of cholera | 277 | ||
| Cholera vaccines are not recommended for most travellers | 278 | ||
| Shigellosis | 278 | ||
| Symptoms of Shigella infection range from mild to severe depending upon the infecting species | 278 | ||
| Shigella diarrhea is usually watery at first, but later contains mucus and blood | 278 | ||
| Antibiotics should only be given for severe shigella diarrhea | 278 | ||
| Other bacterial causes of diarrheal disease | 278 | ||
| V. parahaemolyticus and Yersinia enterocolitica are food-borne Gram-negative causes of diarrhea | 279 | ||
| Clostridium perfringens and Bacillus cereus are spore-forming Gram-positive causes of diarrhea | 279 | ||
| Antibiotic-associated diarrhea – Clostridium difficile | 279 | ||
| Treatment with broad-spectrum antibiotics can be complicated by antibiotic associated Cl. difficile diarrhea | 280 | ||
| Viral diarrhea | 281 | ||
| Over 3 million infants die of gastroenteritis each year, and viruses are the most common cause | 281 | ||
| Rotaviruses | 281 | ||
| Replicating rotavirus causes diarrhea by damaging transport mechanisms in the gut | 281 | ||
| Rotavirus infection is confirmed by viral RNA or antigen detection | 282 | ||
| Fluid and salt replacement can be life-saving in rotavirus diarrhea | 283 | ||
| Other viruses | 283 | ||
| Other viruses causing diarrhea in humans include caliciviruses, astroviruses, adenoviruses and coronaviruses | 283 | ||
| Food poisoning | 283 | ||
| Staphylococcus aureus | 283 | ||
| Eight different enterotoxins are produced by different strains of Staph. aureus | 283 | ||
| Botulism | 283 | ||
| Exotoxins produced by Cl. botulinum cause botulism | 283 | ||
| Infant botulism is the most common form of botulism | 284 | ||
| Laboratory diagnosis of botulism involves injecting faecal and food samples into mice | 284 | ||
| Polyvalent antitoxin is recommended as an adjunct to intensive supportive therapy for botulism | 284 | ||
| Helicobacter pylori and gastric ulcer disease | 284 | ||
| Helicobacter pylori is associated with most duodenal and gastric ulcers | 284 | ||
| Parasites and the gastrointestinal tract | 284 | ||
| Transmission of intestinal parasites is maintained by the release of life cycle stages in faeces | 285 | ||
| Protozoan infections | 285 | ||
| Entamoeba histolytica | 285 | ||
| Entamoeba histolytica infection is particularly common in subtropical and tropical countries | 285 | ||
| E. histolytica infection may cause mild diarrhea or severe dysentery | 285 | ||
| E. histolytica infection can be diagnosed in asymptomatic patients from the presence of characteristic four-nucleate cyst ... | 286 | ||
| Acute E. histolytica infection can be treated with metronidazole or tinidazole | 286 | ||
| Giardia intestinalis | 287 | ||
| Like Entamoeba , Giardia has only two life cycle stages | 287 | ||
| Mild Giardia infections are asymptomatic, more severe infections cause diarrhea | 287 | ||
| Diagnosis of Giardia infection is based on identifying cysts or trophozoites in the stool | 287 | ||
| Giardia infection can be treated with a variety of drugs | 287 | ||
| Cryptosporidium hominis and Cryptosporidium parvum | 288 | ||
| The protozoan genus Cryptosporidium is widely distributed in many animals | 288 | ||
| Cryptosporidial diarrhea ranges from moderate to severe | 288 | ||
| Routine faecal examinations are inadequate for diagnosing cryptosporidial diarrhea | 288 | ||
| In general, only immunocompromised patients need antiparasitic treatment for cryptosporidial diarrhea | 288 | ||
| Cyclospora , Isospora and the Microsporidia | 288 | ||
| ‘Minor’ intestinal protozoa | 288 | ||
| Worm infections | 288 | ||
| The most important intestinal worms clinically are the nematodes known as ‘soil-transmitted helminths’ | 288 | ||
| Life cycle and transmission | 289 | ||
| Female Ascaris and Trichuris lay thick-shelled eggs in the intestine, which are expelled with faeces and hatch after bein ... | 289 | ||
| Adult female hookworms lay thin-shelled eggs that hatch in the faeces shortly after leaving the host | 289 | ||
| The adult female Strongyloides lays eggs that hatch in the intestine | 289 | ||
| Clinical features | 289 | ||
| Large numbers of adult Ascaris worms can cause intestinal obstruction | 289 | ||
| Moderate to severe Trichuris infection can cause chronic diarrhea | 290 | ||
| Hookworm disease can result in iron-deficiency anaemia | 290 | ||
| Strongyloidiasis can be fatal in immunosuppressed people | 290 | ||
| Laboratory diagnosis | 290 | ||
| The eggs of Ascaris , Trichuris and hookworms are characteristic | 290 | ||
| Pinworm infection is diagnosed by finding eggs on perianal skin | 290 | ||
| Treatment and prevention | 290 | ||
| Other intestinal worms | 291 | ||
| Many other worm species can infect the intestine, but most are uncommon in resource-rich countries | 291 | ||
| Systemic infection initiated in the gastrointestinal tract | 291 | ||
| Enteric fevers: typhoid and paratyphoid | 291 | ||
| S. typhi , and paratyphi types S. paratyphi A , S. schottmuelleri (previously named S. paratyphi B), and S. hirschfeldii ... | 292 | ||
| The salmonellae multiply within, and are transported around, the body in macrophages | 292 | ||
| Rose spots on the upper abdomen are characteristic, but absent in up to half of patients with enteric fever | 292 | ||
| Before antibiotics, 12–16% of patients with enteric fever died, usually of complications | 292 | ||
| One to three per cent of patients with enteric fever become chronic carriers | 292 | ||
| Diagnosis of enteric fever depends upon isolating S. typhi or paratyphi types using selective media | 292 | ||
| Antibiotic treatment should be started as soon as enteric fever is diagnosed | 293 | ||
| Prevention of enteric fever involves public health measures, treating carriers and vaccination | 293 | ||
| Listeriosis | 293 | ||
| Listeria infection is associated with pregnancy and reduced immunity | 293 | ||
| Viral hepatitis | 293 | ||
| An alphabetical litany of viruses directly target the liver, from hepatitis A to E | 293 | ||
| Hepatitis A | 294 | ||
| HAV is transmitted by the faecal–oral route | 294 | ||
| Clinically, hepatitis A is milder in young children than in older children and adults | 294 | ||
| Hepatitis E | 295 | ||
| Hepatitis E virus (HEV) spreads by the faecal–oral route | 295 | ||
| Hepatitis B | 295 | ||
| HB surface antigen can be found in blood and other body fluids | 295 | ||
| HBV is not directly cytopathic for liver cells, and the pathology is largely immune mediated | 297 | ||
| Certain groups of people are more likely to become carriers of hepatitis B | 297 | ||
| Serological tests are used in the diagnosis of HBV infection | 297 | ||
| Antiviral therapy is available | 298 | ||
| Hepatitis B infection can be prevented by immunization | 298 | ||
| Hepatitis C | 298 | ||
| Hepatitis C virus was the most common cause of transfusion-associated non-A-non-B viral hepatitis | 298 | ||
| HCV transmission routes share similarities with hepatitis B | 298 | ||
| About 75–85% of HCV-infected individuals develop chronic HCV | 299 | ||
| Treatment with pegylated IFN α and ribavirin is the standard of care | 299 | ||
| Hepatitis D | 299 | ||
| Hepatitis D virus can only multiply in a cell infected with HBV | 299 | ||
| Spread of HDV is similar to that of HBV and HBC | 299 | ||
| Viral hepatitis, the rest of the alphabet | 300 | ||
| Parasitic infections affecting the liver | 300 | ||
| Inflammatory responses to the eggs of Schistosoma mansoni result in severe liver damage | 300 | ||
| Liver abscesses | 301 | ||
| Despite the name, an amoebic liver abscess does not consist of pus | 301 | ||
| Biliary tract infections | 301 | ||
| Infection is a common complication of biliary tract disease | 301 | ||
| Peritonitis and intra-abdominal sepsis | 301 | ||
| Peritonitis is generally classified as primary (withoutapparent source of infection) or secondary (e.g. due toperforated a ... | 301 | ||
| Chapter 23: Obstetric and perinatal infections | 303 | ||
| Infections occurring in pregnancy | 303 | ||
| Immune and hormonal changes during pregnancyworsen or reactivate certain infections | 303 | ||
| The fetus has poor immune defences | 303 | ||
| Congenital infections | 303 | ||
| Intrauterine infection may result in death of the fetusor congenital malformations | 303 | ||
| Congenital rubella | 305 | ||
| The fetus is particularly susceptible to rubella infection when maternal infection occurs during the first 3 months of pre ... | 305 | ||
| Congenital rubella can affect the eye, heart, brain and ear | 305 | ||
