National Institute of Allergy and Infectious Diseases, NIH (eBook)

Foreword 7
Acknowledgments 10
In Memoriam 11
Contents 12
Part I Microbiology and Infectious Diseases 27
Chapter 1 Introduction 28
1.1 Primary NIAID Research Areas in Microbiology and Infectious Diseases (Non-HIV/AIDS) 30
Chapter 2 NIAID International Research Programs: Global Impact 33
2.1 Global Research: Africa 34
2.2 Global Research: Asia 40
2.3 Partnerships 41
References 42
Chapter 3 Bacterial Diseases 43
3.1 Resources for Researchers 43
3.2 Recent Scientific Advances 44
References 45
Chapter 4 Emerging and Re-emerging Infectious Diseases 46
4.1 Recent Outbreaks of Emerging and Re-emerging Infectious Diseases 46
4.2 Research Plans and Priorities 47
4.3 Resources for Researchers 48
4.4 List of NIAID Emerging and Re-emerging Diseases 48
References 49
Chapter 5 Fungal Diseases 51
5.1 Plans, Priorities, and Goals 52
5.2 Resources for Researchers 52
5.3 Recent Scientific Advances 52
References 53
Chapter 6 Tropical Medicine and Parasitic Diseases 54
6.1 Incidence and Prevalence of Morbidity andMortality 54
6.2 Neglected Tropical Diseases 56
6.3 NIAID Involvement in Tropical Medicine and Parasitic Diseases 57
6.4 Recent Scientific Advances 59
References 60
Chapter 7 Virology 62
7.1 Resources for Researchers 62
7.2 Recent Scientific Advances 63
References 63
Chapter 8 Sexually Transmitted Infections 64
8.1 Chlamydia 64
8.2 Gonorrhea 64
8.3 Syphilis 65
8.4 Chancroid 65
8.5 Trichomoniasis 65
8.6 Oral and Genital Herpes 65
8.7 Human Papillomavirus 65
8.8 Bacterial Vaginosis 66
8.9 Impact of STIs onWomen and Infants 67
8.10 Impact of STIs on HIV/AIDS 67
8.11 NIAID Involvement in STI Research 68
8.12 Recent Scientific Advances 69
8.13 Clinical Trials 69
References 69
Chapter 9 Enteric Diseases 70
9.1 Epidemiology of Enteric Diseases 70
9.2 Shigella spp. 71
9.3 Salmonella spp. 71
9.4 Yersinia enterocolitica 72
9.5 Campylobacter spp. 73
9.6 Clostridium botulinum 74
9.7 Listeriamonocytogenes 75
9.8 Escherichia coli Diarrheal Diseases 75
9.9 Novoviruses 80
9.10 Rotaviruses 80
9.11 Recent Scientific Advances 80
9.12 NIAID Involvement in Enteric Diseases Research 81
9.13 Enteric Vaccines for Pediatric Use 82
9.14 Mucosal Immunity 83
9.15 Live Bacteria Vectors 84
9.16 Delivery Platforms 84
References 84
Chapter 10 Respiratory Diseases 87
10.1 Adenoviruses 87
10.2 Mycoplasma pneumoniae 88
10.3 Bordetella pertussis 88
10.4 Respiratory Syncytial Virus 88
10.5 Human Metapneumovirus 89
10.6 Human Parainfluenza Viruses 89
10.7 Respiratory Diphtheria 89
10.8 Chlamydia pneumoniae 89
10.9 Pseudomonas aeruginosa and Cystic Fibrosis 89
10.10 BacterialMeningitis 90
10.11 Recent Scientific Advances 91
10.12 NIAID Involvement in Respiratory Diseases Research 91
10.13 Clinical Trials 92
References 92
Chapter 11 Streptococcus pneumoniae (Pneumococcal) Disease 94
11.1 Streptococcal Vaccines 95
11.2 Recent Scientific Advances 96
11.3 Antimicrobial Drug Resistance 97
11.4 NIAID Involvement in International Research on Pneumococcal Disease 98
References 98
