The African meningitis belt - a semi-arid region stretching from Senegal to Ethiopia - experiences the highest incidence of bacterial meningitis in the world, characterised by seasonal fluctuations in endemic disease, localized outbreaks, and multiennial epidemics. MenAfriVac, a serogroup A meningococcal conjugate vaccine, was introduced in mass campaigns in 2010 and has significantly reduced carriage and incidence of group A disease across the meningitis belt.

However, other meningococcal serogroups and Streptococcus pneumoniae continue to cause outbreaks of meningitis in the region. A new pentavalent meningococcal conjugate vaccine protecting against serogroups A, C, W, Y, and X is in development and promises to help eliminate outbreaks of meningococcal meningitis by 2030. However, questions remain as to how best to respond to outbreaks of pneumococcal meningitis and non-A meningococcal meningitis and how to use the pentavalent meningococcal conjugate vaccine when it becomes available. This thesis aims to evaluate the remaining challenges to control of bacterial meningitis in the African meningitis belt and assess the relative effectiveness and efficiency of various responses.

The first research chapter describes patterns in bacterial meningitis incidence before and after the introduction of MenAfriVac and compares outbreaks where NmA, NmC, NmW, and S. pneumoniae are predominant. The second chapter describes in detail an outbreak of pneumococcal meningitis in Ghana and models the potential impact of reactive vaccination using pneumococcal conjugate vaccine. In the third chapter I present a systematic review and meta-analysis of meningococcal carriage patterns by age and season in the African meningitis belt and propose ways in which it might inform the use of the pentavalent meningococcal conjugate vaccine. In the fourth chapter, I analyse the results of a longitudinal household study to identify behavioural and environmental risk factors for meningococcal carriage acquisition. The final chapter examines the spatio-temporal spread of the novel NmC strain which emerged in Nigeria in 2013, estimates the impact of reactive vaccination campaigns that occurred in the region between 2015 and 2017, and models the effects of alternative outbreak response strategies, including targeting neighbouring districts.