| Fetal rubella IgM is found in cord and infant blood | 305 | ||
| Congenital rubella can be prevented by vaccination | 305 | ||
| Congenital CMV infection | 306 | ||
| Mothers with a poor T-cell proliferative response to CMV antigens are more likely to infect their fetus | 306 | ||
| Congenital syphilis | 307 | ||
| Congenital toxoplasmosis | 307 | ||
| Acute asymptomatic infection by Toxoplasma gondii during pregnancy can cause fetal malformation | 307 | ||
| Congenital HIV infection | 307 | ||
| In resource-poor countries, approximately one-quarter of infants born to mothers with HIV are infected: about one-third of ... | 307 | ||
| Congenital and neonatal listeriosis | 308 | ||
| Maternal exposure to animals or foods infected with Listeria can lead to fetal death or malformations | 308 | ||
| Infections occurring around the time of birth | 308 | ||
| Effects on the fetus and neonate | 308 | ||
| The routes of infection in the fetus and neonate are shown in Figure 23.4 | 308 | ||
| Neonatal septicaemia often progresses to meningitis | 309 | ||
| Fetal infection with herpes simplex must be considered in a baby who is acutely ill within a few weeks of birth | 309 | ||
| Effects on the mother | 309 | ||
| Puerperal sepsis is prevented by aseptic techniques | 309 | ||
| Other neonatal infections | 309 | ||
| Chapter 24: Central nervous system infections | 312 | ||
| Invasion of the central nervous system | 312 | ||
| Natural barriers act to prevent blood-borne invasion | 312 | ||
| Invasion of the CNS via peripheral nerves is a feature of herpes simplex, varicella-zoster and rabies virus infections | 312 | ||
| The body's response to invasion | 312 | ||
| CSF cell counts increase in response to infection | 312 | ||
| The pathologic consequences of CNS infection depend upon the microorganism | 313 | ||
| CNS invasion only rarely assists in the transmission of infection | 314 | ||
| Meningitis | 314 | ||
| Bacterial meningitis | 314 | ||
| Acute bacterial meningitis is a life-threatening infection, needing urgent specific treatment | 314 | ||
| Meningococcal meningitis | 314 | ||
| Neisseria meningitidis is carried by about 20% of the population, but higher rates are seen in epidemics | 314 | ||
| Clinical features of meningococcal meningitis include a haemorrhagic skin rash | 315 | ||
| A diagnosis of acute meningitis is usually suspected on clinical examination | 316 | ||
| Type b H. influenzae causes meningitis in infants and young children | 316 | ||
| Acute H. influenzae meningitis is commonly complicated by severe neurologic sequelae | 316 | ||
| H. influenzae type b (Hib) vaccine is effective for children from 2 months of age | 317 | ||
| Pneumococcal meningitis | 317 | ||
| Streptococcus pneumoniae is a common cause of bacterial meningitis, particularly in children and the elderly | 317 | ||
| Listeria monocytogenes causes meningitis in immunocompromised adults | 317 | ||
| Neonatal meningitis | 317 | ||
| Although mortality rates due to neonatal meningitis in resource-rich countries are declining, the problem is still serious | 317 | ||
| Tuberculous meningitis | 317 | ||
| Tuberculous meningitis usually presents with a gradual onset over a few weeks | 317 | ||
| Fungal meningitis | 319 | ||
| Cryptococcus neoformans meningitis is seen in patients with depressed cell-mediated immunity | 319 | ||
| Coccidioides immitis infection is common in particular geographic locations | 319 | ||
| Protozoal meningitis | 319 | ||
| Viral meningitis | 319 | ||
| Viral meningitis is the most common type of meningitis | 319 | ||
| Encephalitis | 320 | ||
| Encephalitis is usually caused by viruses, but thereare many cases where the infectious aetiology is notidentified | 320 | ||
| HSV encephalitis (HSE) is the most common form of severe sporadic acute focal encephalitis | 320 | ||
| Other herpesviruses less commonly cause encephalitis | 321 | ||
| Enteroviral infections | 321 | ||
| Poliovirus used to be a common cause of encephalitis | 321 | ||
| Enterovirus-71-associated hand, foot and mouth epidemic resulted in a high rate of neurologic complications | 322 | ||
| Paramyxoviral infections | 322 | ||
| Mumps virus is a common cause of mild encephalitis | 322 | ||
| Nipah virus encephalitis, a zoonotic paramyxovirus infection | 323 | ||
| Rabies encephalitis | 323 | ||
| More than 55000 people die of rabies worldwide each year | 323 | ||
| Clinical features of rabies include muscle spasms, convulsions and hydrophobia | 323 | ||
| Rabies can be diagnosed by detecting viral antigen or RNA | 323 | ||
| After exposure to a possibly infected animal, immediate preventive action should be taken | 324 | ||
| Togavirus meningitis and encephalitis | 324 | ||
| Numerous arthropod-borne togaviruses can cause meningitis or encephalitis | 324 | ||
| West Nile virus, another emerging viral cause of encephalitis | 324 | ||
| HIV meningitis and encephalitis | 324 | ||
| HIV can cause subacute encephalitis, often with dementia | 324 | ||
| Viral myelopathy | 325 | ||
| Post-vaccinial and post-infectious encephalitis | 325 | ||
| Encephalitis following viral infection or vaccination possibly has an autoimmune basis | 325 | ||
| Neurologic diseases of possible viral Aetiology | 325 | ||
| Spongiform encephalopathies caused by scrapie-type agents | 325 | ||
| Scrapie-type agents are closely associated with hostcodedprion protein | 325 | ||
| CNS Disease caused by parasites | 325 | ||
| The CNS is an important target in toxoplasmosis | 325 | ||
| Cerebral malaria is a major killer | 325 | ||
| Toxocara infection can result in granuloma formation in the brain and retina | 325 | ||
| Cystic hydatid disease is characterized by cyst formation, potentially in any organ but most commonly in the liver | 326 | ||
| Cysticercosis is characterized by cyst formation in the brain and eye | 326 | ||
| Brain abscesses | 326 | ||
| Brain abscesses are usually associated withpredisposing factors | 326 | ||
| Tetanus and botulism | 327 | ||
| Tetanus | 327 | ||
| Cl. tetani toxin is carried to the CNS in peripheral nerve axons | 327 | ||
| Clinical features of tetanus include muscle rigidity and spasms | 327 | ||
| Human antitetanus immunoglobulin should be given as soon as tetanus is suspected clinically | 327 | ||
| Botulism | 327 | ||
| Cl. botulinum toxin blocks acetylcholine release from peripheral nerves | 327 | ||
| Clinical features of botulism include weakness and paralysis | 327 | ||
| Botulism is treated with antibodies and respiratory support | 328 | ||
| Chapter 25: Infections of the eye | 330 | ||
| Conjunctivitis | 330 | ||
| Chlamydial infections | 330 | ||
| Different serotypes of Chlamydia trachomatis cause inclusion conjunctivitis and trachoma | 330 | ||
| Eight million people worldwide are visually impaired because of trachoma | 330 | ||
| Chlamydial infections are treated with antibiotic and prevented by face washing | 330 | ||
| Other conjunctival infections | 331 | ||
| In resource-rich countries, conjunctivitis is caused by a variety of bacteria | 331 | ||
| Direct infection of the eye may be associated with wearing contact lenses | 331 | ||
| Conjunctival infection may be transmitted by the blood or nervous system | 331 | ||
| Infection of the deeper layers of the eye | 333 | ||
| Entry into the deeper layers occurs by many routes | 333 | ||
| Toxoplasmosis | 333 | ||
| Toxoplasma gondii infection can cause retinochoroiditis leading to blindness | 333 | ||
| Parasitic worm infections | 333 | ||
| Toxocara canis larvae cause an intense inflammatory response and can lead to retinal detachment | 333 | ||
| Onchocerca volvulus infection causes ‘river blindness’ and is transmitted by Simulium flies | 334 | ||
| Chapter 26: Infections of the skin, soft tissue, muscle and associated systems | 335 | ||
| Infections of the skin | 335 | ||
| Microbial disease of the skin may result from any of three lines of attack | 335 | ||
| Bacterial infections of skin, soft tissue and muscle | 337 | ||
| These can be classified on an anatomic basis | 337 | ||
| Staphylococcal skin infections | 338 | ||
| Staphylococcus aureus is the most common cause of skin infections and provokes an intense inflammatory response | 338 | ||
| Staph. aureus infections are often diagnosed clinically and treatment includes drainage and antibiotics | 338 | ||
| Staphylococcal scalded skin syndrome is caused by toxin-producing Staph. aureus | 338 | ||
| Toxic shock syndrome is caused by toxic shock syndrome toxin-producing Staph. aureus | 338 | ||
| Streptococcal skin infections | 339 | ||
