List of Contributors.

1 Historical Aspects (Keith Cartwright).

1.1 The Origins of Meningococcal Disease.

1.2 The 19th Century.

1.3 From 1900 to 1920.

1.4 From 1921 to 1939.

1.5 From World War II to 1960 – Epidemiology.

1.6 From 1961 to 2005.

1.7 Conclusion.

References.

Part I Epidemiology of Meningococcal Disease.

2 The Population Biology of Neisseria meningitidis: Implications for Meningococcal Disease, Epidemiology and Control (Martin C. J. Maiden and Dominique A. Caugant).

2.1 Introduction: The Meningococcus, an Enigmatic Pathogen.

2.2 Meningococcal Diversity and its Consequences.

2.3 Mechanisms of Diversification and Structuring in Meningococcal Populations.

2.4 Meningococcal Genotypes in Carriage and Disease.

2.5 Global Epidemiology of Meningococcal Disease.

2.6 Conclusions: Implications of Meningococcal Population Biology for Disease Control.

References.

3 Methods for Typing of Meningococci (Keith A. Jolley, Steve J. Gray, Janet Suker and Rachel Urwin).

3.1 Introduction.

3.2 Phenotypic Typing Methods.

3.3 Serological Typing Methods.

3.4 Immunotyping.

3.5 Multilocus Enzyme Electrophoresis.

3.6 Genetic Characterization.

3.7 Conclusion.

References.

4 Antibiotic Resistance (Colin Block and Julio A. Vázquez).

4.1 Introduction.

4.2 Testing Antibiotics Against N. meningitidis.

4.3 Clinical Impact and Spread of Antibiotic Resistance in Meningococcal Disease.

4.4 Are There New Drugs or New Strategies on the Horizon?

4.5 Molecular Tools for Definition of Antimicrobial Susceptibility in N. meningitidis.

References.

Part II Genetics and Genomics of the Meningococcus.

5 Neisseria meningitidis Genome Sequencing Projects (Christoph Schoen and Heike Claus).

5.1 Introduction.

5.2 The Genomes of Neisseria meningitidis.

5.3 Repetitive DNA Sequences Abound in the Meningococcal Genomes.

5.4 Genome-wide Mutational Analyses.

5.5 DNA Microarray Analyses.

5.6 Conclusion.

References.

6 Phase Variation and Adaptive Strategies of N. meningitidis: Insights into the Biology of a Commensal and Pathogen (Peter M. Power and E. Richard Moxon).

6.1 Introduction.

6.2 Early Studies and Genome Sequencing Identify Large Numbers of Phase-variable Genes.

6.3 Repetitive DNA Mediates Most Phase Variation.

6.4 When is a “Potentially Phase-variable Gene” Really Phase Variable?

6.5 Mechanisms of Phase Variation: An Example of Convergent Evolution.

6.6 Trans-acting Genetic and Environment Factors Regulate Phase Variation.

6.7 Local Factors May Influence Rates of Phase Variation.

6.8 Examples of Phase Variation.

6.9 Conclusion: N. meningitidis is Adapted to Adapt.

References.

7 Meningococcal Transformation and DNA Repair (Tonje Davidsen, Ole Herman Ambur and Tone Tønjum).

7.1 Introduction.

7.2 Meningococcal Transformation.

7.3 Mechanisms of Meningococcal Genome Instability.

7.4 Meningococcal DNA Repair Profile.

7.5 Mutator Alleles and Fitness for Survival.

7.6 Concluding Remarks.

References.

8 Structure and Genetics of the Meningococcal Capsule (Matthias Frosch and Ulrich Vogel).

8.1 Introduction.

8.2 Chemical Structure of Meningococcal Capsular Polysaccharides.

8.3 Genetics of Capsule Expression.

8.4 Biochemistry and Genetics of Capsule Biosynthesis.

8.5 Genetics of O-Acetylation.

8.6 Molecular Mechanisms of Capsular Polysaccharide Transport.

8.7 Genetics of Capsule Expression in Serogroup A and Other Rare Serogroups.

8.8 Adaptation, Phase Variation.

Acknowledgements.

