Chagas Disease (eBook)

Front Cover 1
Chagas Disease, Part A 4
Copyright 5
Contents of Volume 75 6
Contributors of Volume 75 16
Preface 22
Chapter 1: Epidemiology of American Trypanosomiasis (Chagas Disease) 28
1.1 Historical Background 29
1.2 Mechanisms of Transmission of Trypanosoma cruzi 30
1.3 Epizootiology of Trypanosoma cruzi 34
1.4 Epidemiology of Human Trypanosoma cruzi Infection in the Endemic Countries 34
1.5 Epidemiology of Trypanosoma cruzi Infection in the United States 37
1.6 Trypanosoma cruzi Infection in Non-Endemic Countries Other than the United States 40
1.7 Perspectives on the Control of Chagas Disease 41
References 41
Chapter 2: Acute and Congenital Chagas Disease 46
2.1 Introduction 47
2.2 Acute Phase 48
2.3 Clinical and Diagnostic Aspects of Congenital Trypanosoma cruzi Infection 51
2.4 Antitrypanosomal Drug Treatment 54
2.5 Epidemiology of Congenital Chagas Disease 57
2.6 Approaches to the Control of Congenital Chagas Disease 64
2.7 Conclusions 66
References 66
Chapter 3: Cell-Based Therapy in Chagas Disease 76
3.1 Introduction 77
3.2 Cell Therapy in Cardiac Diseases 78
3.3 Cell Therapy in Chagas Disease 80
3.4 Clinical Trials 82
3.5 Future Perspectives for Cell-Based Therapies in Chagas Disease 84
References 87
Chapter 4: Targeting Trypanosoma cruzi Sterol 14a-Demethylase (CYP51) 92
4.1 Introduction 93
4.2 Sterol Biosynthesis 94
4.3 Potential Drug Targets in the Pathway 96
4.4 Trypanosoma cruzi Sterol 14a-Demethylase (CYP51) 97
4.5 Inhibitors of Trypanosoma cruzi CYP51 100
4.6 Structural Basis for CYP51 Druggability 103
4.7 Anti-Parasitic Effects of CYP51 Inhibition in Trypanosoma cruzi 108
Acknowledgements 111
References 111
Chapter 5: Experimental Chemotherapy and Approaches to Drug Discovery for Trypanosoma cruzi Infection 116
5.1 Introduction 117
5.2 Compound Selection 120
5.3 In Vitro Efficacy Testing 123
5.4 Toxicity Testing 130
5.5 In Vivo Efficacy Testing 132
5.6 Testing for Drug-Like Properties and Safety 135
5.7 Advances in Experimental Chemotherapy for Trypanosoma cruzi Infection 138
5.8 Conclusions 139
Acknowledgements 139
References 139
Chapter 6: Vaccine Development Against Trypanosoma cruzi and Chagas Disease 148
6.1 Vector, Parasite and Disease Burden 149
6.2 Treatment 150
6.3 A Case for Vaccine Development Against Trypanosoma cruzi 150
6.4 Immunity to Trypanosoma cruzi 152
6.5 Vaccine Development Against Trypanosoma cruzi 153
6.6 Future Prospects 165
Acknowledgements 166
References 166
Chapter 7: Genetic Epidemiology of Chagas Disease 174
7.1 Introduction 175
7.2 Genetic Epidemiological Approaches to Chagas Disease 177
7.3 Exploring the Genetic Architecture of Chagas disease 182
7.4 Mapping the Future of Genetic Epidemiological Studies of Chagas Disease 189
Acknowledgements 189
References 189
Chapter 8: Kissing Bugs. The Vectors of Chagas 196
8.1 Introduction 197
8.2 Vector Genera and Species 198
8.3 Evolution of the Triatomines 201
8.4 Biology of the Bugs 204
8.5 Urbanization of the Bugs 206
8.6 Control of Vectors 207
8.7 Non-Infectious Consequences of Atriatomine Bite 210
8.8. Conclusion 212
Acknowledgement 213
References 213
Chapter 9: Advances in Imaging of Animal Models of Chagas Disease 220
9.1 Introduction 221
9.2 Larger Animal Models 223
9.3 Mouse Models 224
9.4 Future Directions: Multimodality Imaging Approaches 231
Acknowledgements 231
References 232
Chapter 10: The Genome and Its Implications 236
10.1 Genome Organization, Gene Content and Gene Expression Mechanisms 237
10.2 Comparative Genome Analyses 242
10.3 Antigen Discovery and Identification of Other Parasite Molecules Involved in Host-Parasite Interactions 244
10.4 Manipulating the Trypanosoma cruzi Genome and the Perspectives of Developing New Tools for the Study of Chagas Disease.. 248
References 252
Chapter 11: Genetic Techniques in Trypanosoma cruzi 258
11.1 Introduction 259
11.2 Genetic Tools Applicable to Trypanosoma cruzi 259
11.3 The use of Genetic Techniques to Investigate Trypanosoma cruzi Oxidative Defence and Drug-Resistance Mechanisms... 269
11.4 Concluding Remarks 273
Acknowledgements 274
References 274
Chapter 12: Nuclear Structure of Trypanosoma cruzi 278
12.1 General Aspects of Nuclear Organization in Eukaryotic Cells 279
12.2 The Nucleus of Trypanosoma cruzi 283
12.3 The Nucleus Under Stress 300
12.4 Conclusion and Perspectives 302
Acknowledgements 305
References 305
Chapter 13: Aspects of Trypanosoma cruzi Stage Differentiation 312
13.1 Introduction 313
13.2 Trypanosoma cruzi Differentiation 313
13.3 Stage-Specific Antigens 316
13.4 Proteinases and Differentiation 320
13.5 Stage-Specific Gene Expression 321
13.6 Conclusion 323
References 323
Chapter 14: The Role of Acidocalcisomes in the Stress Response of Trypanosoma cruzi 334
14.1 Introduction 335
14.2 Acidocalcisomes in Trypanosoma cruzi 336
14.3 Volume Regulation 339
14.4 The Contractile Vacuole Complex 340
14.5 Acidocalcisomes and the CVC 341
14.6 Signalling Pathways Involved in Volume Regulation 342
14.7 Drug Targeting of the Volume-Regulatory Pathway 343
14.8 Model for Volume Regulation 344
14.9 Poly P, Stress Response and Virulence 346
14.10 Conclusions 347
Acknowledgements 347
References 347
Chapter 15: Signal Transduction in Trypanosoma cruzi 352
15.1 Introduction 353
15.2 cAMP-Dependent Pathway in Trypanosoma cruzi 354
15.3 MAPK Pathways in Trypanosoma cruzi 359
15.4 Protein Phosphatases in Trypanosoma cruzi 363
15.5 Protein kinases and Protein Phosphatases as Drug Target in Trypanosoma cruzi 365
15.6 Concluding Remarks 366
Acknowledgements 366
References 366
Index 372
Contents of Volumes in this Series 380
Color Plates 392