| Streptococcal skin infections are caused by Strep. pyogenes (group A streptococci) | 339 | ||
| Clinical features of streptococcal skin infections are typically acute | 339 | ||
| M protein is a major virulence factor in Strep. pyogenes with over 100 types, some of which (e.g. M49) are specifically as ... | 340 | ||
| Streptococcal skin infections are usually diagnosed clinically and treated with penicillin | 340 | ||
| Cellulitis and gangrene | 340 | ||
| Cellulitis is an acute spreading infection of the skin that involves subcutaneous tissues | 340 | ||
| Anaerobic cellulitis may develop in areas of traumatized or devitalized tissue | 341 | ||
| Synergistic bacterial gangrene is a relentlessly destructive infection | 341 | ||
| Necrotizing fasciitis, myonecrosis and gangrene | 341 | ||
| Necrotizing fasciitis is a frequently fatal mixed infection caused by anaerobes and facultative anaerobes | 341 | ||
| Traumatic or surgical wounds can become infected with Clostridium species | 341 | ||
| Amputation may be necessary to prevent further spread of clostridial infection | 342 | ||
| Propionibacterium acnes and acne | 342 | ||
| P. acnes go hand in hand with the hormonal changes of puberty which result in acne | 342 | ||
| Treatment of acne includes long-term administration of oral antibiotics | 343 | ||
| Mycobacterial diseases of the skin | 343 | ||
| Leprosy | 343 | ||
| Leprosy is decreasing in incidence but still remains a concern | 343 | ||
| Leprosy is caused by Mycobacterium leprae | 343 | ||
| The clinical features of leprosy depend upon the cell-mediated immune response to M. leprae | 343 | ||
| M. leprae are seen as acid-fast rods in nasal scrapings and lesion biopsies | 344 | ||
| Treatment | 344 | ||
| Leprosy is treated with dapsone given as part of a multidrug regimen to avoid resistance | 344 | ||
| Other mycobacterial skin infections | 345 | ||
| Mycobacterium marinum, M. ulcerans and M. tuberculosis also cause skin lesions | 345 | ||
| Fungal infections of the skin | 345 | ||
| Superficial and cutaneous mycoses | 345 | ||
| Pityriasis versicolor | 345 | ||
| M. furfur is the cause of pityriasis or tinea versicolor | 345 | ||
| Diagnosis of pityriasis versicolor can be confirmed by direct microscopy of scrapings | 345 | ||
| Cutaneous dermatophytes | 346 | ||
| Dermatophyte infections are acquired from many sources and are spread by arthrospores | 346 | ||
| Dermatophytes invade skin, hair and nails | 347 | ||
| Most dermatophyte species fluoresce under ultraviolet light | 348 | ||
| Dermatophyte infections are treated topically if possible | 348 | ||
| Candida requires moisture for growth | 349 | ||
| Subcutaneous mycoses | 349 | ||
| Subcutaneous fungal infections can be caused by a number of different species | 349 | ||
| Sporotrichosis is a nodular condition caused by Sporothrix schenckii | 349 | ||
| Systemic fungal infections with skin manifestations include blastomycosis, coccidioidomycosis and cryptococcosis | 349 | ||
| Parasitic infections of the skin | 350 | ||
| Leishmaniasis may be cutaneous or mucosal (formerly termed mucocutaneous) | 350 | ||
| Schistosome infection can cause a dermatitis | 350 | ||
| Cutaneous larval migrans is characterized by itchy inflammatory hookworm larvae trails | 350 | ||
| Onchocerciasis is characterized by hypersensitivity responses to larval antigens | 350 | ||
| Arthropod infections | 350 | ||
| Some flies, mainly in the tropics and subtropics, have larvae that develop within the skin | 350 | ||
| Certain ticks, lice and mites live on blood or tissue fluids from humans | 350 | ||
| Mucocutaneous lesions caused by viruses | 351 | ||
| Papillomavirus infection | 352 | ||
| Over 120 different types of papillomavirus can infect humans and are species specific | 352 | ||
| Papillomavirus infects cells in the basal layers of skin or mucosa and are tissue tropic | 352 | ||
| Papillomavirus infections are associated with cancer of the cervix, vulva, penis, rectum, head, and neck | 352 | ||
| Diagnosis of papillomavirus infection is clinical and there are many treatments | 352 | ||
| Molluscum contagiosum is an umbilicated lesion caused by a poxvirus | 353 | ||
| Orf is a papulovesicular lesion caused by a poxvirus | 353 | ||
| Herpes simplex virus infection | 353 | ||
| Herpes simplex virus infection is universal and occurs in early childhood | 353 | ||
| Clinical features of HSV infection are vesicles and latency | 353 | ||
| Herpes simplex virus reactivation is provoked by a variety of factors | 353 | ||
| Herpes simplex virus is readily isolated from vesicle fluid, and infection is treated with aciclovir | 354 | ||
| Varicella-zoster virus (VZV) infection | 355 | ||
| Varicella-zoster virus causes chickenpox (varicella) and zoster (shingles) and is highly infectious | 355 | ||
| Varicella is characterized by crops of vesicles that develop into pustules and then scab over | 355 | ||
| Varicella is usually more severe and more likely to cause complications in adults | 355 | ||
| Zoster results from reactivation of latent VZV | 356 | ||
| Postherpetic neuralgia is a common complication of zoster | 356 | ||
| Treatment of varicella and zoster infection | 356 | ||
| Rashes caused by coxsackieviruses and echoviruses | 356 | ||
| Coxsackieviruses and echoviruses cause a variety of exanthems (skin rashes) | 356 | ||
| Rashes caused by human parvovirus B19 | 357 | ||
| Parvovirus B19 causes slapped cheek syndrome | 357 | ||
| Symptomless parvovirus B19 infection is common and spreads by respiratory droplets | 357 | ||
| Rashes caused by human herpesviruses 6 and 7 (HHV-6 and -7) | 357 | ||
| Human herpesviruses-6 is present in the saliva of over 85% of adults and causes roseola infantum | 357 | ||
| Human herpesviruses -7 is acquired slightly later in early childhood | 357 | ||
| Human herpesviruses-8 is associated with all forms of Kaposi's sarcoma skin lesions | 357 | ||
| Smallpox | 358 | ||
| Global smallpox eradication was officially certified in December 1979 | 358 | ||
| Global eradication of smallpox was possible for a variety of reasons | 358 | ||
| Measles | 358 | ||
| Aetiology and transmission | 359 | ||
| Measles outbreaks occur every few years in unvaccinated populations | 359 | ||
| Clinical features of measles include respiratory symptoms, Koplik's spots and a rash | 359 | ||
| Measles rash results from a cell-mediated immune response | 359 | ||
| Complications of measles are particularly likely among children in resource-poor countries | 360 | ||
| Diagnosis, treatment and prevention | 360 | ||
| Measles is usually diagnosed clinically; ribavirin can be used as antiviral treatment if clinically indicated and there is ... | 360 | ||
| Rubella | 360 | ||
| Rubella virus infection causes a multisystem infection, but its main impact is on the fetus | 360 | ||
| Rubella is diagnosed serologically; there is no treatment, but there is a vaccine | 361 | ||
| Other infections producing skin lesions | 361 | ||
| Other bacterial, fungal and rickettsial infections produce a variety of rashes or other skin lesions | 361 | ||
| Kawasaki syndrome | 361 | ||
| Kawasaki syndrome is an acute vasculitis and is probably caused by superantigen toxins | 361 | ||
| Viral infections of muscle | 361 | ||
| Viral myositis, myocarditis and pericarditis | 361 | ||
| Some viruses, particularly coxsackievirus B, cause myocarditis and myalgia | 361 | ||
| Postviral fatigue syndrome | 362 | ||
| It has been difficult to establish postviral fatigue syndrome as a clinical entity | 362 | ||
| Parasitic infections of muscle | 362 | ||
| Trypanosoma cruzi infection | 362 | ||
| Trypanosoma cruzi is a protozoan and causes Chagas disease | 362 | ||
| Chagas disease is complicated by cardiac conduction disorders, ventricular aneurysm formation or heart failure many years l ... | 362 | ||
| Taenia solium infection | 362 | ||
| The larval stages of Taenia solium invade body tissues | 362 | ||
| Trichinella spiralis infection | 363 | ||
| The larvae of Trichinella spiralis invade striated muscle | 363 | ||
| Sarcocystis | 363 | ||
| Sarcocystis is a rare muscle parasite | 363 | ||
| Joint and bone infections | 363 | ||
| Reactive arthritis, arthralgia and septic arthritis | 363 | ||
| Arthralgia and arthritis occur in a variety of infections and are often immunologically mediated | 363 | ||
| Circulating bacteria sometimes localize in joints, especially following trauma | 363 | ||
| Osteomyelitis | 364 | ||
| Bone can become infected by adjacent infection or haematogenously | 364 | ||
| Osteomyelitis is treated with antibiotics and sometimes surgery | 364 | ||
