The Malaria Genome Projects: Promise, Progress, and Prospects

by Irwin W Sherman

Overview

The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project.This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Projects came into being, the people who created them, and the cadre of scientists who are attempting to see the promise of the Projects realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines.Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.

Product Details

ISBN-13:	9781848169036
Publisher:	Imperial College Press
Publication date:	09/07/2012
Pages:	388
Product dimensions:	6.20(w) x 9.10(h) x 1.10(d)

Table of Contents

Preface xi

Chapter 1 Introduction 1

Plasmodium discovered 2

Plasmodium transmitted 10

Plasmodium in hiding 19

Chapter 2 Respice: Before the Genome Project 23

Chapter 3 The Nature of Plasmodium falciparum and its Genome 41

A home for the genome 43

Location, location, location 47

The malaria genome capers 49

Chapter 4 Chipping Away at the Genome 63

Turning "on," turning "off" 71

Evasion 77

Chapter 5 The Importance of Import 85

Chapter 6 Remodeling the Genome's Home 103

Chapter 7 Getting on the Inside 111

Chapter 8 The Great Escape 125

Chapter 9 The Neglected Malaria, Plasmodium vivax 133

Resistance 135

Secrets hidden in the genome 141

Chapter 10 The Anopheles Genome and Transmission Control 145

Making mosquitoes immune 147

Making mosquitoes insecticide resistant 150

Replacement and/or reduction 150

Chapter 11 The Monkey's Tale 155

Chapter 12 A Not so Sweet Solution 171

Isoenzymes, the Achilles' heels of Plasmodium 178

Tackling the Krebs "cycle" 181

Chapter 13 To Search and Find 187

Rapid diagnostic tests 188

Nucleic acid-based tests 189

Loop-mediated isothermal amplification 193

Chapter 14 The Elusive Vaccines 195

Antigens before the genome 196

Two blood-stage vaccine candidates 217

The road to merozoite surface protein 218

The road to apical membrane antigen 1 222

A failed promise, SPf66 224

Transmission-blocking vaccines 227

The sporozoite vaccine revisited 233

Development of the pre-blood-stage vaccine, RTS, S 242

Back to the future 249

Learning from the liver 253

Vaccine approaches before sequencing the genome 261

Vaccine approaches after sequencing the genome 264

Chapter 15 New Medicines, Old Problems 269

The old problem of resistance 273

Chloroquine 275

Resistance to anti-folate drugs 281

Mefloquine and multidrug resistance 284

The fall of mefloquine 288

Atovaquone 289

Artemisia to artemisinins 293

Chapter 16 Prospice: Looking to the Future 301

References 305

Index 359