Chapter 12 Severe Acute Respiratory Syndrome 100
12.1 NIAID Agenda for SARS Research 100
12.2 Recent Scientific Advances 101
References 102
Chapter 13 Influenza 103
13.1 Pathophysiology 103
13.2 Influenza A (H1N1) Pandemic of 1918–1919 104
13.3 Asian Influenza A Pandemics of 1957 and 1968 106
13.4 Avian Influenza A (H5N1) 106
13.5 Avian Influenza A (H9N2) 108
13.6 NIAID and Influenza Research 108
13.7 Influenza Vaccine Research 112
References 117
Chapter 14 Tuberculosis 121
14.1 Mycobacterium tuberculosis Co-infection in AIDS Patients 121
14.2 Mycobacteriumtuberculosis 122
14.3 Diagnostic and Differentiation Procedures for Mycobacterium tuberculosis 124
14.4 Host Defense AgainstMycobacteria 125
14.5 Evolution of Therapies and Treatment of Mycobacterium tuberculosis 125
14.6 Recent Scientific Advances 131
14.7 NIAID Research Agenda in Tuberculosis 133
References 138
Chapter 15 Viral Hepatitis 143
15.1 Hepatitis A 143
15.2 Hepatitis B 143
15.3 Hepatitis C 143
15.4 Hepatitis D (Delta) 145
15.5 Recent Scientific Advances 145
15.6 NIAID Involvement in Viral Hepatitis Research 145
References 146
Chapter 16 West Nile Virus 148
16.1 NIAID Involvement in West Nile Virus Research 148
16.2 Recent Scientific Advances 150
16.3 Clinical Trials 151
References 151
Chapter 17 Herpesviruses 152
17.1 Cytomegalovirus 152
17.2 Varicella-Zoster Virus 153
17.3 Herpes Simplex Virus 153
17.4 Epstein-Barr Virus 154
17.5 Human Herpesvirus 6 155
17.6 Human Herpesvirus 7 155
17.7 Human Herpesvirus 8 155
17.8 Recent Scientific Advances 155
17.9 Clinical Trials 156
References 156
Chapter 18 Paramyxoviridae: Nipah Virus and Hendra Virus 159
18.1 Phylogeny 159
18.2 Molecular Biology of Paramyxoviruses 160
18.3 Henipavirus Zoonoses 162
References 164
Chapter 19 Arthropod-Borne Viral Encephalitis 167
19.1 Flaviviruses 167
19.2 Alphaviruses 171
19.3 Bunyaviruses 175
References 175
Chapter 20 Malaria 179
20.1 Life Cycle and Morphology of Plasmodium 179
20.2 Cellular and Molecular Biology of Plasmodium 180
20.3 Human Malaria and Inherited Hemoglobin Abnormalities 184
20.4 Molecular Mechanisms of Virulence 186
20.5 Human Malaria: Clinical Manifestations 187
20.6 Treatment of Malaria 189
20.7 Vaccines Against Malaria 192
20.7.7 Sexual-Stage Vaccines 20.8 NIAID Involvement inMalaria Research 196
20.8 NIAID Involvement inMalaria Research 196
20.9 Recent Scientific Advances 200
References 200
Chapter 21 Rickettsia: The Typhus Group 208
21.1 Rickettsia prowazekii Genome 208
21.2 Epidemiology and Clinical Manifestations of Typhus 209
References 209
Chapter 22 Tick-Borne Bacterial, Rickettsial, Spirochetal, and Protozoal Diseases 211
22.1 Lyme Disease (Lyme Borreliosis,Lyme Arthritis) 211
22.2 Tick-Borne Rickettsial Diseases 222
22.3 Tularemia 227
22.4 Southern Tick-Associated Rash Illness 228
22.5 Babesiosis 229
22.6 Tick-Borne Relapsing Fever 230
References 231
Chapter 23 Defense Against BiologicalWeapons (Biodefense) 235
23.1 History of Biological Warfare 235
23.2 Biological and ToxinWeapons Factors 237
23.3 Anthrax (Bacillus anthracis) 238
23.4 Variola Major Virus (Smallpox) 241