| Infections of the haemopoietic system | 365 | ||
| Many infectious agents cause changes in circulating blood cells | 365 | ||
| Human T-lymphotropic virus-1 infection | 365 | ||
| Human T-lymphotropic virus -1 is mainly transmitted by maternal milk | 365 | ||
| Human T-lymphotropic virus -1 infects T cells, and up to 5% of those infected develop T-cell leukaemia | 365 | ||
| Human T-lymphotropic virus-2 infection | 366 | ||
| Chapter 27: Vector-borne infections | 367 | ||
| Transmission of disease by vectors | 367 | ||
| In sparsely populated areas, transmission by insectsis an effective means of spread | 367 | ||
| Arbovirus infections | 367 | ||
| Arboviruses are arthropod-borne viruses | 367 | ||
| Only a small number of arboviruses are important causes of human disease | 367 | ||
| Yellow fever | 368 | ||
| Yellow fever virus is transmitted by mosquitoes and is restricted to Africa, Central and South America and the Caribbean | 368 | ||
| Clinical features of yellow fever may be mild, but in 10% to 20% of cases classic yellow fever with liver damage occurs, w ... | 368 | ||
| The diagnosis is usually clinical; there is no specific treatment, but there is a vaccine | 368 | ||
| Dengue fever | 368 | ||
| Dengue virus is transmitted by mosquitoes and occurs in SE Asia, the Pacific area, India, South and Central America | 368 | ||
| Dengue fever may be complicated by dengue haemorrhagic fever/dengue shock syndrome | 368 | ||
| Chikungunya virus infection (CHIKV) | 368 | ||
| Arbovirus encephalitis | 369 | ||
| The encephalitic arboviruses only occasionally cause encephalitis | 369 | ||
| Arboviruses and haemorrhagic fevers | 369 | ||
| Arboviruses are major causes of fever in endemic areas of the world | 369 | ||
| Infections caused by rickettsiae | 369 | ||
| The rickettsiae are small bacteria and infections tend to be persistent or become latent | 369 | ||
| Typical clinical symptoms of rickettsial infection are fever, headache and rash | 371 | ||
| Laboratory diagnosis is based on serologic tests | 371 | ||
| All rickettsiae are susceptible to tetracyclines | 372 | ||
| Rocky Mountain spotted fever | 372 | ||
| Rocky Mountain spotted fever is transmitted by dog ticks and has a mortality of up to 10% | 372 | ||
| Mediterranean spotted fever | 372 | ||
| Mediterranean spotted fever is transmitted by dog ticks | 372 | ||
| African tick-bite fever | 372 | ||
| Rickettsialpox | 372 | ||
| Rickettsialpox is a mild infection | 372 | ||
| Epidemic typhus | 372 | ||
| Epidemic typhus is transmitted by the human body louse | 372 | ||
| Untreated epidemic typhus has a mortality as high as 60% | 372 | ||
| Endemic (murine) typhus | 372 | ||
| Scrub typhus | 373 | ||
| Borrelia infections | 373 | ||
| Relapsing fever | 373 | ||
| The epidemic form of relapsing fever is caused by Borrelia recurrentis , which is transmitted by human body lice | 373 | ||
| The endemic form of relapsing fever in humans is transmitted by tick bites | 373 | ||
| Relapsing fever is characterized by repeated febrile episodes due to antigenic variation in the spirochetes | 373 | ||
| Relapsing fever is diagnosed in the laboratory and treated with tetracycline | 374 | ||
| Lyme disease | 374 | ||
| Lyme disease is caused by Borrelia spp. and is transmitted by Ixodes ticks | 374 | ||
| Erythema migrans is a characteristic feature of Lyme disease | 374 | ||
| Lyme disease commonly causes additional disease 1 week to 2 years after the initial illness | 374 | ||
| Lyme disease is diagnosed serologically and treated with antibiotic | 375 | ||
| Protozoal infections | 375 | ||
| Malaria | 375 | ||
| Malaria is initiated by the bite of an infected female anopheline mosquito | 375 | ||
| The life cycle of the malaria parasite comprises three stages | 375 | ||
| Clinical features of malaria include a fluctuating fever and drenching sweats | 375 | ||
| Malaria has an immunosuppressive effect and interacts with HIV infection | 377 | ||
| Immunity to malaria develops gradually and seems to need repeated boosting | 377 | ||
| Malaria is diagnosed by finding parasitized red cells in thin and thick blood films | 378 | ||
| Trypanosomiasis | 378 | ||
| Three species of the protozoan Trypanosoma cause human disease | 378 | ||
| African trypanosomiasis | 378 | ||
| African trypanosomiasis is transmitted by the tsetse fly and restricted to equatorial Africa | 378 | ||
| Clinical features of African trypanosomiasis include lymphadenopathy and sleeping sickness | 378 | ||
| T. brucei evades host defences by varying the antigens in its glycoprotein coat | 378 | ||
| Pentamidine prophylaxis is no longer deployed | 379 | ||
| Chagas disease | 379 | ||
| T. cruzi is transmitted by the reduviid (‘kissing’) bug | 379 | ||
| Chagas disease has serious long-term effects, which include fatal heart disease | 379 | ||
| Chronic Chagas disease is usually diagnosed serologically | 379 | ||
| Leishmaniasis | 379 | ||
| Leishmania parasites are transmitted by sandflies and cause New World and Old World leishmaniasis | 379 | ||
| Leishmania is an intracellular parasite and inhabits macrophages | 379 | ||
| Untreated visceral leishmaniasis (‘kala-azar’) is fatal in 80–90% of cases | 379 | ||
| Cutaneous leishmaniasis is characterized by plaques, nodules or ulcers | 380 | ||
| Immunodeficient patients may suffer more severe leishmaniasis | 380 | ||
| Leishmaniasis is diagnosed by demonstrating the organism microscopically and is treated with antimonials | 380 | ||
| Helminth infections | 380 | ||
| Schistosomiasis | 380 | ||
| Schistosomiasis is transmitted through a snail vector | 380 | ||
| Clinical features of schistosomiasis result from allergic responses to the different life cycle stages | 380 | ||
| Schistosomiasis is treated with praziquantel | 381 | ||
| Filariasis | 381 | ||
| Filarial nematodes depend upon blood-feeding arthropod vectors for transmission | 381 | ||
| Lymphatic filariasis caused by Brugia and Wuchereria is transmitted by mosquitoes | 381 | ||
| Few drugs are really satisfactory for treating filariasis | 382 | ||
| Chapter 28: Multisystem zoonoses | 383 | ||
| Arenavirus infections | 383 | ||
| Arenaviruses are transmitted to humans in rodentexcreta | 383 | ||
| Arenavirus infection is diagnosed by viral genome detection, serology or virus isolation | 383 | ||
| Lassa fever virus is an arenavirus that occurs naturally in bush rats in parts of West Africa | 385 | ||
| Lymphocytic choriomeningitis virus occurs worldwide | 385 | ||
| Haemorrhagic fever with renal syndrome (HFRS) | 385 | ||
| The Hantaan and Seoul viruses infect rodentsand cause HFRS in Asia | 385 | ||
| Marburg and ebola haemorrhagic fevers | 385 | ||
| Fruit bats are the reservoir for Marburg and Ebolaviruses | 385 | ||
| Crimean–congo haemorrhagic fever, a tick-borne virus | 385 | ||
| Q Fever | 386 | ||
| Coxiella burnetii is the rickettsial cause of Q fever | 386 | ||
| C. burnetii is transmitted to humans by inhalation | 386 | ||
| Q fever is diagnosed serologically and treated with antibiotics | 386 | ||
| Anthrax | 386 | ||
| Anthrax is caused by Bacillus anthracis and is primarily a disease of herbivores | 386 | ||
| Anthrax is characterized by a black eschar, and the disease can be fatal if untreated | 386 | ||
| Anthrax is diagnosed by culture and treated with penicillin | 386 | ||
| Anthrax, as a natural infection, is now mainly confined to resource-poor countries. Vaccines are available. Bioterrorism i ... | 387 | ||
| Plague | 387 | ||
| The plague is caused by Yersinia pestis, which infectsrodents and is spread from them by fleas to humans | 387 | ||
| Clinical features of plague include buboes, pneumonia and a high death rate | 387 | ||
| Plague is diagnosed microscopically and treated with antibiotics | 387 | ||
| Yersinia enterocolitica infection | 389 | ||
| Tularaemia | 389 | ||
| Tularaemia is caused by Francisella tularensis andis spread by arthropods from infected animals | 389 | ||
| Clinical features of tularaemia include painful swollen lymph nodes | 389 | ||
| Tularaemia is diagnosed clinically and serologically. Streptomycin is the drug of choice, although other antimicrobials ha ... | 389 | ||
| Pasteurella multocida infection | 389 | ||
| Pasteurella multocida is part of the normal flora of catsand dogs and is transmitted to humans by an animalbite or scratch | 389 | ||
| P. multocida infection causes cellulitis, is diagnosed by microscopy and treated with amoxicillin/clavulanate | 389 | ||
| Leptospirosis | 389 | ||
| Leptospirosis is caused by the spirochete Leptospirainterrogans, which infects mammals such as rats | 389 | ||