References.

9 Genetics, Structure and Function of Lipopolysaccharide (J. Claire Wright, Joyce S. Plested and E. Richard Moxon).

9.1 Introduction.

9.2 Lipid A Structure.

9.3 Core Oligosaccharide Structure.

9.4 Genetics.

9.5 LPS and the Biology of Commensal and Virulence Behavior.

9.6 LPS as a Vaccine Candidate.

Acknowledgements.

References.

10 Major Outer Membrane Proteins of Meningococci (Jeremy Derrick, John E. Heckels and Mumtaz Virji).

10.1 Introduction.

10.2 Mechanisms of Expression, Biological and Immunochemical Properties of Meningococcal MOMPs.

10.3 The Three-dimensional Structures of Meningococcal Outer Membrane Proteins.

References.

11 Iron Metabolism in Neisseria meningitidis (Andrew Ekins and Anthony B. Schryvers).

11.1 Iron Homeostasis in Humans.

11.2 Potential Sources of Iron in the Host for the Meningococcus.

11.3 Iron Acquisition from Transferrin and Lactoferrin.

11.4 Acquisition of Heme Iron.

11.5 Acquisition of Siderophore Iron.

11.6 Regulation of Iron Import and Storage.

References.

12 Genetics, Structure and Function of Pili (Philippe C. Morand and Thomas Rudel).

12.1 Introduction.

12.2 Macromolecular Structure and Biogenesis.

12.3 Genetics.

12.4 Functions Associated with tfp.

12.5 Conclusions.

References.

Part III Infection Biology.

13 Mechanisms of Attachment and Invasion (Sandrine Bourdoulous and Xavier Nassif).

13.1 Introduction.

13.2 Mechanisms of Attachment.

13.3 Mechanisms of Cellular Invasion.

13.4 N. meningitidis Survival and Replication Within Host Cells.

13.5 Interactions with Extracellular Matrix Proteins.

13.6 Conclusions.

References.

14 Role of Complement in Defense Against Meningococcal Infection (Sanjay Ram and Ulrich Vogel).

14.1 Introduction.

14.2 The Complement Cascade.

14.3 Complement Deficiencies and Meningococcal Infections.

14.4 Capsular Polysaccharide and Serum Resistance.

14.5 Lipooligosaccharide Sialylation and Serum Resistance.

14.6 Complement Evasion by Meningococci.

14.7 The MBL Pathway.

14.8 Blocking Antibodies.

14.9 Summary.

References.

15 Cellular Immune Responses in Meningococcal Disease (Oliver Kurzai and Matthias Frosch).

15.1 Introduction.

15.2 Cellular Immunity Against N. meningitidis at the Mucosal Barrier.

15.3 Neutrophils and Invasive Meningococcal Disease.

15.4 Cells of the Adaptive Immune System.

15.5 Conclusions and Perspectives.

References.

Part IV Development of Vaccines.

16 Surrogates of Protection (Ray Borrow and Elizabeth Miller).

16.1 Definitions: Surrogate Versus Correlate of Protection.

16.2 Group C Vaccines.

16.3 Group A Vaccines.

16.4 Tetravalent Conjugate Vaccines.

16.5 Subcapsular Vaccines.

16.6 Conclusions.

References.

17 Conjugate Vaccines (Neil Ravenscoft and Ian M. Feavers).

17.1 Introduction.

17.2 Preparation of Conjugate Vaccines.

17.3 Control Testing of Conjugate Vaccines.

17.4 Immunogenicity of Meningococcal Conjugate Vaccines.

17.5 Future Developments.

References.

18 Outer Membrane Vesicle-based Meningococcal Vaccines (Jan T. Poolman, Philippe Denoël, Christiane Feron, Karine Goraj and Vincent Weynants).