23.5 Yersinia pestis: Plague 245
23.6 Brucellosis 248
23.7 Coxiella burnetii: Q Fever 250
23.8 Glanders 253
23.9 Melioidosis 256
23.10 Viral Hemorrhagic Fever: Filoviruses 259
23.11 Viral Hemorrhagic Fever: Bunyaviridae 262
23.12 Viral Hemorrhagic Fever: Arenaviruses 273
23.13 Viral Hemorrhagic Fever: Flaviviruses 279
23.14 Protein ToxinWeapons 286
23.15 Arthropod-Borne Viral Fever and Arthropathy 292
23.16 NIAID Research Agenda in Biodefense 294
23.17 Recent Scientific Advances 300
References 304
Chapter 24 Antimicrobial Resistance and Health Care–Acquired Infections 320
24.1 Environmental Factors of Drug Resistance 321
24.2 Methicillin-Resistant Staphylococcus aureus 321
24.3 Drug Resistance and Nosocomial Infections 323
24.4 Cellular Physiology and Genetics of Antimicrobial Resistance 323
24.5 NIAID Involvement in Research 324
24.6 Recent Programmatic Accomplishments/Developments 325
24.7 Resources for Researchers 326
24.8 Recent Scientific Advances 326
References 326
Chapter 25 Genomic and Postgenomic Research 328
25.1 Computational Methods for Genome Analysis 328
25.2 Genomes of Pathogenic Enterobacteria 328
25.3 Bacterial Proteomes as Complements of Genomes 331
25.4 NIAID Research Programs in Genomic Research 332
25.5 Recent Scientific Advances 339
References 339
Chapter 26 Drug Development Research 342
26.1 Recent Programmatic Accomplishments/Developments 342
26.2 Recent Research Programs in Drug Development 345
26.3 Recent NIAID-Supported Scientific Advances 345
References 347
Part II Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome 348
Chapter 27 Introduction 349
27.1 Human Immunodeficiency Virus 349
27.2 HIV/AIDS Global Pandemic 362
References 363
Chapter 28 NIAID: Extramural Basic Research Programs 371
28.1 Research Activities 371
28.2 Recent Scientific Advances 374
References 374
Chapter 29 NIAID: Programs in HIV Prevention 375
29.1 Research Areas of NIAID Support 375
29.2 Clinical Trials 382
References 385
Chapter 30 NIAID: Programs in HIV/AIDS Therapeutics 386
30.1 Drug Discovery 386
30.2 Preclinical Drug Development 387
30.3 Clinical Research 387
30.4 Resources for Researchers 389
30.6 Clinical Trials 390
Chapter 31 NIAID: Programs in HIV Vaccines 392
31.1 Research Activities 392
31.2 Resources for Researchers 395
31.3 NIAID Research Initiatives 396
Chapter 32 NIAID: International Involvement in HIV/AIDS Research 397
32.1 The Division of AIDS at NIAID 397
32.2 Clinical Trials Network Studies 397
References 414
Chapter 33 HIV/AIDS Epidemiology 415
33.1 HIV Epidemiology and Transmission Factors: Risks and Risk Contexts 416
33.2 HIV Epidemiology in Children 417
33.3 Epidemiology of HIV in the United States 418
33.4 NIAID Involvement in Epidemiology Research 420
33.5 Recent Scientific Advances 422
References 422
Chapter 34 HIV Therapeutics: Antiretroviral Drugs and Immune-Based Therapies 425
34.1 HIV Reverse Transcriptase 425
34.2 HIV Reverse Transcriptase Inhibitors: Nucleoside Analogues 426
34.3 Nucleotide Analogues: Tenofovir DF 434
34.4 HIV Reverse Transcriptase Inhibitors: Non-nucleoside Analogues 436
