Contents

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'["1-Prelace ix 10. Adaptive responses provide aAcknowledgements xi 'quantum leap' in eHective defense

(\1 .The role 01 antibodies 93

A contemporary approach to microbiology The role of T Iymphocytes 96

Microbes and parasites 1 Extracellularattack on large inlectious agents 99

The context for contemporary medical Local delenses at mucosal surlaces 100

microbiology 111. The cellular basis of adaptive

Microbiology post, present and luture 2

The approach adopted in this book 4 immune responsesB-and T-cellreceptors 105

SECTlON 1 THEADVERSARIES- MICROBES Clonal expansion of Iymphocytes 105

The role 01 memory cells 107

1. Microbes as parasites Stimulation 01 Iymphocytes 109The varieties 01 microbes 9 Cytokines 111

Livinginside or outside cells 10 Regulatory mechanisms 115

Systems 01 classilication 11 ToIerance mechanisms 115

2. The bacteria.1 SECTlON3 THECONFUCTS

Structure 15Nutrition 17 12. Background to the infectious diseasesGrowth and division 18 Host-parasite relationships 121

Gene expression 20 Causes of inlectious diseases 125Extrachromosomal elements 24 The biologic response gradient 127

Mutation and gene transler 2613. Entry, exit and transmissionSurvival under adverse conditions 32

The genomics of medically important bacteria 32 Sites 01 entry 129Exitand transmission 136

3. The viruses Types 01 transmission belween humans 138Inlection 01 host cells 37 Transmission Irom animals 143

Replication 3914. Immune defenses in action

Outcome of viral inlection 42Complement 149

Major groups 01viruses 46Acute phase proteins and pattern recognition

4. The fungi receptors 149

Major groups of disease-causing lungi 47 Fever 150

5. The protozoa 51Natural killercells 150

Phagocytosis 151

6. The helminths and arthropods Cytokines 154The helminths 53 Antibody-mediated immunity 156

The arthropods 56 Cell-mediated immunity 158

7. Prions Recovery from inlection 163

'Rogue protein' pathogenesis 59 15. Spread and replicationDevelopment and transmission 01 prion diseases 60 Features 01 surlace and systemic inlections 165

Medical problems posed by prion diseases 61 Mechanisms of spread through the body 167

8. The host-parasite relationshipGenetic determinants 01 spread and replication 170

The normal llora 63 Other lactors affecting spread and replication 173

Symbiotic associations 66 16. Parasite survival strategies andThe characteristics 01 parasitism 68 persistent infectionsThe evolution 01 parasitism 69 Parasite survival strategies 176

SECTION2 THEADVERSARIES- HOST DISEASESAntigenic variation 181

Immunosuppression 182

9. The innate defenses of the bodyPersistent inlections 185

Delense against entry into the body 77 17. Pathologic consequences of infectionDelenses once the microorganism penetrates Pathology caused directly by microorganism 191

the body 77 Diarrhea 195

. :-.."!:IHI - - - --- - ------

Pathologic activation of natural immune Genital herpes 273mechanisms 197 Human papillomavirus infection 274

Pathologic consequences of the immune Human immunodeficiency virus 274

response 200 Opportunist STDs 285Skin rashes 204 Arthropod infestations 285Viruses and cancer 205

22. Gastrointestinal tract infectionsSECTION4 CLlNICALMANIFESTATIONAND Diarrheal diseases caused by bacteria! orDIAGNOSIS OF INFECTIONSBY BODY SYSTEM virol infection 288

Introduction to Section 4: The Clinical Food poisoning 302

Manifestations of Infection 211 Helicobacter pylori and gastric ulcer disease 303

Parasites and the gastrointestinal tract 30418. Upper respiratory tract infections Systemic infection initiated in the

The common cold 213 gastrointestinal tract 311Pharyngitis and tonsillitis 215Parotitis 222 23. Obstetric and perinatal infectionsOtitis and sinusitis 223 Infectionsoccurring in pregnancy 323

Acute epiglottitis 225 Congenital infections 323

Oral cavity infections 225 Infections occurring around the time of birth 328

19. Lower respiratory tract infections 24. Central nervous system infectionsLaryngitisand tracheitis 227 Invasion of the central nervous system 333

Diphtheria 227 The body' s response to invasion 333

Whooping cough 228 Meningitis 335Acute bronchitis 229 Encephalitis 341

Acute exacerbations of chronic bronchitis 230 Neurologic diseases of possible viral etiology 346Bronchiolitis 230 Spongiform encephalopathies caused byRespiratory syncytial virus infection 230 scrapie-type agents 346

Hantavirus cardiopulmonary syndrome 231 CNS disease caused by parasites 347Pneumonia 231 Brain abscesses 348

