Student Number : 9704202D - MSc dissertation - School of Clinical Microbiology and Infectious Diseases - Faculty of Science / Meningococcal disease is an important cause of morbidity and mortality worldwide, particularly in children and young adults. Epidemics caused by Neisseria meningitidis continue to plague many countries on a global scale, none more so than countries of the African ‘meningitis belt’, where attack rates can reach up to 1000/100,000 population. It has been well recognized that most epidemic and endemic cases of meningococcal disease are caused by a limited number of genetically defined clonal groups. The objective of this molecular epidemiological study was to genotypically characterize strains of N. meningitidis collected in South Africa from July 1999 to July 2002. Characterization of meningococcal strains belonging to serogroup A, B, C, W135 and Y, by PFGE and MLST allowed us to determine the genetic population structure of N. meningitidis in South Africa, and thus identify the predominant clonal groups responsible for the majority of meningococcal disease in the country over this period. The results from the genotypic characterization revealed that the greatest majority of meningococcal disease in South Africa was caused by a strains belonging to only a few “hyperinvasive lineages”, most notably strains of the ST-44 complex (lineage III), ST-32 complex (ET-5 complex), ST-11 complex (ET-37 complex), and the ST-1 complex (subgroup I/II) which have all been responsible for major epidemics worldwide. These findings have direct implications on public health decision, particularly with regards to the development of effective intervention and control strategies, and emphasize the need for continuous long-term monitoring of the circulation of these strains in the population.