34.5 HIV Protease 449
34.6 HIV Protease Inhibitors 450
34.7 Fixed-Dose Combinations 475
34.8 Viral Entry/Fusion Inhibitors 479
34.9 Integrase Inhibitors 484
34.10 Maturation Inhibitors 489
34.11 HAART: Triple Highly Active Antiretroviral Combinations 491
34.12 Recent Scientific Advances 493
References 494
Chapter 35 Vaccine Development 525
35.1 Vaccine Clinical Trials 526
35.2 Vaccine Discovery and Development/Clinical Research 526
35.3 The Failure of the STEP Trial 535
References 537
Chapter 36 Opportunistic Infections 541
36.1 Fungal Infections 541
36.2 Viral Infections 549
36.3 Parasitic Infections 551
36.4 Recent NIAID-Supported Clinical Studies on HIV Disease Complications and Co-Infections 563
References 565
Part III Immunology Research 582
Chapter 37 Introduction 583
References 583
Chapter 38 Mammalian Host Defenses: Innate and Adaptive Immunity 585
38.1 Toll-like Receptors 585
38.2 The Macrophage Mannose Receptor and Innate Immunity 586
38.3 Lung Collectins in Pulmonary Innate Immunity 587
38.4 Complement Control Proteins 588
38.5 Lipopolysaccharide-Binding Protein and CD14 591
38.6 Chemokines in Innate and Adaptive Immunity 591
38.7 Innate Immune Signaling During Phagocytosis 598
38.8 Mast Cells and Innate Immunity 602
38.9 CD1-Restricted T Cells as Effectors of Innate Immunity 606
38.10 Interleukin-17 Family of Cytokines 610
References 615
Chapter 39 Immune Adjuvants 635
39.1 Adjuvants and the Initiation of T-Cell Responses 635
39.2 Bacterial Deoxyribonucleic Acid:Cytosine Phosphate Guanine 638
39.3 Modified Bacterial Toxins 641
39.4 Cholera Toxin and Escherichia coli Enterotoxin 642
39.5 Pertussis Toxin 643
39.6 Monophosphoryl Lipid A and Synthetic Lipid AMimetics 644
39.7 Clinical Experience with Modified Bacterial Toxins 645
39.8 Glycosylphosphatidylinositol Anchors from Protozoan Parasites 646
39.9 Helminth Glycan LNFPIII/Lewis X 647
39.10 Muramyl Peptides: Murabutide 648
39.11 Quillaja Saponins: QS-21 649
References 650
Chapter 40 Immune Tolerance 661
40.1 Concepts of Immune Tolerance 661
40.2 Disruption of Immune Tolerance 663
40.3 NIAID-Supported Research in Immune Tolerance 665
40.4 Immune Tolerance Network 665
40.5 Recent Scientific Advances 667
References 669
Chapter 41 Autoimmune Diseases 673
41.1 Classification of Autoimmune Diseases 673
41.2 Risk Factors in Autoimmune Diseases 674
41.3 Genetic Susceptibility 675
41.4 Disease Progression and Therapeutic Strategies 676
References 679
Chapter 42 Mucosal Immune System 683
42.1 The Mucosal Surface 683
References 688
Chapter 43 The Role of B Cells 691
43.1 Genealogy of B Cells 691
43.2 BlyS and B Cells Homeostasis 693
References 695
Chapter 44 Transplantation 700
44.1 Islet Transplantation 701
44.2 Solid-Organ Transplantation 706
44.3 NIAID Involvement in Transplantation 709
References 711
Chapter 45 Asthma and Allergic Diseases 716
45.1 Pathophysiology of Allergic Diseases 716
45.2 Characteristics of Asthma 717
45.3 Treatment of Asthma 722
45.4 NIAID Involvement in Asthma and Allergic Diseases 727
References 730
Index 736