Determination of the optimal age to vaccinate against dengue using a tetravalent dengue vaccine in Brazil

Dengue is endemic in most of the subtropics and tropics with half of the world's population at risk of acquiring an infection. For decades only mosquito control could aid with disease prevention. However, in December 2015 the first dengue vaccine, Dengvaxia, became available.;In this thesis a single-serotype transmission model considering the effect of vaccination is derived. Three different assumptions regarding the biting rate are made. Initially, a constant biting rate is assumed to determine the optimal vaccination age for Brazil. For a more accurate description of the dynamics, mosquito biting rate data is used later on to determine an age-dependent rate.;Lastly, instead of determining the force of infection from the biting rate, agedependent serological data is used to estimate both of these functions. The description of the human population dynamics is also improved upon by using a step-death function rather than a constant death rate.;In order to reduce the burden of dengue, the optimal vaccination age is defined to minimise the lifetime expected risk of hospitalisation or lethality. For both risk functions several theories and uncertainties surrounding the disease outcome and the effect of vaccination are studied. The impact of antibody dependent enhancement and permanent cross-immunity on the vaccination age is determined. Additionally, a vaccine-induced increase is incorporated for the risk of hospitalisation. All possible serotype combinations are considered.;The results of this work demonstrate that the optimal vaccination age depends on how the biting rate and force of infection are defined. A variety of different optimal ages for immunisation are found. These vary with the assumptions relating to serotype cross-reactions and depend particularly on whether a vaccine-induced risk is considered. Consequently, a better understanding of the disease and the effect of the vaccine is paramount for finding an accurate optimal age for dengue immunisation.Dengue is endemic in most of the subtropics and tropics with half of the world's population at risk of acquiring an infection. For decades only mosquito control could aid with disease prevention. However, in December 2015 the first dengue vaccine, Dengvaxia, became available.;In this thesis a single-serotype transmission model considering the effect of vaccination is derived. Three different assumptions regarding the biting rate are made. Initially, a constant biting rate is assumed to determine the optimal vaccination age for Brazil. For a more accurate description of the dynamics, mosquito biting rate data is used later on to determine an age-dependent rate.;Lastly, instead of determining the force of infection from the biting rate, agedependent serological data is used to estimate both of these functions. The description of the human population dynamics is also improved upon by using a step-death function rather than a constant death rate.;In order to reduce the burden of dengue, the optimal vaccination age is defined to minimise the lifetime expected risk of hospitalisation or lethality. For both risk functions several theories and uncertainties surrounding the disease outcome and the effect of vaccination are studied. The impact of antibody dependent enhancement and permanent cross-immunity on the vaccination age is determined. Additionally, a vaccine-induced increase is incorporated for the risk of hospitalisation. All possible serotype combinations are considered.;The results of this work demonstrate that the optimal vaccination age depends on how the biting rate and force of infection are defined. A variety of different optimal ages for immunisation are found. These vary with the assumptions relating to serotype cross-reactions and depend particularly on whether a vaccine-induced risk is considered. Consequently, a better understanding of the disease and the effect of the vaccine is paramount for finding an accurate optimal age for dengue immunisation