| Clinical features of leptospirosis include kidney and liver failure | 390 | ||
| Leptospirosis is diagnosed by microscopy and serologic tests and treated with antibiotics | 390 | ||
| Rat-bite fever | 390 | ||
| Rat-bite fever is caused by bacteria transmittedto humans by a rodent bite | 390 | ||
| Clinical features of rat-bite fever can include endocarditis and pneumonia | 390 | ||
| Rat-bite fever is diagnosed by microscopy or culture and is treated with antibiotics | 390 | ||
| Brucellosis | 390 | ||
| Brucellosis occurs worldwide and is caused byBrucella species | 390 | ||
| Clinical features of brucellosis are immune-mediated and include an undulant fever and chronicity | 391 | ||
| Brucellosis is diagnosed by culture and by serologic tests and treated with antibiotics | 391 | ||
| Helminth infections | 391 | ||
| Few helminth infections are true multisystem diseases | 391 | ||
| Echinococcus | 392 | ||
| Echinococcus granulosus (cystic echinococcosis; cystic hydatid disease) | 392 | ||
| Echinococcus multilocularis (alveolar echinococcosis; alveolar hydatid disease) | 392 | ||
| Trichinella | 392 | ||
| Trichinella spiralis is transmitted in undercooked pork and causes the disease trichinosis | 392 | ||
| The clinical features of trichinosis are mainly immunopathologic in origin | 392 | ||
| Trichinosis is diagnosed by microscopy and serologically and treated with anthelmintics and anti-inflammatories | 392 | ||
| Strongyloides | 393 | ||
| Strongyloides infections are generally passed between humans, but can develop in animal hosts including dogs | 393 | ||
| Strongyloides infections are usually asymptomatic, but can cause disseminated disease in patients with immunodeficiency s ... | 393 | ||
| Chapter 29: Fever of unknown origin | 395 | ||
| Definitions of fever of unknown origin | 395 | ||
| Causes of FUO | 395 | ||
| Infection is the most common cause of FUO | 395 | ||
| Infective causes of classical FUO | 395 | ||
| Investigation of classic FUO | 396 | ||
| Steps in the investigative procedure | 396 | ||
| Stage 1 comprises careful history-taking, physical examination and screening tests | 396 | ||
| Stage 2 involves reviewing the history, repeating the physical examination, specific diagnostic tests and non-invasive inv ... | 397 | ||
| Stage 3 comprises invasive tests | 398 | ||
| Stage 4 involves therapeutic trials | 399 | ||
| Treatment of FUO | 399 | ||
| FUO in specific patient groups | 399 | ||
| The main difference between FUO in these groups andclassic FUO is the time course | 399 | ||
| Infective endocarditis | 400 | ||
| Almost any organism can cause endocarditis, but native valves are usually infected by oral streptococci and staphylococci | 400 | ||
| A patient with infective endocarditis almost always has a fever and a heart murmur | 401 | ||
| Blood culture is the most important test for diagnosing infective endocarditis | 401 | ||
| The mortality of infective endocarditis is 20–50% despite treatment with antibiotics | 401 | ||
| The antibiotic treatment regimen for infective endocarditis depends upon the susceptibility of the infecting organism | 401 | ||
| People with heart defects need prophylactic antibiotics during invasive procedures | 401 | ||
| Most people with an FUO have a treatable disease presenting in an unusual manner | 401 | ||
| Chapter 30: Infections in the compromised host | 403 | ||
| The compromised host | 403 | ||
| The host can be compromised in many different ways | 403 | ||
| Primary defects of innate immunity include congenital defects in phagocytic cells or complement synthesis | 403 | ||
| Secondary defects of innate defences include disruption of the body's mechanical barriers | 403 | ||
| Primary adaptive immunodeficiency results from defects in the primary differentiation environment or in cell differentiati ... | 404 | ||
| Causes of secondary adaptive immunodeficiency include malnutrition, infections, neoplasia, splenectomy and certain medical ... | 404 | ||
| Microbes that infect the compromised host | 405 | ||
| Infections of the host with deficient innate immunity due to physical factors | 405 | ||
| Burn wound infections | 405 | ||
| Burns damage the body's mechanical barriers, neutrophil function and immune responses | 405 | ||
| The major pathogens in burns are aerobic and facultatively anaerobic bacteria and fungi | 407 | ||
| P. aeruginosa is a devastating Gram-negative pathogen of burned patients | 407 | ||
| Staph. aureus is the foremost pathogen of burn wounds | 407 | ||
| The high transmissibility of Strep. pyogenes makes it the scourge of burns wards | 407 | ||
| Traumatic injury and surgical wound infections | 407 | ||
| Staph. aureus is the most important cause of surgical wound infection | 407 | ||
| Catheter-associated infection of the urinary tract is common | 407 | ||
| Staphylococci are the most common cause of intravenous and peritoneal dialysis catheter infections | 407 | ||
| Infections of plastic devices in situ | 408 | ||
| Staph. epidermidis is the most common cause of prosthetic valve and joint infections | 408 | ||
| Infections due to compromised clearance mechanisms | 408 | ||
| Infections associated with secondary adaptive immunodeficiency | 408 | ||
| Haematologic malignancy and bone marrow transplant infections | 408 | ||
| A lack of circulating neutrophils following bone marrow failure predisposes to infection | 408 | ||
| Solid organ transplant infections | 409 | ||
| Most infections occur within 3–4 months of transplantation | 409 | ||
| HIV infection leading to AIDS | 409 | ||
| The clinical definition of AIDS includes the presence of one or more opportunistic infections | 409 | ||
| Other important opportunist pathogens | 409 | ||
| Fungi | 409 | ||
| Candida is the most common fungal pathogen in compromised patients | 409 | ||
| Cryptococcus neoformans infection is most common in people with impaired cell-mediated immunity | 410 | ||
| Disseminated Histoplasma capsulatum infection may occur years after exposure in immunocompromised patients | 410 | ||
| Invasive aspergillosis has a very high mortality rate in the compromised patient | 411 | ||
| Pneumocystis jirovecii (formerly P. carinii) only causes symptomatic disease in people with deficient cellular immunity | 412 | ||
| Bacteria | 412 | ||
| Nocardia asteroides is an uncommon opportunist pathogen with a worldwide distribution | 412 | ||
| Mycobacterium avium-intracellulare disease is often a terminal event in AIDS | 413 | ||
| Protozoa and helminths | 413 | ||
| Cryptosporidium and Isospora belli infections cause severe diarrhea in AIDS | 413 | ||
| Immunosuppression may lead to reactivation of dormant Strongyloides stercoralis | 414 | ||
| Viruses | 414 | ||
| Certain virus infections are both more common and more severe in compromised patients, and regular surveillance is critical | 414 | ||
| EBV infection can lead to tumour development | 414 | ||
| Respiratory virus infections | 415 | ||
| Adenovirus infection has a high mortality rate | 415 | ||
| Hepatitis B and C infection in transplant recipients | 415 | ||
| Polyomaviruses can cause haemorrhagic cystitis and progressive multifocal leukoencephalopathy | 415 | ||
| Section 5: Diagnosis and control | 417 | ||
| Chapter 31: Diagnosis of infection and assessment of host defence mechanisms | 419 | ||
| Aims of the clinical microbiology laboratory | 419 | ||
| Identification is achieved by detecting the microorganism or its products or the patient's immune response | 419 | ||
| Specimen processing | 419 | ||
| Specimen handling and interpretation of resultsis based upon a knowledge of normal flora andcontaminants | 419 | ||
| Routine culture takes at least 18 th to produce a result | 420 | ||
| Non-cultural techniques for the laboratory diagnosis of infection | 420 | ||
| Non-cultural techniques do not require microorganism multiplication before detection | 420 | ||
| Microscopy | 421 | ||
| Microscopy is an important first step in the examination of specimens | 421 | ||
| Light microscopy | 421 | ||
| Bright field microscopy is used to examine specimens and cultures as wet or stained preparations | 421 | ||
| The most important differential staining technique in bacteriology is the ‘Gram’ stain | 422 | ||
| Acid-fast stains are used to detect mycobacteria | 422 | ||
| Other staining techniques can be used to demonstrate particular features of cells | 422 | ||
| Dark field (dark ground) microscopy is useful for observing motility and thin cells such as spirochetes | 423 | ||
| Phase contrast microscopy increases the contrast of an image | 423 | ||
