Advances in Malaria Research

Content: List of contributors xiii    Foreword xvii    Preface xix    1 Introduction: An overview of malaria and Plasmodium 1  Virander S. Chauhan, Chetan E. Chitnis, and Deepak Gaur    History 1    The life cycle of Plasmodium 3    A significant milestone in malaria research: Adaptation of Plasmodium to laboratory culture 4    The advent of present   day technologies and their applications in malaria research 5    Bibliography 6    2 Exoerythrocytic development of Plasmodium parasites 9  Volker T. Heussler, Annika Rennenberg, and Rebecca R. Stanway    The sporozoite   s journey from the skin to the liver 10    Sporozoite invasion 14    Parasite development 15    Protein export from the parasite into the host cell 20    Parasite egress 23    The role of innate immune responses during merosome formation 26    Acknowledgments 27    Bibliography 27    3 Molecular basis of erythrocyte invasion by Plasmodium merozoites 33  Deepak Gaur, Chetan E. Chitnis, and Virander S. Chauhan    The structure of the merozoite 39    The steps of erythrocyte invasion 41    Redundancy and ligand   receptor interactions that mediate parasite adhesion during erythrocyte invasion 57    Signaling events during erythrocyte invasion by malaria parasites 74    Summary and conclusions 75    Bibliography 75    4 The biology of malaria transmission 87  Robert E. Sinden    Purpose 87    History 87    The current research agenda 88    Biology 88    Population dynamics 106    Transmission   blocking interventions 110    Bibliography 114    5 Comparative and functional genomics of malaria parasites 125  Martine M. Zilversmit, Sittiporn Pattaradilokrat, and Xin   zhuan Su    An Introduction to Plasmodium genomes 125    Genome structure of malaria parasites 127    From genome sequences to gene function 133    Summary 139    Acknowledgments 139    Bibliography 139    6 Gene regulation: New insights and possible intervention strategies 149  Artur Scherf, Nicholas A. Malmquist, Rafael M. Martins, Shruthi S. Vembar, and Jose   Juan Lopez   Rubio    Introduction 149    Modes of gene regulation 150    Drug targeting 164    Perspectives 169    Bibliography 171    7 Molecular genetic approaches to malaria research 179  Brendan Elsworth, Mauro F. Azevedo, Brendan S. Crabb, and Paul R. Gilson    Transfection methods 179    Genetic approaches for deriving gene function 184    Conditional knockdown of protein function 187    Protein reporters 190    Conclusions 192    Bibliography 192    8 Transcriptomics and proteomics 197  Archana P. Gupta, Zbynek Bozdech, and Peter R. Preiser    Transcriptional profiling throughout the parasite life cycle 198    Transcriptional regulation 201    Transcriptional variation 205    Biological insights 208    Proteomics 208    Translational regulation 209    Conclusion 212    Bibliography 212    9 The biochemistry of Plasmodium falciparum: An updated overview 219  Hagai Ginsburg    MPMP 219    Carbohydrates 219    Lipid metabolism 227    Amino acids 240    Nucleotide metabolism 252    Cofactors 256    Redox metabolism 265    Mitochondrial functions 268    Hemoglobin digestion and hemozoin production 273    Some reflections for the future 276    Bibliography 277    10 Signaling in malaria parasites 291  Pushkar Sharma and Sudhir Kumar    Protein phosphorylation in Plasmodium 291    Calcium   mediated signaling in Plasmodium 292    Phosphoinositide signaling and trafficking in malaria parasites 295    Cyclic nucleotide signaling in the malaria parasite 296    Future challenges 300    Bibliography 300    11 Membrane transport proteins as therapeutic targets in malaria 307    Sanjay A. Desai, Kempaiah Rayavara, Paresh Sharma, Sayeed K. Syed, Wang Nguitragool, and Praveen Balabaskaran Nina    Host erythrocyte membrane: A shared ion and nutrient channel 308    Parasitophorous vacuolar membrane: Protein export and solute uptake 311    Parasite plasma membrane: Similar to other eukaryotic cells, but different 314    Digestive vacuole: A specialized lysosome   equivalent in the parasite 316    Mitochondrial inner membrane: An unusual ATP synthase with uncertain function 318    Conclusions 319    Acknowledgments 319    Bibliography 319    12 The proteolytic repertoire of malaria parasites 325  Puran Singh Sijwali and Philip J. Rosenthal    Aspartic proteases 325    Cysteine proteases 330    Metalloproteases 333    Serine proteases 335    Threonine proteases 338    Roles of proteases in parasite development 340    Summary and conclusions 343    Acknowledgments 343    Bibliography 343    13 Development of medicines for the control and elimination of malaria 353  Jeremy N. Burrows and Timothy N. C. Wells    Targets for the development of future medicines for malaria 356    The process of drug development 359    Advances in drug development made in the 21st century 365    The global pipeline of new medicines for treating malaria 368    Medicines in the broader context of malaria eradication 370    Conclusion 377    Acknowledgments 377    Bibliography 377    14 Antimalarial drug resistance 383  Naman K. Shah and Neena Valecha    Background 383    Causes of drug resistance 386    Detection of drug resistance 390    Managing drug resistance 397    Conclusion 401    Disclosures 401    Bibliography 401    Further reading 407    15 Epidemiology of Plasmodium falciparum malaria 409  Alberto L. Garcia   Basteiro, Quique Bassat, and Pedro L. Alonso    Burden of disease 409    Geographical distribution of the disease 411    Chain of transmission and infection cycle 413    Malaria endemicity and malaria transmission 415    Malaria elimination and eradication 423    Bibliography 424    16 Malaria pathogenesis 427  Bronner P. Goncalves, Michal Fried, and Patrick E. Duffy    Malaria illness 427    Host susceptibility 439    Parasite virulence 444    Conclusions 450    Bibliography 451    17 Host genetics 465  Thomas N. Williams    What evidence is there that the risk of malaria is genetically determined? 465    Identifying the genes involved 466    Why is genetic resistance important? 467    Genetic polymorphisms of the red blood cell 468    Hemoglobinopathies 474    G6PD deficiency 478    Non   red blood cell polymorphisms 479    Concluding remarks 481    Bibliography 481    18 The immune response in mild and severe malaria: Two sides of the same coin 495  Michael Waisberg, Peter D. Crompton, Louis H. Miller, and Susan K. Pierce    The picture of the acquisition of resistance to uncomplicated and severe malaria: Framing the questions 495    Searching for host genes that confer immune resistance to severe malaria 506    SLE susceptibility and resistance to severe malaria 507    The relationship between the pathogen environment and susceptibility to severe malaria 510    Summary 511    Acknowledgments 511    Bibliography 512    19 Progress in development of malaria vaccines 521  Chetan E. Chitnis, Deepak Gaur, and Virander S. Chauhan    Immunity to malaria 521    Life cycle of malaria parasites and points of intervention with vaccines 522    Pre   erythrocytic stage vaccines 524    Blood   stage vaccines 526    Transmission   blocking vaccines 533    Live attenuated vaccines for malaria 534    Conclusion 535    Bibliography 535    20 Plasmodium vivax: Insights on burden and pathobiology 547  Ivo Mueller, Quique Bassat, Marcus V. G. Lacerda, and Hernando A. del Portillo    Burden of Plasmodium vivax infection and disease 547    Severe Plasmodium vivax malaria 550    Molecular basis of severe disease 552    Concluding remarks and outstanding research questions 558    Bibliography 558    Index 565