Using mathematical models to evaluate and inform immunisation strategies with MenAfriVac in the African meningitis belt

The countries of the African meningitis belt suffer from frequent epidemics due to meningococcal meningitis. The introduction of a tailor-made vaccine, known as MenAfriVac, in these countries through mass campaigns of 1-29 year olds has led to a remarkable decline in the burden of disease due to Neisseria meningitides serogroup A. The aim of this work is to identify immunisation strategies with MenAfriVac that best sustain population protection in the long-term and predict vaccine impact across all 26 meningitis belt countries. Firstly, I developed an age-structured transmission dynamic model to explore the impact of a range of different immunisation schedules. Numerical simulations of the model show a period of very low incidence following MenAfriVac introduction, while strong resurgence is predicted in the absence of any long-term immunisation strategy. Of the strategies considered, the introduction of the vaccine into the Expanded Programme on Immunisation at 9 months, 5 years after the initial campaign, together with a mini catch-up campaign resulted in the lowest average annual incidence. Next, my model is compared to an existing model, published two years earlier through a model comparison exercise. The comparison exercise identified a number of errors in the other study which explained the different predictions made by the two models and also led to a correction to the original study being published by the authors. As part of the Vaccine Impact Modelling Consortium, the model was adapted and used to provide estimates on the impact of MenAfriVac on disease incidence for the 26 countries of the meningitis belt under the current schedule of each country. The model consists of 100 age groups and keeps track of the number of cases, deaths and Disability Adjusted Life Years (DALYs) for each age group per year for the period 2010-2100. Assuming that the current schedule continues unchanged until 2100, the model predicts that more than 9 million cases will be prevented in total across all 26 countries. Further, the routine immunisation of school-age children is simulated as an alternative strategy to better understand the role of vaccine induced protection, as new data suggest that antibody response is short-lived when children under the age of two years are vaccinated. Assuming that vaccine protection lasts longer for individuals targeted after the age of five years, model simulations suggest that vaccination of older children would be more efficient in reducing the disease incidence and would also result in a smaller number of people needed to vaccinate to prevent one case. The main conclusion of this work is that sustained use of MenAfriVac is essential to maintain high levels of direct and indirect population protection. Results from this thesis have been used to inform the current immunisation strategy in the countries of the African meningitis belt. Assuming that vaccine duration is shorter for children less than 5 years old, it may be wiser to change the age of routine immunisation and target older children instead. This conclusion can be useful in the near future to inform strategies which will include the new pentavalent vaccine