Cover -- Half Title -- Title Page -- Copyright -- Contents -- Contributors -- Preface -- 1 Clinical Disease: Current Treatment and New Challenges -- Introduction -- Classification and Pathogens -- Rickettsioses -- Ehrlichiosis and Anaplasmosis -- Management, Antimicrobial Efficacy, and Treatment Failures in Rickettsioses and Ehrlichioses -- Controversies and New Challenges in Rickettsial Treatment -- References -- 2 Public Health: Rickettsial Infections and Epidemiology -- Introduction -- Historical Public Health Concerns -- Contemporary Public Health Concerns -- Epidemiology of Rickettsial Diseases in The United States -- RMSF -- Global Impact of Rickettsial Infections -- Tools for Public Health Investigations of Rickettsial Diseases -- Conclusions -- References -- 3 Phylogeny and Comparative Genomics: The Shifting Landscape in The Genomics Era -- Introduction -- Classification and The DNA Revolution -- Age of Genomics (1998 to Present) -- Future Directions -- References -- 4 Invasion of The Mammalian Host: Early Events at The Cellular and Molecular Levels -- Introduction -- Actin Dynamics Involved in Rickettsial Invasion -- Activation of Protein Tyrosine Kinase and P13-Kinase Activities -- Ku70 Is A Receptor Involved in SFGR Invasion -- Rickettsial Surface Cell Antigens -- rOmpB And Its Role in Rickettsial Invasion -- Other Important Adhesin and Invasinlike Proteins -- Concluding Remarks -- 5 Establishing Intracellular Infection: Escape from The Phagosome and Intracellular Colonization (Rickettsiaceae) -- Introduction -- Escape from The Phagosome -- Intracytoplasmic Growth and Effect on Host Cell Structure and Physiology -- Actin-Based Motility and Cell-to-Cell Spread -- Conclusions -- References -- 6 Establishing Intracellular Infection: Modulation of Host Cell Functions (Anaplasmataceae) -- The Family Anaplasmataceae Introduction.

Notable Genomic Features -- Life Cycle and Intracellular Infection -- Two-Component System -- Subverting Host Cellular Processes -- Modulation of Host Cell Gene Expression -- Exploitation of Host Signaling Pathways -- The Anaplasmataceae Pathogen-Occupied Vacuole -- Hijacking Host Lipid and Membrane-Trafficking Pathways -- References -- 7 Rickettsial Physiology and Metabolism in The Face of Reductive Evolution -- Introduction -- A Brief History of Rickettsial Physiology in The Pre-Genomics Era -- Rickettsial Physiology in The Genomics Era -- Rickettsial Gene Regulation -- Perspective -- References -- 8 Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (Rickettsiaceae) -- Target Host Cells, Intracellular Behavior, and Cell-to-Cell Dissemination of Pathogenic Rickettsia Species -- Endothelial Cell Activation by Rickettsia Infection In Vitro -- Mechanisms Underlying Host Cell Transcriptional Activation by Pathogenic Rickettsiae -- Expression and Secretion of Mediators of Inflammation During Infection of Cultured Host Cells with SFGR and TGR -- Inhibition of Apoptosis to Preserve Host Cell Niche Early During The Infection -- Oxidative Stress and Antioxidant Defense Mechanisms During Rickettsia-Host Cell Interactions -- Protective Roles of IFNs Against Rickettsia Infection -- Mechanisms for Intracellular Killing of Rickettsiae Within Host Cells -- Role of Dendritic Cells, NK Cells,and Pattern Recognition Receptors -- Conclusions and Future Perspectives -- References -- 9 Innate Immune Response and Inflammation: Roles in Pathogenesis and Protection (Anaplasmataceae) -- Introduction -- Biology of Early Ehrlichia and Anaplasma Infections -- Clinical Manifestations and Pathology of HME -- Murine Models of Ehrlichia and Anaplasma Infection -- Acquired Immune Responses to Ehrlichia and Immune-Mediated Pathology.

Innate Immune Responses Against Ehrlichia and Anaplasma -- Concluding Remarks and Future Directions -- References -- 10 Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (Rickettsiaceae) -- Introduction -- The Immune Response -- The Endothelium in The Antirickettsial Immune Response -- Vaccine Development -- References -- 11 Adaptive Immune Responses to Infection and Opportunities for Vaccine Development (Anaplasmataceae) -- Introduction -- Response to Infection and Pathogen Immune Modulation -- Known Effective Immunogens -- The Protective Immune Response and Response to Immunization -- Immunodominant, Variable Surface Proteins as Protective Antigens and Immunologic Strain Determinants -- Immunodominant Surface Proteins as Vaccine Candidates -- Identification of Subdominant, Potentially Protective Antigens -- Virulence Factors as Vaccine Candidates -- Future Directions -- References -- 12 Persistence and Antigenic Variation -- Persistence -- Antigenic Variation -- The MSP2 Superfamily In Ehrlichia -- Summary -- References -- 13 Transmission and The Determinants of Transmission Efficiency -- Introduction -- Vectors of The Rickettsiales -- Sylvatic and Zoonotic Cycles of The Order Rickettsiales -- Cofeeding, Modulation of Host Immunity, and Acquisition -- Maintenance of Rickettsial Agents by Arthropod Vectors -- Effects of Climate Change on Rickettsial Challenge -- Perspectives on The Role of Innate Immunity and Transmission of Rickettsiae -- Conclusion -- References -- 14 The Way Forward: Improving Genetic Systems -- Introduction -- Genetic Transformation Systems for Rickettsiales -- Conclusions -- References -- Index.