18.1 Introduction.

18.2 Candidate Protein and LPS Immunogens.

18.3 Development of Adapted OMV Vaccines.

18.4 Process for MenB OMV.

18.5 The Upregulation of Vaccine Candidates in OMV: Immunogenicity Data.

References.

19 Genome Mining and Reverse Vaccinology (Rosanna Leuzzi, Silvana Savino, Mariagrazia Pizza and Rino Rappuoli).

19.1 Impact of Genomics on Vaccine Design: the Reverse Vaccinology Approach.

19.2 Candidate Antigen Prediction.

19.3 Antigen Screening.

19.4 GNA1870 as an Example of Immunological Characterization.

19.5 Exploring the Genome: Functional Characterization of Vaccine Candidates.

19.6 Advantages of Multiple-genome Analysis in Vaccine Design: the Example of GBS.

References.

20 Vaccination for the Control of Meningococcal Disease: the Use of Meningococcal Vaccines from the Public Health Perspective (Elisabeth Miller, Mary Ramsay and Helen Campbell).

20.1 Considerations Before the Introduction of New Vaccines or Revised Immunization Programs.

20.2 The UK Example of the Introduction of Meningococcal C Conjugate Vaccine.

20.3 Other Examples of the Introduction of Meningococcal Vaccines.

20.4 Other Meningococcal Vaccines.

20.5 Future Direction for Meningococcal Vaccines.

References.

Part V Clinical and Public Health Management.

21 Pathogenesis and Pathophysiology of Invasive Meningococcal Disease (Petter Brandtzaeg).

21.1 Introduction.

21.2 Classification of the Clinical Presentations.

21.3 Localized Oropharyngeal Infection.

21.4 Generalized Infection.

21.5 Lipopolysaccharides Triggering the Innate Immune System.

21.6 Molecular Mimicry Between Meningococcus and Man.

21.7 N. meningitidis LPS Reacting with the Innate Immune System.

21.8 LPS Activates Human Cells During Meningococcal Infection.

21.9 The Biological Effect of Outer Membrane Vesicles.

21.10 The LPS-deficient N. meningitidis Mutant.

21.11 Distinct Differences Between Meningococcal and Pneumococcal Lethal Septic Shock Plasma.

21.12 Plasma Systems Neutralizing N. meningitidis LPS.

21.13 Compartmentalized Inflammatory Response in the Vasculature Versus Subarachnoid Space.

21.14 Dysfunction of the Cardiovascular System.

21.15 Capillary Leak Syndrome.

21.16 Renal Failure.

21.17 Altered Adrenal Function.

21.18 Other Endocrine Reactions Associated with Meningococcal Septic Shock.

21.19 Coagulopathy in Meningococcal Disease.

21.20 The Natural Coagulation Inhibitors.

21.21 The Fibrinolytic System.

21.22 The Complement System.

21.23 Activation of Neutrophils Related to Disease Severity.

21.24 Meningitis.

21.25 Chronic Meningococcemia.

21.26 Conclusion and Future Aspects.

References.

22 Course of Disease and Clinical Management (Andrew J. Pollard and Simon Nadel).

22.1 Introduction.

22.2 Disease Burden.

22.3 Susceptibility to Infection and Severity of Disease.

22.4 Carriage.

22.5 Presentation and Clinical Features.

22.6 Lumbar Puncture.

22.7 Cardiovascular Shock.

22.8 Initial Assessment and Management.

22.9 Transfer to Intensive Care or Treatment on the General Ward.

22.10 Adjunctive Therapy for Sepsis.

22.11 Conclusion.

Acknowledgements.

References.

23 Public Health Management (James Stuart).

23.1 Introduction.

23.2 Action Before a Case.

23.3 After a Case.

23.4 Outbreaks.

23.5 Conclusion.

References.

Subject Index.