| Fluorescence microscopy is used for substances that are either naturally fluorescent or have been stained with fluorescent ... | 423 | ||
| Electron microscopy | 423 | ||
| The specimen needs to be cut into thin sections for electron microscopy | 423 | ||
| Although not routinely used in the clinical laboratory, electron microscopy can aid in the identification of virus particl ... | 424 | ||
| Detection of microbial antigens in specimens | 424 | ||
| Specific antibody coated onto latex particles will react with the organism or its product, resulting in visible clumping | 424 | ||
| Immunoassay can be used to measure antigen concentration | 425 | ||
| Monoclonal antibodies can distinguish between species and between strains of the same species on the basis of antigenic di ... | 425 | ||
| Detection of microbes by probing for their genes | 426 | ||
| Organisms carrying genes for virulence factors can be detected by nucleic acid probes for the virulence factors | 426 | ||
| Polymerase chain reaction can be used to amplify a specific DNA sequence to produce millions of copies within a few hours | 426 | ||
| The specificity of PCR is determined by careful choice of primers | 426 | ||
| Dideoxy chain terminator sequencing | 427 | ||
| Cultivation (culture) of microorganisms | 428 | ||
| Bacteria and fungi can be cultured on solid nutrientor liquid media | 428 | ||
| Different species of bacteria and fungi have different growth requirements | 428 | ||
| Viruses, chlamydia and rickettsia must be grown in cell or tissue cultures | 429 | ||
| Identification of microorganisms grown in culture | 429 | ||
| Bacteria are identified by simple characteristicsand biochemical properties | 429 | ||
| Antibiotic susceptibility can only be determined after the bacteria have been isolated in a pure culture | 429 | ||
| Fungi are identified by their colonial characteristics and cell morphology | 431 | ||
| Protozoa and helminths are identified by direct examination although newer molecular methods are also available | 431 | ||
| Viruses are usually identified using serologic tests | 431 | ||
| Mass spectrometry heralds a novel diagnostic era | 431 | ||
| Antibody detection methods for the diagnosis of infection | 432 | ||
| Diagnoses based on detecting antibodies in patients’ sera are retrospective | 432 | ||
| Antibody detection can be invaluable for identifying organisms that grow either slowly or with difficulty | 432 | ||
| Common serologic tests used in the laboratory to diagnose infection | 432 | ||
| Solid-phase immunoassays can be used to estimate antibody in a given sample | 432 | ||
| A variety of tests assess the ability of antibodies to inhibit microbial activity | 432 | ||
| Antibodies to cytopathic viruses can be detected by the ability of the patient's serum to prevent virus infectivity | 432 | ||
| Point of care tests | 432 | ||
| New simpler diagnostic tests are being developed that can be used at the point of care | 432 | ||
| Assessment of host defence systems | 432 | ||
| The opsonic activity and activities of individualcomponents of complement can also be assessed | 432 | ||
| The nitroblue tetrazolium (NBT) test is used to assess phagocytic activity | 433 | ||
| Lymphocytes | 433 | ||
| Lymphocytes are counted and classified by detecting their cell surface molecules | 434 | ||
| Individual cells secreting antibodies or cytokines can be counted by the ELISPOT technique or by flow cytometry | 435 | ||
| The ability of cytotoxic T cells to attack targets is conventionally assayed using a radioisotope | 436 | ||
| Putting it all together: detection, diagnosis, and epidemiology | 436 | ||
| Chapter 32: Epidemiology and control of infectious diseases | 439 | ||
| Outcome measurements | 439 | ||
| Types of epidemiological studies | 439 | ||
| Cross-sectional study | 439 | ||
| Case–control study | 440 | ||
| Cohort study | 440 | ||
| Intervention study | 440 | ||
| Transmission of infectious disease | 444 | ||
| Infectiousness ( Box 32.3) | 444 | ||
| Time periods of infections | 444 | ||
| Time periods of infectious disease | 444 | ||
| Basic and net reproductive rate | 445 | ||
| Vaccine efficacy | 446 | ||
| Chapter 33: Attacking the enemy: antimicrobial agents and chemotherapy | 447 | ||
| Selective toxicity | 447 | ||
| Discovery and design of antimicrobial agents | 447 | ||
| Classification of antibacterial agents | 448 | ||
| Some antibacterial agents are bactericidal, others are bacteriostatic | 449 | ||
| There are five main target sites for antibacterial action | 449 | ||
| Antibacterial agents have diverse chemical structures | 449 | ||
| Resistance to antibacterial agents | 449 | ||
| The genetics of resistance | 449 | ||
| Chromosomal mutation may result in resistance to a class of antimicrobial agents (cross-resistance) | 450 | ||
| Genes on transmissible plasmids may result in resistance to different classes of antimicrobial agents (multiple resistance) | 450 | ||
| Resistance may be acquired from transposons and other mobile elements | 450 | ||
| ‘Cassettes’ of resistance genes may be organized into genetic elements called integrons | 450 | ||
| Staphylococcal genes for methicillin resistance are organized into a unique cassette structure | 451 | ||
| Mechanisms of resistance | 451 | ||
| The target site may be altered | 452 | ||
| Access to the target site may be altered (altered uptake or increased exit) | 452 | ||
| Enzymes that modify or destroy the antibacterial agent may be produced (drug inactivation) | 452 | ||
| Classes of antibacterial agents | 452 | ||
| Inhibitors of cell wall synthesis | 452 | ||
| Beta-lactams | 452 | ||
| Beta-lactams contain a beta-lactam ring and inhibit cell wall synthesis by binding to penicillin-binding proteins (PBPs) | 452 | ||
| Most beta-lactams have to be administered parenterally | 452 | ||
| Different beta-lactams have different clinical uses, but are not active against species that lack a cell wall | 453 | ||
| Resistance to beta-lactams may involve one ormore of the three possible mechanisms | 453 | ||
| Resistance by alteration in target site | 453 | ||
| Resistance by alteration in access to the target site | 454 | ||
| Resistance by production of beta-lactamases | 454 | ||
| Side effects | 454 | ||
| Toxic effects of beta-lactam drugs include mild rashes and immediate hypersensitivity reactions | 454 | ||
| Glycopeptides | 454 | ||
| Glycopeptides are large molecules and act at an earlier stage than beta-lactams | 454 | ||
| Vancomycin and teicoplanin must be given by injection for systemic infections | 455 | ||
| Both vancomycin and teicoplanin are active only against Gram-positive organisms | 455 | ||
| Resistance | 457 | ||
| Some organisms are intrinsically resistant to glycopeptides | 457 | ||
| Organisms may acquire resistance to glycopeptides | 457 | ||
| VanA is the best understood mechanism of acquired glycopeptide resistance | 457 | ||
| Glycopeptide resistance in the staphylococci occurs by mutation or by acquisition from the enterococci | 457 | ||
| Side effects | 457 | ||
| The glycopeptides are potentially ototoxic and nephrotoxic | 457 | ||
| Inhibitors of protein synthesis | 458 | ||
| Aminoglycosides | 458 | ||
| The aminoglycosides are a family of related molecules with bactericidal activity | 458 | ||
| Aminoglycosides must be given intravenously or intramuscularly for systemic treatment | 459 | ||
| Gentamicin and the newer aminoglycosides are used to treat serious Gram-negative infections | 459 | ||
| Production of aminoglycoside-modifying enzymes is the principal cause of resistance to aminoglycosides | 460 | ||
| The aminoglycosides are potentially nephrotoxic and ototoxic | 460 | ||
| Tetracyclines | 460 | ||
| Tetracyclines are bacteriostatic compounds that differ mainly in their pharmacological properties rather than in their ant ... | 460 | ||
| Tetracyclines are active against a wide variety of bacteria, but their use is restricted due to widespread resistance | 460 | ||
| Tetracyclines should be avoided in pregnancy and in children under 8 years of age | 461 | ||
| Chloramphenicol | 461 | ||
| Chloramphenicol contains a nitrobenzene nucleus and prevents peptide bond synthesis, with a bacteriostatic result | 461 | ||
| Resistance and toxicity have limited the use of chloramphenicol | 461 | ||
| The most important toxic effects of chloramphenicol are in the bone marrow | 462 | ||
| Macrolides, lincosamides and streptogramins | 462 | ||
| Macrolides | 462 | ||
| Erythromycin is a widely used macrolide preventing the release of transfer RNA after peptide bond formation | 462 | ||