Bacterial pneumonia 233 Tetanus and botulism 348

Viral pneumonia 23725. Infections of the eyeParainlluenza virus inlection 237

Adenovirus infection 237 Conjunctivitis 351

Human metapneumovirus 238 Inlection of the deeper layers 01 the eye 352

Human bocavirus 238 26. Infections of the skin, 50ft tissue,Influenza virus inlection 238 muscle and associated systemsSevere acute respiratory syndrome-associated Bacterial infections 01 skin, soft tissue

coronavirus infection 243 and muscle 357Measles 244 Mycobacterial diseases of the skin 365Cytomegalovirus inlection 244 Fungal infections of the skin 368Tuberculosis 245 Parasitic infections of the skin 373Cystic fibrosis 248 Mucocutaneous lesions caused by viruses 374

Lungabscess 248 Smallpox 382

Fungal infections 249 Measles 382Parasitic infections 250 Rubella 384

20. Urinary tract infections Other inlections producing skin lesions 385

Acquisition and etiology 253 Kawasaki syndrome 385Viral infections of muscle 386

Pathogenesis 254Parasitic inlections of muscle 386

Clinical features and complications 256Joint and bone infections 387

Laboratory diagnosis 257Infections of the hemopoietic system 389

Treatment 259Prevention 260 27. Vector-borne infections

21. Sexually transmitted diseasesArbovirus infections 391

STDsand sexual behaviour 261 Infections caused by Rickettsiae 393

Syphilis 261Borrelia infections 397ProtozooI inlections 399Gonorrhea 266Helminth inlections 405

Chlamydial infection 268

Other causes of inguinallymphadenopathy 270 28. Multisystem zoonosesMycoplasmas and non-gonococcal urethritis 272 Arenavirus inlections 409

Other causes 01 vaginitis and urethritis 272 Korean hemorrhagic fever 410

Marburg and Ebola hemorrhagic fevers 410 33. Attacking the enemy: antimicrobialCrimean-Congo hemorrhagic fever, agents and chemotherapy

a tick-borne virus 412 Selective toxicity 479Q fever 412 Discovery and design of antimicrobial agents 479Anthrax 412 Classification of antibacterial agents 479

Plague 413 Resistance to antibacterial agents 481Yersinio enterocolitico infection 414 Classes of antibacterial agents 484Tularemia 414 Inhibitors of cell wall synthesis 484Posteurel/o mu/tocida infection 416 Inhibitors of protein synthesis 490

Leptospirosis 416 Inhibitorsof nucleicacid synthesis 498Ratbite fever 417 Antimetabolitesaffecting nucleicacid synthesis 500Brucellosis 417 Other agents that affect DNA 502Helminthinfections 418 Inhibitorsof cytoplasmicmembranefunction 502

29. Fever of unknown origin Urinarytract antiseptics 503

Definitionsof feverof unknownorigin 421 Antituberculous agents 503

Causesof FUO 421 Antibacterialagents in practice 504

Investigationof classicalFUO 422 Antibiotic assays 506

Treatmentof FUO 425 Antiviral therapy 507

FUO in specific patient groups 426 Antifungalagents 513

Infectiveendocarditis 426 Antiparasiticagents 515

Use and misuseof antimicrobialagents 51530. Infedions in the compromised host 34. Protedion the host: vaccination

The compromised host 429Aims of vaccination 519

Infectionsof the hostwith deficient innateRequirementsof a good vaccine 519

immunitydue to physicalfactors 432

Infectionsassociatedwith secondaryadaptiveTypesof vaccine 521

immunodeficiency 435 Special considerations 526

Other importantopportunistpathogens 436 Currentvaccine practice 530New and experimentalvaccines 538

SECTIONS - DIAGNOSIS AND CONTROL 35. Passive and non-specific

31. Strategies for controlimmunotherapyPassiveimmunization with antibody 543

Epidemiologicconsiderations 445Non-specificcellular immunostimulation 546

Detectionand diagnosis 450Correctionof host immunodeficiency 548

Epidemiologicaspectsof vaccinations 450Probiotics 548

Factorsinfluencingthe successof vaccination 453More immunogenicvaccinesprovide better 36. Hospital infedion, sterilization and

protection,but may be lesssafe 454 disinfedion

Control by chemotherapyversusvaccination 455 Common hospital infections 551Control versuseradication 457 Importat causesof hospital infection 551

32. Diagnosis of infedion and assessmentSources and routesof spread of hospital

infection 553of host defense mechanisms

Hostfactorsand hospital infection 554Aimsof the clinical microbiology laboratory 459

Consequencesof hospital infection 557Specimenprocessing 459

Preventionof hospital infection 558Non-culturaltechniquesfor the laboratory

Investigatinghospital infection 561diagnosisof infection 461

Sterilizationand disinfection 568Cultivation(culturelof microorganisms 468Identificationof microorganismsgrown

Appendix - Pathogen parade 573in culture 469

Antibody detectionmethodsfor the diagnosis Bibliography 625of infection 471

Assessment of host defense systems 472 Index 635