| Preface | p. ix |
| Contributors | p. xi |
| Introduction | |
| The Haldane Hypothesis | p. 2 |
| Glucose-6-Phosphate Dehydrogenase Deficiency and Malarial Resistance | p. 5 |
| Phagocytosis of Ring Forms | p. 6 |
| Evolutionary Considerations: Malaria's Eve Hypothesis | p. 6 |
| Malaria Vaccines | p. 8 |
| References | p. 10 |
| J.B.S. Haldane (1892-1964) | |
| Population Genetics | p. 16 |
| Beanbag Genetics | p. 17 |
| Terminology | p. 17 |
| Human Genetics | p. 18 |
| Genetic Load Theory | p. 19 |
| Immunogenetics | p. 19 |
| Sociobiology | p. 21 |
| Daedalus and Eugenics | p. 21 |
| References | p. 22 |
| Removal of Early Parasite Forms from Circulation as a Mechanism of Resistance Against Malaria in Widespread Red Blood Cell Mutations | |
| Introduction | p. 25 |
| Malaria is Responsible for High Frequency and Regional Distribution of Major Protective RBC Mutations: Geographical Evidence | p. 27 |
| Epidemiological Evidence: Degree of Protection Afforded by RBC Mutations | p. 29 |
| Hemoglobin AS (Sickle-Cell Trait) | p. 29 |
| Thalassemias | p. 29 |
| Hemoglobin C | p. 30 |
| Hemoglobin E | p. 30 |
| Glucose-6-Phosphate Dehydrogenase | p. 31 |
| Southeast Asian Ovalocytosis | p. 32 |
| A Critical Assessment of the Current Mechanism of Protection by Widespread RBC Mutations | p. 32 |
| Sickle-Cell Anemia | p. 36 |
| Beta-Thalassemia | p. 36 |
| Alpha-Thalassemia | p. 37 |
| Glucose-6-Phosphate Dehydrogenase Deficiency | p. 38 |
| Modifications in the RBC Membrane Elicited by the Developing Parasite Induce Phagocytosis | p. 39 |
| Similarity of Ring Phagocytosis to Phagocytosis of Normal Senescent or Oxidatively Stressed RBCs | p. 39 |
| Enhanced Phagocytosis of Ring Forms as a Model of Protection for Widespread RBC Mutations | p. 41 |
| Membrane Binding of Hemichromes, Autologous IgG, Complement C3c Fragment; Aggregated Band 3 and Phagocytosis in Nonparasitized and Ring-Parasitized Normal and Mutant RBCs | p. 41 |
| Why are Rings Developing in Beta-Thalassemia, Sickle-Cell Trait, HbH, and G6PD-deficient RBCs Phagocytosed More Intensely than Rings Developing in Normal RBCs? | p. 43 |
| What is the Evidence that Ring-Parasitized Mutant RBCs are Also Preferentially Removed In Vivo? | p. 45 |
| Why is Preferential Removal of Ring-Forms Advantageous to the Host? | p. 46 |
| Why are Rings Developing in Alpha-Thalassemia Very Similar to Controls? | p. 46 |
| Conclusions | p. 48 |
| References | p. 50 |
| Clinical, Epidemiological, and Genetic Investigations on Thalassemia and Malaria in Italy | |
| The Evolution of the Knowledge of Thalassemia Genetics: The Italian Contribution | p. 56 |
| Early Observations on the Association between Malaria and Thalassemia | p. 58 |
| Collaboration of Silvestroni and Bianco with Montalenti: At Work on Haldane's Hypothesis | p. 63 |
| Research of Carcassi et al. | p. 68 |
| Studies on Microcythemia Genetics in Italy Funded by the Rockefeller Foundation | p. 69 |
| The Results of Siniscalco's Genetic Studies on the Distribution of Thalassemia, G-6-PD Deficit, and of Malaria | p. 74 |
| The Malaria Hypothesis and the Consequences of Eradicating the Plasmodia and of Thalassemia Prevention | p. 75 |
| Conclusions | p. 76 |
| Acknowledgements | p. 77 |
| References | p. 77 |
| Resistance to Antimalarial Drugs: Parasite and Host Genetic Factors | |
| Introduction | p. 81 |
| Malaria | p. 82 |
| Antimalarial Chemotherapy and Chemoprophylaxis | p. 83 |
| Drugs Available for Treatment of Malaria | p. 83 |
| Antimalarial Drug Resistance | p. 86 |
| Current Status of Drug-Resistant Malaria | p. 86 |
| Parasite Genetic Polymorphism As a Basis for Antimalarial Resistance | p. 89 |
| Genes Associated with Chloroquine Resistance in P. falciparum | p. 90 |
| Mechanism of Resistance to Antifolate Combination Drugs in P. falciparum | p. 93 |
| Mechanism of Atovaquone Resistance in P. falciparum | p. 94 |
| Mechanisms of Drug Resistance in P. vivax | p. 95 |
| Human Drug Metabolism | p. 96 |
| Cytochrome P450 Enzyme Superfamily | p. 96 |
| Uridine Diphosphate Glucuronosyltransferase Enzyme Superfamily | p. 98 |
| Antimalarial Drug Metabolism | p. 100 |
| Antimalarial Drug Levels and Treatment Outcome | p. 104 |
| Conclusions | p. 109 |
| Acknowledgments | p. 110 |
| References | p. 110 |
| Evolutionary Origins of Human Malaria Parasites | |
| The Phylum Apicomplexa | p. 125 |
| The Genus Plasmodium | p. 127 |
| Transfers Between Human and Monkey Hosts | p. 132 |
| Population Structure of Plasmodium falciparum | p. 135 |
| Malaria's Eve Hypothesis | p. 137 |
| Malaria's Eve Counterarguments | p. 140 |
| Appendix | p. 142 |
| References | p. 143 |
| Vector Genetics in Malaria Control | |
| Abstract | p. 147 |
| Introduction | p. 147 |
| The Anopheles culicifacies Complex | p. 149 |
| Paradox Resolved | p. 154 |
| Application in Malaria Control | p. 156 |
| Stratification | p. 157 |
| Insecticide Resistance | p. 158 |
| Bioenvironmental Malaria Control | p. 162 |
| Acknowledgments | p. 164 |
| References | p. 165 |
| The Rate of Mutation of Human Genes | p. 169 |
| Disease and Evolution | p. 175 |
| Index | p. 189 |
| Table of Contents provided by Publisher. All Rights Reserved. |