| Erythromycin is an alternative to penicillin for streptococcal infections, but resistant strains of streptococci are common | 462 | ||
| Newer generation macrolides have fewer side effects than erythromycins | 462 | ||
| Ketolides are new semi-synthetic derivatives of erythromycin with improved activity against respiratory pathogens | 462 | ||
| Lincosamides | 462 | ||
| Clindamycin inhibits peptide bond formation | 462 | ||
| Clindamycin has a spectrum of activity similar to that of erythromycin | 462 | ||
| Pseudomembranous colitis caused by Cl. difficile was first noted following clindamycin treatment | 464 | ||
| Streptogramins | 464 | ||
| Oxazolidinones | 464 | ||
| Fusidic acid | 464 | ||
| Fusidic acid is a steroid-like compound that inhibits protein synthesis | 464 | ||
| Fusidic acid is a treatment for staphylococcal infections, but should be used with other antistaphylococcal drugs to preve ... | 465 | ||
| Fusidic acid has few side effects | 465 | ||
| Inhibitors of nucleic acid synthesis | 465 | ||
| Quinolones | 465 | ||
| Quinolones are synthetic agents that interfere with replication of the bacterial chromosome | 465 | ||
| Resistance to quinolones is usually chromosomally mediated | 465 | ||
| Because of their safety and tolerability, quinolones are commonly used as alternatives to beta-lactam antibiotics for trea ... | 466 | ||
| Fluoroquinolones are not recommended for children or pregnant or lactating women because of possible toxic effects on cart ... | 466 | ||
| Rifamycins | 467 | ||
| Rifampicin is clinically the most important rifamycin and blocks the synthesis of mRNA | 467 | ||
| The primary use for rifampicin is in the treatment of mycobacterial infections, but resistance is a concern | 467 | ||
| Rashes and jaundice are side effects of rifampicin treatment | 467 | ||
| Antimetabolites affecting nucleic acid synthesis | 467 | ||
| Sulphonamides | 467 | ||
| Sulphonamides are structural analogues of and act in competition with para -aminobenzoic acid | 467 | ||
| Sulphonamides are useful in the treatment of urinary tract infection, but resistance is widespread | 468 | ||
| Rarely, sulphonamides cause Stevens–Johnson syndrome | 468 | ||
| Trimethoprim (and co-trimoxazole) | 468 | ||
| Trimethoprim is a structural analogue of the aminohydroxypyrimidine moiety of folic acid and prevents the synthesis of THFA | 468 | ||
| Trimethoprim is often given with sulphamethoxazole as co-trimoxazole for urinary tract infections | 469 | ||
| Resistance to trimethoprim is provided by plasmid-encoded dihydrofolate reductases | 469 | ||
| People with AIDS seem to be more prone to the side effects of trimethoprim and co-trimoxazole | 469 | ||
| Other agents that affect dna | 469 | ||
| Nitroimidazoles | 469 | ||
| Metronidazole is a nitroimidazole with antiparasitic and antibacterial properties | 469 | ||
| Metronidazole was originally introduced for the treatment of the flagellate parasite Trichomonas vaginalis | 469 | ||
| Rarely, metronidazole causes central nervous system side effects | 469 | ||
| Inhibitors of cytoplasmic membrane function | 469 | ||
| Lipopeptides | 469 | ||
| Lipopeptides are a new class of membrane-active antibiotics | 469 | ||
| Polymyxins | 469 | ||
| Polymyxins act on the membranes of Gram-negative bacteria | 469 | ||
| Polymyxins are primarily used topically but have also been used in the past for gut decontamination, wound irrigation and ... | 469 | ||
| Urinary tract antiseptics | 470 | ||
| Nitrofurantoin and methenamine inhibit urinary pathogens | 470 | ||
| Antituberculosis agents | 470 | ||
| M. tuberculosis and other mycobacterial infections need prolonged treatment | 470 | ||
| The drugs for first-line therapy of tuberculosis are isoniazid, ethambutol, rifampicin, pyrazinamide and streptomycin | 470 | ||
| Isoniazid | 470 | ||
| Isoniazid inhibits mycobacteria and is given with pyridoxine to prevent neurologic side effects | 470 | ||
| Ethambutol | 470 | ||
| Ethambutol inhibits mycobacteria, but can cause optic neuritis | 470 | ||
| Pyrazinamide | 471 | ||
| Mycobacterial resistance | 471 | ||
| Drug resistance and immunocompromised patients complicate tuberculosis therapy | 471 | ||
| Treatment of leprosy | 471 | ||
| The development of resistance during dapsone monotherapy for leprosy has led to its use in combination with rifampicin | 471 | ||
| Antibacterial agents in practice | 471 | ||
| Susceptibility tests | 471 | ||
| Diffusion tests involve seeding the organism on an agar plate and applying filter paper disks containing antibiotics | 471 | ||
| A dilution test provides a quantitative estimate of susceptibility to an antibiotic | 471 | ||
| Killing curves provide a dynamic estimate of bacterial susceptibility | 472 | ||
| Combining antibacterial agents can lead to synergism or antagonism | 473 | ||
| Antibiotic assays | 473 | ||
| Antiviral therapy | 473 | ||
| Prodrugs that target the viral DNA polymerase | 477 | ||
| Acyclovir (acycloguanosine) | 477 | ||
| Acyclovir inhibits HSV and varicella-zoster virus (VZV) DNA polymerase | 477 | ||
| Ganciclovir (dihydroxypropoxy-methylguanine,DHPG) | 477 | ||
| Valganciclovir | 477 | ||
| Cidofovir (HPMPC) | 477 | ||
| Pyrophosphate analogue that blocks the pyrophosphate binding site on the viral DNA polymerase | 477 | ||
| Foscarnet (phosphonoformate) | 477 | ||
| Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) | 477 | ||
| Zidovudine (azidothymidine, AZT) | 478 | ||
| Non-nucleoside reverse transcriptase inhibitors (NNRTIs) | 478 | ||
| Nevirapine, efavirenz (EFV), delavirdine and etravirine | 478 | ||
| Protease inhibitors | 478 | ||
| Nelfinavir, saquinavir, indinavir, ritonavir,lopinavir plus ritonavir (Kaletra) | 478 | ||
| Fusion inhibitors | 479 | ||
| Integrase inhibitors | 479 | ||
| Chemokine receptor antagonists | 479 | ||
| Inosine monophosphate dehydrogenase inhibitor | 479 | ||
| Ribavirin (tribavirin) | 479 | ||
| Antivirals targeting influenza viruses | 479 | ||
| Amantadine and rimantadine | 479 | ||
| Neuraminidase inhibitors: zanamivir, oseltamivir, and peramivir | 479 | ||
| Hepatitis B treatment | 480 | ||
| Hepatitis C treatment | 480 | ||
| Intereferons – immunomodulatory agents | 480 | ||
| Other targets | 480 | ||
| Clinical management of antiviral therapy | 481 | ||
| Viral load and antiviral resistance tests as well as therapeutic drug monitoring assist in clinical management | 481 | ||
| Antifungal agents | 481 | ||
| Antifungals can be classified on the basis of target site and chemical structure | 481 | ||
| Azole compounds inhibit cell membrane synthesis | 481 | ||
| Echinocandins interfere with cell wall synthesis | 482 | ||
| Polyenes inhibit cell membrane function | 482 | ||
| Flucytosine and griseofulvin inhibit nucleic acid synthesis | 482 | ||
| Other topical antifungal agents include Whitfield's ointment, tolnaftate, ciclopirox, haloprogin and naftifine | 482 | ||
| No single antifungal agent is ideal | 482 | ||
| Fungi develop resistance to antifungal agents | 483 | ||
| There is an urgent need for safer more efficacious antifungal agents | 483 | ||
| Antiparasitic agents | 483 | ||
| Parasites pose particular problems | 483 | ||
| Drug resistance is an increasing problem | 483 | ||
| Control by chemotherapy versus vaccination | 483 | ||
| The concept of selectivity, or specificity, is central to both chemotherapy and vaccination | 486 | ||
| The specificity of an antimicrobial drug resides in its ability to damage the microbe and not the host | 486 | ||
| Control versus eradication | 487 | ||
| Control and eradication are different objectives,although eradication is always an ideal endpoint | 487 | ||
| Realism is required when considering the long-term aims of antimicrobial control strategies | 487 | ||
| Use and misuse of antimicrobial agents | 487 | ||
| Antimicrobial agents should only be used appropriately for prophylaxis or treatment | 488 | ||
| Antimicrobial use results in the selection of resistant strains | 488 | ||
| Chapter 34: Protecting the host: vaccination | 491 | ||
| Vaccination - four hundred year history | 491 | ||
| Aims of vaccination | 491 | ||
| The aims of vaccination can vary from preventingsymptoms to eradication of disease | 491 | ||
| The importance of herd immunity | 493 | ||
| Vaccines can be of different types | 493 | ||
| Adjuvants | 495 | ||
| Vaccine safety | 495 | ||
| Vaccines in current use | 495 | ||
| Diphtheria, tetanus and pertussis | 495 | ||
| Measles, mumps and rubella vaccines | 496 | ||
| Mumps vaccine | 496 | ||
| Rubella vaccine | 496 | ||
| Polio vaccine | 496 | ||
| Pneumococcal vaccines | 498 | ||
| Meningococcal vaccines | 498 | ||
| Haemophilus influenzae type b (Hib) | 498 | ||
| Influenza | 498 | ||
| BCG and new vaccines for TB | 500 | ||
| Vaccines against hepatitis | 501 | ||
| Human papillomavirus (HPV) | 501 | ||
| Rotavirus vaccine | 501 | ||
| Vaccines that are required for entry into particular countries, or for particular regions | 501 | ||
| Vaccines for subgroups at high risk | 501 | ||
| Complexity of vaccine schedules | 501 | ||
| Changes in demography means new vaccine strategies are needed | 502 | ||
| New vaccines in development | 502 | ||
| HIV vaccines | 503 | ||
| Malaria | 503 | ||
| Vaccines for neglected tropical diseases | 503 | ||
| New delivery systems and technologies for future vaccines | 503 | ||
| New routes of vaccination | 503 | ||
| The Decade of Vaccines | 504 | ||
| Chapter 35: Passive and non-specific immunotherapy | 505 | ||
| Passive immunization with antibody | 505 | ||
| Certain diseases are treated by a passive transferof immunity, which can be life-saving | 505 | ||
| The use of antiserum raised in animals can cause serum sickness | 505 | ||
| Antibody in pooled normal serum can provide protection against infection | 505 | ||
| Theoretically, the most effective therapy is provided by one or more monoclonal antibodies specific for a known target ant ... | 506 | ||
| Engineering antibodies | 507 | ||
| Bacteriophage libraries provide an invaluable technology for engineering new antibody fragments | 507 | ||
| Single domain variable region fragments have several advantages | 508 | ||
| Non-specific cellular immunostimulation | 508 | ||
| Cytokines and other molecular mediators stimulatethe immune system | 508 | ||
| There is an interesting ‘grey area’ where immunostimulation and nutrition overlap | 509 | ||
| Correction of host immunodeficiency | 509 | ||
| Antibody defects are the easiest to treat | 509 | ||
| Probiotics | 510 | ||
| Chapter 36: Hospital infection, sterilization and disinfection | 511 | ||
| Many hospital infections are preventable | 511 | ||
| Common hospital infections | 511 | ||
| Urinary tract infections are the most common hospitalinfections in adults | 511 | ||
| Important causes of hospital infection | 511 | ||
| Staphylococci and Escherichia coli are the mostimportant Gram-positive and Gram-negative causesof infection, respectively, ... | 511 | ||
| Some infections historically associated with hospitals are now increasingly seen outside of the healthcare setting | 512 | ||
| Viral infections probably account for more hospital infections than previously realized | 513 | ||
| Sources and routes of spread of hospital infection | 513 | ||
| Sources of hospital infection are people andcontaminated objects | 513 | ||
| Hospital infections are spread in the air and by contact and common vehicle | 514 | ||
| Host factors and hospital infection | 514 | ||
| Underlying disease, certain treatments and invasiveprocedures reduce host defences | 514 | ||
| A variety of factors predispose to wound infection | 515 | ||
| Consequences of hospital infection | 515 | ||
| Hospital infections affect both the patientand the community | 515 | ||
| Prevention of hospital infection | 517 | ||
| There are three main strategies for preventing hospital infection | 517 | ||
| Exclusion of sources of infection | 517 | ||
| Exclusion of inanimate sources of infection is achievable, but it can be difficult to avoid contamination by humans | 517 | ||
| Breaking the chain of infection | 518 | ||
| Control of airborne transmission of infection | 518 | ||
| Ventilation systems and air flow can play an important role in the dissemination of organisms by the airborne route | 518 | ||
| Airborne transmission of infection can be reduced significantly by isolating patients | 518 | ||
| Facilitation of aseptic behaviour | 519 | ||
| Bacteriologically effective handwashing is one of the most important ways of controlling hospital infection | 519 | ||
| Enhancing the host's ability to resist infection | 519 | ||
| Host resistance can be enhanced by boosting immunity and reducing risk factors | 519 | ||
| Boosting specific immunity | 520 | ||
| Passive immunization provides short-term protection | 520 | ||
| Appropriate use of prophylactic antibiotics | 520 | ||
| There are well-documented uses for prophylaxis, but antibiotics tend to be misused | 520 | ||
| Gut decontamination regimens and selective bowel contamination aim to reduce the reservoir of potential pathogens in the g ... | 520 | ||
| Care of invasive devices | 520 | ||
| Care of invasive devices is essential to reduce the risk of endogenous infection | 520 | ||
| The majority of hospital-associated bacteraemias and candidaemias are infusion-related | 520 | ||
| Reducing the risks of postoperative infection | 521 | ||
| Prevention of postoperative infection involves minimizing the risks | 521 | ||
| Investigating healthcare-associated infection | 521 | ||
| Surveillance | 522 | ||
| Surveillance allows early recognition of any change in the number or type of hospital infections | 522 | ||
| Investigation of outbreaks | 522 | ||
| There must be a description of an outbreak in epidemiologic terms | 522 | ||
| The causative organism needs to be isolated and/or detected in all patients in the outbreak | 522 | ||
| Stages in tracking infection | 522 | ||
| Epidemiologic typing techniques | 522 | ||
| A variety of phenotypic and genotypic characters are used to ‘fingerprint’ bacteria for epidemiologic purposes | 522 | ||
| Antibiotic susceptibility patterns | 523 | ||
| Specialized typing techniques | 523 | ||
| Serotyping distinguishes between strains, using specific antisera | 523 | ||
| Bacteriophage (phage) typing has been used to type Staph. aureus , Staph. epidermidis and Salmonella typhi | 523 | ||
| Molecular typing | 523 | ||
| Molecular typing techniques involve characterizing an organism's DNA | 523 | ||
| Plasmid profiles are an example of ‘first-generation’ molecular epidemiology | 523 | ||
| Restriction enzymes and probes represent ‘second-generation’ molecular epidemiology | 524 | ||
| PFGE and PCR are ‘third-generation’ approaches to molecular epidemiology | 525 | ||
| ‘Fourth-generation’ molecular epidemiology is based on DNA sequence analysis | 525 | ||
| Molecular techniques for epidemiologic fingerprinting have many advantages | 525 | ||
| Investigation of viral infections | 526 | ||
| Corrective / Preventive measures | 526 | ||
| Once tracking is complete, corrective and preventive measures can be introduced | 526 | ||
| Sterilization and disinfection | 526 | ||
| Definitions | 526 | ||
| Sterilization is the process of killing or removing all viable organisms | 526 | ||
| Disinfection is a process of removing or killing most, but not all, viable organisms | 526 | ||
| Antiseptics are used to reduce the number of viable organisms on the skin | 526 | ||
| Pasteurization can be used to eliminate pathogens in heat-sensitive products | 527 | ||
| Deciding whether sterilization or disinfection should be used | 527 | ||
| It is easier to sterilize a clean object than a physically dirty one | 527 | ||
| The rate of killing of microorganisms depends upon the concentration of the killing agent and time of exposure | 527 | ||
| Techniques for sterilization | 528 | ||
| Heat | 528 | ||
| Dry heat sterilizes by oxidation of the cell components | 528 | ||
| The most effective agent for sterilization is saturated steam (moist heat) under pressure | 528 | ||
| Immersion in boiling water for a few minutes can be used as a rapid emergency measure to disinfect instruments | 528 | ||
| Pasteurization uses heat at 62.8–65.6°C for 30 min | 528 | ||
| Irradiation | 528 | ||
| Gamma irradiation energy is used to sterilize large batches of small-volume items | 528 | ||
| Filtration | 529 | ||
| Filters are used to produce particle- and pyrogen-free fluid | 529 | ||
| Chemical agents | 529 | ||
| The gases ethylene oxide and formaldehyde kill by damaging proteins and nucleic acids | 529 | ||
| The liquid glutaraldehyde is used to disinfect heat-sensitive articles | 529 | ||
| Many different antimicrobial chemicals are available, but few are sterilant | 529 | ||
| Controlling sterilization and disinfection | 529 | ||
| In general, it is preferable to control the process rather than the product | 529 | ||
| Disinfectants can be monitored by microbiologic ‘in-use’ tests | 530 | ||
| Bibliography | 531 | ||
| Index | 539 | ||
| Pathogen parade | e1 | ||
| Viruses | e1 | ||
| Bacteria | e13 | ||
| Fungi | e37 | ||
| Protozoa | e40 |